JAIDS Journal of Acquired Immune Deficiency Syndromes:
Translation of Biomedical Prevention Strategies for HIV: Prospects and Pitfalls
Vermund, Sten H. MD, PhD*,†,‡,§,‖; Tique, José A. MD*,‖; Cassell, Holly M. MPH*; Pask, Megan E. MS*; Ciampa, Philip J. MD, MPH*,†,‡; Audet, Carolyn M. PhD*,§
*Vanderbilt Institute for Global Health, Vanderbilt University School of Medicine, Nashville, TN;
Departments of †Pediatrics;
§Preventive Medicine, Vanderbilt University School of Medicine, Nashville, TN; and
‖Friends in Global Health, Quelimane, Mozambique.
Correspondence to: Sten H. Vermund, MD, PhD, 2525 West End Ave, Suite 750, Nashville, TN 37203 (e-mail: firstname.lastname@example.org).
Support for this supplement was provided by R13 MH-081733-01A1.
The authors have no conflicts of interest to disclose.
Abstract: Early achievements in biomedical approaches for HIV prevention included physical barriers (condoms), clean injection equipment (both for medical use and for injection drug users), blood and blood product safety, and prevention of mother-to-child transmission. In recent years, antiretroviral drugs to reduce the risk of transmission (when the infected person takes the medicines; treatment as prevention) or reduce the risk of acquisition (when the seronegative person takes them; preexposure prophylaxis) have proven to be efficacious. Circumcision of men has also been a major tool relevant for higher prevalence regions such as sub-Saharan Africa. Well-established prevention strategies in the control of sexually transmitted diseases and tuberculosis are highly relevant for HIV (ie, screening, linkage to care, early treatment, and contact tracing). Unfortunately, only slow progress is being made in some available HIV-prevention strategies such as family planning for HIV-infected women who do not want more children and prevention of mother-to-child HIV transmission. Current studies seek to integrate strategies into approaches that combine biomedical, behavioral, and structural methods to achieve prevention synergies. This review identifies the major biomedical approaches demonstrated to be efficacious that are now available. We also highlight the need for behavioral risk reduction and adherence as essential components of any biomedical approach.
Condom barriers, blood and needle safety, and the prevention of mother-to-child transmission of HIV (PMTCT) were the first biomedical strategies to control HIV that did not focus on behavioral risk reduction alone. In the early 1990s, the hopes for an HIV vaccine led to capacity building in HIV-prevention studies and a boost in large-scale trials for prevention.1,2 The use of antiretroviral therapy (ART) in a pregnant woman for the prevention of infection to her infant was a prescient test of concept for the use of ART as prevention [treatment as prevention (TasP)]. The utility of TasP for preventing sexual transmission was demonstrated by the high efficacy demonstrated by the HIV-Prevention Trials Network (HPTN) 052 protocol. Since 2005, compelling biomedical prevention strategies have been added to the armamentarium for HIV prevention, notably male circumcision and ART for the prevention of sexual transmission. Efficacy of combining several of these biomedical techniques into a synergistic (additive or multiplicative) approach remains to be determined.
The history of disease control and prevention is replete with examples of effective tools that are available for use, but are underutilized in the field or the clinic. HIV/AIDS prevention is a prominent case in point, a challenge that the National HIV/AIDS Strategy for HIV in the United States seeks to address.3 Both journalists and scientists have highlighted the disappointing missed opportunities in the HIV epidemic.4–13 Combination prevention approaches are now available that combine multiple efficacious strategies to block transmission, but all must include behavioral components to avoid risk compensation—the increased risk-taking behavior that may accompany prevention approaches that clients perceive to be more effective than they really are.14 All 3 early approaches (condoms, clean needles/syringes, and PMTCT) also required structural reform and technical capacity building to enable widespread dissemination of the interventions. Widespread condom and needle distribution confronted political opposition that inhibited program scale-up in many venues. Even blood safety measures were resisted in the pre-HIV screening era by many blood-banking authorities for economic reasons.
In this article, we will review key biomedical tools for the prevention of HIV transmission (Table 1) and what the prospects and obstacles are for their further utilization in global HIV control. A recurring theme is that we have technologies that can reduce the epidemic, but we have not deployed them widely or consistently.15–20 Other articles in this JAIDS supplement will address behavioral interventions per se, so we will restrict our discussion to the issues arising in the translation of biomedical tools. We acknowledge the subjective nature of a manuscript such as this one; it is challenging to predict how these tools will have an impact on the global pandemic. However, we believe that speculations regarding the scale-up and application of biomedical prevention can be well informed based on the present knowledge of disease control and prevention for HIV/sexually transmitted infections (STI), tuberculosis, and blood-borne infections such as hepatitis B and C.
Antiretroviral Treatment to Reduce Infectiousness of HIV-Infected Persons
TasP is founded on evidence that persons who are HIV-infected and are on combination ART (cART) are less likely to transmit the virus sexually than those not on cART. Higher viral load has been associated with a higher HIV transmission risk in observational studies.21–30 The use of cART has been associated with reduced risk for sexual transmission. In 2011, the HPTN 052 trial demonstrated definitively the huge benefit of cART use in persons with higher CD4+ T-lymphocyte counts in protecting their sexual partners [hazard ratio of 96% protective efficacy; 95% confidence interval (CI): 73% to 99%].31–33 As this benefit was apparent when cART was offered to persons who would not have qualified for HIV treatment for their own sakes [as per 2009 World Health Organization (WHO) treatment guidelines], WHO issued new guidelines in 2012, suggesting that where possible, more persons should be treated with cART than had been recommended heretofore.34 Although expanding the eligibility of cART with the aim of TasP represents a significant opportunity to prevent new infection, issues of drug resistance, disinhibition, and logistics complexities must be addressed for this approach to be effective in nonclinical trial conditions.35
Efforts in high access cities such as San Francisco and Vancouver have made progress in expanding TasP.36–39 It may be that >30 years of work for HIV risk reduction among men who have sex with men (MSM), with mixed success, has contributed to a higher uptake of HIV therapy in these settings.40,41 In the United States as a whole, however, the overall program coverage with testing, linkage to care, and therapy remains disappointing.42–46 Several new controlled community-randomized studies are being launched to study combination prevention, including implementation of expanded ART coverage, to assess the impact on community-HIV transmission. Four groups intend to launch such studies in 2012 or 2013, some with combinations of TasP, medical male circumcision, and strategic and behavioral intervention innovations. The HPTN 071 POPArt study [Richard Hayes, principal investigator (PI)], the Botswana study (Max Essex, PI), and the ANRS/Africa Center study all intend to address the ART for the prevention question within rigorous community-randomized studies. There are a number of smaller studies that also intend to address the question of reducing HIV at a population level, some of which are in the field for preliminary work.
TasP for Injection Drug Users
Although much has been achieved among injection drug users in risk reduction using needle and syringe exchange and opiate agonist–based heroin addiction therapy, there are still regions of the world that do not implement these measures. It is plausible that TasP could also be implemented effectively in this population, and such studies are in progress.
Prevention of Mother-to-Child Transmission of HIV
The earliest test of concept for the use of antiretroviral drugs to reduce HIV viral load and infectiousness in one person to protect another was in PMTCT. Evidence from many definitive randomized controlled trial (RCT), for example, the AIDS Clinical Trials Group 076 trial, HPTN's HIVNET 012 trial confirmed that reducing viral loads with ART could reduce transmission markedly to newborn infants. Subsequently, both cART use in HIV-infected pregnant women during the months of breastfeeding and use of preexposure prophylaxis (PrEP) with ART in breastfeeding infants were judged to be safe and effective in reducing transmission in low-income settings where replacement feeding is neither safe nor affordable.47–52
Despite the proven efficacy of antiretroviral prophylaxis or treatment for PMTCT and the high degree of successful implementation in high and middle income countries,53–55 the proportion of women and infants receiving all stages of PMTCT in resource-limited settings has been disappointing.56–64 Failure to engage mothers and/or infants at any step of prevention continuum (Fig. 1) can lead to a failure in preventive efficacy during pregnancy or the postpartum periods. Each of these steps are amenable to clinical and community interventions to improve engagement and coverage. In an effort to document barriers to PMTCT uptake, researchers have often focused on patients, although there is movement toward complementary hospital-based quality improvement approaches.65–70 Well-documented barriers include the lack of PMTCT-related care systems capable of delivering quality service,57,67,71–73 lack of family or community support,65,74,75 stigma,66,67 and concern with confidentiality/treatment at the clinical site.66 Additional barriers include cost/transportation for travel to the clinic,65 cultural pressure to breastfeed (or concern that not breastfeeding would “out” the mother as being HIV positive),66,76 inadequate alternative food sources for infant feeding,64 inadequate knowledge about HIV transmission,65,74 and a desire to deliver at home or with a traditional birth attendant.65 These and other barriers to full coverage of PMTCT represent some of the challenges of translating the benefits of biomedical knowledge effectively into real-world settings56–58,77–82; other prevention strategies such as TasP and adult circumcision will likely face similar challenges, and will benefit from the lessons learned from PMTCT field experience in low-resource settings.
Systems Strengthening for Implementation of PMTCT and TasP
Widespread health-system deficiencies have been identified in a number of low-income countries that lead to a low uptake and adherence to ARV prophylaxis56,61,83 and EID.84 Although socioeconomic factors are often cited as drivers of poor access to PMTCT or EID,85–88 there is increasing attention to the role that strengthening health systems may play in improving access and other program outcomes,89–91 and efforts are underway to strengthen health systems to improve PMTCT-related care.92,93 In 1 study at 2 district hospitals in rural Mozambique, health-system barriers preventing access to EID were addressed using a conceptual framework for quality improvement adapted from Langley et al.92 The process of maternal postpartum care for HIV-infected mothers was analyzed at each hospital; a 2-phase intervention was designed with the help of nursing staff and patients and evaluated using a before/after intervention study design.69,70 Hospital staff were introduced to the Langley model for quality improvement and given the opportunity to participate in the study by describing the process of care, identifying modifiable health system barriers, and designing an intervention aimed at impacting infant retention in EID. The standard process of referral to the EID clinic during maternity discharge was identified as a target for improvement and an intervention was designed that enhanced referral by more tightly linking maternity and EID services through direct accompaniment and by providing privacy for women during counseling. After 2 cycles of intervention, the proportion of mother/infant pairs that succeeded in accessing Early Infant Diagnosis (EID) within 3 months of the child's life improved by 55%. This is but 1 example highlighting the potential benefit of practical site based innovations to improve retention for HIV prevention from mother to child.90,93 Scaling up of quality improvement–based strategies is an essential approach to strengthen health systems and make the best use of available resources in developing countries.
