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AIDS:
doi: 10.1097/QAD.0b013e32832b7dca
Epidemiology and social

Sexual transmission of HIV according to viral load and antiretroviral therapy: systematic review and meta-analysis

Attia, Suzannaa; Egger, Matthiasa,b; Müller, Monikaa; Zwahlen, Marcela; Low, Nicolaa,b

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Author Information

aInstitute of Social and Preventive Medicine (ISPM), University of Bern, Switzerland

bDepartment of Social Medicine, University of Bristol, UK.

Received 1 February, 2009

Revised 25 February, 2009

Accepted 5 March, 2009

Correspondence to Professor Matthias Egger, Institute of Social and Preventive Medicine (ISPM), Finkenhubelweg 11, Bern, CH-3012, Switzerland. Tel: +41 31 631 35 01; e-mail: egger@ispm.unibe.ch

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Abstract

Objectives: To synthesize the evidence on the risk of HIV transmission through unprotected sexual intercourse according to viral load and treatment with combination antiretroviral therapy (ART).

Design: Systematic review and meta-analysis.

Methods: We searched Medline, Embase and conference abstracts from 1996–2009. We included longitudinal studies of serodiscordant couples reporting on HIV transmission according to plasma viral load or use of ART and used random-effects Poisson regression models to obtain summary transmission rates [with 95% confidence intervals, (CI)]. If there were no transmission events we estimated an upper 97.5% confidence limit.

Results: We identified 11 cohorts reporting on 5021 heterosexual couples and 461 HIV-transmission events. The rate of transmission overall from ART-treated patients was 0.46 (95% CI 0.19–1.09) per 100 person-years, based on five events. The transmission rate from a seropositive partner with viral load below 400 copies/ml on ART, based on two studies, was zero with an upper 97.5% confidence limit of 1.27 per 100 person-years, and 0.16 (95% CI 0.02–1.13) per 100 person-years if not on ART, based on five studies and one event. There were insufficient data to calculate rates according to the presence or absence of sexually transmitted infections, condom use, or vaginal or anal intercourse.

Conclusion: Studies of heterosexual discordant couples observed no transmission in patients treated with ART and with viral load below 400 copies/ml, but data were compatible with one transmission per 79 person-years. Further studies are needed to better define the risk of HIV transmission from patients on ART.

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Introduction

The efficacy of antiretroviral drugs in the prevention of mother-to-child transmission of HIV is well documented [1] and there may also be a role of antiretroviral therapy (ART) in the prevention of sexual transmission of HIV [2]. Any reduction in the capacity of HIV to replicate is likely to reduce the risk of HIV transmission, unless the effect is offset by behavioural risk compensation [2,3]. HIV-infected men treated with zidovudine monotherapy in Italy were half as likely to transmit infection to their female partners than untreated men, after controlling for their more advanced disease [4]. Highly active antiretroviral combination therapy (ART) that can suppress HIV viraemia sustainably should have greater impact [2,3].

In January 2008 the Swiss Federal AIDS Commission stated that HIV-infected people on effective antiretroviral therapy and without other sexually transmitted infections were sexually noninfectious [5]. National public health bodies [6,7] have, however, reasserted existing guidance about the need for consistent condom use whereas some groups have supported the statement [8]. Our objective was to review the literature and obtain summary estimates of the risk of HIV transmission according to viral load, treatment with ART and presence of other sexually transmitted infections.

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Methods

We included original articles and conference abstracts reporting on longitudinal studies of couples with one HIV-infected partner and documenting the number of HIV infections in previously seronegative sexual partners, and information about viral load in the HIV-seropositive partner, use of ART, or both. We excluded studies of preexposure prophylaxis and case-reports.

We searched the Medline and EMBASE databases from January 1996 to May 2008 and updated searches in February 2009. We used subject-heading terms for ‘HIV infections’ and ‘disease transmission’ and combined these with terms for either ‘viral load’ or ‘antiretroviral therapy, highly active’ (full search strategies available on request). We examined the reference lists of full text reports. We also searched the abstracts of the International AIDS Society conferences from 2001–2008 and the Conference on Retroviruses and Opportunistic Infections from 1997–2009 using key words ‘HIV’ and ‘discordant’, or ‘discordant’ and ‘couple’. There was no restriction on the language of published articles.

Two reviewers independently assessed all titles and abstracts of published articles (S.A., M.M.) and conference abstracts (S.A., N.L.). If there was insufficient information in the title or abstract we retrieved the full text. We determined eligibility by consensus, with a third reviewer (M.E.) making a final decision in the case of disagreement. Two reviewers (S.A., M.M.) extracted the same information about each study. A third reviewer (N.L. or M.E.) resolved discrepancies. We extracted information about: study characteristics and population; the number of HIV transmission events and duration of follow-up; plasma viral load, use of ART and sexually transmitted infections in the seropositive partner; types and frequency of sexual intercourse; and condom use.

We contacted authors of potentially eligible studies identified in the first search to confirm eligibility and to request additional information. We asked about numbers of HIV transmissions and follow-up time according to the viral load of the HIV seropositive partner (<400, 400–499, 500–9999, 10 000–49 999, 50 000 and more copies/ml) [9]. We defined an undetectable viral load as fewer than 400 copies/ml of blood viral load, according to the detection limit of tests used in most eligible studies. We asked for the lowest measured viral load at which transmission to a seronegative partner had occurred. We relied on published data if the authors were not contacted, could not be reached or additional data were not provided.

