Persisting with prevention: The importance of adherence for HIV prevention
© Weiss et al; licensee BioMed Central Ltd. 2008
Received: 21 March 2008
Accepted: 11 July 2008
Published: 11 July 2008
Only four out of 31 completed randomized controlled trials (RCTs) of HIV prevention strategies against sexual transmission have shown significant efficacy. Poor adherence may have contributed to the lack of effect in some of these trials. In this paper we explore the impact of various levels of adherence on measured efficacy within an RCT.
We used simple quantitative methods to illustrate the impact of various levels of adherence on measured efficacy by assuming a uniform population in terms of sexual behavior and the binomial model for the transmission probability per partnership.
At 100% adherence the measured efficacy within an RCT is a reasonable approximation of the true biological efficacy. However, as adherence levels fall, the efficacy measured within a trial substantially under-estimates the true biological efficacy. For example, at 60% adherence, the measured efficacy can be less than half of the true biological efficacy.
Poor adherence during a trial can substantially reduce the power to detect an effect, and improved methods of achieving and maintaining high adherence within trials are needed. There are currently 12 ongoing HIV prevention trials, all but one of which require ongoing user-adherence. Attention must be given to methods of maximizing adherence when piloting and designing RCTs and HIV prevention programmes.
Randomised controlled trials of HIV prevention with HIV incidence as an outcome for sexual transmission
Individual or cluster randomization
RCTs completed or stopped
RCTs showing efficacy
Behavior change (abstinence/delay, sex partner reduction, counseling and testing, condoms, diaphragms, microfinance)
Oral pre-exposure prophylaxis (PrEP)
Multiple factors are likely to be responsible for the failure of the trials to see a protective effect, including interventions which are truly non-efficacious, trials which were under-powered to detect an effect, and poor adherence to the intervention under study. It is striking that the only intervention for which multiple trials have shown efficacy in preventing HIV is male circumcision [5–7], a non-reversible surgical procedure for which post-intervention 'adherence' is 100%. In contrast, some of the recent RCTs of other interventions have suggested that poor adherence may have contributed to the lack of effect [1, 3].
In this paper, we use simple quantitative methods to explore the impact of various levels of adherence on observed efficacy in randomized controlled trials, and discuss the implications for designing future HIV intervention trials.
The impact of adherence in an RCT for an intervention with different levels of efficacy was calculated by linking the risk per sexual exposure to the cumulative risk calculated in longitudinal trials using simplifying assumptions . We assume a uniform population in terms of sexual behavior and the binomial model for the transmission probability per partnership . These simplifying assumptions give illustrative results of the effect of varying adherence within the population on measured efficacy within a RCT.
Here, p = 0.0015 is the average HIV transmission probability per coital act over all HIV stages for vaginal intercourse , p = 0.0082 for receptive anal intercourse , n = 10 is the frequency of coital acts per month , and τ is the average duration of the trial follow-up (here assumed to be 18 months). The term EffInt is the biological efficacy of the intervention under study in reducing HIV transmission probability per coital act, and fAdh is the mean adherence level achieved in the trial (i.e. fraction of coital acts protected by the intervention).
and EffMeasured = 1 - RR is interpreted as the "measured efficacy" of the intervention during the trial.
Similar results also hold for an intervention targeting unprotected receptive anal intercourse (Figure 1B). The measured efficacy here further underestimates the true biological efficacy even at full adherence. The measured efficacy is 13%, 32% and 60% respectively at 100% adherence compared to EffInt of 25%, 50% and 75%. At 80% adherence, the measured efficacy is 10%, 24% and 42%; and at 60% adherence, it is 7%, 16% and 28% respectively.
The mean level of adherence achieved during an RCT affects the measured efficacy of the intervention, and as adherence falls, the measured efficacy will increasingly under-estimate the true biological efficacy. The main implications of this finding are that trials need to be powered to detect this smaller measured efficacy rather than the true biological efficacy, and that methods to maximize adherence within trials are urgently needed.