Complementary Strategies to PMTCT
Implementing an intervention designed to create and sustain behavior change is another alternative to increasing access to biomedical interventions, but this may be a gradual process of education and culture change.94 Attempting to change maternal birthing practices and early child-rearing behavior can be especially challenging, as target behavior may conflict with culturally accepted practices and beliefs. Traditionally, interventions to improve uptake have been targeted at pregnant women.95–97 Recently, the importance of support from husbands in ensuring the uptake of PMTCT has been addressed through the engagement of men in antenatal HIV counseling65,98 and changes to hospital or clinical systems.58,59,68,93,99
Many HIV-infected women who would like to plan their family size do not have access to contraception; it has been estimated that filling the unmet need for contraception among all the HIV-infected women who need it would result in a huge decline in mother-to-child transmissions.100–121 Although this is not TasP, it is another PMTCT intervention that depends on capacity building and broadening of the HIV-prevention mandate to include other primary health care needs in afflicted communities. Concerns that hormonal contraception use in seronegative women may result in a higher risk of acquisition do not apply in the case of seropositive women.122,123 Furthermore, there are alternative approaches to hormonal use that are being underutilized, including the intrauterine device.124–127
Antiretroviral Prophylaxis to Reduce Susceptibility of HIV-Uninfected Persons
At a May 10, 2012, meeting, the US Food and Drug Administration's Antiviral Drugs Advisory Committee recommended the approval of a drug labeled “efficacy supplement” for the use of Truvada tablets [each tablet has 200 mg of emtricitabine (FTC) and 300 mg of tenofovir disoproxil fumarate (TDF), made by Gilead Sciences, Inc.] for PrEP, namely, oral tablet use for the prevention of HIV transmission in HIV-uninfected persons. Oral PrEP has been consistently effective in successive trials in men, ranging from 44% to 68% efficacy in clinical trials such as iPrEx, Partners PrEP, and TDF-2.128–132 In women, the Partners PrEP and TDF-2 studies suggested oral PrEP efficacy, but the FEMPrEP133 and Vaginal and Oral Interventions to Control the Epidemic (VOICE)134,135 trials did not, though the FTC/TDF oral PrEP arm of the VOICE trial continues as of this writing (June 2012). Similarly, the use of a topical 1% tenofovir microbicide intravaginally worked to protect against HIV in women in the CAPRISA 004 trial,136 but it did not work in the VOICE trial.137,138 Hence, the evidence is more consistent that oral PrEP works well in men but is less consistent for oral and for topical PrEP in women (Table 1). Rectal microbicides (also topical PrEP, but designed for anal sex protection) are theoretically useful for women and men practicing anal sex, but they have not yet been tested in phase 3 clinical efficacy trials. Topical PrEP remains an area of intense current investigation.139–144 Opinions differ as to the likely utility of PrEP as a substantial public health tool for HIV prevention, though a female-controlled product could be a valuable addition to women's options.145–148
Occupational exposure to needle stick injuries, surgical instruments, or other substantial medical injuries within the context of caring for an HIV-infected person can expose health care workers (or even sanitation workers) to HIV.149–151 Postexposure prophylaxis (PEP) with cART is now standard practice for many high-risk exposures (with a higher volume in persons who are not viral load suppressed, to give 1 example) and is an option for prophylaxis even in lower risk exposures.152,153 Again, implementation issues loom large: successful PEP requires reducing the risk of the needle exposure to begin with, prompt reporting of needle stick injuries, and successful adherence of exposed staff to the cART PEP regimen.154
PEP is also an alternative for inadvertent sexual exposure, as with condom breakage or nonuse, or with rape. RCT evidence is lacking for both occupational and nonoccupational PEP, but epidemiology suggests cART to be possibly effective for reducing transmission risk.155,156 Again, the translation of PEP efficacy to population effectiveness depends on working systems of surveillance, availability of expertise and cART, willingness of the exposed person to uptake the PEP intervention, and their success in adherence to PEP. The HPTN 040 study demonstrated in an RCT that PEP given to infants born to mothers who had not received ART worked to prevent infant infection.157–160 Intrapartum transmission occurred in 3.2% (47) of the infants studied. Transmission rates were significantly lower in the Zidovudine + Nevirapine arm 2.2% (11) (95% CI: 1.2 to 4.0, P = 0.045) and the ZDV + NFV + 3 TC 2.5% (12) (95% CI: 1.4% to 4.3%, P = 0.045) compared with the ZDV arm.157–159
MEDICAL MALE CIRCUMCISION TO REDUCE SUSCEPTIBILITY
Ecological and epidemiological evidence has suggested that infant or later circumcision might reduce HIV transmission risk.161–165 Voluntary medical male circumcision in adults was tested in 3 RCTs in sub-Saharan Africa, and their results were remarkably consistent.166–168 Hence, when the cheaper, simpler, and safer infant circumcision had not been performed previously, adult male circumcision is deemed advisable in high HIV prevalence settings. There are obstacles to uptake: cultural acceptability, fear of pain and/or surgical mistakes, and poor understanding about the risks and benefits of circumcision.169–183 The decision to circumcise or not is often based more on social acceptability than on medical evidence. In sub-Saharan Africa, rites of passage for men often include circumcision (traditionally conducted outside of a clinical setting) presenting an opportunity for health workers to incorporate safe surgical practices into traditional rituals. Education campaigns and improved access to safe surgical services have led to an increased uptake among communities where circumcision was uncommon.184,185 Western countries are experiencing the opposite trend. The belief that male circumcision is akin to genital mutilation is becoming more widespread. Some researchers and laypeople argue that it leads to long-term psychological trauma in the male infant, impacting everything from mother–son bonding to future sexual relationships, although there is no scientific evidence to support this belief.
Male circumcision of either HIV-infected men or HIV-uninfected men who later seroconvert may reduce their infectiousness to others through reduction of STIs (such as the very common human papillomavirus) among other potential mechanisms.186–199 However, if men have sex before their wounds are healed, after surgery, the risk could rise as has been observed in Uganda.200 Also, risk compensation is a concern if men increase high-risk behavior because they have been circumcised and no longer perceive personal risk.201,202 If proper technical procedures, risk reduction counseling, and community consultations are adhered to, male circumcision is a theoretically powerful tool, especially when incorporated into a combination prevention strategy designed to reduce the risk through behavioral modification and biological interventions.164,203–207
Evidence that circumcision will prevent HIV acquisition or transmission among MSM is not consistent and is less likely to be as strong in its association as with heterosexual transmission.195,208–211 For example, being circumcised may not help much if one is the receptive partner in MSM sexual relations. Infant circumcision is cheaper, easier, and less risky than is adult circumcision. An excellent long-term investment is to seek universal male infant circumcision in high prevalence regions to nurture a new generation of lower risk men.169,212–219
HIV VACCINES TO REDUCE SUSCEPTIBILITY (PREVENTIVE VACCINES)
In a huge RCT in Thailand (n = 16,402), a 4-dose priming live vector canarypox vaccine [ALVAC-HIV (vCP1521)] vaccine followed by 2-dose gp120 subunit bivalent (AIDSVAX B/E) booster regimen proved to be somewhat efficacious in preventing HIV infection.220 The modified intention-to-treat analysis excluded 7 participants who had acute HIV-1 infection at baseline unbeknownst to the investigators, finding a vaccine efficacy of 31% (95% CI: 1% to 52%).221 The vaccine regimen did not reduce the viral set point in participants who seroconverted despite being in the vaccine group. Despite this success, neither product is being carried forward into production nor is the trial being confirmed to propose licensure. This illustrates the global economic dynamics of vaccine development; only a more efficacious product is likely to inspire the private sector to license and market the vaccine.
Successful vaccine development is no longer just a theoretical possibility; having succeeded in primate animal models and now in a human RCT, investigators will not rest until a viable and more efficacious product is developed.222,223 This suggests a host of challenges from which we can learn from other vaccine experiences. HIV is an STI, so suboptimal coverage with hepatitis B vaccine and human papillomavirus vaccine (the only licensed STI vaccines) in adolescents and adults suggests that HIV vaccine deployment would run into the same problems.224–229 We have no good global vaccine infrastructures or routine health care engagement for adult vaccination. There is some reticence to agree to STI vaccines given stigma, including among parents for their children.230 Continued challenges in global vaccine coverage, even for childhood vaccines, are to be expected to be relevant for HIV vaccines, once available.231 This includes antivaccine forces claiming the lack of cost–benefit evidence for vaccines, spurious toxicities attributed falsely to vaccines, and arguments about immunological overload that have no evidence to support them.232,233
One of the principal objections voiced to STI vaccines is that of disinhibition or risk compensation, the possibility that if someone is protected against an STI, then they might be more likely to engage in risky behavior. In the early hepatitis B virus (HBV) vaccine RCTs, there was a rise in HBV incidence after the first dose of HBV vaccine, attributed to the disinhibition among MSM who were in the trial.234,235 Hence, this potential risk must be taken seriously and studied alongside prevention technology benefits.
HIV VACCINES TO REDUCE TRANSMISSIBILITY (THERAPEUTIC VACCINES)
An effective vaccine given to HIV-infected persons could theoretically reduce the viral load in the infected person by enhancing or complementing natural imperfect immune responses. Animal models have suggested feasibility of such approaches in idealized experiments, but no human data have been convincing enough to suggest that any tested products have been effective.236
TREATMENT OF COINFECTIONS TO REDUCE HIV VIRAL LOAD AND TRANSMISSION RISK
Coinfection with such infectious agents as Mycobacterium tuberculosis, helminthes, herpesviruses, and syphilis can cause immune activation and upmodulate HIV expression.27,237–239 Coinfection with Schistosoma haematobium is associated with increased HIV risk, as was seen previously for STIs, perhaps related to the disruption of integumentary integrity and/or local inflammation.240–243 Rhesus macaques infected with Schistosoma mansoni are more susceptible to HIV and shed more HIV once infected.244–247 Treatment or suppression of the coinfections can reduce plasma and presumably genital viral load, as suggested in genital herpesvirus–suppression studies.248–255 Thus, excellent primary care for HIV-infected persons that involves coinfection treatment or suppression could reduce the transmissibility of HIV by reducing HIV viral load and transmissibility.
CLEAN NEEDLES AND SYRINGES FOR INJECTION
Despite global reductions in HIV infection, substance use specifically injection drug use (IDU) continues to be a significant driver of the epidemic.256 IDU has been estimated to be responsible for about 9% (3 million) of the 34 million persons of persons living with HIV globally, including about 17% of the prevalent HIV cases in the United States.257,258 The WHO estimates that 1 out of 10 new HIV infections globally is attributed to IDU, and CDC suggests IDU to be associated with 9% of new HIV infections in the United States.258,259 Eastern Europe and Central Asia continue to incur high rates due to IDU; the numbers infected with HIV in these regions have tripled over the past decade.259–261 To stem the impending surge in new cases in regions not yet saturated and/or effectively implemented control measures, multiple prevention strategies have been implemented with various degrees of success. Harm-reduction efforts such as opioid substitution therapy (OST) and needle and syringe programs (NSPs) have shown to be effective at reducing HIV in IDUs.9,262–264 Needle exchange was one of the first methods used in the public health arsenal to control the epidemic. NSPs not only provide sterile needles and equipment but they also provide an avenue for HIV, STI, substance abuse, and mental health care and treatment to a marginalized risk group. Since the mid-1980s, NSPs have emerged around the world with great success, most notably in Canada, Western Europe, and Australia.260 However coverage has been stymied by controversy, government-imposed regulations, and lack of available resources. Out of the 151 countries where IDU is prevalent, only 82 countries have implemented NSPs, and OST is provided in 71 countries; however, coverage is variable across programs and regions.260 Low- and middle-income countries countries have been unable to meet the WHO distribution guidelines of 200 syringes per IDU per year.265 In the United States, NSP support is wrought by politics and regulation. In 2009, the ban on using US federal funds for NSPs was lifted by the Executive Branch of government only to be reinstated by the Congress in the 2012 federal budget.266,267
The peril of extensive nosocomial HIV transmission has been demonstrated in major outbreaks in Russia, Libya, Romania, and other countries.268–271 Medical injections were implicated in each of these outbreaks. The importance attributed to unsafe medical injections in the transmission of HIV in sub-Saharan Africa has been minimized by the enormous attentions given to sexually transmitted HIV.272,273 The perception that unsafe medical injections are rare in sub-Saharan Africa rests on the assurance in health workers' training and supervision, and compliance with existing safety guidelines. In Cameroon, health workers admit to selling syringes and needles for extra income and then reusing syringes and needles.274 These workers were often unhappy with their own behaviors, suggesting that education and efforts to improve working conditions might reduce the practice.274 Programs to improve provider practices; reduce community demand for injections; support the procurement of appropriate injection commodities to eliminate reuse of syringes and needles and improve safety are still needed in these settings.