We also asked for data in the predefined viral load categories according to whether the seropositive partner had any other sexually transmitted infections. We defined any sexually transmitted infection as: positive serological tests or microscopy for syphilis, positive test results for Neisseria gonorrhoeae, or Chlamydia trachomatis from swabs or urine specimens, or positive genital ulcer swab results or serological tests for herpes simplex virus. We defined ulcerative sexually transmitted infections as syphilis and genital herpes. If this information was not available, or if diagnosis was based on self-report we categorized the status as unclear.

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Statistical analysis

We aimed to estimate the risk of HIV transmission per unprotected act of sexual intercourse. In the absence of data about frequency of unprotected sexual intercourse we used the HIV transmission risk per 100 person years of follow-up. If the exact follow-up time was not available we estimated this from the reported mean or median. We used a random effects Poisson regression model to obtain a summary estimate of the transmission rate with 95% confidence intervals (95% CI). For each study or stratum, the total number of events was considered to be Poisson distributed for a given sum of person years. Poisson regression models were fitted with a logarithmic link function and total exposure time per study as an offset variable, and included γ-distributed random effects on the study or stratum level. If there were no events observed, we assumed that the number of events was Poisson distributed and obtained an upper 97.5% confidence limit based on exact Poisson probabilities. All analyses were conducted using STATA version 10 (Stata Corporation, College Station, Texas, USA).

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Results

Our searches yielded 305 publications, including 56 conference abstracts. Figure 1 depicts the process of identifying studies. We contacted the authors of 21 of 26 potentially eligible studies: nine replied and four provided additional information [10–13]. We identified 11 eligible cohorts reporting on 5021 couples and 461 HIV transmission events in 16 publications or abstracts from eight countries [9–24] (Table 1). The largest number of serodiscordant couples was reported in five studies from sub-Saharan Africa [9,17,18,23,24]. All included studies were conducted amongst heterosexual couples. There were insufficient data to allow estimation of summary rates of transmission through sexual intercourse without condoms, or to separate female–male and male–female transmission.

Fig. 1
Fig. 1
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Table 1
Table 1
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We analysed the risk of HIV transmission per 100 person-years of follow up because we only identified one study reporting on HIV transmission per coital act and stratified by viral load [15,16]. Data about coital frequency and transmission events were collected from the same population of untreated HIV-infected individuals in Rakai, Uganda. The estimated probability of HIV transmission per coital act, after controlling for age, ranged from 0.0001 when viral load was below 1700 copies/ml (sexual intercourse 10.4 times per month) to 0.0023 when viral load was greater than 38 500 copies/ml (sexual intercourse 7.9 times per month) [15].

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HIV transmission and highly active antiretroviral therapy

Five studies included couples in which the HIV-seropositive partners used antiretroviral therapy, with 1098 person years of follow-up [10,11,18,23,24] (Table 1). One study reported specific antiretroviral regimens [10]. We did not identify any studies that reported on both viral load and all microbiologically diagnosed sexually transmitted infections.

The overall HIV transmission risk from antiretroviral-treated patients to heterosexual partners, irrespective of viral load and other sexually transmitted infections, was 0.46 (95% CI 0.19–1.09) per 100 person-years, based on five episodes of HIV seroconversion (Fig. 2) [10,11,18,23,24]. Information on the lowest measured viral load at which transmission had occurred while taking antiretroviral therapy was not available for either of the studies in which new HIV infections occurred [18,23]. In the two studies with information stratified according to viral load there were no reported episodes of HIV transmission from HIV seropositive people with undetectable viral load in 291 person years of follow-up (upper 97.5% confidence limit 1.27 per 100 person years) [10,11]. Three studies did not report on associations between HIV transmission and other sexually transmitted infections [18,23,24]. Melo et al. [10] and Castilla et al. [11] reported no association with the infections assessed in their studies (Table 1).

Fig. 2
Fig. 2
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HIV transmission from people not on antiretroviral therapy

Ten studies included HIV seropositive people not receiving antiretroviral therapy with 9998 person years of follow up [9–14,17,21,23,24]. The overall HIV transmission rate, irrespective of viral load category and sexually transmitted infections, was 5.64 (95% CI 3.28–9.70) per 100 person years (Fig. 2). Amongst people with viral load below 400 copies/ml, irrespective of sexually transmitted infections, the transmission rate was 0.16 (95% CI 0.02–1.13) per 100 person years, based on one episode of HIV transmission in six studies [9,11–14,17]. The transmission rate increased with increasing viral load to 9.03 (95% CI 3.87–21.09) per 100 person years amongst individuals with viral load at least 50 000 copies/ml (Fig. 2).

The lowest measured viral load values around the time of HIV-transmission events were available for seven studies (Table 1). Three values, all in untreated individuals, were below 1500 copies/ml: at 362 copies/ml (Castilla J, 17 July 2008, personal communication), 600 copies/ml (Ragni M, 21 July 2008, personal communication) and 1497 copies/ml [10].

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Discussion

This systematic review did not identify any study from which the risk of HIV transmission per act of unprotected sexual intercourse amongst persons with suppressed viraemia following ART could be quantified directly. The available studies found no episodes of HIV transmission in discordant heterosexual couples if the HIV-infected partner was treated with ART and had a viral load below 400 copies/ml, but the data were also compatible with one transmission per 79 person-years. There were insufficient data to stratify rates according to the presence or absence of sexually transmitted infections, use of condoms, direction of transmission, or practise of vaginal or anal intercourse. The comparison of overall rates in patients on ART and not on ART nevertheless indicate that heterosexual transmission was reduced by 92%, from 5.64 to 0.46 per 100 person-years. Of note, our review did not identify any study with data on ART and transmission risk in homosexual men.

