Search tips
Search criteria 


Logo of nihpaAbout Author manuscriptsSubmit a manuscriptHHS Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
Am J Public Health. Author manuscript; available in PMC 2011 December 11.
Published in final edited form as:
PMCID: PMC2936983

Antiretroviral Therapy for HIV Prevention: Present status and future prospects

HIV continues to spread rapidly with over 2.5 million new infections each year1. Since efficacious behavioral interventions have not resulted in durable declines in HIV incidence when scaled-up to achieve sufficient coverage in many populations, and it will take years for highly effective HIV preventive vaccines to demonstrate efficacy2-4, an increasing amount of attention has focused on whether available antiretroviral drugs could be used to slow the epidemic. For over a decade, increasingly well-tolerated highly active antiretroviral therapy (HAART) has dramatically changed HIV-associated morbidity and mortality and has improved the quality of life of HIV-infected individuals5, 6. Recent global initiatives have concentrated on expanding access to HIV treatment in resource-limited settings7; so, by the end of 2008, close to 4 million people were receiving ART8. In addition to the individual clinical benefits accrued from increased access to treatment, a growing group of researchers and public officials have suggested that ART maybe used to decrease HIV transmission globally9, 10. ART has already dramatically decreased mother-to-child HIV transmission (MTCT)11, and could conceivably be used to prevent the sexual transmission of HIV via reductions in genital tract HIV concentrations in individuals who are already infected12, 13, or as pre- or post- exposure prophylaxis for uninfected people exposed to HIV14 (See Figure 1).

Figure 1
Potential approaches to prevent HIV transmission

However despite increasing drug availability, the effectiveness of ART for prevention may be limited by concurrent sexually transmitted infections (STIs) that increase infectiousness and susceptibility, non-adherence to therapy, drug-related toxicities, viral resistance, cost considerations, and risk compensation. The effects of HAART initiation can manifest differently in diverse social settings as sexual behavior involves concerns over pleasure and procreation. While early data from the developed world suggested that HAART could be associated with increased sexual risk15-18, more recent data from sub-Saharan Africa has suggested that wider access to HAART is not associated with increased sexual risk taking behaviors19-21. This paper reviews the potential uses of ART for HIV prevention and examines future directions for ART preventive interventions (See Figure 2).

Figure 2
How HAART could alter HIV transmission

Can early ART slow HIV spread?

HIV transmission remains a low probability but high consequence event, occurring in less than 1 in 100 contacts on average22-24, but the global pandemic is potentiated by the frequency of humans having sexual intercourse and factors that amplify infectiousness and susceptibility in specific settings. The per contact calculation is based on composite data, and transmission probabilities vary considerably during the course of the disease, with higher transmission probability in the acute and late phases of HIV infection, as a reflection of plasma and genital HIV concentrations25-29. The best empirical data related to our understanding of how viral suppression could lead to decreased HIV sexual transmission comes from the Rakai study conducted among Ugandan serodiscordant couples30, though this study was completed before generic ART had become widely accessible in Uganda. HIV was not transmitted in discordant couples when the infected partner had a plasma HIV RNA level of less than 400 copies/ml30. This association between viral load and the risk of HIV transmission among serodiscordant couples was confirmed in subsequent studies in Zambia and Thailand31, 32 in the pre-HAART era, and more recent data33 showed that HIV-infected partners in discordant relationships were substantially less likely to transmit HIV to their partners if they were on HAART.

However, other variables may affect genital tract HIV, besides systemic HIV burden. Mucosal HIV transmission is complex, since animal models suggest that either cell-free or cell-infected virus can replicate in a variety of host cells34-36. The minimum inoculum of HIV that can cause human infection remains to be elucidated37. Although some studies have documented HIV preferential binding to cervical and foreskin tissues through dendritic cells38, 39, women who have undergone hysterectomy and circumcised men can also be HIV-infected12, 40, so other urogenital cells can support HIV replication. The temporal window of opportunity for halting transmission through host defenses is very limited, as submucosal viral replication occurs within hours of exposure41. In the first study examining the relationship between treatment and the detection of genital tract HIV, the virus was more readily cultured from seminal plasma and leukocytes in participants with leukocytospermia and/or advanced disease stage, and less likely to be detected in semen among men taking zidovudine (AZT)42. Subsequent semen studies found that genital white blood cells were a significant source of viral burden43,44. These data suggest that factors that increase genital tract inflammation may potentiate infectiousness, and ART could decrease infectiousness, presumably by decreasing viral burden.

Several groups have demonstrated that HAART suppresses viral replication not only in the blood and lymphoid tissues, but also in the male and female genital tract12, 13, 45, 46. While treatment generally suppresses cell-free virus in the semen, many treated individuals can still harbor proviral CD4 cells in their semen44, 47. A further complication is that not all drug combinations of HAART may be equally effective in the genital and systemic compartments12, 48. Differential penetration of ART drugs in genital tissues may be a function of protein binding and other pharmacodynamic properties49. Highly protein-bound drugs, like protease inhibitors, achieve lower concentrations in genital tract secretions compared to blood plasma14, 50. Nucleoside analogues and non-nucleoside reverse transcriptase inhibitors achieve higher concentrations in genital tract secretions than blood plasma51-53, which might make them particularly effective in decreasing sexual transmission of HIV.

