These interventions include: IEC; school-based sexual education; VCT; and peer-based programs that rely on influential peers to change behavior norms.
As discussed above, discerning the efficacy of IEC is difficult. Because it is such an integrated part of condom promotion and distribution, it is rarely evaluated alone. We consider the efficacy of IEC in concert with condom promotion and distribution below in the section on ‘Interventions to prevent sexual transmission.’
Knowledge of serostatus may lead individuals to avoid engaging in risky behaviors . Several studies have shown that VCT increases condom use [22–24] and increases abstinence . In a large randomized study of adults in Kenya, Tanzania and Trinidad, individuals who had received HIV testing and counseling reported significant reductions in unprotected intercourse in comparison with those who had received basic health information (35% reduction in intervention men versus 13% in the control group; 39% reduction in intervention women versus17% in the control group, P < 0.05) . However, evidence of the impact of VCT on biological outcomes such as HIV and STI incidence is limited.
Although we have much evidence of the success of peer-based HIV prevention programs in the US [25–29], evidence from resource-poor countries is limited. Studies conducted among sex workers and employed urban women have resulted in increased condom use [30,31], and in a multiyear cross-sectional study conducted among sex workers in Cote d'Ivoire, a peer education program resulted in a lower prevalence of HIV infection (from 89 to 32%, P < 0.001) and STI infection (from 21 to 2%, P < 0.001, for syphilis) .
Interventions to prevent sexual transmission include condom promotion and distribution and STI screening and treatment.
Studies overwhelmingly demonstrate that condoms are highly effective in preventing HIV transmission. A workshop co-sponsored by four government agencies responsible for condom research, condom regulation, and HIV/AIDS and sexually transmitted disease (STD) prevention programs (US Agency for International Development, Food and Drug Administration, Center for Disease Control and Prevention, National Institutes of Health, Bethesda, Maryland, USA) was held in June 2000 to evaluate the published evidence establishing the effectiveness of latex male condoms in preventing HIV/AIDS and other STDs. The workshop panel concluded that consistent users of the male condom significantly reduced the risk of HIV infection in men and women . In fact, condoms appear on average to be at least 90% effective in preventing HIV when used consistently and correctly . Given the efficacy of condoms in preventing HIV transmission, condom promotion and distribution programs should be one of the most effective prevention programs.
The available evidence on condom promotion/distribution programs, which often include IEC components, indicates their efficacy. Such programs have increased condom use [35–42] and decreased STI incidence [37,43] and HIV incidence . Programs that have combined aspects of condom promotion, VCT and STI treatment have increased condom use [36,44] and decreased STIs [36,45].
Evidence from studies indicates that STI treatment programs decrease both HIV and STI incidence [35,51]. In a community randomized study of improved syndromic STI management conducted among adults in Tanzania, the HIV risk ratio among those in the intervention community was 0.58 (P = 0.007) . However, other studies conducted in Uganda have shown no effect of STI treatment programs on HIV incidence [52,53]. The most recent analyses suggests that the reason for the different study outcomes may be due to a low prevalence of curable STIs resulting from lower-risk sexual behavior in Uganda and the fact that the epidemic in Uganda was mature, with most HIV transmission occurring outside core groups with high STI rates .
Prevention of MTCT can be viewed as a package containing aspects of the specific interventions described below.
Available evidence from numerous studies indicates that provision of antiretroviral drugs (nevirapine, lamivudine and zidovudine) to infected mothers significantly reduces vertical transmission, with values ranging from 33–63% reduction in transmission [10–14,55–57]. The range of drug regimens in these studies included: a single dose of maternal nevirapine at the onset of labor and to the infant upon delivery; antepartum and intrapartum maternal zidovudine and to the infant upon delivery; maternal zidovudine twice daily from 36 weeks gestation until labor, at the beginning of labor and post-partum; and maternal zidovudine and lamivudine at 36 weeks gestation until labor, at the beginning of labor and post-partum. Despite these advances in reducing vertical transmission, recent data indicates that women receiving antiretroviral therapy may develop resistance [58,59].