In higher income countries, public concern has obliged blood-collection agencies and policy makers to continue to search for more sensitive HIV screening tests, despite a dramatic decrease in the transmission of HIV infection through blood transfusions.275–278 The availability of HIV-1 p24 antigenic testing and state-of-the art genomic amplification techniques, although expensive, allow for the identification of the vast majority of window-phase donations.277,279 The impact of other less-expensive strategies on HIV transmission risk reduction, such as donor deferral and the nonuse of donations from higher-risk subpopulations has been highlighted in low-income countries.280–284 Unfortunately, these cost-effective strategies are not being applied consistently.280,281,285–287 Although progress toward improving safe and adequate supplies of blood is being made,285 continued government commitment is critical for ensuring quality, safety, and adequacy of the blood supply, particularly in lower-income nations where challenges in capacity, logistics, and infrastructure are common.
PHYSICAL BARRIERS TO VIRUS–CELL CONTACT
Consistent and correct condom use is estimated to provide an 80% reduction in HIV seroconversion.288 Male condoms are inexpensive, widely accessible, have few side effects, and (among many populations) are a culturally acceptable HIV-prevention intervention. The number of condoms used worldwide is increasing, possibly due to increased social marketing campaigns to increase social acceptability in casual and committed relationships.289 Although condoms reduce the risk of HIV transmission, evidence suggests they are used inconsistently.289–291 Negotiating condom use can be difficult for women as the decision to use a condom often rests with her partner.
Female condoms were designed to provide women with more control over their sexual safety, but uptake has been low.292,293 Women needed considerable training and motivation to use the first generation products successfully.294–297 New generation products are better designed and may be more appealing; studies are in progress.298 Among couples where both partners actively participate in the decision-making process, condoms may be eschewed for other reasons: cost, feel, availability, desire for pregnancy, the belief that they are unnecessary in a “serious” relationship, or religious beliefs may sway partners to have unprotected sex.299–301
The finding of an efficacious intervention in one venue does not guarantee success in a different cultural context. A prime example is the control of the HIV epidemic among IDUs in Australia vs. the continuing spread in Russia; lack of political support for universal NSP and a ban on OST in Russia fuel their IDU-related HIV epidemic.260,302,303 A second example is the success in the 1990s with HIV prevention in Uganda, contrasted to that seen in its neighboring nations.304–307 Standardized approaches for adapting interventions to new contexts have been developed, including RE-AIM308,309 and ADAPT-ITT,94,310 but adaption of behavioral interventions is time consuming and fraught with potential challenges. The tailoring of a given epidemic response to local drivers of transmission is needed for both effectiveness and efficiency. Combination prevention approaches are most promising, but they require substantial success in achieving coverage metrics beyond those achieved in most global programs.311–313 The good news is that the myriad of biomedical intervention strategies now demonstrated to be effective in reducing HIV transmission can be combined to make major inroads into the global pandemic.314,315 Even as we research new approaches, the scientific community shares an urgent obligation to communicate current opportunities to policy makers, funders, and communities to motivate HIV control and prevention.316
1. Vermund SH. The role of prevention research in HIV vaccine trials. AIDS Res Hum Retroviruses. 1994;10(suppl 2):S303–S305.
2. Sista ND, Abdool Karim Q, Hinson K, et al.. Experience in international clinical research: the HIV Prevention Trials Network. Clin Investig (Lond). 2011;1:1609–1618.
3. Millett GA, Crowley JS, Koh H, et al.. A way forward: the National HIV/AIDS Strategy and reducing HIV incidence in the United States. J Acquir Immune Defic Syndr. 2010;55(suppl 2):S144–S147.
4. Shilts R. And the Band Played on: Politics, People, and the AIDS Epidemic. New York, NY: Penguin Books; 1988.
5. Dorell CG, Sutton MY, Oster AM, et al.. Missed opportunities for HIV testing in health care settings among young African American men who have sex with men: implications for the HIV epidemic. AIDS Patient Care STDS. 2011;25:657–664.
6. Tragard A, Shrestha IB. System-wide effects of Global Fund investments in Nepal. Health Policy Plan. 2010;25(suppl 1):i58–i62.
7. Bassett IV, Walensky RP. Integrating HIV screening into routine health care in resource-limited settings. Clin Infect Dis. 2010;50(suppl 3):S77–S84.
8. Lurie P, Drucker E. An opportunity lost: HIV infections associated with lack of a national needle-exchange programme in the USA. Lancet. 1997;349:604–608.
9. Drucker E, Lurie P, Wodak A, et al.. Measuring harm reduction: the effects of needle and syringe exchange programs and methadone maintenance on the ecology of HIV. AIDS. 1998;12(suppl A):S217–S230.
10. Perumal R, Padayatchi N, Stiefvater E. The whole is greater than the sum of the parts: recognising missed opportunities for an optimal response to the rapidly maturing TB-HIV co-epidemic in South Africa. BMC Public Health. 2009;9:243.
11. Makwiza I, Nyirenda L, Bongololo G, et al.. Who has access to counseling and testing and anti-retroviral therapy in Malawi—an equity analysis. Int J Equity Health. 2009;8:13.
12. Girardi E, Sabin CA, Monforte AD. Late diagnosis of HIV infection: epidemiological features, consequences and strategies to encourage earlier testing. J Acquir Immune Defic Syndr. 2007;46(suppl 1):S3–S8.
13. Walensky RP, Wood R, Fofana MO, et al.. The clinical impact and cost-effectiveness of routine, voluntary HIV screening in South Africa. J Acquir Immune Defic Syndr. 2011;56:26–35.
14. Vermund SH, Hodder SL, Justman JE, et al.. Addressing research priorities for prevention of HIV infection in the United States. Clin Infect Dis. 2010;50(suppl 3):S149–S155.
15. Hussein M, Jira C, Girma B. Assessment of effective coverage of HIV prevention of pregnant mother to child transmission services in Jimma Zone, South West Ethiopia. Ethiop J Health Sci. 2011;21(suppl 1):1–7.
16. Boyer S, Koulla-Shiro S, Abe C, et al.. Implementing operational research to scale-up access to antiretroviral therapy for HIV infection: lessons learned from the Cameroonian experience. Curr Opin HIV AIDS. 2011;6:239–244.
17. Srikantiah P, Ghidinelli M, Bachani D, et al.. Scale-up of national antiretroviral therapy programs: progress and challenges in the Asia Pacific region. AIDS. 2010;24(suppl 3):S62–S71.
18. Nakanjako D, Colebunders R, Coutinho AG, et al.. Strategies to optimize HIV treatment outcomes in resource-limited settings. AIDS Rev. 2009;11:179–189.
19. Bowen A, Palasanthiran P, Sohn AH. Global challenges in the development and delivery of paediatric antiretrovirals. Drug Discov Today. 2008;13:530–535.
20. Meyers T, Moultrie H, Naidoo K, et al.. Challenges to pediatric HIV care and treatment in South Africa. J Infect Dis. 2007;196(suppl 3):S474–S481.
21. Donnell D, Baeten JM, Kiarie J, et al.. Heterosexual HIV-1 transmission after initiation of antiretroviral therapy: a prospective cohort analysis. Lancet. 2010;375:2092–2098.
22. Lingappa JR, Hughes JP, Wang RS, et al.. Estimating the impact of plasma HIV-1 RNA reductions on heterosexual HIV-1 transmission risk. PLoS One. 2010;5:e12598.
23. Hallett TB, Baeten JM, Heffron R, et al.. Optimal uses of antiretrovirals for prevention in HIV-1 serodiscordant heterosexual couples in South Africa: a modelling study. PLoS Med. 2011;8:e1001123.
24. Castilla J, Del Romero J, Hernando V, et al.. Effectiveness of highly active antiretroviral therapy in reducing heterosexual transmission of HIV. J Acquir Immune Defic Syndr. 2005;40:96–101.
25. Pedraza MA, del Romero J, Roldan F, et al.. Heterosexual transmission of HIV-1 is associated with high plasma viral load levels and a positive viral isolation in the infected partner. J Acquir Immune Defic Syndr. 1999;21:120–125.
26. Fideli US, Allen SA, Musonda R, et al.. Virologic and immunologic determinants of heterosexual transmission of human immunodeficiency virus type 1 in Africa. AIDS Res Hum Retroviruses. 2001;17:901–910.
27. Modjarrad K, Chamot E, Vermund SH. Impact of small reductions in plasma HIV RNA levels on the risk of heterosexual transmission and disease progression. AIDS. 2008;22:2179–2185.
28. Reynolds SJ, Makumbi F, Nakigozi G, et al.. HIV-1 transmission among HIV-1 discordant couples before and after the introduction of antiretroviral therapy. AIDS. 2011;25:473–477.
29. Tovanabutra S, Robison V, Wongtrakul J, et al.. Male viral load and heterosexual transmission of HIV-1 subtype E in northern Thailand. J Acquir Immune Defic Syndr. 2002;29:275–283.
30. Quinn TC, Wawer MJ, Sewankambo N, et al.. Viral load and heterosexual transmission of human immunodeficiency virus type 1. Rakai Project Study Group. N Engl J Med. 2000;342:921–929.
31. Cohen MS, Chen YQ, McCauley M, et al.. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med. 2011;365:493–505.
32. Eshleman SH, Hudelson SE, Redd AD, et al.. Analysis of genetic linkage of HIV from couples enrolled in the HIV Prevention Trials Network 052 trial. J Infect Dis. 2011;204:1918–1926.
33. Cohen MS, McCauley M, Gamble TR. HIV treatment as prevention and HPTN 052. Curr Opin HIV AIDS. 2012;7:99–105.
34. WHO. Guidance on Couples HIV Testing and Counselling Including Antiretroviral Therapy for Treatment and Prevention in Serodiscordant Couples: Recommendations for a Public Health Approach. Geneva, Switzerland: World Health Organization; 2012. ISBN: 978 92 4 150197 2.
35. Smith K, Powers KA, Kashuba AD, et al.. HIV-1 treatment as prevention: the good, the bad, and the challenges. Curr Opin HIV AIDS. 2011;6:315–325.
36. Das M, Chu PL, Santos GM, et al.. Decreases in community viral load are accompanied by reductions in new HIV infections in San Francisco. PLoS One. 2010;5:e11068.
37. Charlebois ED, Das M, Porco TC, et al.. The effect of expanded antiretroviral treatment strategies on the HIV epidemic among men who have sex with men in San Francisco. Clin Infect Dis. 2011;52:1046–1049.