The main strengths of this study were that we searched systematically for published and unpublished literature and attempted to quantify statistical uncertainty around the transmission rate. Additional information from several authors allowed us to combine data in consistent viral load categories to increase the precision of estimated transmission risks [10–13] and to report the minimum viral load at which HIV transmission occurred. The main limitations of the study relate to the lack of data that could be combined statistically. Four included studies were only available as conference abstracts with limited details [18,21,23,24]. Precision was also limited by small or zero numbers of events in each viral load category and short follow-up times. There are recognized difficulties in obtaining confidence intervals when no events have been observed [25]. The interpretation of the lower limit of zero and upper 97.5% limit obtained using exact Poisson distribution probabilities differs from the standard 95% confidence interval. However, they demonstrate the uncertainty about the true HIV transmission rate by describing a range of values for the true quantity of interest that are compatible with the observed data. Describing the likelihood function about the true value of the parameter is an alternative but the results obtained would not alter our conclusion.

We found no direct evidence that, as stated by the Swiss Federal AIDS commission [5], the HIV transmission risk through unprotected sexual intercourse from an infected individual taking ART consistently under medical supervision, with blood viral load below 40 copies/ml and without any other sexually transmitted infection was ‘much lower than one per 100 000 acts of sexual intercourse.’ We found that there is considerable uncertainty about this risk: first, although there were no observed episodes of HIV transmission from people with undetectable viral load on highly active antiretroviral therapy, data are compatible with one new HIV infection for every 79 person-years of follow-up (one per 7900 sex acts if the yearly average is 100 contacts [15] and transmission probability is constant). Second, episodes of HIV transmission were found to have occurred at viral load levels lower than reported in earlier studies [9]. There might therefore be no transmission threshold or a lower threshold than previously believed [5,26].

Mathematical models have been developed to predict the effects of antiretroviral therapy on HIV transmission but variability in assumptions based on epidemiological and biological data makes them difficult to interpret [27]. The reduction in HIV transmissibility due to antiretroviral therapy includes estimates from two to 100 times [28], two to 10 times [29], and 100 times [30]. Our meta-analysis should be useful in this context and inform future modelling studies.

There is also uncertainty about the role of sexually transmitted infections. Focusing on ulcerative conditions and symptoms as a proxy for lower genital tract inflammation [5] is problematic. First, symptoms in women correlate poorly with clinical signs of inflammation or diagnosed infections [31]. Second, HIV transmission appears to be enhanced by bacterial vaginosis [32], a vaginal infection characterized by an absence of inflammation [31]. Third, sexual transmission of herpes simplex virus, the most common cause of genital ulcer disease in many countries, can occur during asymptomatic virus shedding [33]. Suppressing clinical recurrences with acyclovir does not reduce the risk of HIV transmission [34,35]. Furthermore, adherence to recommendations for regular testing for sexually transmitted infections in HIV-infected people would have to improve from current levels [36].

The risk of HIV transmission from people on highly active antiretroviral therapy is likely to be very low but it is nevertheless important that statements on transmission risk are based on thorough evaluation of the available data [37,38]. The need for systematic searches and clear documentation about the design, quality and consistency of evidence, and the availability or absence of direct evidence to address important clinical and public health questions is well recognized [38]. The users of recommendations can then distinguish between statements based on appraisal of evidence by experts and those based on systematic methods. The results of our systematic review show where there is a lack of direct evidence and where further research is required.

Greater precision about the HIV transmission rate per sexual act on highly active antiretroviral therapy can be obtained from empirical studies. An upper 95% confidence interval of one in 100 000 per unprotected sex acts would be obtained if the observed HIV transmission rate were one in 550 000 sex acts. This is equivalent to 5500 person years of observation with an average of 100 unprotected sex acts per year, or 1100 couples followed for 5 years having unprotected sex and free of sexually transmitted infections, assuming a constant transmission probability and each act as an independent event. An ongoing randomized trial to follow 1750 HIV serodiscordant heterosexual couples for a median of 5.75 years with the infected partner receiving highly active antiretroviral therapy will help to provide this information [39]. Studies to determine HIV transmissibility through insertive and receptive anal intercourse when viraemia is fully suppressed are needed to provide direct evidence for men who have sex with men. The implications of differences between antiretroviral agents in drug levels in plasma and genital tract, and of intermittent viral ‘blips’ also need to be clarified [3].

In conclusion, our study supports the World Health Organization's view [2] that at present there is insufficient evidence to formulate guidance on the role of ART in HIV prevention, both at the level of the individual and the population. Further studies quantifying transmission risk in different patient groups and under different conditions are required to inform such recommendations.

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Acknowledgements

We are grateful to Jesús Castilla, Jorge del Romero, Kenrad Nelson, Margaret Ragni, and Breno Santos who provided additional data from their studies that contributed to the results presented in this paper. S.A. was supported by a ThinkSwiss! Fellowship from the Swiss Government.

Author contributions: S.A. did the literature searches, study selection, data extraction, and wrote the first draft; M.E. obtained funding, designed and supervised the study, and revised the paper; M.M. contributed to study selection, data extraction, and revision of the paper, M.Z. provided statistical advice and revised the paper; N.L. designed and supervised the study, conducted the analysis, and revised the paper.