Many HIV prevention strategies rely on good levels of adherence. To our knowledge, 31 RCTs have reported results, of which 7 were behavioural interventions and 24 were primarily biomedical (Table 1). The behavioural interventions include voluntary counseling and testing, and educational interventions to promote abstinence, reduce number of sexual partners, and increase use of male condoms and female diaphragms. All of these rely on ongoing user-adherence. None of the behavioural RCTs found a significantly reduced risk of HIV acquisition. This may be partly due to truly ineffective interventions, low power (due for example, to under-estimates of HIV incidence, higher than expected loss to follow-up, or effective interventions in the control arm), and difficulty in achieving sustained, consistent behaviour change i.e. poor adherence.
Biomedical interventions against HIV acquisition include male circumcision, vaginal microbicides, oral pre-exposure prophylaxis (PrEP), STI treatment and HIV vaccines. The only one of these for which there has been consistent efficacy in multiple trials is male circumcision in heterosexual men. These trial results were striking both in the magnitude of effect (summary efficacy 58%, 95% CI 43%–69%) which led to all 3 trials being halted early, and also in the consistency of the results across trials and with a previous meta-analysis of observational studies . One plausible reason for the strong, consistent impact of male circumcision on HIV acquisition is the in-built 100% 'adherence' of foreskin removal. Other biomedical interventions, such as treatment of bacterial STDs, also have the potential for substantial efficacy based on observational studies but only one of these RCTs afforded significant protection against HIV acquisition [8, 14–16]. Reasons for the inconsistent results of the bacterial STD treatment trials have been widely discussed [17–20] and include poor adherence to the intervention as well as other factors such as the stage of the epidemic and prevalence of curable STDs in the trial population.
The importance of adherence is also suggested by the MIRA trial, and one of the HSV-2 suppressive therapy trials [1, 3]. In the MIRA trial, participants in the intervention arm were asked to insert a diaphragm and use a lubricant gel before each coital act. In the HSV suppressive therapy trials, women were asked to take two tablets of acyclovir daily for up to 30 months. However, it is not clear whether suboptimal adherence was one of the factors contributing to the lack of efficacy. The median estimated adherence in the two trials was 90–94%, but was difficult to verify due to missing visits and reliance on self-report. It is possible that adherence was not the main problem in these trials, but rather that the drug or dosage used was insufficient to switch off the frequent subclinical HSV reactivations. In the Mwanza trial , there was little impact on detection of genital HSV, again suggesting suboptimal adherence overall, although the trial was not powered to measure an impact on this endpoint. In the MIRA trial , there was some evidence of impact among those women reporting high levels of adherence, and suboptimal adherence is suggested by the annual incidence of first pregnancy being similar in both intervention and control groups (13%), and consistent with the reported rates of pregnancy in these populations (13.7% in Zimbabwe in 2005–2006  and 10.0% in South Africa in 1998 ). Moreover, the similar HIV incidence rates in both arms for each site, and across each pre-defined baseline subgroup in the trial may suggest that poor adherence was common in different sites.
Methods of achieving and maintaining high adherence both within trial and general populations must be a research priority. To our knowledge, there are currently 12 ongoing HIV prevention trials, examining a range of interventions including community-based HIV voluntary counseling and testing, vaginal microbicides, oral PrEP, herpes therapy, and an HIV vaccine (Table 1). All of these interventions, except an HIV vaccine, require ongoing user-adherence. Consistent use of pharmaceutical interventions such as, oral PrEP or vaginal microbicides may be easier to achieve than maintenance of behavioural interventions, as suggested by experience with anti-retroviral therapy, for which adherence in sub-Saharan African populations is high compared with that for condoms . However, adherence to these preventive interventions is likely to be harder to maintain in uninfected individuals than adherence to therapeutic interventions, and adherence at population-level will be lower than within carefully monitored trials.