Based on these findings, questions arise as to when would be the best time to initiate HAART if a primary goal is to decrease infectiousness among those who could transmit HIV to others. One key period for treatment could be the acute phase of HIV infection when patients have elevated viremia for about three weeks, until host defenses suppress replication, creating a “viral set point” 29, 54, 55. When viral replication is unimpeded during acute HIV infection, individuals may have more than 1 million copies/ml of virus in their blood56, and the potential to infect many individuals54, 57. Studies from North America and Africa have shown between 40% and 50% of new transmissions were from recently infected patients54, 57. Through employing discordant HIV rapid test results and RNA pooling, almost 2% of STI clinic patients in Malawi were identified with acute HIV infection58. These findings suggest that promptly identifying “hot spot” microepidemics of newly infected persons may present an opportunity for early ART and behavioral interventions to slow the spread of HIV in high-risk settings59, 60. Studies are underway to determine if early identification and treatment of acutely infected individuals can have a public health impact on local epidemics, but other questions will take more time to address, such as whether treatment can be discontinued without being detrimental to the patient if it is initiated in the setting of acute HIV infection. Public health challenges to identifying patients with acute infection include very short duration, frequent lack of clinical detection, and the expense of performing RNA-pooling in the era of constrained health resources.

Acute HIV infection is followed by a longer period of chronic viral homeostasis in which an infected person may be asymptomatic with good systemic virological control. This period can be interrupted by STI infections, which may override the suppressive effects of ART in the genital tract by causing inflammation, potentiating local HIV replication27. Due to the relatively shorter periods of acute- and late-stage infection, the prolonged asymptomatic period, which may last more than a decade, may be the time in which substantial transmission events occur61-63. An analysis from Sub-Saharan Africa suggests that acutely infected persons play a major role in HIV transmission during early highly concentrated epidemics, while the contribution of chronically infected persons becomes more prominent during advanced and stabilized epidemics61. A recent projection suggested that annual HIV testing followed by immediate initiation of ART for all HIV-infected patients regardless of CD4 cell count could have a major impact by reducing the number of new HIV infections64.

So, can HAART effectively suppress genital tract HIV over a sufficiently long period of time to stop HIV sexual transmission?65. Studies from Taiwan and British Columbia, Canada have documented a greater than 50% reduction in anticipated number of incident HIV cases following the free provision of ART in 19979, 66. A study among 393 couples in the pre- and post-HAART eras in Spain observed an 80% reduction in HIV transmission following the introduction of HAART67. A recent observational study of discordant African couples showed substantially lower rates of HIV transmission among patients who were on HAART, but these individuals also tended to practice safer sex more than those who remained untreated33. In order to better understand the preventive effects of therapy in discordant couples, the Health Prevention Trials Network of the National Institutes of Health is in the midst of a randomized controlled trial to assess the impact of HAART on transmission among 1750 discordant couples in eight countries (HPTN052)68. HIV-infected partners in serodiscordant, monogamous relationships who have CD4 counts that would not warrant immediate initiation of HAART (ie >350 cells/ul) based on current guidelines are being randomized to either initiate HAART right away or are clinically monitored until their immunological or clinical status warrants treatment. This study will be fully enrolled in the coming year, and should provide important information shortly thereafter.

As more individuals live with HIV because of HAART, there is a larger pool of individuals who could transmit HIV, if HAART is not fully suppressive and they increase risk taking behavior. Studies on the impact of ART on sexual behavior among HIV-infected individuals have been inconsistent, and it is not clear whether the provision of ART may be associated with high risk sexual behavior in some subpopulations69, 70. Though data from injecting drug users and men who have sex with men (MSM) in the developed world suggest that high risk behavior can increase with ART17, 71, studies from resource-limited settings to date have not shown that the provision of ART does increase HIV risk taking behaviors72.

Despite the increasing interest in the evaluation of “test and treat” strategies, other genital tract factors could mitigate the public health impact of early initiation of HAART. For example, concurrent STIs can increase HIV transmission probabilities73, by attracting CD4 T-lymphocytes and releasing cytokines (TNF-alpha, IL-1) that enhance HIV transmission37. Bacterial STIs can increase genital tract HIV concentrations74, and interventions that provide treatment of these infections can decrease viral shedding27, 75-77. In the Rakai study, HSV-2 antibody negative participants with viral loads >38500 copies/ml and HSV-2 antibody positive participants with viral loads <1700 copies/ml had a similar probability of transmitting HIV to the uninfected partner78. Unfortunately, in many settings HSV-2 seroprevalence in young adult populations exceeds 50%79, and 2 studies have documented that thymidine-kinase inhibitor chemoprophylaxis does not decrease HIV transmission to uninfected patients80, 81. It is feasible that the removal of a pathogen that initiated a genitourinary inflammatory response may not be enough to restore the local cellular milieu.

Another concern about the wider use of ART for prevention has been the potential for the development and transmission of antiretroviral resistance if healthy individuals are expected to be fully adherent over many years. Multiple reports have now documented that resistant HIV has been sexually transmitted82. Though ART resistance has been demonstrated with increased frequency in newly diagnosed and treatment-naïve patients over time83, 84, recent findings suggest that ART-resistant HIV strains may have lower viral transmisability85. Thus, public health systems around the world will need to track some of the potential unintended consequences of earlier initiation of antiretroviral therapy for prevention, including risk compensation, trends in STI co-epidemics, and the prevalence and incidence of transmitted ART-resistant HIV, in order to fully understand the costs, as well as the benefits of treatment as prevention.