One of the most effective strategies to reduce HIV among infants is to provide better contraception services to infected mothers. One modeling study estimated that in a population of 1,000 HIV-infected women, approximately 150 infants would be infected with HIV during delivery. If nevirapine were available, the number of infected infants would be reduced to 82 (the expected 47% decline). If effective contraceptive services were available, this number would be reduced to 49. If both strategies were adopted, the number of infected infants would be further reduced to 25 .
Although complete avoidance of breastfeeding is recommended for HIV-infected mothers in developed countries to prevent postnatal HIV transmission, the feasibility of this approach in less developed countries is often limited by such factors as cost, sustainability, lack of safe water, health, child spacing, and socio-cultural factors [61–63]. However, prolonged breastfeeding can more than double the likelihood of mother-to-child transmission of HIV .
One study indicated that mixed feeding (breastmilk and formula or other substance) may have a higher risk of transmission than exclusive breastfeeding . In this prospective study, investigators compared transmission rates in exclusively breastfed, mixed-fed, and formula-fed (never breastfed) infants to assess whether the pattern of breastfeeding affects early mother-to-child transmission of HIV. The proportion of infants who were HIV infected by 3 months was significantly lower for those exclusively breastfed to 3 months in comparison with those who received mixed feeding before 3 months (proportion, 14.6%; 95% CI, 7.7–21.4 versus 24.1%; 95% CI, 19.0–29.2; P = 0.03). After adjustment for potential confounders, exclusive breastfeeding carried a significantly lower risk of HIV transmission than mixed feeding [hazard ratio (HR), 0.52; 95% CI, 0.28–0.98] and a similar risk to no breastfeeding (HR, 0.85; 95% CI, 0.51–1.42). This data, albeit limited, suggests exclusive breastfeeding may offer HIV-infected women in developing countries an affordable, culturally acceptable, and effective means of reducing mother-to-child transmission of HIV while maintaining the overwhelming benefits of breastfeeding. Nevertheless, data are still needed to guide the optimal duration of breastfeeding. In addition, the nutritional and immunologic benefits of breastfeeding should be weighed when developing an effective breastfeeding strategy .
Prevention of blood-borne transmission includes harm reduction for injection drug users (IDUs), implementation of blood safety practices, and providing sterile injections.
Harm reduction involves a combination of health promotion strategies for IDUs, including needle and syringe exchange programs (NEP), ready access to effective drug treatment and substitution, and provision of counseling and condoms. Brazil, which has reduced HIV incidence from earlier levels and kept HIV prevalence from reaching projected levels, has relied on strong official support for harm reduction as a cornerstone of its national prevention program . In fact, in Santos and Salvador, two of the cities in which harm reduction programs were implemented, HIV servoprevalence among IDUs dropped from 63% in 1994 to 42% in 1999 and from 50% in 1996 to 7% in 2000, respectively.
Drug substitution programs. Methadone maintenance is both safe and effective as treatment for drug addiction  and may help reduce the risk of HIV transmission by enabling individuals to avoid the drug-using behaviors that can lead to HIV infection [78,79] data. As with NEP effectiveness data, much of the methadone maintenance data is from the US. In one study examining the differences in the sexual behaviors of IDUs who received methadone treatment in the previous 6 months and those who did not, methadone patients reported significantly fewer sexual partners and significantly greater use of condoms . Furthermore, in a meta-analysis of 11 studies investigating the impact of methadone maintenance treatment on HIV risk behaviors, investigators found such treatment programs demonstrate a consistently significant reduction in risk behaviors .
HIV can be virtually eliminated through a blood safety program that ensures: (1) a national blood transfusion service; (2) the recruitment of voluntary low-risk donors; (3) the screening of all donated blood for HIV; (4) the reduction of unnecessary and inappropriate transfusions . The available sensitivity and specificity evidence indicates that HIV screening is effective in reducing HIV infections [82–84]. In one study, after HIV rapid transfusion screen tests were implemented, it was estimated that at least 265 cases of HIV-positive blood donation were prevented , and in a study investigating the feasibility and efficacy of routine screening of donors for HIV-1 by polymerase chain reaction (PCR), investigators found that PCR screening contributes to a reduction in viral transmission .