38. Hogg RS, Moore DM, Michelow WD, et al.. Reduction of HIV incidence in men who have sex with men. Lancet Infect Dis. 2010;10:655–656.
39. Wood E, Milloy MJ, Montaner JS. HIV treatment as prevention among injection drug users. Curr Opin HIV AIDS. 2012;7:151–156.
40. McDaid LM, Hart GJ. Sexual risk behaviour for transmission of HIV in men who have sex with men: recent findings and potential interventions. Curr Opin HIV AIDS. 2010;5:311–315.
41. Hart GJ, Elford J. Sexual risk behaviour of men who have sex with men: emerging patterns and new challenges. Curr Opin Infect Dis. 2010;23:39–44.
42. Gardner EM, McLees MP, Steiner JF, et al.. The spectrum of engagement in HIV care and its relevance to test-and-treat strategies for prevention of HIV infection. Clin Infect Dis. 2011;52:793–800.
43. Centers for Disease Control and Prevention. Vital signs: HIV prevention through care and treatment—United States. MMWR Morb Mortal Wkly Rep. 2011;60:1618–1623.
44. Blair JM, McNaghten AD, Frazier EL, et al.. Clinical and behavioral characteristics of adults receiving medical care for HIV infection—Medical Monitoring Project, United States, 2007. MMWR Surveill Summ. 2011;60:1–20.
45. Centers for Disease Control and Prevention. Results of the expanded HIV testing initiative—25 jurisdictions, United States, 2007–2010. MMWR Morb Mortal Wkly Rep. 2011;60:805–810.
46. Burns DN, Dieffenbach CW, Vermund SH. Rethinking prevention of HIV type 1 infection. Clin Infect Dis. 2010;51:725–731.
47. Wilfert CM, Sripipatana T, Spensley A, et al.. Prevention of vertical transmission of HIV in resource-limited countries. Adv Exp Med Biol. 2011;697:41–57.
48. Mepham SO, Bland RM, Newell ML. Prevention of mother-to-child transmission of HIV in resource-rich and -poor settings. BJOG. 2011;118:202–218.
49. Read JS. Prevention of mother-to-child transmission of HIV: antiretroviral strategies. Clin Perinatol. 2010;37:765–776, viii.
50. Kourtis AP, Bulterys M. Mother-to-child transmission of HIV: pathogenesis, mechanisms and pathways. Clin Perinatol. 2010;37:721–737, vii.
51. Coutsoudis A, Kwaan L, Thomson M. Prevention of vertical transmission of HIV-1 in resource-limited settings. Expert Rev Anti Infect Ther. 2010;8:1163–1175.
52. Mofenson LM. Prevention in neglected subpopulations: prevention of mother-to-child transmission of HIV infection. Clin Infect Dis. 2010;50(suppl 3):S130–S148.
53. Fowler MG, Gable AR, Lampe MA, et al.. Perinatal HIV and its prevention: progress toward an HIV-free generation. Clin Perinatol. 2010;37:699–719, vii.
54. Mofenson LM. Antiretroviral drugs to prevent breastfeeding HIV transmission. Antivir Ther. 2010;15:537–553.
55. McIntyre J. Use of antiretrovirals during pregnancy and breastfeeding in low-income and middle-income countries. Curr Opin HIV AIDS. 2010;5:48–53.
56. Stringer EM, Sinkala M, Stringer JS, et al.. Prevention of mother-to-child transmission of HIV in Africa: successes and challenges in scaling-up a nevirapine-based program in Lusaka, Zambia. AIDS. 2003;17:1377–1382.
57. Stringer JS, Sinkala M, Maclean CC, et al.. Effectiveness of a city-wide program to prevent mother-to-child HIV transmission in Lusaka, Zambia. AIDS. 2005;19:1309–1315.
58. Megazzini KM, Sinkala M, Vermund SH, et al.. A cluster-randomized trial of enhanced labor ward-based PMTCT services to increase nevirapine coverage in Lusaka, Zambia. AIDS. 2010;24:447–455.
59. Mandala J, Torpey K, Kasonde P, et al.. Prevention of mother-to-child transmission of HIV in Zambia: implementing efficacious ARV regimens in primary health centers. BMC Public Health. 2009;9:314.
60. Torpey K, Kabaso M, Kasonde P, et al.. Increasing the uptake of prevention of mother-to-child transmission of HIV services in a resource-limited setting. BMC Health Serv Res. 2010;10:29.
61. van Lettow M, Bedell R, Landes M, et al.. Uptake and outcomes of a prevention-of mother-to-child transmission (PMTCT) program in Zomba district, Malawi. BMC Public Health. 2011;11:426.
62. Oladokun RE, Awolude O, Brown BJ, et al.. Service uptake and performance of the prevention of mother-to-child transmission (PMTCT) programme in Ibadan, Nigeria. Afr J Med Med Sci. 2010;39:81–87.
63. Karamagi CA, Tumwine JK, Tylleskar T, et al.. Antenatal HIV testing in rural eastern Uganda in 2003: incomplete rollout of the prevention of mother-to-child transmission of HIV programme? BMC Int Health Hum Rights. 2006;6:6.
64. Bulterys M, Ellington S, Kourtis AP. HIV-1 and breastfeeding: biology of transmission and advances in prevention. Clin Perinatol. 2010;37:807–824, ix–x.
65. Peltzer K, Jones D, Weiss SM, et al.. Promoting male involvement to improve PMTCT uptake and reduce antenatal HIV infection: a cluster randomized controlled trial protocol. BMC Public Health. 2011;11:778.
66. Bond V, Chase E, Aggleton P. Stigma, HIV/AIDS and prevention of mother-to-child transmission in Zambia. Eval Program Plann. 2002;25:347–356.
67. Sprague C, Chersich MF, Black V. Health system weaknesses constrain access to PMTCT and maternal HIV services in South Africa: a qualitative enquiry. AIDS Res Ther. 2011;8:10.
68. Doherty TM, McCoy D, Donohue S. Health system constraints to optimal coverage of the prevention of mother-to-child HIV transmission programme in South Africa: lessons from the implementation of the national pilot programme. Afr Health Sci. 2005;5:213–218.
69. Ciampa PJ, Burlison JR, Blevins M, et al.. Improving retention in the early infant diagnosis of HIV program in rural Mozambique by better service integration. J Acquir Immune Defic Syndr. 2011;58:115–119.
70. Ciampa PJ, Tique JA, Juma N, et al.. Addressing poor retention of infants exposed to HIV: a quality improvement study in rural Mozambique. J Acquir Immune Defic Syndr. 2012;60:e46–e52.
71. Bratt JH, Torpey K, Kabaso M, et al.. Costs of HIV/AIDS outpatient services delivered through Zambian public health facilities. Trop Med Int Health. 2011;16:110–118.
72. Ekouevi DK, Stringer E, Coetzee D, et al.. Health facility characteristics and their relationship to coverage of PMTCT of HIV services across four African countries: the PEARL study. PLoS One. 2012;7:e29823.
73. Stringer EM, Sinkala M, Kumwenda R, et al.. Personal risk perception, HIV knowledge and risk avoidance behavior, and their relationships to actual HIV serostatus in an urban African obstetric population. J Acquir Immune Defic Syndr. 2004;35:60–66.
74. Bajunirwe F, Muzoora M. Barriers to the implementation of programs for the prevention of mother-to-child transmission of HIV: a cross-sectional survey in rural and urban Uganda. AIDS Res Ther. 2005;2:10.
75. Nkuoh GN, Meyer DJ, Tih PM, et al.. Barriers to men's participation in antenatal and prevention of mother-to-child HIV transmission care in Cameroon, Africa. J Midwifery Womens Health. 2010;55:363–369.
76. Doherty T, Chopra M, Nkonki L, et al.. Effect of the HIV epidemic on infant feeding in South Africa: When they see me coming with the tins they laugh at me. Bull World Health Organ. 2006;84:90–96.
77. Reithinger R, Megazzini K, Durako SJ, et al.. Monitoring and evaluation of programmes to prevent mother to child transmission of HIV in Africa. BMJ. 2007;334:1143–1146.
78. Stringer EM, Ekouevi DK, Coetzee D, et al.. Coverage of nevirapine-based services to prevent mother-to-child HIV transmission in 4 African countries. JAMA. 2010;304:293–302.
79. Coetzee D, Hilderbrand K, Boulle A, et al.. Effectiveness of the first district-wide programme for the prevention of mother-to-child transmission of HIV in South Africa. Bull World Health Organ. 2005;83:489–494.
80. Colvin M, Chopra M, Doherty T, et al.. Operational effectiveness of single-dose nevirapine in preventing mother-to-child transmission of HIV. Bull World Health Organ. 2007;85:466–473.
81. Stringer EM, Chi BH, Chintu N, et al.. Monitoring effectiveness of programmes to prevent mother-to-child HIV transmission in lower-income countries. Bull World Health Organ. 2008;86:57–62.
82. Experts/Researchers UUWECH. Consultative Meeting on: Evaluating the Impact of Prevention of Mother-to-Child Transmission of HIV (PMTCT) Services in Low- and Middle-Income Countries in Averting New HIV Infections in Children and Improving Child Survival. Nashville, TN: Vanderbilt University School of Medicine; 2009:1–42.
83. Peltzer K, Sikwane E, Majaja M. Factors associated with short-course antiretroviral prophylaxis (dual therapy) adherence for PMTCT in Nkangala district, South Africa. Acta Paediatr. 2011;100:1253–1257.
84. Cook RE, Ciampa PJ, Sidat M, et al.. Predictors of successful early infant diagnosis of HIV in a rural district hospital in Zambezia, Mozambique. J Acquir Immune Defic Syndr. 2011;56:e104–e109.
85. Perez F, Mukotekwa T, Miller A, et al.. Implementing a rural programme of prevention of mother-to-child transmission of HIV in Zimbabwe: first 18 months of experience. Trop Med Int Health. 2004;9:774–783.
86. Manzi M, Zachariah R, Teck R, et al.. High acceptability of voluntary counselling and HIV-testing but unacceptable loss to follow up in a prevention of mother-to-child HIV transmission programme in rural Malawi: scaling-up requires a different way of acting. Trop Med Int Health. 2005;10:1242–1250.
87. Nyandiko WM, Otieno-Nyunya B, Musick B, et al.. Outcomes of HIV-exposed children in western Kenya: efficacy of prevention of mother to child transmission in a resource-constrained setting. J Acquir Immune Defic Syndr. 2010;54:42–50.
88. Jones SA, Sherman GG, Varga CA. Exploring socio-economic conditions and poor follow-up rates of HIV-exposed infants in Johannesburg, South Africa. AIDS Care. 2005;17:466–470.
89. Braun M, Kabue MM, McCollum ED, et al.. Inadequate coordination of maternal and infant HIV services detrimentally affects early infant diagnosis outcomes in Lilongwe, Malawi. J Acquir Immune Defic Syndr. 2011;56:e122–e128.
90. Youngleson MS, Nkurunziza P, Jennings K, et al.. Improving a mother to child HIV transmission programme through health system redesign: quality improvement, protocol adjustment and resource addition. PLoS One. 2010;5:e13891.
91. Leatherman S, Ferris TG, Berwick D, et al.. The role of quality improvement in strengthening health systems in developing countries. Int J Qual Health Care. 2010;22:237–243.