Post-Exposure Prophylaxis

The evidence that suggests that ART can prevent HIV acquisition comes from the success of MTCT86, animal studies87, 88, and a case-control study of post-exposure prophylaxis (PEP) following needle stick injury in healthcare settings89. The Centers for Disease Control and Prevention (CDC) registry documented that individuals who took AZT monotherapy following occupational exposure were one fifth as likely to be HIV-infected as those who did not take medication89, 90. Data from the rhesus macaque model have suggested that 28 days of ART is needed for effective post-exposure prophylaxis88. Concerns have been raised that the use of PEP in non-occupational settings might result in increased risk taking in some populations, such as among MSM. In a Brazilian MSM study, high risk participants in a behavioral risk reduction study were educated about PEP while being counseled about safer sex, and participants were given 4 day “starter packs” of zidovudine/lamivudine. They were educated that if they were risky and began to take the medication, they needed to come back to the study site as soon as possible, so they could get the rest of the 28 day course that they would be expected to take. About a third of the 200 high risk men followed for 24 months (68 men) used PEP 109 times91, another third were risky, but did not use PEP, and the remainder heeded the counseling messages and did not engage in risk. The overall HIV incidence in the cohort was 2.9 per 100 person-years, but there were 10 infections among men who did not utilize PEP, compared to only one among the men who used PEP. Although HIV risk taking behavior may not be constant over time,92 most studies of PEP after sexual exposure have not demonstrated increases in risk taking behavior after PEP, and some have effectively included counseling so that PEP could provide an entry for intensified risk reduction interventions91, 93, 94.

A major impediment to the wider use of PEP in the past was the relative intolerability of some of the first-line recommended drugs, like azidothymidine and protease inhibitors95. However, the use of newer drugs like Tenofovir seems to be associated with increased tolerability and completion rates, although randomized controlled trials have never been done to compare PEP regimens head-to-head due to logistical issues, such as the huge sample size needed to compare two effective regimens. Tenofovir has many features that are desirable in a chemoprophylactic agent, including long intracellular half-life, activity in macrophages, and high concentrations in genital tissues96. A case-control study found that men who took dual therapy with tenofovir-emtricitabine were more likely to complete a 28-day day PEP regimen than historical controls taking 2 drug regimens containing AZT97. It is still not known if it is preferable to use 2 drugs versus 3 drugs for PEP, with the argument for 2 being increased tolerability and completion rates98, versus the view that because the person had already been exposed to HIV, more drugs would be extra protective against drug-selected or spontaneous mutant strains. Other newer drugs may offer opportunities for novel PEP strategies, because they are well-tolerated (e.g. Atazanavir or Raltegravir)99 or achieve high genital tract concentrations (e.g. Maraviroc)100. Although several lines of data suggest that PEP may decrease the likelihood of HIV transmission, in many settings it may be underutilized because of clinician concerns about risk compensation and cost, and because many at risk individuals are unfamiliar with its potential or how to access chemoprophylactic treatment.

Pre-Exposure Prophylaxis (PrEP)

In situations when the likelihood of exposure to HIV can be anticipated ahead of time, ART pre-exposure prophylaxis (PrEP) delivered either as oral therapy or as topical microbicide, could be a logical method of primary prevention. In the field of infectious disease preventive care, patients are routinely provided with prophylaxis prior to exposure when the risk of infection is imminent, including anti-tuberculosis therapy and anti-malarials. Simian-based data suggests that tenofovir-containing regimens protect against infection with rapid drug absorption and high drug levels remaining in intracellular genital tissues101, and with the possibility of intermittent dosing102. Over the past decade, animal studies have provided the basis for clinical PrEP research103, though concerns about access to optimal preventive services and medical treatment for vulnerable populations has impeded initial PrEP research104. Concerns about PrEP include possible behavioral disinhibition, ART cost, acquisition of resistant viral strains, treatment adherence, and chronic medication toxicities.

A phase II, randomized double-blinded placebo controlled trial was completed three years ago in Cameroon, Nigeria, and Ghana which demonstrated the safety of daily oral tenofovir compared to a placebo for HIV prevention among high-risk women also receiving HIV testing, counseling, and condoms105. After enrollment, 8 on-product seroconversions occurred with 2 in the women who took tenofovir and 6 on placebo. Although this difference was not statistically significant, the trend was in the right direction, and both groups of women had reduced their behavioral risk in the course of the study. The number of sex partners went down and the proportion of participants reporting condom use increased over time (52% at baseline to 95% at 12 months)105, 106. Despite concerns that PrEP could lead to behavioral disinhibition, an important finding in this study was that risk behavior decreased over time after initiating PrEP.

These reassuring data helped public health researchers feel comfortable in studying PrEP in efficacy trials in several high risk populations around the world. Over the next few years, data will be available to see whether oral tenofovir by itself, oral tenofovir co-formulated with emtricitabine, or topical tenofovir gel will be more effective than placebos among MSM in the Americas, Thailand and South Africa; among at risk women in sub-Saharan Africa; among HIV-discordant couples in Africa; and among Thai injection drug users. Prior studies have demonstrated that topical tenofovir is safe and well-tolerated, but in more than half of the women in a pharmacokinetic substudy, systemic levels of tenofovir were detected when administered topically to low risk women107. For some, this is good news, since systemic absorption means that significant genital tissue levels were achieved, but low concentrations might be less likely to be associated with clinical toxicities. For others, this would be a concern, since the levels were very low compared to the effects of taking a 300 mg oral dose. The ability of topical 1% tenofovir gel to deliver high drug levels to the genital tissues with lower systematic drug levels108 has led to the first study (known as the VOICE Trial) to compare daily use of 1% tenofovir gel to placebo gel and also compare oral tenofovir or tenofovir/emtricitabine compared to oral placebo109, 110. Assessment of the relative merits and limitations of oral versus topical PrEP agents will require careful anthropological work in addition to clinical trials in order to understand people’s beliefs about whether one approach is associated with more sexual pleasure, fewer systemic side effects, and perceptions of efficacy in one culture compared to another.