Conflicts of interest: N.L. became a member of the Swiss Federal AIDS Commission on 1 January 2008. M.Z. was employed at the Swiss Federal Office of Public Health from 1998–2000 and head of the office of the Swiss Federal AIDS Commission at the Swiss Federal Office of Public Health from 1988–1989. The views expressed here are those of the authors.

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References

1. Dao H, Mofenson LM, Ekpini R, Gilks CF, Barnhart M, Bolu O, et al. International recommendations on antiretroviral drugs for treatment of HIV-infected women and prevention of mother-to-child HIV transmission in resource-limited settings: 2006 update. Am J Obstet Gynecol 2007; 197(3 Suppl):S42–S55.

2. De Cock KM, Gilks CF, Lo YR, Guerma T. Can antiretroviral therapy eliminate HIV transmission? Lancet 2009; 373:7–9.

3. Cohen MS, Gay C, Kashuba AD, Blower S, Paxton L. Narrative review: antiretroviral therapy to prevent the sexual transmission of HIV-1. Ann Intern Med 2007; 146:591–601.

4. Musicco M, Lazzarin A, Nicolosi A, Gasparini M, Costigliola P, Arici C, et al. Antiretroviral treatment of men infected with human immunodeficiency virus type 1 reduces the incidence of heterosexual transmission. Italian Study Group on HIV Heterosexual Transmission. Arch Intern Med 1994; 154:1971–1976.

5. Vernazza P, Hirschel B, Bernasconi E, Flepp M. HIV- infizierte Menschen ohne andere STD sind unter wirksamer antiretroviraler Therapie sexuell nicht infektiös [HIV-infected people free of other STDs are sexually not infectious on effective antiretroviral therapy]. Schweizerische Ärztezeitung 2008; 89:165–169.

6. Centers for Disease Control and Prevention. CDC underscores current recommendation for preventing HIV transmission. 1 February 2008. http://www.cdc.gov/hiv/resources/press/020108.htm. [Accessed 1 February 2009]

7. Public Health Agency of Canada. PHAC continues to emphasize safer sex for preventing HIV transmission. 17 April 2008. http://www.phac-aspc.gc.ca/aids-sida/new-nouv-eng.php. [Accessed February 2009]

8. Mexico Manifesto: a call to action by people with HIV and AIDS. 3 August 2008. http://www.ondamaris.de/wp-content/uploads/2008/07/lhive-mexico-manifesto1.pdf. [Accessed February 2009]

9. Quinn TC, Wawer MJ, Sewankambo N, Serwadda D, Li C, Wabwire-Mangen F, 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.

10. Melo MG, Santos BR, Lira Rd, Varella IS, Turella ML, Rocha TM, et al. Sexual transmission of HIV-1 among serodiscordant couples in Porto Alegre, Southern Brazil. Sex Transm Dis 2008; 35:912–915.

11. Castilla J, del Romero J, Hernando V, Marincovich B, Garcia S, Rodriguez C. Effectiveness of highly active antiretroviral therapy in reducing heterosexual transmission of HIV. J Acquir Immune Defic Syndr 2005; 40:96–101.

12. Ragni MV, Faruki H, Kingsley LA. Heterosexual HIV-1 transmission and viral load in hemophilic patients. J Acquir Immune Defic Syndr Hum Retrovirol 1998; 17:42–45.

13. Tovanabutra S, Robison V, Wongtrakul J, Sennum S, Suriyanon V, Kingkeow D, 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.

14. Operskalski EA, Stram DO, Busch MP, Huang W, Harris M, Dietrich SL, et al. Role of viral load in heterosexual transmission of human immunodeficiency virus type 1 by blood transfusion recipients. Am J Epidemiol 1997; 146:655–661.

15. Gray RH, Wawer MJ, Brookmeyer R, Sewankambo NK, Serwadda D, Wabwire-Mangen F, et al. Probability of HIV-1 transmission per coital act in monogamous, heterosexual, HIV-1-discordant couples in Rakai, Uganda. Lancet 2001; 357:1149–1153.

16. Wawer MJ, Gray RH, Sewankambo NK, Serwadda D, Li X, Laeyendecker O, et al. Rates of HIV-1 transmission per coital act, by stage of HIV-1 infection, in Rakai, Uganda. J Infect Dis 2005; 191:1403–1409.

17. Fideli US, Allen SA, Musonda R, Trask S, Hahn BH, Weiss H, 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.

18. Bunnell R, Ekwaru JP, King R, Bechange S, Moore D, Khana K, et al. 3-year follow-up of sexual behavior and HIV transmission risk of persons taking ART in rural Uganda. 15th Conference on Retroviruses and Oppportunistic Infections. 3–6 February 2008. Boston, USA.

19. Brill I, Macaluso M, the Rwanda/Zambia HIV Research Group. A SAS program for the computation of seroconversion rates in a prospective study of HIV discordant couples in Lusaka, Zambia. 2nd IAS Conference on HIV Pathogenesis and Treatment: Poster Abstract no. 1130. 13–16 July 2003. Paris, France.

20. Kayitenkore K, Bekan B, Rufagari J, Marion-Landais S, Karita E, Allen S. The impact of ART on HIV transmission among HIV serodiscordant couples. AIDS 2006 - XVI International AIDS Conference: Abstract no. MOKC101. 13–18 August 2006. Toronto, Canada.

21. Mehendale SM, Kishore Kumar B, Ghate MV, Sahay S, Gamble T, Godbole SV, et al. Low HIV incidence in HIV sero-discordant couples in Pune, India. AIDS 2004 - XV International AIDS Conference: Abstract no. MoPeC3462. 11–16 July 2004. Bangkok, Thailand.