92. Langley G, Nolan K, Nolan T, et al.. The Improvement Guide: A Practical Approach to Enhancing Organizational Performance. San Francisco, CA: Jossey-Bass; 1996.
93. Doherty T, Chopra M, Nsibande D, et al.. Improving the coverage of the PMTCT programme through a participatory quality improvement intervention in South Africa. BMC Public Health. 2009;9:406.
94. Wingood GM, DiClemente RJ. The ADAPT-ITT model: a novel method of adapting evidence-based HIV Interventions. J Acquir Immune Defic Syndr. 2008;47(suppl 1):S40–S46.
95. Baek C, Rutenberg N. Implementing programs for the prevention of mother-to-child HIV transmission in resource-constrained settings: Horizons studies, 1999–2007. Public Health Rep. 2010;125:293–304.
96. Horwood C, Haskins L, Vermaak K, et al.. Prevention of mother to child transmission of HIV (PMTCT) programme in KwaZulu-Natal, South Africa: an evaluation of PMTCT implementation and integration into routine maternal, child and women's health services. Trop Med Int Health. 2010;2.
97. Futterman D, Shea J, Besser M, et al.. Mamekhaya: a pilot study combining a cognitive-behavioral intervention and mentor mothers with PMTCT services in South Africa. AIDS Care. 2010;22:1093–1100.
98. Tshibumbu DD. Prevention of Mother to Child Transmission of HIV (PMTCT) Programme in KwaZulu-Natal, South Africa: An Evaluation of PMTCT Implementation and Integration into Routine Maternal, Child and Women's Health Services. South Africa: Master of Public Health, University of South Africa; 2006;15:992–999.
99. Kasenga F, Byass P, Emmelin M, et al.. The implications of policy changes on the uptake of a PMTCT programme in rural Malawi: first three years of experience. Glob Health Action. 2009;2 [doi: 10.3402/gha.v2i0.1883].
100. Friend DR, Doncel GF. Combining prevention of HIV-1, other sexually transmitted infections and unintended pregnancies: development of dual-protection technologies. Antiviral Res. 2010;88(suppl 1):S47–S54.
101. Reynolds HW, Janowitz B, Wilcher R, et al.. Contraception to prevent HIV-positive births: current contribution and potential cost savings in PEPFAR countries. Sex Transm Infect. 2008;84(suppl 2):ii49–ii53.
102. Reynolds HW, Janowitz B, Homan R, et al.. The value of contraception to prevent perinatal HIV transmission. Sex Transm Dis. 2006;33:350–356.
103. Wilcher R, Petruney T, Reynolds HW, et al.. From effectiveness to impact: contraception as an HIV prevention intervention. Sex Transm Infect. 2008;84(suppl 2):ii54–ii60.
104. Hladik W, Stover J, Esiru G, et al.. The contribution of family planning towards the prevention of vertical HIV transmission in Uganda. PLoS One. 2009;4:e7691.
105. King R, Estey J, Allen S, et al.. A family planning intervention to reduce vertical transmission of HIV in Rwanda. AIDS. 1995;9(suppl 1):S45–S51.
106. Wanyenze RK, Tumwesigye NM, Kindyomunda R, et al.. Uptake of family planning methods and unplanned pregnancies among HIV-infected individuals: a cross-sectional survey among clients at HIV clinics in Uganda. J Int AIDS Soc. 2011;14:35.
107. Stuart GS. Fourteen million women with limited options: HIV/AIDS and highly effective reversible contraception in sub-Saharan Africa. Contraception. 2009;80:412–416.
108. Johnson KB, Akwara P, Rutstein SO, et al.. Fertility preferences and the need for contraception among women living with HIV: the basis for a joint action agenda. AIDS. 2009;23(suppl 1):S7–S17.
109. Mark KE, Meinzen-Derr J, Stephenson R, et al.. Contraception among HIV concordant and discordant couples in Zambia: a randomized controlled trial. J Womens Health (Larchmt). 2007;16:1200–1210.
110. Massad LS, Evans CT, Wilson TE, et al.. Contraceptive use among U.S. women with HIV. J Womens Health (Larchmt). 2007;16:657–666.
111. Rutenberg N, Baek C. Field experiences integrating family planning into programs to prevent mother-to-child transmission of HIV. Stud Fam Plann. 2005;36:235–245.
112. Hoffman IF, Martinson FE, Powers KA, et al.. The year-long effect of HIV-positive test results on pregnancy intentions, contraceptive use, and pregnancy incidence among Malawian women. J Acquir Immune Defic Syndr. 2008;47:477–483.
113. Adair T. Unmet need for contraception among HIV-positive women in Lesotho and implications for mother-to-child transmission. J Biosoc Sci. 2009;41:269–278.
114. Kaida A, Laher F, Strathdee SA, et al.. Contraceptive use and method preference among women in Soweto, South Africa: the influence of expanding access to HIV care and treatment services. PLoS One. 2010;5:e13868.
115. Todd CS, Stibich MA, Laher F, et al.. Influence of culture on contraceptive utilization among HIV-positive women in Brazil, Kenya, and South Africa. AIDS Behav. 2011;15:454–468.
116. Stanwood NL, Cohn SE, Heiser JR, et al.. Contraception and fertility plans in a cohort of HIV-positive women in care. Contraception. 2007;75:294–298.
117. Delvaux T, Nostlinger C. Reproductive choice for women and men living with HIV: contraception, abortion and fertility. Reprod Health Matters. 2007;15(suppl):46–66.
118. Allen S, Stephenson R, Weiss H, et al.. Pregnancy, hormonal contraceptive use, and HIV-related death in Rwanda. J Womens Health (Larchmt). 2007;16:1017–1027.
119. Kongnyuy EJ, Soskolne V, Adler B. Hormonal contraception, sexual behaviour and HIV prevalence among women in Cameroon. BMC Womens Health. 2008;8:19.
120. Mitchell HS, Stephens E. Contraception choice for HIV positive women. Sex Transm Infect. 2004;80:167–173.
121. Weinberg A, Forster-Harwood J, McFarland EJ, et al.. Resistance to antiretrovirals in HIV-infected pregnant women. J Clin Virol. 2009;45:39–42.
122. Heffron R, Donnell D, Rees H, et al.. Use of hormonal contraceptives and risk of HIV-1 transmission: a prospective cohort study. Lancet Infect Dis. 2012;12:19–26.
123. WHO, Department of Reproductive Health and Research. Hormonal Contraception and HIV: Technical Statement. Geneva, Switzerland: World Health Organization; 2012.
124. Stringer EM, Kaseba C, Levy J, et al.. A randomized trial of the intrauterine contraceptive device vs hormonal contraception in women who are infected with the human immunodeficiency virus. Am J Obstet Gynecol. 2007;197:144; e141–148.
125. Curtis KM, Nanda K, Kapp N. Safety of hormonal and intrauterine methods of contraception for women with HIV/AIDS: a systematic review. AIDS. 2009;23(suppl 1):S55–S67.
126. Heikinheimo O, Lahteenmaki P. Contraception and HIV infection in women. Hum Reprod Update. 2009;15:165–176.
127. Sinei SK, Morrison CS, Sekadde-Kigondu C, et al.. Complications of use of intrauterine devices among HIV-1-infected women. Lancet. 1998;351:1238–1241.
128. Grant RM, Lama JR, Anderson PL, et al.. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med. 2010;363:2587–2599.
129. Baeten J, Donnell D, Ndase P, et al.. Abstract #29: ARV PrEP for HIV-1 prevention among heterosexual men and women. Paper presented at: 19th Conference on Retroviruses and Opportunistic Infections; March 5–8, 2012; Seattle, WA.
130. Thigpen MC, Kebaabetswe PM, Smith DK, et al.. Abstract # WELBC01: daily oral antiretroviral use for the prevention of HIV infection in heterosexually active young adults in Botswana: results from the TDF2 study. Paper presented at: 6th IAS Conference on HIV Pathogenesis, Treatment, and Prevention; July 17–20, 2011; Rome, Italy.
131. Grohskopf L, Gvetadze R, Pathak S, et al.. Abstract # FRLBC102: preliminary analysis of biomedical data from the phase II clinical safety trial of tenofovir disoproxil fumarate (TDF) for HIV-1 pre-exposure prophylaxis (PrEP) among U.S. men who have sex with men (MSM). Paper presented at: XVIII International AIDS Conference; July 18–23, 2010; Vienna, Austria.
133. Van Damme L, Corneli A, Ahmed K, et al.. Abstract # 32LB: the FEM-PrEP trial of emtricitabine/tenofovir disoproxil fumarate (Truvada) among African women. Paper presented at: 19th Conference on Retroviruses and Opportunistic Infections; March 5–8, 2012; Seattle, WA.
136. Abdool Karim Q, Abdool Karim SS, Frohlich JA, et al.. Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women. Science. 2010;329:1168–1174.
137. Quinones-Mateu ME, Vanham G. HIV microbicides: where are we now? Curr HIV Res. 2012;10:1–2.
138. McEnery R. Oral tenofovir arm of VOICE trial discontinued early. IAVI Rep. 2011;15:21.
139. Morris GC, Lacey CJ. Microbicides and HIV prevention: lessons from the past, looking to the future. Curr Opin Infect Dis. 2010;23:57–63.
140. Nuttall J. Microbicides in the prevention of HIV infection: current status and future directions. Drugs. 2010;70:1231–1243.
141. Kelly CG, Shattock RJ. Specific microbicides in the prevention of HIV infection. J Intern Med. 2011;270:509–519.
142. Belec L, Jenabian MA, Charpentier C, et al.. Combinatorial prevention of HIV transmission in women: the case for a vaginal microbicide. Future Microbiol. 2011;6:731–737.
143. Pirrone V, Thakkar N, Jacobson JM, et al.. Combinatorial approaches to the prevention and treatment of HIV-1 infection. Antimicrob Agents Chemother. 2011;55:1831–1842.
144. Hladik F, Doncel GF. Preventing mucosal HIV transmission with topical microbicides: challenges and opportunities. Antiviral Res. 2010;88(suppl 1):S3–S9.
145. Underhill K, Operario D, Mimiaga MJ, et al.. Implementation science of pre-exposure prophylaxis: preparing for public use. Curr HIV/AIDS Rep. 2010;7:210–219.
146. Myers GM, Mayer KH. Oral preexposure anti-HIV prophylaxis for high-risk U.S. populations: current considerations in light of new findings. AIDS Patient Care STDS. 2011;25:63–71.
147. Romanelli F, Murphy B. Systemic preexposure prophylaxis for human immunodeficiency virus infection. Pharmacotherapy. 2010;30:1021–1030.
148. van de Vijver DA, Boucher CA. The risk of HIV drug resistance following implementation of pre-exposure prophylaxis. Curr Opin Infect Dis. 2010;23:621–627.
149. Panlilio AL, Cardo DM, Grohskopf LA, et al.; Service USPH. Updated U.S. Public Health Service guidelines for the management of occupational exposures to HIV and recommendations for postexposure prophylaxis. MMWR Recomm Rep. 2005;54:1–17.
150. Cardo DM, Culver DH, Ciesielski CA, et al.. A case–control study of HIV seroconversion in health care workers after percutaneous exposure. Centers for Disease Control and Prevention Needlestick Surveillance Group. N Engl J Med. 1997;337:1485–1490.