One broad area of concern is the development of drug resistance through the continued use of PrEP after becoming infected, either by a resistant virus, suboptimal adherence, or failure of the prophylactic regimen. In the early phase studies of therapeutic uses of tenofovir, when HIV-infected patients initiated therapy with tenofovir alone, no resistance was detected after 28 days111. In non-human primate-based studies, enriched resistant minor variants were detected in monkeys and tenofovir PEP was still partially effective compared to drug resistant SHIV112. One study noted no tenofovir resistance after tenofovir or tenofovir/emtricitabine failure113, while another study detected intermittent emtricitabine resistance114. When the virus develops tenofovir and emtricitabine resistance, the resistant virus is hypersusceptible to zidovudine, but diminishes the activity of other nucleoside reverse transcriptase inhibitors; there is no effect on other classes of drugs.

Two potential concerns emerge with tenofovir prophylaxis in light of current treatment regimens. First, in resource-limited settings, stavudine is routinely used as part of first-line drug treatment because it is inexpensive. Of concern is that clade C virus that is most common in these settings may preferentially select for K65R resistance after exposure to stavudine-containing HAART, which could create tenofovir resistance115, 116. Thus, wider stavudine use may be selecting for a larger pool of circulating strains with K65R, which potentially could result in failure of tenofovir-based prophylaxis. Another concern is that individuals on tenofovir-based PrEP will develop tenofovir resistance after becoming infected. However, mathematical modeling of HIV prophylaxis for primary prevention suggests that less than 1% of the predicted seroconversions would acquire or develop a tenofovir-resistant strain117, but in a world where tenofovir is being increasingly used for first line antiretroviral therapy, continued monitoring to assess the potential ecological effects of PrEP is warranted. Unlike clinical trials in which participants receive frequent antibody-based HIV testing, patients in clinical settings will require ongoing HIV testing to avoid substandard therapy if they potentially become HIV infected. In either of these situations, more individuals with tenofovir resistant virus could compromise their own available treatment choices and spread resistant virus to their partners.

Currently, clinical trials of PrEP are underway at multiple sites that will enroll >20,000 HIV-uninfected men and women from sites in Asia, South and North America, and Africa, and will address the role of continuous vs intermittent PrEP, topical vs oral PrEP, selection of specific drugs, and the influence of PrEP on risk practices118. Some of the first PrEP efficacy data may be available within the next year or two, so public health officials and clinicians will need to think about how to train providers to make the medications available to at risk populations and provide careful monitoring, and how to use PrEP to create “educable moments” that facilitate HIV prevention if PrEP “works.” Partial efficacy and potential toxicity management issues (e.g. what if tenofovir PrEP decreases the likelihood of HIV acquisition by 50% and a few participants develop renal failure?) are two examples of the kinds of challenges in the development of clear and succinct messages as clinical trial data matures. One community-based organization, the AIDS Vaccine Advocacy Coalition ( has developed a PrEPWatch feature that provides continuously updated information about the status of the clinical trials.

Many clinical questions will arise whatever the results of the first generation PrEP studies show (Figure 3). Other antiviral drugs are being considered for chemoprophylaxis, ranging from the oral CCR5 antagonist, Maraviroc, which achieves high genital tract levels, to UC-781 and TMC-120, which are poorly absorbable non-nucleoside reverse transcriptase agents and thus are being developed as topical microbicides. Injectable agents and compounds that can be delivered through a slow release ring may alter the need to be adherent to a stringent daily regimen. Some agents may be considered as optimal parts of PrEP regimens, such as lamivudine and emtricitabine, because the virus that is resistant to these drugs has decreased viral fitness 119, 120. So individuals who would become infected with this less virulent viral stain would be less likely to transmit to their own partners. Because of the long intracellular half-life of drugs like tenofovir, intermittent dosing strategies may make sense. Pre- and post-coital application of tenofovir gel is being studied in the Caprisa 004 study among high-risk women in South Africa.

Figure 3
Current PrEP studies.

One challenge of the use of ART for prevention is the possibility that at risk persons might obtain off-label drugs even in advance of any efficacy data being available. One recent report suggested that ART was being sold at clubs and self-administered prior to high risk sexual activity121, but other reports from San Francisco and Boston found minimal use among MSM in the past 2 years122, 123. Clearly, the potential for widespread and unregulated use is great, and the environment could change quickly once data become available to suggest a beneficial effect from antiretroviral PrEP. Early work suggests that context matters, i.e. the levels of interest in using PrEP were substantially affected by perceived efficacy, side effects, and cost122. Public health authorities, led by the CDC in the US and WHO globally, have begun to meet regularly to anticipate community responses and will be mobilized to work with clinicians, national governments, and representatives of high risk communities, once efficacy data become available124.