The importance of adherence in prevention trials has several implications for the design and analysis of such trials. Firstly, the anticipated levels of adherence must be taken into account when designing a trial, as sub-optimal adherence can dramatically reduce the power of the trial. Pilot studies may be most useful in estimating realistic levels of adherence, although it might be difficult to determine in advance what level of adherence would be necessary to achieve a meaningful impact. Secondly, every effort must be made to measure adherence accurately in trials and validation of self-reported adherence with biomarkers must become a priority. Thirdly, studies should ideally have adequate power to conduct sub-group analyses by adherence level, to detect whether there is an intervention effect among those with highest adherence in the absence of a significant impact overall. However, to avoid biases, these sub-group analyses would be best undertaken when the controls receive a placebo, and in practice it is unlikely that studies could be powered for such sub-group analyses. Fourthly, simulation of trial outcome using mathematical modeling at various levels of adherence can be valuable in assessing the feasibility of the trials to answer the intended research questions. Finally, when interpreting trial results, it is important to consider that a null finding does not necessarily indicate an ineffective intervention, but may reflect poor adherence to the intervention. Related to the issue of adherence within a trial is adherence during roll-out of a prevention strategy, which is likely to be lower than in controlled trials. Improved measurement of adherence within trials will help programs estimate the effectiveness of a prevention strategy during roll-out.
Poor adherence during a trial can substantially reduce the power to detect an effect, and improved methods of achieving and maintaining high adherence within trials are needed. There are currently 12 ongoing HIV prevention trials, all but one of which require ongoing user-adherence. Maintaining good adherence to HIV prevention strategies will continue to be pivotal in their success. When designing and piloting both RCTs and HIV prevention programs, every effort should be made to maximize adherence.
- Watson-Jones D, Weiss HA, Rusizoka M, Changalucha J, Baisley K, Mugeye K, Tanton C, Ross D, Everett D, Clayton T, Balira R, Knight L, Hambleton I, LeGoff J, Belec L, Hayes R: Effect of herpes simplex suppression on incidence of HIV among women in Tanzania. N Engl J Med. 2008, 358: 1560-1571. 10.1056/NEJMoa0800260PubMed CentralView ArticlePubMedGoogle Scholar
- Celum C, Wald A, Hughes J, Sanchez J, Reid S, Delany-Moretlwe S, Cowan F, Casapia M, Oritz A, Fuchs J, Buchbinder S, Koblin B, Zwerski S, Rose S, Wang J, Corey L: Twice Daily Acyclovir Does Not Reduce the Risk of HIV-1 Acquisition among HSV-2 Seropositive Women and Men who have sex with Men (MSM). Lancet. 2008, 371: 2109-2191. 10.1016/S0140-6736(08)60920-4PubMed CentralView ArticlePubMedGoogle Scholar
- Padian NS, Straten van der A, Ramjee G, Chipato T, de Bruyn G, Blanchard K, Shiboski S, Montgomery ET, Fancher H, Cheng H, Rosenblum M, Laan van der M, Jewell N, McIntyre J: Diaphragm and lubricant gel for prevention of HIV acquisition in southern African women: a randomised controlled trial. Lancet. 2007, 370: 251-261. 10.1016/S0140-6736(07)60950-7PubMed CentralView ArticlePubMedGoogle Scholar