151. Chin RL. Postexposure prophylaxis for HIV. Emerg Med Clin North Am. 2010;28:421–429, Table of Contents.
152. Landovitz RJ, Currier JS. Clinical practice. Postexposure prophylaxis for HIV infection. N Engl J Med. 2009;361:1768–1775.
153. Bryant J, Baxter L, Hird S. Non-occupational postexposure prophylaxis for HIV: a systematic review. Health Technol Assess. 2009;13:iii, ix–x, 1–60.
154. Tolle MA, Schwarzwald HL. Postexposure prophylaxis against human immunodeficiency virus. Am Fam Physician. 2010;82:161–166.
155. Almeda J, Casabona J, Allepuz A, et al.. Recommendations for non-occupational postexposure HIV prophylaxis. Spanish working group on non-occupational postexposure HIV prophylaxis of the Catalonian center for epidemiological studies on AIDS and the AIDS study group [in Spanish]. Enferm Infecc Microbiol Clin. 2002;20:391–400.
156. Myles JE, Hirozawa A, Katz MH, et al.. Postexposure prophylaxis for HIV after sexual assault. JAMA. 2000;284:1516–1518.
157. Nielsen-Saines K, Watts H, Veloso VG, et al.. Abstract # 124LB: phase III randomized trial of the safety and efficacy of 3 neonatal ARV regimens for prevention of intrapartum HIV-1 transmission: NICHD HPTN 040/PACTG 1043. Paper presented at: 18th Conference on Retroviruses and Opportunistic Infections; February 27–March 2, 2011; Boston, MA.
158. Mirochnick M, Nielsen-Saines K, Pilotto JH, et al.. Nelfinavir and lamivudine pharmacokinetics during the first two weeks of life. Pediatr Infect Dis J. 2011;30:769–772.
159. Mirochnick M, Nielsen-Saines K, Pilotto JH, et al.. Nevirapine concentrations in newborns receiving an extended prophylactic regimen. J Acquir Immune Defic Syndr. 2008;47:334–337.
160. NIAID/NIH. 18th Conference on Retroviruses and Opportunistic Infections: day four: selected highlights of NIH-supported research preventing mother-to-child transmission, HIV transmission factors among key topics presented. NIAID Media Availability, 2011. Available at: http://www.niaid.nih.gov/news/newsreleases/2011/Pages/CROIwed11.asp
. Accessed June 3, 2012.
161. Bongaarts J, Reining P, Way P, et al.. The relationship between male circumcision and HIV infection in African populations. AIDS. 1989;3:373–377.
162. Wamai RG, Morris BJ, Bailis SA, et al.. Male circumcision for HIV prevention: current evidence and implementation in sub-Saharan Africa. J Int AIDS Soc. 2011;14:49.
163. Weiss HA, Quigley MA, Hayes RJ. Male circumcision and risk of HIV infection in sub-Saharan Africa: a systematic review and meta-analysis. AIDS. 2000;14:2361–2370.
164. Siegfried N, Muller M, Volmink J, et al.. Male circumcision for prevention of heterosexual acquisition of HIV in men. Cochrane Database Syst Rev. 2003:CD003362.
165. Weiss HA, Thomas SL, Munabi SK, et al.. Male circumcision and risk of syphilis, chancroid, and genital herpes: a systematic review and meta-analysis. Sex Transm Infect. 2006;82:101–109; discussion 110.
166. Gray RH, Kigozi G, Serwadda D, et al.. Male circumcision for HIV prevention in men in Rakai, Uganda: a randomised trial. Lancet. 2007;369:657–666.
167. Bailey RC, Moses S, Parker CB, et al.. Male circumcision for HIV prevention in young men in Kisumu, Kenya: a randomised controlled trial. Lancet. 2007;369:643–656.
168. Auvert B, Taljaard D, Lagarde E, et al.. Randomized, controlled intervention trial of male circumcision for reduction of HIV infection risk: the ANRS 1265 Trial. PLoS Med. 2005;2:e298.
169. White RG, Glynn JR, Orroth KK, et al.. Male circumcision for HIV prevention in sub-Saharan Africa: who, what and when? AIDS. 2008;22:1841–1850.
170. Auvert B, Buve A, Lagarde E, et al.. Male circumcision and HIV infection in four cities in sub-Saharan Africa. AIDS. 2001;15(suppl 4):S31–S40.
171. Shaffer DN, Bautista CT, Sateren WB, et al.. The protective effect of circumcision on HIV incidence in rural low-risk men circumcised predominantly by traditional circumcisers in Kenya: two-year follow-up of the Kericho HIV Cohort Study. J Acquir Immune Defic Syndr. 2007;45:371–379.
172. Drain PK, Halperin DT, Hughes JP, et al.. Male circumcision, religion, and infectious diseases: an ecologic analysis of 118 developing countries. BMC Infect Dis. 2006;6:172.
173. Westercamp N, Bailey RC. Acceptability of male circumcision for prevention of HIV/AIDS in sub-Saharan Africa: a review. AIDS Behav. 2007;11:341–355.
174. Edgil D, Stankard P, Forsythe S, et al.. Voluntary medical male circumcision: logistics, commodities, and waste management requirements for scale-up of services. PLoS Med. 2011;8:e1001128.
175. Templeton DJ. Male circumcision to reduce sexual transmission of HIV. Curr Opin HIV AIDS. 2010;5:344–349.
176. Weiss HA, Dickson KE, Agot K, et al.. Male circumcision for HIV prevention: current research and programmatic issues. AIDS. 2010;24(suppl 4):S61–S69.
177. Muula AS, Prozesky HW, Mataya RH, et al.. Prevalence of complications of male circumcision in Anglophone Africa: a systematic review. BMC Urol. 2007;7:4.
178. Lagarde E, Dirk T, Puren A, et al.. Acceptability of male circumcision as a tool for preventing HIV infection in a highly infected community in South Africa. AIDS. 2003;17:89–95.
179. Wang AL, Duke W, Schmid GP. Print media reporting of male circumcision for preventing HIV infection in sub-Saharan Africa. Bull World Health Organ. 2009;87:595–603.
180. Boily MC, Desai K, Masse B, et al.. Incremental role of male circumcision on a generalised HIV epidemic through its protective effect against other sexually transmitted infections: from efficacy to effectiveness to population-level impact. Sex Transm Infect. 2008;84(suppl 2):ii28–ii34.
181. Begley EB, Jafa K, Voetsch AC, et al.. Willingness of men who have sex with men (MSM) in the United States to be circumcised as adults to reduce the risk of HIV infection. PLoS One. 2008;3:e2731.
182. Grund JM, Hennink MM. A qualitative study of sexual behavior change and risk compensation following adult male circumcision in urban Swaziland. AIDS Care. 2012;24:245–251.
183. Weiss HA, Plummer ML, Changalucha J, et al.. Circumcision among adolescent boys in rural northwestern Tanzania. Trop Med Int Health. 2008;13:1054–1061.
184. Mwandi Z, Murphy A, Reed J, et al.. Voluntary medical male circumcision: translating research into the rapid expansion of services in Kenya, 2008–2011. PLoS Med. 2011;8:e1001130.
185. Lissouba P, Taljaard D, Rech D, et al.. Adult male circumcision as an intervention against HIV: an operational study of uptake in a South African community (ANRS 12126). BMC Infect Dis. 2011;11:253.
186. Tobian AA, Grabowski MK, Kigozi G, et al.. High-risk human papillomavirus prevalence is associated with HIV infection among heterosexual men in Rakai, Uganda. Sex Transm Infect. 2013;89:122–127.
187. Albero G, Castellsague X, Giuliano AR, et al.. Male circumcision and genital human papillomavirus: a systematic review and meta-analysis. Sex Transm Dis. 2012;39:104–113.
188. Marrazzo JM, Cates W. Interventions to prevent sexually transmitted infections, including HIV infection. Clin Infect Dis. 2011;53(suppl 3):S64–S78.
189. Vanbuskirk K, Winer RL, Hughes JP, et al.. Circumcision and acquisition of human papillomavirus infection in young men. Sex Transm Dis. 2011;38:1074–1081.
190. Larke N, Thomas SL, Dos Santos Silva I, et al.. Male circumcision and human papillomavirus infection in men: a systematic review and meta-analysis. J Infect Dis. 2011;204:1375–1390.
191. Backes DM, Bleeker MC, Meijer CJ, et al.. Male circumcision is associated with a lower prevalence of human papillomavirus-associated penile lesions among Kenyan men. Int J Cancer. 2012;130:1888–1897.
192. Tobian AA, Kong X, Wawer MJ, et al.. Circumcision of HIV-infected men and transmission of human papillomavirus to female partners: analyses of data from a randomised trial in Rakai, Uganda. Lancet Infect Dis. 2011;11:604–612.
193. Wawer MJ, Tobian AA, Kigozi G, et al.. Effect of circumcision of HIV-negative men on transmission of human papillomavirus to HIV-negative women: a randomised trial in Rakai, Uganda. Lancet. 2011;377:209–218.
194. Mabey D, Ndowa F, Latif A. What have we learned from sexually transmitted infection research in sub-Saharan Africa? Sex Transm Infect. 2010;86:488–492.
195. Jozkowski K, Rosenberger JG, Schick V, et al.. Relations between circumcision status, sexually transmitted infection history, and HIV serostatus among a national sample of men who have sex with men in the United States. AIDS Patient Care STDS. 2010;24:465–470.
196. Smith JS, Moses S, Hudgens MG, et al.. Increased risk of HIV acquisition among Kenyan men with human papillomavirus infection. J Infect Dis. 2010;201:1677–1685.
197. Smith DK, Taylor A, Kilmarx PH, et al.. Male circumcision in the United States for the prevention of HIV infection and other adverse health outcomes: report from a CDC consultation. Public Health Rep. 2010;125(suppl 1):72–82.
198. Gray RH, Serwadda D, Kong X, et al.. Male circumcision decreases acquisition and increases clearance of high-risk human papillomavirus in HIV-negative men: a randomized trial in Rakai, Uganda. J Infect Dis. 2010;201:1455–1462.
199. Serwadda D, Wawer MJ, Makumbi F, et al.. Circumcision of HIV-infected men: effects on high-risk human papillomavirus infections in a randomized trial in Rakai, Uganda. J Infect Dis. 2010;201:1463–1469.
200. Wawer MJ, Makumbi F, Kigozi G, et al.. Circumcision in HIV-infected men and its effect on HIV transmission to female partners in Rakai, Uganda: a randomised controlled trial. Lancet. 2009;374:229–237.
201. Bridges JF, Selck FW, Gray GE, et al.. Condom avoidance and determinants of demand for male circumcision in Johannesburg, South Africa. Health Policy Plan. 2011;26:298–306.
202. Gust DA, Kretsinger K, Pals SL, et al.. Male circumcision as an HIV prevention intervention in the U.S.: influence of health care providers and potential for risk compensation. Prev Med. 2011;52:270–273.
203. Kigozi G, Gray RH, Wawer MJ, et al.. The safety of adult male circumcision in HIV-infected and uninfected men in Rakai, Uganda. PLoS Med. 2008;5:e116.
204. Mehta SD, Gray RH, Auvert B, et al.. Does sex in the early period after circumcision increase HIV-seroconversion risk? Pooled analysis of adult male circumcision clinical trials. AIDS. 2009;23:1557–1564.