Operational issues

After nearly two decades of using HAART, clinicians and public health officials must consider how to optimally utilize these medicines in a focused manner to reduce the number of new infections. Major questions requiring operational research include long-term safety, adherence, benefits of different modes of drug delivery and dosing, and selection of resistant virus. Some of these issues will be addressed in the context of phase IV expanded safety studies, while others will require the strengthening of public health monitoring systems. Increasing efforts are now underway to monitor the emergence of acquired antiretroviral drug resistance in resource-limited settings via the WHO’s Global Network HIVResNet, which provides standardized tools, training, technical assistance, laboratory quality assurance, analysis of results and recommendations for guidelines and public health action125. The recent expansion of WHO treatment guidelines to initiate treatment at a higher CD4 cell count of 350 cells/ul rather than 200 cells/ul will mean that a larger pool of HIV-infected patients will be in need of treatment126. Recent curtailment in the US President’s Emergency Plan for AIDS Relief (PEPFAR) for HIV treatment could raise further ethical concerns regarding the need to provide life-saving medicine to those already infected with HIV relative to preventing future HIV infections127. Moreover, many resource-limited nations may have limited budgets for HIV treatment, and thus will have to carefully decide how to make best use of limited resources in order to also decrease the number of new infections.

Conclusion: Future of Antiretrovirals for HIV Prevention

The degree of public health benefits reaped through the use of ART for prevention will depend on the number of HIV-infected individuals treated, the ability to effectively engage individuals most likely to transmit HIV, the relative stage of a given epidemic, the efficacy of specific ART regimens to reduce viral load in the genital tract, the development of drug-resistant viral strains, and changes in risk taking behaviors that could compromise the protective effects of ART. While targeting ART preventive therapy to infectious individuals or individuals at greatest risk of acquiring HIV can be a major challenge, there is yet a lack of consensus over the preventive benefits of the widespread administration of ART for the general population. Mathematical models have suggested that the widespread provision of ART could substantially reduce HIV incidence, but this benefit could be potentially undermined by behavioral disinhibition128, 129.

In summary, the use of ART to reduce HIV transmission has moved to the forefront of public health approaches to HIV prevention because of the increased tolerability of the medications, decreased cost, expanded formulary, and limitations of other approaches. Due to clinical indications that earlier initiation of ART for infected individuals is warranted, optimizing the benefit will require attention to adherence, sustained access, behavioral risk reduction, and STI diagnosis and treatment. Although the use of ART for uninfected individuals holds great promise, public health authorities will need to assess the potential of local decreases in HIV infection relative to financial costs and ecological impact, if efficacy trial data shows benefit. The field is at an early stage, with major questions remaining to be answered, such as what is the least amount of medication that can be effective with pre-/post-coital dosing and what are the optimal routes of drug delivery (e.g. topical, oral, and injectable).

It is conceivable that in the future the ART formulary will consist of drugs to be utilized for specific preventive and therapeutic interventions, such as topical agents for stopping viral entry. An effective HIV vaccine is still years away3, but the utility of ARVs for prevention will need to be tempered by the fact that these agents are not likely to be 100% effective in the real world. Further studies in pharmacology, virology, and behavioral science will be needed to best understand the intended, and unintended, clinical consequences of increasingly using ART. The use of ART as a critical tool for HIV prevention will need to be part of a larger toolbox to reduce the number of new infections globally, including circumcision, prevention of MTCT, behavioral change, and treatment of STIs. It is possible that the life-saving agents that have transformed the natural history of HIV disease and the quality of life of infected patients may become part of HAARP: highly active antiretroviral prevention130, but their ultimate potential in preventing HIV transmission remains to be fully defined.