- Robertson M, Mehrotra D, Fitzgerald D, Duerr A, Casimiro J, McElrath J, Lawrence D, Buchbinder S: Efficacy Results from the STEP Study (Merck V520 Protocol 023/HVTN 502): A Phase II Test-of-Concept Trial of the MRKAd5 HIV-1 Gag/Pol/Nef Trivalent Vaccine. CROI; February 3–6, 2008; Boston. 2008Google Scholar
- Gray RH, Kigozi G, Serwadda D, Makumbi F, Watya S, Nalugoda F, Kiwanuka N, Moulton LH, Chaudhary MA, Chen MZ, Sewankambo N, Wabwire-Mangen F, Bacon MC, Williams CF, Opendi P, Reynolds SJ, Laeyendecker O, Quinn TC, Wawer MJ: Male circumcision for HIV prevention in men in Rakai, Uganda: a randomised trial. Lancet. 2007, 369: 657-666. 10.1016/S0140-6736(07)60313-4View ArticlePubMedGoogle Scholar
- Bailey RC, Moses S, Parker CB, Agot K, Maclean I, Krieger JN, Williams CF, Campbell RT, Ndinya-Achola JO: Male circumcision for HIV prevention in young men in Kisumu, Kenya: a randomised controlled trial. Lancet. 2007, 369: 643-656. 10.1016/S0140-6736(07)60312-2View ArticlePubMedGoogle Scholar
- Auvert B, Taljaard D, Lagarde E, Sobngwi-Tambekou J, Sitta R, Puren A: Randomized, controlled intervention trial of male circumcision for reduction of HIV infection risk: the ANRS 1265 Trial. PLoS Med. 2005, 2: e298. 10.1371/journal.pmed.0020298PubMed CentralView ArticlePubMedGoogle Scholar
- Grosskurth H, Mosha F, Todd J, Mwijarubi E, Klokke A, Senkoro K, Mayaud P, Changalucha J, Nicoll A, ka-Gina G, Newell J, Mugeye K, Mabey D, Hayes RJ: Impact of improved treatment of sexually transmitted diseases on HIV infection in rural Tanzania: randomised controlled trial. Lancet. 1995, 346: 530-536. 10.1016/S0140-6736(95)91380-7View ArticlePubMedGoogle Scholar
- Hayes RJ, Schulz KF, Plummer FA: The cofactor effect of genital ulcers on the per-exposure risk of HIV transmission in sub-Saharan Africa. J Trop Med Hyg. 1995, 98: 1-8.PubMedGoogle Scholar
- Rottingen JA, Garnett GP: The epidemiological and control implications of HIV transmission probabilities within partnerships. Sex Transm Dis. 2002, 29: 818-827. 10.1097/00007435-200212000-00014View ArticlePubMedGoogle Scholar
- Wawer MJ, Gray RH, Sewankambo NK, Serwadda D, Li X, Laeyendecker O, Kiwanuka N, Kigozi G, Kiddugavu M, Lutalo T, Nalugoda F, Wabwire-Mangen F, Meehan MP, Quinn TC: Rates of HIV-1 transmission per coital act, by stage of HIV-1 infection, in Rakai, Uganda. J Infect Dis. 2005, 191: 1403-1409. 10.1086/429411View ArticlePubMedGoogle Scholar
- Vittinghoff E, Douglas J, Judson F, McKirnan D, MacQueen K, Buchbinder SP: Per-contact risk of human immunodeficiency virus transmission between male sexual partners. Am J Epidemiol. 1999, 150: 306-311.View ArticlePubMedGoogle Scholar
- 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. 10.1097/00002030-200010200-00018View ArticlePubMedGoogle Scholar
- Kaul R, Kimani J, Nagelkerke NJ, Fonck K, Ngugi EN, Keli F, MacDonald KS, Maclean IW, Bwayo JJ, Temmerman M, Ronald AR, Moses S: Monthly antibiotic chemoprophylaxis and incidence of sexually transmitted infections and HIV-1 infection in Kenyan sex workers: a randomized controlled trial. Jama. 2004, 291: 2555-2562. 10.1001/jama.291.21.2555View ArticlePubMedGoogle Scholar