22. del Romero J, Hernando V, Castilla J, Garcia S, Gil S, Rodriquez C. Lack of HIV heterosexual transmission attributable to HAART in serodiscordant couples. AIDS 2008 - XVII International AIDS Conference 2008: Abstract no. THPE0543. 3–8 August 2008. Mexico City, Mexico.

23. Sullivan P, Kayitenkore K, Chomba E, Karita E, Mwananyanda L, Vwalika C, et al. Reduction of HIV transmission risk and high risk sex while prescribed ART: results from discordant couples in Rwanda and Zambia. 16th Conference on Retroviruses and Opportunistic Infections: Abstract 52bLB. Montreal, 8–11 February 2009; Montreal, Canada.

24. Reynolds S, Makumbi F, Kagaayi J, Nakigozi G, Galiwongo R, Quinn T, et al. ART reduced the rate of sexual transmission of HIV among HIV-discordant couples in rural Rakai, Uganda. 16th Conference on Retroviruses and Opportunistic Infections: Abstract 52a. Montreal, 8–11 February 2009; Montreal, Canada.

25. Hanley JA, Lippman-Hand A. If nothing goes wrong, is everything all right? Interpreting zero numerators. JAMA 1983; 249:1743–1745.

26. Wilson DP, Law MG, Grulich AE, Cooper DA, Kaldor JM. Relation between HIV viral load and infectiousness: a model-based analysis. Lancet 2008; 372:314–320.

27. Baggaley RF, Ferguson NM, Garnett GP. The epidemiological impact of antiretroviral use predicted by mathematical models: a review. Emerg Themes Epidemiol 2005; 2:9.

28. Blower SM, Gershengorn HB, Grant RM. A tale of two futures: HIV and antiretroviral therapy in San Francisco. Science 2000; 287:650–654.

29. Law MG, Prestage G, Grulich A, Van d, V, Kippax S. Modelling the effect of combination antiretroviral treatments on HIV incidence. AIDS 2001; 15:1287–1294.

30. Granich RM, Gilks CF, Dye C, de Cock KM, Williams BG. Universal voluntary HIV testing with immediate antiretroviral therapy as a strategy for elimination of HIV transmission: a mathematical model. Lancet 2009; 373:48–57.

31. Holmes KK, Sparling PF, Stamm WE, Piot P, Wasserheit JN, Corey L, et al. Sexually transmitted diseases. New York: McGraw-Hill; 2008.

32. Myer L, Kuhn L, Stein ZA, Wright TC Jr, Denny L. Intravaginal practices, bacterial vaginosis, and women's susceptibility to HIV infection: epidemiological evidence and biological mechanisms. Lancet Infect Dis 2005; 5:786–794.

33. Wald A, Zeh J, Selke S, Ashley RL, Corey L. Virologic characteristics of subclinical and symptomatic genital herpes infections. New Eng J Med 1995; 333:770–775.

34. Watson-Jones D, Weiss HA, Rusizoka M, Changalucha J, Baisley K, Mugeye K, et al. Effect of herpes simplex suppression on incidence of HIV among women in Tanzania. N Engl J Med 2008; 358:1560–1571.

35. Celum C, Wald A, Hughes J, Sanchez J, Reid S, any-Moretlwe S, et al. Effect of aciclovir on HIV-1 acquisition in herpes simplex virus 2 seropositive women and men who have sex with men: a randomised, double-blind, placebo-controlled trial. Lancet 2008; 371:2109–2119.

36. Nandwani R. 2006 United Kingdom national guideline on the sexual health of people with HIV: sexually transmitted infections. Int J STD AIDS 2006; 17:594–606.

37. Hayward RS, Wilson MC, Tunis SR, Bass EB, Guyatt G. Users' guides to the medical literature. VIII. How to use clinical practice guidelines. A. Are the recommendations valid? The Evidence-Based Medicine Working Group. JAMA 1995; 274:570–574.

38. Guyatt GH, Oxman AD, Kunz R, Vist GE, Falck-Ytter Y, Schunemann HJ. What is ‘quality of evidence’ and why is it important to clinicians? BMJ 2008; 336:995–998.

39. Cohen MS, Bollinger RC, Celentano D, Chariyalertsak S, Grinstejn B, Hakim J, et al. HPTN 052. A randomized trial to evaluate the effectiveness of antiretroviral therapy plus HIV primary care versus HIV primary care alone to prevent the sexual transmission of HIV-1 in serodiscordant couples. http://www.hptn.org/research_studies/HPTN052StudyDocuments.asp#Protocol. [Accessed February 2009]