205. Kelly R, Kiwanuka N, Wawer MJ, et al.. Age of male circumcision and risk of prevalent HIV infection in rural Uganda. AIDS. 1999;13:399–405.
206. Baeten JM, Celum C, Coates TJ. Male circumcision and HIV risks and benefits for women. Lancet. 2009;374:182–184.
207. Sanchez J, Sal YRVG, Hughes JP, et al.. Male circumcision and risk of HIV acquisition among MSM. AIDS. 2011;25:519–523.
208. Vermund SH, Qian HZ. Circumcision and HIV prevention among men who have sex with men: no final word. JAMA. 2008;300:1698–1700.
209. Schneider JA, Michaels S, Gandham SR, et al.. A protective effect of circumcision among receptive male sex partners of Indian men who have sex with men. AIDS Behav. 2012;16:350–359.
210. Millett GA, Flores SA, Marks G, et al.. Circumcision status and risk of HIV and sexually transmitted infections among men who have sex with men: a meta-analysis. JAMA. 2008;300:1674–1684.
211. Buchbinder SP, Vittinghoff E, Heagerty PJ, et al.. Sexual risk, nitrite inhalant use, and lack of circumcision associated with HIV seroconversion in men who have sex with men in the United States. J Acquir Immune Defic Syndr. 2005;39:82–89.
212. Mavhu W, Hatzold K, Laver SM, et al.. Acceptability of early infant male circumcision as an HIV prevention intervention in Zimbabwe: a qualitative perspective. PLoS One. 2012;7:e32475.
213. Waters E, Stringer E, Mugisa B, et al.. Acceptability of neonatal male circumcision in Lusaka, Zambia. AIDS Care. 2012;24:12–19.
214. Mugwanya KK, Whalen C, Celum C, et al.. Circumcision of male children for reduction of future risk for HIV: acceptability among HIV serodiscordant couples in Kampala, Uganda. PLoS One. 2011;6:e22254.
215. Perez F, Aung KD, Ndoro T, et al.. Participation of traditional birth attendants in prevention of mother-to-child transmission of HIV services in two rural districts in Zimbabwe: a feasibility study. BMC Public Health. 2008;8:401.
216. Wambura M, Mwanga JR, Mosha JF, et al.. Acceptability of medical male circumcision in the traditionally circumcising communities in Northern Tanzania. BMC Public Health. 2011;11:373.
217. Waiswa P, Kemigisa M, Kiguli J, et al.. Acceptability of evidence-based neonatal care practices in rural Uganda—implications for programming. BMC Pregnancy Childbirth. 2008;8:21.
218. Madhivanan P, Krupp K, Chandrasekaran V, et al.. Acceptability of male circumcision among mothers with male children in Mysore, India. AIDS. 2008;22:983–988.
219. Mshana G, Wambura M, Mwanga J, et al.. Traditional male circumcision practices among the Kurya of North-eastern Tanzania and implications for national programmes. AIDS Care. 2011;23:1111–1116.
220. Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S, et al.. Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. N Engl J Med. 2009;361:2209–2220.
221. Haynes BF, Gilbert PB, McElrath MJ, et al.. Immune-correlates analysis of an HIV-1 vaccine efficacy trial. N Engl J Med. 2012;366:1275–1286.
222. Paris RM, Kim JH, Robb ML, et al.. Prime-boost immunization with poxvirus or adenovirus vectors as a strategy to develop a protective vaccine for HIV-1. Expert Rev Vaccines. 2010;9:1055–1069.
223. Vaccari M, Poonam P, Franchini G. Phase III HIV vaccine trial in Thailand: a step toward a protective vaccine for HIV. Expert Rev Vaccines. 2010;9:997–1005.
224. Fairley CK, Read TR. Vaccination against sexually transmitted infections. Curr Opin Infect Dis. 2012;25:66–72.
225. Bar-On ES, Goldberg E, Fraser A, et al.. Combined DTP–HBV–HIB vaccine versus separately administered DTP–HBV and HIB vaccines for primary prevention of diphtheria, tetanus, pertussis, hepatitis B and Haemophilus influenzae
B (HIB). Cochrane Database Syst Rev 2009:CD005530.
226. Garland SM, Skinner SR, Brotherton JM. Adolescent and young adult HPV vaccination in Australia: achievements and challenges. Prev Med. 2011;53(suppl 1):S29–S35.
227. Humiston SG, Rosenthal SL. Challenges to vaccinating adolescents: vaccine implementation issues. Pediatr Infect Dis J. 2005;24(suppl):S134–S140.
228. Mast EE, Williams IT, Alter MJ, et al.. Hepatitis B vaccination of adolescent and adult high-risk groups in the United States. Vaccine. 1998;16(suppl):S27–S29.
229. Suh CA, Saville A, Daley MF, et al.. Effectiveness and net cost of reminder/recall for adolescent immunizations. Pediatrics. 2012;129:1437–1445.
230. Liddon N, Pulley L, Cockerham WC, et al.. Parents'/guardians' willingness to vaccinate their children against genital herpes. J Adolesc Health. 2005;37:187–193.
231. Rainey JJ, Watkins M, Ryman TK, et al.. Reasons related to non-vaccination and under-vaccination of children in low and middle income countries: findings from a systematic review of the published literature, 1999–2009. Vaccine. 2011;29:8215–8221.
232. Offit PA. Studying complementary and alternative therapies. JAMA. 2012;307:1803–1804.
233. Offit PA. Should childhood vaccination be mandatory? Yes. BMJ. 2012;344:e2434.
234. Szmuness W, Stevens CE, Zang EA, et al.. A controlled clinical trial of the efficacy of the hepatitis B vaccine (Heptavax B): a final report. Hepatology. 1981;1:377–385.
235. Szmuness W, Stevens CE, Harley EJ, et al.. Hepatitis B vaccine: demonstration of efficacy in a controlled clinical trial in a high-risk population in the United States. N Engl J Med. 1980;303:833–841.
236. Garcia F, Leon A, Gatell JM, et al.. Therapeutic vaccines against HIV infection. Hum Vaccines Immunother. 2012;8:569–581.
237. Modjarrad K, Vermund SH. An addition to the effect of treating co-infections on HIV-1 viral load. Lancet Infect Dis. 2011;11:81.
238. Modjarrad K, Vermund SH. Effect of treating co-infections on HIV-1 viral load: a systematic review. Lancet Infect Dis. 2010;10:455–463.
239. Barnabas RV, Webb EL, Weiss HA, et al.. The role of coinfections in HIV epidemic trajectory and positive prevention: a systematic review and meta-analysis. AIDS. 2011;25:1559–1573.
240. Mbabazi PS, Andan O, Fitzgerald DW, et al.. Examining the relationship between urogenital schistosomiasis and HIV infection. PLoS Negl Trop Dis. 2011;5:e1396.
241. Hayes R, Watson-Jones D, Celum C, et al.. Treatment of sexually transmitted infections for HIV prevention: end of the road or new beginning? AIDS. 2010;24(suppl 4):S15–S26.
242. White RG, Orroth KK, Glynn JR, et al.. Treating curable sexually transmitted infections to prevent HIV in Africa: still an effective control strategy? J Acquir Immune Defic Syndr. 2008;47:346–353.
243. Steen R, Wi TE, Kamali A, et al.. Control of sexually transmitted infections and prevention of HIV transmission: mending a fractured paradigm. Bull World Health Organ. 2009;87:858–865.
244. Siddappa NB, Hemashettar G, Shanmuganathan V, et al.. Schistosoma mansoni
enhances host susceptibility to mucosal but not intravenous challenge by R5 Clade C SHIV. PLoS Negl Trop Dis. 2011;5:e1270.
245. Chenine AL, Shai-Kobiler E, Steele LN, et al.. Acute Schistosoma mansoni
infection increases susceptibility to systemic SHIV clade C infection in rhesus macaques after mucosal virus exposure. PLoS Negl Trop Dis. 2008;2:e265.
246. Ayash-Rashkovsky M, Chenine AL, Steele LN, et al.. Coinfection with Schistosoma mansoni
reactivates viremia in rhesus macaques with chronic simian–human immunodeficiency virus clade C infection. Infect Immun. 2007;75:1751–1756.
247. Chenine AL, Buckley KA, Li PL, et al.. Schistosoma mansoni
infection promotes SHIV clade C replication in rhesus macaques. AIDS. 2005;19:1793–1797.
248. Mugwanya K, Baeten JM, Mugo NR, et al.. High-dose valacyclovir HSV-2 suppression results in greater reduction in plasma HIV-1 levels compared with standard dose acyclovir among HIV-1/HSV-2 coinfected persons: a randomized, crossover trial. J Infect Dis. 2011;204:1912–1917.
249. Zuckerman RA, Lucchetti A, Whittington WL, et al.. Herpes simplex virus (HSV) suppression with valacyclovir reduces rectal and blood plasma HIV-1 levels in HIV-1/HSV-2-seropositive men: a randomized, double-blind, placebo-controlled crossover trial. J Infect Dis. 2007;196:1500–1508.
250. Celum C, Wald A, Lingappa JR, et al.. Acyclovir and transmission of HIV-1 from persons infected with HIV-1 and HSV-2. N Engl J Med. 2010;362:427–439.
251. Baeten JM, Strick LB, Lucchetti A, et al.. Herpes simplex virus (HSV)-suppressive therapy decreases plasma and genital HIV-1 levels in HSV-2/HIV-1 coinfected women: a randomized, placebo-controlled, cross-over trial. J Infect Dis. 2008;198:1804–1808.
252. Mayaud P, Legoff J, Weiss HA, et al.. Impact of acyclovir on genital and plasma HIV-1 RNA, genital herpes simplex virus type 2 DNA, and ulcer healing among HIV-1-infected African women with herpes ulcers: a randomized placebo-controlled trial. J Infect Dis. 2009;200:216–226.
253. Dunne EF, Whitehead S, Sternberg M, et al.. Suppressive acyclovir therapy reduces HIV cervicovaginal shedding in HIV- and HSV-2-infected women, Chiang Rai, Thailand. J Acquir Immune Defic Syndr. 2008;49:77–83.
254. Ouedraogo A, Nagot N, Vergne L, et al.. Impact of suppressive herpes therapy on genital HIV-1 RNA among women taking antiretroviral therapy: a randomized controlled trial. AIDS. 2006;20:2305–2313.
255. Drake AL, Roxby AC, Ongecha-Owuor F, et al.. Valacyclovir suppressive therapy reduces plasma and breast milk HIV-1 RNA levels during pregnancy and postpartum: a randomized trial. J Infect Dis 2012;205:366–375.
256. (UNAIDS) JUNPoHA. Global report: UNAIDS report on the global AIDS epidemic, 2010. Geneva, Switzerland: Joint United Nations Programme on HIV/AIDS; 2010.
257. Shurtleff D, Lawrence D. HIV and substance abuse: a commentary. Curr HIV Res. 2012;10:366–368.
258. Centers for Disease C. HIV in the United States: at a Glance. Centers for Disease Control website: Atlanta: Centers for Disease Control; 2012.
260. Mathers BM, Degenhardt L, Ali H, et al.. HIV prevention, treatment, and care services for people who inject drugs: a systematic review of global, regional, and national coverage. Lancet. 2010;375:1014–1028.
261. Des Jarlais DC, Arasteh K, Gwadz M. Increasing HIV prevention and care for injecting drug users. Lancet. 2010;375:961–963.