1. 2008 update on the global AIDS epidemic. 2008 Accessed at
2. Markel H. The search for effective HIV vaccines. New. 2005;353(8):753–7. [PubMed]
3. Johnston M, Fauci AS. An HIV vaccine--evolving concepts. New England Journal of Medicine. 2007;356(20):2073–81. [PubMed]
4. Klasse P, Shattock R, Moore JP. Antiretroviral drug-based microbicides to prevent HIV-1 sexual transmission. Annual Review of Medicine. 2008;59:455–71. [PubMed]
5. Mocroft A, Ledergerber B, Katlama C, Kirk O, Reiss P, d’Arminio Monforte A, Knysz B, Dietrich M, Phillips AN, Lundgren JD, EuroSIDA study group Decline in the AIDS and death rates in the EuroSIDA study: an observational study. Lancet. 2003;362(9377):22–9. [PubMed]
6. Palella F, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, Aschman DJ, Holmberg SD, HIV Outpatient Study Investigators Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. New England Journal of Medicine. 1998;338:853–60. [PubMed]
7. [Accessed August 2, 2007];Scaling up antiretroviral therapy in resource-limited settings: treatment guidelines for a public health approach—2006 revision. 2006 at
8. [Accessed February 3, 2009];Towards universal access: Scaling up priority HIV/AIDS interventions in the health sector. 2008 at
9. Montaner J, Hogg R, Wood E, Kerr T, Tyndall M, Levy AR, Harrigan PR. The case for expanding access to highly active antiretroviral therapy to curb the growth of the HIV epidemic. Lancet. 2006;368(9534):531–6. [PubMed]
10. Salomon J, Hogan DR, Stover J, Stanecki KA, Walker N, Ghys PD, Schwartländer B. Integrating HIV prevention and treatment: from slogans to impact. PLoS Medicine. 2005;2(1):e16. [PMC free article] [PubMed]
11. De Cock K, Fowler MG, Mercier E, de Vincenzi I, Saba J, Hoff E, Alnwick DJ, Rogers M, Shaffer N. Prevention of mother-to-child HIV transmission in resource-poor countries: translating research into policy and practice. Journal of the American Medical Association. 2000;283(9):1175–82. [PubMed]
12. Cu-Uvin S, Caliendo AM, Reinert S, et al. Effect of highly active antiretroviral therapy on cervicovaginal HIV-1 RNA. Aids. 2000;14(4):415–21. [PubMed]
13. Vernazza P, Gilliam BL, Flepp M, Dyer JR, Frank AC, Fiscus SA, Cohen MS, Eron JJ. Effect of antiviral treatment on the shedding of HIV-1 in semen. AIDS. 1997;11(10):1249–54. [PubMed]
14. Cohen M, Gay C, Kashuba AD, Blower S, Paxton L. Narrative review: antiretroviral therapy to prevent the sexual transmission of HIV-1. Annals of Internal Medicine. 2007;146(8):591–601. [PubMed]
15. Kelly J, Otto-Salaj LL, Sikkema KJ, Pinkerton SD, Bloom FR. Implications of HIV treatment advances for behavioral research on AIDS: protease inhibitors and new challenges in HIV secondary prevention. Health Psychology. 1998;17(4):310–9. [PubMed]
16. Dukers N, Goudsmit J, de Wit JB, Prins M, Weverling GJ, Coutinho RA. Sexual risk behaviour relates to the virological and immunological improvements during highly active antiretroviral therapy in HIV-1 infection. AIDS. 2001;15(3):369–78. [PubMed]
17. Ostrow D, Fox KJ, Chmiel JS, Silvestre A, Visscher BR, Vanable PA, Jacobson LP, Strathdee SA. Attitudes towards highly active antiretroviral therapy are associated with sexual risk taking among HIV-infected and uninfected homosexual men. AIDS. 2002;16(5):775–80. [PubMed]
18. Katz M, Schwarcz SK, Kellogg TA, Klausner JD, Dilley JW, Gibson S, McFarland W. Impact of highly active antiretroviral treatment on HIV seroincidence among men who have sex with men: San Francisco. American Journal of Public Health. 2002;92(3):388–94. [PubMed]
19. Moatti J, Prudhomme J, Traore DC, Juillet-Amari A, Akribi HA, Msellati P, Côte d’Ivoire HIV Drug Access Initiative Socio-Behavioural Evaluation Group Access to antiretroviral treatment and sexual behaviours of HIV-infected patients aware of their serostatus in Côte d’Ivoire. AIDS. 2003;17(Supplement 3):S69–S77. [PubMed]
20. Bunnell R, Ekwaru JP, Solberg P, Wamai N, Bikaako-Kajura W, Were W, Coutinho A, Liechty C, Madraa E, Rutherford G, Mermin J. Changes in sexual behavior and risk of HIV transmission after antiretroviral therapy and prevention interventions in rural Uganda. AIDS. 2006;20(1):85–92. [PubMed]
21. Bateganya M, Colfax G, Shafer LA, Kityo C, Mugyenyi P, Serwadda D, Mayanja H, Bangsberg D. Antiretroviral therapy and sexual behavior: a comparative study between antiretroviral- naive and -experienced patients at an urban HIV/AIDS care and research center in Kampala, Uganda. AIDS Patient Care and STDs. 2005;19(11):760–8. [PubMed]
22. Chakraborty H, Sen PK, Helms RW, Vernazza PL, Fiscus SA, Eron JJ, Patterson BK, Coombs RW, Krieger JN, Cohen MS. Viral burden in genital secretions determines male-to-female sexual transmission of HIV-1: a probabilistic empiric model. AIDS. 2001;15(5):621–7. [PubMed]
23. Royce R, Sena A, Cates WJ, Cohen MS. Sexual Transmission of HIV. New England Journal of Medicine. 1997;336:1072–8. [PubMed]