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Pinkerton, SD; Kibicho, J; Galletly, CL
AIDS and Behavior, 17(1): 1-4.
10.1007/s10461-012-0321-z
CrossRef
Annual Review of Public Health, Vol 34
HIV Prevention Among Women in Low- and Middle-Income Countries: Intervening Upon Contexts of Heightened HIV Risk
Strathdee, SA; Wechsberg, WM; Kerrigan, DL; Patterson, TL
Annual Review of Public Health, Vol 34, 34(): 301-316.
10.1146/annurev-publhealth-031912-114411
CrossRef
AIDS and Behavior
Early Uptake of HIV Clinical Care After Testing HIV-Positive During Home-Based Testing and Counseling in Western Kenya
Medley, A; Ackers, M; Amolloh, M; Owuor, P; Muttai, H; Audi, B; Sewe, M; Laserson, K
AIDS and Behavior, 17(1): 224-234.
10.1007/s10461-012-0344-5
CrossRef
Health Education Journal
Brief training of HIV medical providers increases their frequency of delivering prevention counselling to patients at risk of transmitting HIV to others
Patel, SN; Marks, G; Gardner, L; Golin, CE; Shinde, S; O' Daniels, C; Wilson, TE; Quinlivan, EB; Banderas, JW
Health Education Journal, 72(4): 431-442.
10.1177/0017896912446740
CrossRef
Plos One
Clinical Impact and Cost-Effectiveness of Expanded Voluntary HIV Testing in India
Venkatesh, KK; Becker, JE; Kumarasamy, N; Nakamura, YM; Mayer, KH; Losina, E; Swaminathan, S; Flanigan, TP; Walensky, RP; Freedberg, KA
Plos One, 8(5): -.
ARTN e64604
CrossRef
Culture Health & Sexuality
Falling short of universal access to reproductive health: unintended pregnancy and contraceptive use among Mexican women with HIV
Kendall, T
Culture Health & Sexuality, 15(): S166-S179.
10.1080/13691058.2013.798685
CrossRef
Annual Review of Medicine, Vol 64
Systemic and Topical Drugs for the Prevention of HIV Infection: Antiretroviral Pre-exposure Prophylaxis
Baeten, J; Celum, C
Annual Review of Medicine, Vol 64, 64(): 219-232.
10.1146/annurev-med-050911-163701
CrossRef
British Medical Journal
Combined antiretroviral treatment and heterosexual transmission of HIV-1: cross sectional and prospective cohort study
Del Romero, J; Castilla, J; Hernando, V; Rodriguez, C; Garcia, S
British Medical Journal, 340(): -.
ARTN c2205
CrossRef
Clinical Infectious Diseases
Setting the Stage: Current State of Affairs and Major Challenges
Reynolds, SJ; Quinn, TC
Clinical Infectious Diseases, 50(): S71-S76.
10.1086/651476
CrossRef
Plos One
Hidden Drug Resistant HIV to Emerge in the Era of Universal Treatment Access in Southeast Asia
Hoare, A; Kerr, SJ; Ruxrungtham, K; Ananworanich, J; Law, MG; Cooper, DA; Phanuphak, P; Wilson, DP
Plos One, 5(6): -.
ARTN e10981
CrossRef
Clinical Infectious Diseases
Prevention of Tuberculosis in People Living with HIV
Granich, R; Akolo, C; Gunneberg, C; Getahun, H; Williams, P; Williams, B
Clinical Infectious Diseases, 50(): S215-S222.
10.1086/651494
CrossRef
Plos One
Decreases in Community Viral Load Are Accompanied by Reductions in New HIV Infections in San Francisco
Das, M; Chu, PL; Santos, GM; Scheer, S; Vittinghoff, E; McFarland, W; Colfax, GN
Plos One, 5(6): -.
ARTN e11068
CrossRef
Medecine Et Maladies Infectieuses
New treatments and indetectability of HIV. A risk in the doctor-patient relationship?
Lebouche, B; Levy, JJ
Medecine Et Maladies Infectieuses, 39(): 8-11.

Lancet
HIV drugs for treatment, and for prevention
Dabis, F; Newell, ML; Hirschel, B
Lancet, 375(): 2056-2057.
10.1016/S0140-6736(10)60838-0
CrossRef
Lancet
Heterosexual HIV-1 transmission after initiation of antiretroviral therapy: a prospective cohort analysis
Donnell, D; Baeten, JM; Kiarie, J; Thomas, KK; Stevens, W; Cohen, CR; McIntyre, J; Lingappa, JR; Celum, C
Lancet, 375(): 2092-2098.
10.1016/S0140-6736(10)60705-2
CrossRef
Human Reproduction
Human immunodeficiency virus serodiscordant couples on highly active antiretroviral therapies with undetectable viral load: conception by unprotected sexual intercourse or by assisted reproduction techniques?
Vandermaelen, A; Englert, Y
Human Reproduction, 25(2): 374-379.
10.1093/humrep/dep412
CrossRef
Addiction
Next Steps for Ukraine Abolition of Hiv Registries, Implementation of Routine Human Immunodeficiency Virus Testing and Expansion of Services
Izenberg, JM; Altice, FL
Addiction, 105(3): 569-570.

Health Affairs
Investing To Meet The Scientific Challenges Of HIV/AIDS
Fauci, AS; Folkers, GK
Health Affairs, 28(6): 1629-1641.
10.1377/hlthaff.28.6.1629
CrossRef
British Medical Journal
HIV transmission in serodiscordant heterosexual couples
Boily, MC; Buve, A; Baggaley, RF
British Medical Journal, 340(): -.
ARTN c2449
CrossRef
Bmj Open
Does antiretroviral therapy initiation increase sexual risk taking in Kenyan female sex workers? A retrospective case-control study
Mawji, E; McKinnon, L; Wachihi, C; Chege, D; Thottingal, P; Kariri, A; Plummer, F; Ball, TB; Jaoko, W; Ngugi, E; Kimani, J; Gelmon, L; Nagelkerke, N; Kaul, R
Bmj Open, 2(2): -.
ARTN e000565
CrossRef
Bmc Infectious Diseases
Missed opportunities for HIV testing in newly-HIV-diagnosed patients, a cross sectional study
Champenois, K; Cousien, A; Cuzin, L; Le Vu, S; Deuffic-Burban, S; Lanoy, E; Lacombe, K; Patey, O; Bechu, P; Calvez, M; Semaille, C; Yazdanpanah, Y
Bmc Infectious Diseases, 13(): -.
ARTN 200
CrossRef
AIDS Reviews
What is the Place of Pre-Exposure Prophylaxis in HIV Prevention?
De Man, J; Colebunders, R; Florence, E; Laga, M; Kenyon, C
AIDS Reviews, 15(2): 102-111.