262. Strathdee SA, Shoptaw S, Dyer TP, et al., for the Substance Use Scientific Committee of the HIVPTN. Towards combination HIV prevention for injection drug users: addressing addictophobia, apathy and inattention. Curr Opin HIV AIDS. 2012;7:320–325.
263. Degenhardt L, Mathers B, Vickerman P, et al.. Prevention of HIV infection for people who inject drugs: why individual, structural, and combination approaches are needed. Lancet. 2010;376:285–301.
264. Wodak A, Maher L. The effectiveness of harm reduction in preventing HIV among injecting drug users. N S W Public Health Bull. 2010;21:69–73.
265. WHO/UNAIDS/UNICEF. Global HIV/AIDS Response: Epidemic Update and Health Sector Progress Towards Universal Access: Progress Report 2011. Geneva, Switzerland: World Health Organization; 2011.
266. Barr S. Needle-exchange programs face new federal funding ban. KHN: Kaiser Health News. December 21, 2011; Public Health Politics.
267. Staff OoNDCP. Federal funding ban on needle exchange programs, Vol 2012. January 5, 2012; US White House. Available at:www.whitehouse.gov/blog
. Accessed June 12, 2012.
268. Yerly S, Quadri R, Negro F, et al.. Nosocomial outbreak of multiple bloodborne viral infections. J Infect Dis. 2001;184:369–372.
269. Visco-Comandini U, Capiello G, Liuzzi G, et al.; Libya Project Task Force. Monophyletic HIV type 1 CRF02-AG in a nosocomial outbreak in Benghazi, Libya. AIDS Res Hum Retroviruses. 2002;18:727–732.
270. Apetrei C, Descamps D, Panzaru C, et al.. Plasma HIV-1 load and nosocomial transmission in Romanian children. AIDS. 1995;9:977.
271. Ganczak M, Barss P. Nosocomial HIV infection: epidemiology and prevention—a global perspective. AIDS Rev. 2008;10:47–61.
272. Hiemstra R, Rabie H, Schaaf H, et al.. Unexplained HIV-1 infection in children—documenting cases and assessing for possible risk factors. S Afr Med J. 2004;94:188–193.
273. Reid S, Van Niekerk AA. Injection risks and HIV transmission in the Republic of South Africa. Int J STD AIDS. 2009;20:816–819.
274. Okwen MP, Ngem BY, Alomba FA, et al.. Uncovering high rates of unsafe injection equipment reuse in rural Cameroon: validation of a survey instrument that probes for specific misconceptions. Harm Reduct J. 2011;8:4. doi: 10.1186/1477-7517-8-4.
275. Lackritz EM, Satten GA, Aberle-Grasse J, et al.. Estimated risk of transmission of the human immunodeficiency virus by screened blood in the United States. N Engl J Med. 1995;333:1721–1725.
276. Dreier J, Gotting C, Wolff C, et al.. Recent experience with human immunodeficiency virus transmission by cellular blood products in Germany: antibody screening is not sufficient to prevent transmission. Vox Sang. 2002;82:80–83.
277. Velati C, Romano L, Fomiatti L, et al.. Impact of nucleic acid testing for hepatitis B virus, hepatitis C virus, and human immunodeficiency virus on the safety of blood supply in Italy: a 6-year survey. Transfusion. 2008;48:2205–2213.
278. Weinberg PD, Hounshell J, Sherman LA, et al.. Legal, financial, and public health consequences of HIV contamination of blood and blood products in the 1980s and 1990s. Ann Intern Med. 2002;136:312–319.
279. Ling AE, Robbins KE, Brown TM, et al.. Failure of routine HIV-1 tests in a case involving transmission with preseroconversion blood components during the infectious window period. JAMA. 2000;284:210–214.
280. Wake DJ, Cutting WA. Blood transfusion in developing countries: problems, priorities and practicalities. Trop Doctor. 1998;28:4–8.
281. McFarland W, Mvere D, Shandera W, et al.. Epidemiology and prevention of transfusion-associated human immunodeficiency virus transmission in sub-Saharan Africa. Vox Sang. 1997;72:85–92.
282. McFarland W, Kahn JG, Katzenstein DA, et al.. Deferral of blood donors with risk factors for HIV infection saves lives and money in Zimbabwe. J Acquir Immune Defic Syndr Hum Retrovirol. 1995;9:183–192.
283. Cruz JR, Perez-Rosales MD, Zicker F, et al.. Safety of blood supply in the Caribbean countries: role of screening blood donors for markers of hepatitis B and C viruses. J Clin Virol. 2005;34(suppl 2):S75–S80.
284. Schutz R, Savarit D, Kadjo JC, et al.. Excluding blood donors at high risk of HIV infection in a west African city. BMJ. 1993;307:1517–1519.
285. Centers for Disease Control and Prevention. Progress toward strengthening national blood transfusion services—14 countries, 2008–2010. MMWR Morb Mortal Wkly Rep. 2011;60:1577–1582.
286. Lackritz EM. Prevention of HIV transmission by blood transfusion in the developing world: achievements and continuing challenges. AIDS. 1998;12(suppl A): S81–S86.
287. Heyns Adu P, Benjamin RJ, Swanevelder JP, et al.. Prevalence of HIV-1 in blood donations following implementation of a structured blood safety policy in South Africa. JAMA. 2006;295:519–526.
288. Weller S, Davis K. Condom effectiveness in reducing heterosexual HIV transmission. Cochrane Database Syst Rev. 2002:CD003255.
289. Tavory I, Swidler A. Condom semiotics: meaning and condom use in rural Malawi. Am Sociol Rev. 2009;74:171–189.
290. Lagarde E, Carael M, Glynn JR, et al.. Educational level is associated with condom use within non-spousal partnerships in four cities of sub-Saharan Africa. AIDS. 2001;15:1399–1408.
291. Irungu E, Chersich MF, Sanon C, et al.. Changes in sexual behaviour among HIV-infected women in west and east Africa in the first 24 months after delivery. AIDS. 2012;26:997–1007.
292. Agha S. Intention to use the female condom following a mass-marketing campaign in Lusaka, Zambia. Am J Public Health. 2001;91:307–310.
293. Pool R. Acceptability of the female condom and vaginal spermicidal products in Uganda. Sex Health Exch. 1999;1:5–7.
294. Galvao LW, Oliveira LC, Diaz J, et al.. Effectiveness of female and male condoms in preventing exposure to semen during vaginal intercourse: a randomized trial. Contraception. 2005;71:130–136.
295. Beksinska M, Smit J, Joanis C, et al.. Female condom technology: new products and regulatory issues. Contraception. 2011;83:316–321.
296. Macaluso M, Blackwell R, Jamieson DJ, et al.. Efficacy of the male latex condom and of the female polyurethane condom as barriers to semen during intercourse: a randomized clinical trial. Am J Epidemiol. 2007;166:88–96.
297. Macaluso M, Lawson ML, Hortin G, et al.. Efficacy of the female condom as a barrier to semen during intercourse. Am J Epidemiol. 2003;157:289–297.
298. Joanis C, Beksinska M, Hart C, et al.. Three new female condoms: which do South-African women prefer? Contraception. 2011;83:248–254.
299. MacPhail C, Campbell C. 'I think condoms are good but, aai, I hate those things': condom use among adolescents and young people in a Southern African township. Soc Sci Med. 2001;52:1613–1627.
300. Agha S, Karlyn A, Meekers D. The promotion of condom use in non-regular sexual partnerships in urban Mozambique. Health Policy Plan. 2001;16:144–151.
301. Grimley DM, Hook EW III, DiClemente RJ, et al.. Condom use among low-income African American males attending an STD clinic. Am J Health Behav. 2004;28:33–42.
302. Kwon JA, Iversen J, Maher L, et al.. The impact of needle and syringe programs on HIV and HCV transmissions in injecting drug users in Australia: a model-based analysis. J Acquir Immune Defic Syndr. 2009;51:462–469.
303. Aceijas C, Hickman M, Donoghoe MC, et al.. Access and coverage of needle and syringe programmes (NSP) in Central and Eastern Europe and Central Asia. Addiction. 2007;102:1244–1250.
304. Stoneburner RL, Low-Beer D. Sexual partner reductions explain human immunodeficiency virus declines in Uganda: comparative analyses of HIV and behavioural data in Uganda, Kenya, Malawi, and Zambia. Int J Epidemiol. 2004;33:624.
305. Hallett TB, Aberle-Grasse J, Bello G, et al.. Declines in HIV prevalence can be associated with changing sexual behaviour in Uganda, urban Kenya, Zimbabwe, and urban Haiti. Sex Transm Infect. 2006;82(suppl 1):i1–i8.
306. Bunnell R, Opio A, Musinguzi J, et al.. HIV transmission risk behavior among HIV-infected adults in Uganda: results of a nationally representative survey. AIDS. 2008;22:617–624.
307. Stoneburner RL, Low-Beer D. Population-level HIV declines and behavioral risk avoidance in Uganda. Science. 2004;304:714–718.
308. Dzewaltowski DA, Glasgow RE, Klesges LM, et al.. Evidence-based standards and a Web resource to improve translation of research into practice. Ann Behav Med. 2004;28:75–80.
309. Dzewaltowski DA, Estabrooks PA, Klesges LM, et al.. Behavior change intervention research in community settings: how generalizable are the results? Health Promot Int. 2004;19:235–245.
310. Latham TP, Sales JM, Boyce LS, et al.. Application of ADAPT-ITT: adapting an evidence-based HIV prevention intervention for incarcerated African American adolescent females. Health Promot Pract. 2010;11(suppl):53S–60S.
311. Matovu JK. Preventing HIV transmission in married and cohabiting HIV-discordant couples in sub-Saharan Africa through combination prevention. Curr HIV Res. 2010;8:430–440.
312. Granich R, Crowley S, Vitoria M, et al.. Highly active antiretroviral treatment as prevention of HIV transmission: review of scientific evidence and update. Curr Opin HIV AIDS. 2010;5:298–304.
313. DeGruttola V, Smith DM, Little SJ, et al.. Developing and evaluating comprehensive HIV infection control strategies: issues and challenges. Clin Infect Dis. 2010;50(suppl 3):S102–S107.
314. Kurth AE, Celum C, Baeten JM, et al.. Combination HIV prevention: significance, challenges, and opportunities. Curr HIV/AIDS Rep. 2011;8:62–72.
315. Padian NS, McCoy SI, Karim SS, et al.. HIV prevention transformed: the new prevention research agenda. Lancet. 2011;378:269–278.
316. Katsidzira L, Hakim JG. HIV prevention in southern Africa: why we must reassess our strategies? Trop Med Int Health. 2011;16:1120–1130.
condoms; PMTCT; TasP; PrEP; PEP; male circumcision; vaccines; complimentary strategies
© 2013 Lippincott Williams & Wilkins, Inc.
What does "Remember me" mean?
By checking this box, you'll stay logged in until you logout. You'll get easier access to your articles, collections,
media, and all your other content, even if you close your browser or shut down your
To protect your most sensitive data and activities (like changing your password),
we'll ask you to re-enter your password when you access these services.
What if I'm on a computer that I share with others?
If you're using a public computer or you share this computer with others, we recommend
that you uncheck the "Remember me" box.
Highlight selected keywords in the article text.
Data is temporarily unavailable. Please try again soon.