24. Boily M, Baggaley RF, Wang L, Masse B, White RG, Hayes RJ, Alary M. Heterosexual risk of HIV-1 infection per sexual act: systematic review and meta-analysis of observational studies. Lancet Infectious Diseases. 2009;9(2):118–29. [PubMed]
25. Coombs R, Reichelderfer PS, Landay AL. Recent observations on HIV type-1 infection in the genital tract of men and women. AIDS. 2003;17(4):455–80. [PubMed]
26. Lampinen T, Critchlow CW, Kuypers JM, Hurt CS, Nelson PJ, Hawes SE, Coombs RW, Holmes KK, Kiviat NB. Association of antiretroviral therapy with detection of HIV-1 RNA and DNA in the anorectal mucosa of homosexual men. AIDS. 2000;14(5):F69–F75. [PubMed]
27. Cohen M, Hoffman IF, Royce RA, Kazembe P, Dyer JR, Daly CC, Zimba D, Vernazza PL, Maida M, Fiscus SA, Eron JJ, Jr., AIDSCAP Malawi Research Group Reduction of concentration of HIV-1 in semen after treatment of urethritis: implications for prevention of sexual transmission of HIV-1. The Lancet. 1997;349(9069):1868–73. [PubMed]
28. Powers K, Poole C, Pettifor AE, Cohen MS. Rethinking the heterosexual infectivity of HIV-1: a systematic review and meta-analysis. Lacet Infectious Diseases. 2008;8(9):553–63. [PMC free article] [PubMed]
29. Pilcher C, Tien HC, Eron JJ, Jr, Vernazza PL, Leu SY, Stewart PW, Goh LE, Cohen MS, Quest Study; Duke-UNC-Emory Acute HIV Consortium Brief but efficient: acute HIV infection and the sexual transmission of HIV. Journal of Infectious Disease. 2004;189(10):1785–92. [PubMed]
30. Quinn TC, Wawer MJ, Sewankambo N, Serwadda D, Li C, Wabwire-Mangen F, Meehan MO, Lutalo T, Gray RH, Rakai Project Study Group Viral load and heterosexual transmission of human immunodeficiency virus type 1. New England Journal of Medicine. 2000;342:921–9. [PubMed]
31. Fideli U, Allen SA, Musonda R, Trask S, Hahn BH, Weiss H, Mulenga J, Kasolo F, Vermund SH, Aldrovandi GM. Virologic and immunologic determinants of heterosexual transmission of human immunodeficiency virus type 1 in Africa. AIDS Research and Human Retroviruses. 2001;17(10):901–10. [PMC free article] [PubMed]
32. Tovanabutra S, Robison V, Wongtrakul J, Sennum S, Suriyanon V, Kingkeow D, Kawichai S, Tanan P, Duerr A, Nelson KE. Male viral load and heterosexual transmission of HIV-1 subtype E in northern Thailand. Journal of Acquired Immune Deficiency Syndrome. 2002;29(3):275–83. [PubMed]
33. Sullivan P, Kayitenkore K, Chomba E, Karita E, Mwananyanda L, Vwalika C, Conkling M, Luisi N, Tichacek A, Allen S. 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 (CROI); 2009; Montreal. 2009.
34. Stebbing J, Gazzard B, Douek DC. Where does HIV live? New England Journal of Medicine. 2004;350(18):1872–80. [PubMed]
35. Gupta P, Collins KB, Ratner D, Watkins S, Naus GJ, Landers DV, Patterson BK, Gupta P, Collins KB, Ratner D, Watkins S, Naus GJ, Landers DV, Patterson BK. Journal of Virology. 2002;76(19):9868–76. [PMC free article] [PubMed]
36. Miller C. Localization of Simian immunodeficiency virus-infected cells in the genital tract of male and female Rhesus macaques. Journal of Reproductive Immunology. 1998;41(1-2):331–9. [PubMed]
37. Vernazza P, Kashuba ADM, Cohen MS. Biological correlates of sexual tranmission of HIV: practical consequences and potential targets for public health. Reviews in Medical Microbiology. 2001;12(3):131–42.
38. Hu J, Gardner MB, Miller CJ. Simian immunodeficiency virus rapidly penetrates the cervicovaginal mucosa after intravaginal inoculation and infects intraepithelial dendritic cells. Journal of Virology. 2000;74(13):6087–95. [PMC free article] [PubMed]
39. Miller C, Vogel P, Alexander NJ, Dandekar S, Hendrickx AG, Marx PA. Pathology and localization of simian immunodeficiency virus in the reproductive tract of chronically infected male rhesus macaques. Labratory Investigation. 1994;70(2):255–62. [PubMed]
40. Millett G, Flores SA, Marks G, Reed JB, Herbst JH. Circumcision status and risk of HIV and sexually transmitted infections among men who have sex with men: a meta-analysis. Journal of the American Medical Association. 2008;300(14):1674–84. [PubMed]
41. Garg S, Mandl J, Ibegbu C, Kozlowski P, Wilson R, Regoes R, Staprans S. Retrovirus. Montreal: 2009. Low-dose Simian HIVSF162P Vaginal Challenges Reveal Localized Virus Replication and Inoculum Size Effects. 2009. 2009.
42. Anderson D, O’Brien TR, Politch JA, Martinez A, Seage GR, 3rd, Padian N, Horsburgh CR, Jr, Mayer KH. Effects of disease stage and zidovudine therapy on the detection of human immunodeficiency virus type 1 in semen. Journal of the American Medical Association. 1992;267(20):2769–74. [PubMed]
43. Quayle A, Xu C, Mayer KH, Anderson DJ. T lymphocytes and macrophages, but not motile spermatozoa, are a significant source of human immunodeficiency virus in semen. Journal of Infectious Disease. 1997;176(4):960–8. [PubMed]
44. Vernazza P, Troiani L, Flepp MJ, Cone RW, Schock J, Roth F, Boggian K, Cohen MS, Fiscus SA, Eron JJ. Potent antiretroviral treatment of HIV-infection results in suppression of the seminal shedding of HIV. The Swiss HIV Cohort Study. AIDS. 2000;14(2):117–21. [PubMed]