Plos One
Changing Risk Behaviours and the HIV Epidemic: A Mathematical Analysis in the Context of Treatment as Prevention
Ramadanovic, B; Vasarhelyi, K; Nadaf, A; Wittenberg, RW; Montaner, JSG; Wood, E; Rutherford, AR
Plos One, 8(5): -.
ARTN e62321
CrossRef
Plos One
Disparities in the Burden of HIV/AIDS in Canada
Hogg, RS; Heath, K; Lima, VD; Nosyk, B; Kanters, S; Wood, E; Kerr, T; Montaner, JSG
Plos One, 7(): -.
ARTN e47260
CrossRef
Global Public Health
Notes on the concepts of 'serodiscordance' and 'risk' in couples with mixed HIV status
Persson, A
Global Public Health, 8(2): 209-220.
10.1080/17441692.2012.729219
CrossRef
European Physical Journal-Special Topics
Combining social and genetic networks to study HIV transmission in mixing risk groups
Zarrabi, N; Prosperi, MCF; Belleman, RG; Di Giambenedetto, S; Fabbiani, M; De Luca, A; Sloot, PMA
European Physical Journal-Special Topics, 222(6): 1377-1387.
10.1140/epjst/e2013-01932-x
CrossRef
American Journal of Reproductive Immunology
Biology as Population Dynamics: Heuristics for Transmission Risk
Keebler, D; Walwyn, D; Welte, A
American Journal of Reproductive Immunology, 69(): 88-94.
10.1111/aji.12040
CrossRef
Annals Academy of Medicine Singapore
Biomedical Strategies for Human Immunodeficiency Virus (HIV) Prevention? A New Paradigm
Chan, R
Annals Academy of Medicine Singapore, 41(): 595-601.

AIDS and Behavior
Condom Distribution in Jail to Prevent HIV Infection
Leibowitz, AA; Harawa, N; Sylla, M; Hallstrom, CC; Kerndt, PR
AIDS and Behavior, 17(8): 2695-2702.
10.1007/s10461-012-0190-5
CrossRef
Plos One
Understanding the Potential Impact of a Combination HIV Prevention Intervention in a Hyper-Endemic Community
Alsallaq, RA; Baeten, JM; Celum, CL; Hughes, JP; Abu-Raddad, LJ; Barnabas, RV; Hallett, TB
Plos One, 8(1): -.
ARTN e54575
CrossRef
Sociology of Health & Illness
Non/infectious corporealities: tensions in the biomedical era of "HIV normalisation'
Persson, A
Sociology of Health & Illness, 35(7): 1065-1079.
10.1111/1467-9566.12023
CrossRef
Plos One
Systematic Review of HIV Transmission between Heterosexual Serodiscordant Couples where the HIV-Positive Partner Is Fully Suppressed on Antiretroviral Therapy
Loutfy, MR; Wu, W; Letchumanan, M; Bondy, L; Antoniou, T; Margolese, S; Zhang, YM; Rueda, S; McGee, F; Peck, R; Binder, L; Allard, P; Rourke, SB; Rochon, PA
Plos One, 8(2): -.
ARTN e55747
CrossRef
Plos One
Estimating the Impact of State Budget Cuts and Redirection of Prevention Resources on the HIV Epidemic in 59 California Local Health Departments
Lin, F; Lasry, A; Sansom, SL; Wolitski, RJ
Plos One, 8(3): -.
ARTN e55713
CrossRef
Plos One
Ten Year Trends in Community HIV Viral Load in Barbados: Implications for Treatment as Prevention
Landis, RC; Branch-Beckles, SL; Crichlow, S; Hambleton, IR; Best, A
Plos One, 8(3): -.
ARTN e58590
CrossRef
AIDS and Behavior
Alcohol Consumption as a Barrier to Prior HIV Testing in a Population-Based Study in Rural Uganda
Fatch, R; Bellows, B; Bagenda, F; Mulogo, E; Weiser, S; Hahn, JA
AIDS and Behavior, 17(5): 1713-1723.
10.1007/s10461-012-0282-2
CrossRef
Addiction
Decline in incidence of HIV and hepatitis C virus infection among injecting drug users in Amsterdam; evidence for harm reduction?
de Vos, AS; van der Helm, JJ; Matser, A; Prins, M; Kretzschmar, MEE
Addiction, 108(6): 1070-1081.
10.1111/add.12125
CrossRef
Plos One
HIV-1 Transmission within Marriage in Rural Uganda: A Longitudinal Study
Biraro, S; Ruzagira, E; Kamali, A; Whitworth, J; Grosskurth, H; Weiss, HA
Plos One, 8(2): -.
ARTN e55060
CrossRef
Plos One
Averting HIV Infections in New York City: A Modeling Approach Estimating the Future Impact of Additional Behavioral and Biomedical HIV Prevention Strategies
Kessler, J; Myers, JE; Nucifora, KA; Mensah, N; Kowalski, A; Sweeney, M; Toohey, C; Khademi, A; Shepard, C; Cutler, B; Braithwaite, RS
Plos One, 8(9): -.
ARTN e73269
CrossRef
AIDS Patient Care and Stds
Highly Active Antiretroviral Therapy is Associated with Decreased Incidence of Sexually Transmitted Diseases in a Taiwanese HIV-Positive Population
Cheng, SH; Yang, CH; Hsueh, YM
AIDS Patient Care and Stds, 27(3): 155-162.
10.1089/apc.2012.0385
CrossRef
Trials
Evaluation of the impact of immediate versus WHO recommendations-guided antiretroviral therapy initiation on HIV incidence: the ANRS 12249 TasP (Treatment as Prevention) trial in Hlabisa sub-district, KwaZulu-Natal, South Africa: study protocol for a cluster randomised controlled trial
Iwuji, CC; Orne-Gliemann, J; Tanser, F; Boyer, S; Lessells, RJ; Lert, F; Imrie, J; Barnighausen, T; Rekacewicz, C; Bazin, B; Newell, ML; Dabis, F
Trials, 14(): -.
ARTN 230
CrossRef
Clinical Infectious Diseases
Balancing Disease Eradication With the Emergence of Multidrug-Resistant HIV in Test-and-Treat Policies
Jena, AB
Clinical Infectious Diseases, 56(): 1797-1799.
10.1093/cid/cit159
CrossRef
Current Opinion in Hiv and AIDS
Fifteen million people on antiretroviral treatment by 2015: treatment as prevention
Granich, R; Williams, B; Montaner, J
Current Opinion in Hiv and AIDS, 8(1): 41-49.
10.1097/COH.0b013e32835b80dd
CrossRef
Plos One
HIV-DNA in the Genital Tract of Women on Long-Term Effective Therapy Is Associated to Residual Viremia and Previous AIDS-Defining Illnesses
Prazuck, T; Chaillon, A; Avettand-Fenoel, V; Caplan, AL; Sayang, C; Guigon, A; Niang, M; Barin, F; Rouzioux, C; Hocqueloux, L
Plos One, 8(8): -.
ARTN e69686
CrossRef
Bmc Public Health
Acceptability of HIV self-testing: a systematic literature review
Krause, J; Subklew-Sehume, F; Kenyon, C; Colebunders, R
Bmc Public Health, 13(): -.
ARTN 735
CrossRef
AIDS and Behavior
Adherence to Antiretroviral Therapy and Clinical Outcomes Among Young Adults Reporting High-Risk Sexual Behavior, Including Men Who Have Sex with Men, in Coastal Kenya
Graham, SM; Mugo, P; Gichuru, E; Thiong'o, A; Macharia, M; Okuku, HS; van der Elst, E; Price, MA; Muraguri, N; Sanders, EJ
AIDS and Behavior, 17(4): 1255-1265.
10.1007/s10461-013-0445-9
CrossRef
AIDS and Behavior
Aggregate Versus Day Level Association Between Methamphetamine Use and HIV Medication Non-adherence Among Gay and Bisexual Men
Parsons, JT; Kowalczyk, WJ; Botsko, M; Tomassilli, J; Golub, SA
AIDS and Behavior, 17(4): 1478-1487.
10.1007/s10461-013-0463-7
CrossRef
Colombia Medica
From trials to the public health: pre-exposure prophylaxis for HIV prevention
Esper, GK; Miraglia, LJ
Colombia Medica, 44(1): 68-69.