- Kamali A, Quigley M, Nakiyingi J, Kinsman J, Kengeya-Kayondo J, Gopal R, Ojwiya A, Hughes P, Carpenter LM, Whitworth J: Syndromic management of sexually-transmitted infections and behaviour change interventions on transmission of HIV-1 in rural Uganda: a community randomised trial. Lancet. 2003, 361: 645-652. 10.1016/S0140-6736(03)12598-6View ArticlePubMedGoogle Scholar
- Wawer MJ, Sewankambo NK, Serwadda D, Quinn TC, Paxton LA, Kiwanuka N, Wabwire-Mangen F, Li C, Lutalo T, Nalugoda F, Gaydos CA, Moulton LH, Meehan MO, Ahmed S, Gray RH: Control of sexually transmitted diseases for AIDS prevention in Uganda: a randomised community trial. Rakai Project Study Group. Lancet. 1999, 353: 525-535. 10.1016/S0140-6736(98)06439-3View ArticlePubMedGoogle Scholar
- White RG, Orroth KK, Korenromp EL, Bakker R, Wambura M, Sewankambo NK, Gray RH, Kamali A, Whitworth JA, Grosskurth H, Habbema JD, Hayes RJ: Can population differences explain the contrasting results of the Mwanza, Rakai, and Masaka HIV/sexually transmitted disease intervention trials?: A modeling study. J Acquir Immune Defic Syndr. 2004, 37: 1500-1513. 10.1097/01.qai.0000127062.94627.31View ArticlePubMedGoogle Scholar
- Orroth KK, White RG, Korenromp EL, Bakker R, Changalucha J, Habbema JD, Hayes RJ: Empirical observations underestimate the proportion of human immunodeficiency virus infections attributable to sexually transmitted diseases in the Mwanza and Rakai sexually transmitted disease treatment trials: Simulation results. Sex Transm Dis. 2006, 33: 536-544. 10.1097/01.olq.0000204667.11192.71View ArticlePubMedGoogle Scholar
- Korenromp EL, White RG, Orroth KK, Bakker R, Kamali A, Serwadda D, Gray RH, Grosskurth H, Habbema JD, Hayes RJ: Determinants of the impact of sexually transmitted infection treatment on prevention of HIV infection: a synthesis of evidence from the Mwanza, Rakai, and Masaka intervention trials. J Infect Dis. 2005, 191 (Suppl 1): S168-178. 10.1086/425274View ArticlePubMedGoogle Scholar
- Grosskurth H, Gray R, Hayes R, Mabey D, Wawer M: Control of sexually transmitted diseases for HIV-1 prevention: understanding the implications of the Mwanza and Rakai trials. Lancet. 2000, 355: 1981-1987. 10.1016/S0140-6736(00)02336-9View ArticlePubMedGoogle Scholar
- DHS: Zimbabwe 2005–2006 Demographic and Health Surveys.Google Scholar
- DHS: South Africa 1998 Demographic and Health Surveys.Google Scholar
- Mills EJ, Nachega JB, Buchan I, Orbinski J, Attaran A, Singh S, Rachlis B, Wu P, Cooper C, Thabane L, Wilson K, Guyatt GH, Bangsberg DR: Adherence to antiretroviral therapy in sub-Saharan Africa and North America: a meta-analysis. JAMA. 2006, 296: 679-690. 10.1001/jama.296.6.679View ArticlePubMedGoogle Scholar
- Koblin B, Chesney M, Coates T: Effects of a behavioural intervention to reduce acquisition of HIV infection among men who have sex with men: the EXPLORE randomised controlled study. Lancet. 2004, 364: 41-50. 10.1016/S0140-6736(04)16588-4View ArticlePubMedGoogle Scholar
- Corbett EL, Makamure B, Cheung YB, Dauya E, Matambo R, Bandason T, Munyati SS, Mason PR, Butterworth AE, Hayes RJ: HIV incidence during a cluster-randomized trial of two strategies providing voluntary counselling and testing at the workplace, Zimbabwe. Aids. 2007, 21: 483-489. 10.1097/QAD.0b013e3280115402View ArticlePubMedGoogle Scholar
- Pronyk PM, Hargreaves JR, Kim JC, Morison LA, Phetla G, Watts C, Busza J, Porter JD: Effect of a structural intervention for the prevention of intimate-partner violence and HIV in rural South Africa: a cluster randomised trial. Lancet. 2006, 368: 1973-1983. 10.1016/S0140-6736(06)69744-4View ArticlePubMedGoogle Scholar