To prevent blood-borne transmission of HIV and other diseases, health care workers, emergency personnel, and others who might experience occupational exposure to blood or body fluids are advised to take ‘universal precautions’ . This approach, which treats all bodily fluids as potentially infectious, includes gloves, gowns, goggles, proper disposal of waste, sterile injection, and other infection control practices . Studies have demonstrated that protective equipment, such as gloves, reduce the likelihood of blood exposure in health care settings. In one study designed to evaluate factors that affect blood volumes transferred to skin during simulated needlestick injuries, glove material reduced the transferred blood volume by 46–86% . Investigators therefore concluded that gloves may exert some protective effect and should be worn whenever needles are handled.
Post-exposure prophylaxis (PEP) with antiretroviral agents is considered a standard of care after occupational needle-stick exposure to blood from HIV-infected persons. Limited evidence demonstrates the efficacy of this approach. In a case–control study of health care workers in the US with occupational, percutaneous exposure to HIV-infected blood, investigators found that case patients were significantly less likely than the controls to have taken zidovudine after the exposure (OR, 0.19; 95% CI, 0.06–0.52) .
Efficacy data alone are not sufficient to inform decision-making. Randomized, controlled trials, which are used to obtain efficacy data, may not mimic the situation in which an intervention will occur. For example, if the conditions under which an intervention was tested differ from the conditions where it is later scaled up, its impact may be less than anticipated. Similarly, if a highly efficacious intervention is targeted at a population or sub-population that is not responsible for the majority of the new infections, it may have little measurable impact on the trajectory of the intervention.
Thus, in addition to effectiveness data, surveillance data to monitor the epidemic profile and contextual and structural data are essential to appropriately tailor an intervention. Nevertheless, some general observations about tailoring interventions to fit the epidemic context are possible.
UNAIDS has developed epidemiological categories for the characterization of individual epidemics based on the prevalence of infection in particular subpopulations and in the general population. These categories are listed in Table 2. The UNAIDS generalized epidemic category is further subdivided into a low and high category.
Generally, low-level and concentrated epidemics should place greater emphasis on interventions that are targeted to individuals at especially high risk of becoming infected or transmitting the virus, whereas generalized epidemics should adopt population-level interventions that target entire populations or population subgroups. In the following paragraphs, we illustrate how the implementation of two interventions: condom promotion and distribution, and VCT, may vary based on epidemic profiles.
As mentioned previously, we have data indicating some interventions can effectively prevent transmission, including providing antiretroviral therapy for mother-to-child transmission [8–14] and blood safety practices . We also have limited evidence that STI treatment may be effective in reducing HIV incidence [35,51]. However, with the majority of interventions, such as school-based sexual education, VCT, and condom promotion we lack sufficient data on whether they reduce HIV incidence.
One of the most important barriers to HIV control is a dearth of rigorous evaluations of interventions that measure HIV incidence as an outcome. In addition, we have incomplete data on the epidemiologic profile of regions and we lack essential contextual information. Research on policy or structural interventions, which by definition must be conducted on a population level, is also needed. Last, information on how to properly scale-up interventions is necessary for effective decision-making.
Even though the current deficit in evaluation research is glaring, the magnitude and seriousness of the global pandemic demands that action is nevertheless required. Despite such gaps in knowledge, we can improve control strategies by tailoring interventions to the nature and scope of the epidemic. If intervention policies are not guided by firm effectiveness, surveillance and contextual data, national strategies will not accurately reflect the priorities dictated by the particular epidemic profile. As a result, countries will undoubtedly make highly inefficient investments in HIV/AIDS prevention.
The authors are also deeply indebted to Andrew Beggs, Susan Foster, James Kahn, Lilani Kumaranayake, Elliot Marseille, Fern Terris-Prestholt, Seema Vyas, and Charlotte Watts for their background papers that have informed this paper. They would also like to thank Carol Medlin for her valuable input on this paper.
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