Journal of Infectious Diseases
Seminal Human Immunodeficiency Virus Blips and Structured Natural Conception In Serodiscordant Couples Reply
Morris, SR; Smith, DM; Little, SJ; Gianella, S
Journal of Infectious Diseases, 208(4): 711-712.
10.1093/infdis/jit218
CrossRef
AIDS
Combined antiretroviral therapy is effective on blood plasma HIV-1-RNA: what about semen HIV-1-RNA levels?
Ghosn, J; Chaix, M
AIDS, 24(2): 309-311.
10.1097/QAD.0b013e3283323504
PDF (255) | CrossRef
AIDS
Examining the promise of HIV elimination by ‘test and treat’ in hyperendemic settings
Dodd, PJ; Garnett, GP; Hallett, TB
AIDS, 24(5): 729-735.
10.1097/QAD.0b013e32833433fe
PDF (429) | CrossRef
AIDS
No detection of HIV 1-RNA in semen of men on efficient HAART in the past 4 years of a 2002–2009 survey
Dulioust, E; Leruez-Ville, M; Guibert, J; Fubini, A; Jegou, D; Launay, O; Sogni, P; Jouannet, P; Rouzioux, C
AIDS, 24(10): 1595-1598.
10.1097/QAD.0b013e32833b47fc
PDF (320) | CrossRef
AIDS
Per-contact probability of HIV transmission in homosexual men in Sydney in the era of HAART
Jin, F; Jansson, J; Law, M; Prestage, GP; Zablotska, I; Imrie, JC; Kippax, SC; Kaldor, JM; Grulich, AE; Wilson, DP
AIDS, 24(6): 907-913.
10.1097/QAD.0b013e3283372d90
PDF (345) | CrossRef
AIDS
Data are lacking for quantifying HIV transmission risk in the presence of effective antiretroviral therapy
Wilson, DP
AIDS, 23(11): 1431-1433.
10.1097/QAD.0b013e32832d871b
PDF (80) | CrossRef
Back to Top | Article Outline
Keywords:

highly active antiretroviral therapy; infectious; prevention of HIV infections; sexually transmitted diseases; transmission probability; viral load

© 2009 Lippincott Williams & Wilkins, Inc.

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