- Ross DA, Changalucha J, Obasi AI, Todd J, Plummer ML, Cleophas-Mazige B, Anemona A, Everett D, Weiss HA, Mabey DC, Grosskurth H, Hayes RJ: Biological and behavioural impact of an adolescent sexual health intervention in Tanzania: a community-randomized trial. AIDS. 2007, 21: 1943-1955. 10.1097/QAD.0b013e3282ed3cf5View ArticlePubMedGoogle Scholar
- NIMH Collaborative HIV/STD Prevention Trial Group: Methodological overview of a five-country community-level HIV/sexually transmitted disease prevention trial. AIDS. 2007, 21 (Suppl 2): S3-18.View ArticleGoogle Scholar
- NIMH Project Accept/HPTN 043 http://www.cbvct.med.ucla.edu/overview.html#contact
- The Regai Dzive Shiri Programme: 2002–2007 http://spw.org/downloads/SPW_RDS_summary.pdf
- Wawer MJ, Kigozi G, Serwadda D, Watya S, Makumbi F, Nalugoda F, Watya S, Buwembo D, Ssempija V, Moulton L, Gray R: Trial of male circumcision in HIV+ men: effects in men and women. 15th Conference on Retroviruses and Opportunistic Infections. Boston. 2008.Google Scholar
- Feldblum PJ, Adeiga A, Bakare R, Wevill S, Lendvay A, Obadaki F, Olayemi MO, Wang L, Nanda K, Rountree W: SAVVY vaginal gel (C31G) for prevention of HIV infection: a randomized controlled trial in Nigeria. PLoS ONE. 2008, 3: e1474. 10.1371/journal.pone.0001474PubMed CentralView ArticlePubMedGoogle Scholar
- Halpern V, Wang L, Obunge O, Ogunsola F, Mehta N, Onyejepu N, Oduyebo O, Taylor D, Otusanya S, Umo-Otong J, McNeil L, Bragg V, Cates W: Effectiveness of cellulose sulfate gel for prevention of HIV: results of the phase III trial in Nigeria. 4th IAS Conference on HIV Pathogenesis, Treatment and Prevention. 2007.Google Scholar
- Kreiss J, Ngugi E, Holmes K, Ndinya-Achola J, Waiyaki P, Roberts PL, Ruminjo I, Sajabi R, Kimata J, Fleming TR: Efficacy of nonoxynol 9 contraceptive sponge use in preventing heterosexual acquisition of HIV in Nairobi prostitutes. JAMA. 1992, 268: 477-482. 10.1001/jama.268.4.477View ArticlePubMedGoogle Scholar
- Peterson L, Nanda K, Opoku BK, Ampofo WK, Owusu-Amoako M, Boakye AY, Rountree W, Troxler A, Dominik R, Roddy R, Dorflinger L: SAVVY (C31G) gel for prevention of HIV infection in women: a Phase 3, double-blind, randomized, placebo-controlled trial in Ghana. PLoS ONE. 2007, 2: e1312. 10.1371/journal.pone.0001312PubMed CentralView ArticlePubMedGoogle Scholar
- Population Council: Trial Shows Anti-HIV Microbicide Is Safe, but Does Not Prove It Effective. Press Release. New York 2008.Google Scholar
- Richardson BA, Lavreys L, Martin HL Jr, Stevens CE, Ngugi E, Mandaliya K, Bwayo J, Ndinya-Achola J, Kreiss JK: Evaluation of a low-dose nonoxynol-9 gel for the prevention of sexually transmitted diseases: a randomized clinical trial. Sex Transm Dis. 2001, 28: 394-400. 10.1097/00007435-200107000-00006View ArticlePubMedGoogle Scholar
- Roddy RE, Zekeng L, Ryan KA, Tamoufe U, Weir SS, Wong EL: A controlled trial of nonoxynol 9 film to reduce male-to-female transmission of sexually transmitted diseases. N Engl J Med. 1998, 339: 504-510. 10.1056/NEJM199808203390803View ArticlePubMedGoogle Scholar
- Van Damme L, Govinden R, Mirembe F, Guedou F, Solomon S, Becker ML, Pradeep B, Alary M, Nakabiito C, Ramjee G, Murphy S, Deese J, Crucitti T, Taylor D: Phase III trial of 6% cellulose sulfate (CS) gel for the prevention of HIV transmission. 4th IAS Conference on HIV Pathogenesis, Treatment and Prevention. Sydney, Australia 2007.Google Scholar
- Van Damme L, Ramjee G, Alary M, Vuylsteke B, Chandeying V, Rees H, Sirivongrangson P, Mukenge-Tshibaka L, Ettiegne-Traore V, Uaheowitchai C, Karim SS, Masse B, Perriens J, Laga M: Effectiveness of COL- a nonoxynol-9 vaginal gel, on HIV-1 transmission in female sex workers: a randomised controlled trial. Lancet. 1492, 360: 971-977. 10.1016/S0140-6736(02)11079-8. 10.1016/S0140-6736(02)11079-8View ArticleGoogle Scholar
- Phase II/IIb Safety and Effectiveness Study of the Vaginal Microbicides BufferGel and 0.5% PRO2000/5 Gel (P) for the Prevention of HIV Infection in Women http://clinicaltrials.gov/ct/show/NCT00074425?order=1
- Phase IIb Trial to Assess the Safety and Effectiveness of the Vaginal Microbicide 1% Tenofovir Gel for the Prevention of HIV Infection in Women in South Africa http://clinicaltrials.gov/show/NCT00441298
- Trial to Evaluate PRO 2000/5 Gels for the Prevention of Vaginally Acquired HIV Infection http://clinicaltrials.gov/ct/show/NCT00262106?order=2
- Bangkok Tenofovir Study http://clinicaltrials.gov/ct2/show/NCT00119106?term=Thailand+CDC&rank=2
- Botswana TDF/FTC Oral HIV Prophylaxis Trial http://clinicaltrials.gov/ct2/show/NCT00448669?term=botswana&rank=1
- Anti-HIV Medications for the Prevention of HIV Infection in Latin American Men Who Have Sex With Men http://clinicaltrials.gov/ct/show/NCT00350324;jsessionid=C6AE509A400FD7C0031FC56FD42AE515?order=39
- Pre-Exposure Prophylaxis to Prevent HIV-1 Acquisition Within HIV-1 Discordant Couples (PartnersPrEP) http://clinicaltrials.gov/ct2/show/NCT00557245?intr=%22Placebo%22&rank=30
- 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/hptn052.asp
- Herpes Simplex Virus Type 2 (HSV-2) Suppression to Prevent HIV Transmission http://clinicaltrials.gov/show/NCT00194519?order=32
- Gregson S, Adamson S, Papaya S, Mundondo J, Nyamukapa CA, Mason PR, Garnett GP, Chandiwana SK, Foster G, Anderson RM: Impact and process evaluation of integrated community and clinic-based HIV-1 control: a cluster-randomised trial in eastern Zimbabwe. PLoS Med. 2007, 4: e102. 10.1371/journal.pmed.0040102PubMed CentralView ArticlePubMedGoogle Scholar
- Flynn NM, Forthal DN, Harro CD, Judson FN, Mayer KH, Para MF: Placebo-controlled phase 3 trial of a recombinant glycoprotein 120 vaccine to prevent HIV-1 infection. J Infect Dis. 2005, 191: 654-665. 10.1086/428404View ArticlePubMedGoogle Scholar
- Safety and Efficacy of a Three-Dose Regimen of an Adenoviral HIV Vaccine (MRKAd5 HIV-1 Gag/Pol/Nef) in HIV Uninfected South African Adults http://clinicaltrials.gov/ct/show/NCT00413725;jsessionid=A6758E80AEA5A1111E76F301C01DE11E?order=2
- Pitisuttithum P, Gilbert P, Gurwith M, Heyward W, Martin M, van Griensven F, Hu D, Tappero JW, Choopanya K: Randomized, double-blind, placebo-controlled efficacy trial of a bivalent recombinant glycoprotein 120 HIV-1 vaccine among injection drug users in Bangkok, Thailand. J Infect Dis. 2006, 194: 1661-1671. 10.1086/508748View ArticlePubMedGoogle Scholar
- Rerks-Ngarm S, Brown AE, Khamboonruang C, Thongcharoen P, Kunasol P: HIV/AIDS preventive vaccine 'prime-boost' phase III trial: foundations and initial lessons learned from Thailand. Aids. 2006, 20: 1471-1479. 10.1097/01.aids.0000237362.26370.f8View ArticlePubMedGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.