45. Barroso PF, Gupta P, Melo MF, Vieira M, Murta FC, Souza Y, Harrison LH. Effect of antiretroviral therapy on HIV shedding in semen. Annals of Internal Medicine. 1999;133(4):280–4. SM. [PubMed]
46. Cu Uvin S, Caliendo AM, Reinert SE, Mayer KH, Flanigan TP, Carpenter CC. HIV-1 in the female genital tract and the effect of antiretroviral therapy. AIDS. 1998;12(7):826–7. [PubMed]
47. Zhang H, Dornadula G, Beumont M, Livornese L, Jr, Van Uitert B, Henning K, Pomerantz RJ. Human immunodeficiency virus type 1 in the semen of men receiving highly active antiretroviral therapy. New England Journal of Medicine. 1998;339(25):1803–9. [PubMed]
48. Eron J, Vernazza PL, Johnston DM, Seillier-Moiseiwitsch F, Alcorn TM, Fiscus SA, Cohen MS. Resistance of HIV-1 to antiretroviral agents in blood and seminal plasma: implications for transmission. AIDS. 1998;12(15):F181–F91. [PubMed]
49. Taylor S, Pereira AS. Antiretroviral drug concentrations in semen of HIV-1 infected men. Sexually Transmitted Infections. 2001;77(1):4–11. [PMC free article] [PubMed]
50. Ghosn J, Chaix ML, Peytavin G, Rey E, Bresson JL, Goujard C, Katlama C, Viard JP, Tréluyer JM, Rouzioux C. Penetration of enfuvirtide, tenofovir, efavirenz, and protease inhibitors in the genital tract of HIV-1-infected men. AIDS. 2004;18(14):1958–61. [PubMed]
51. Pereira A, Kashuba AD, Fiscus SA, Hall JE, Tidwell RR, Troiani L, Dunn JA, Eron JJ, Jr, Cohen MS. Nucleoside analogues achieve high concentrations in seminal plasma: relationship between drug concentration and virus burden. Journal of Infectious Disease. 1999;180(6):2039–43. [PubMed]
52. Min S, Corbett AH, Rezk N, Cu-Uvin S, Fiscus SA, Petch L, Cohen MS, Kashuba AD. Protease inhibitor and nonnucleoside reverse transcriptase inhibitor concentrations in the genital tract of HIV-1-infected women. Journal of Acquired Immune Deficiency Syndrome. 2004;37(5):1577–80. [PubMed]
53. Taylor S, van Heeswijk RP, Hoetelmans RM, Workman J, Drake SM, White DJ, Pillay D. Concentrations of nevirapine, lamivudine and stavudine in semen of HIV-1-infected men. AIDS. 2000;14(13):1979–84. [PubMed]
54. Brenner B, Roger M, Routy JP, Moisi D, Ntemgwa M, Matte C, Baril JG, Thomas R, Rouleau D, Bruneau J, Leblanc R, Legault M, Tremblay C, Charest H, Wainberg MA, Quebec Primary HIV Infection Study Group High rates of forward transmission events after acute/early HIV-1 infection. Journal of Infectious Disease. 2007;195(7):951–9. [PubMed]
55. Cohen M, Pilcher CD. Amplified HIV transmission and new approaches to HIV prevention. Journal of Infectious Disease. 2005;191(9):1391–3. [PubMed]
56. Pilcher C, Price MA, Hoffman IF, Galvin S, Martinson FE, Kazembe PN, Eron JJ, Miller WC, Fiscus SA, Cohen MS. Frequent detection of acute primary HIV infection in men in Malawi. AIDS. 2004;18(3):517–24. [PubMed]
57. Wawer M, 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. Journal of Infectious Disease. 2005;191(9):1403–9. [PubMed]
58. Pilcher C, Fiscus SA, Nguyen TQ, Foust E, Wolf L, Williams D, Ashby R, O’Dowd JO, McPherson JT, Stalzer B, Hightow L, Miller WC, Eron JJ, Jr, Cohen MS, Leone PA. Detection of acute infections during HIV testing in North Carolina. New England Journal of Medicine. 2005;352(18):1873–83. [PubMed]
59. Colfax G, Buchbinder SP, Cornelisse PG, Vittinghoff E, Mayer K, Celum C. Sexual risk behaviors and implications for secondary HIV transmission during and after HIV seroconversion. AIDS. 2002;16(11):1529–35. [PubMed]
60. Koopman J, Jacquez JA, Welch GW, Simon CP, Foxman B, Pollock SM, Barth-Jones D, Adams AL, Lange K. The role of early HIV infection in the spread of HIV through populations. Journal of Acquired Immune Deficiency Syndrome. 1997;14(3):249–58. [PubMed]
61. Abu-Raddad L, Longini IM., Jr. No HIV stage is dominant in driving the HIV epidemic in sub-Saharan Africa. AIDS. 2008;22(9):1055–61. [PubMed]
62. Hollingsworth T, Anderson RM, Fraser C. HIV-1 transmission, by stage of infection. Journal of Infectious Disease. 2008;198(5):687–93. [PubMed]
63. Pilcher C, Joaki G, Hoffman IF, Martinson FE, Mapanje C, Stewart PW, Powers KA, Galvin S, Chilongozi D, Gama S, Price MA, Fiscus SA, Cohen MS. Amplified transmission of HIV-1: comparison of HIV-1 concentrations in semen and blood during acute and chronic infection. AIDS. 2007;21(13):1723–30. [PMC free article] [PubMed]
64. Granich R, 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. 2008;373(9657):48–57. [PubMed]
65. Hosseinipour M, Cohen MS, Vernazza PL, Kashuba AD. Can antiretroviral therapy be used to prevent sexual transmission of human immunodeficiency virus type 1? Clinical Infectious Disease. 2002;34(10):1391–5. [PubMed]
66. Fang CT, Twu SJ, Chen MY, Chang YY, Hwang JS, Wang JD, Chuang CY, Division of AIDS and STD, Center for Disease Control, Department of Health, Executive Yuan Decreased HIV transmission after a policy of providing free access to highly active antiretroviral therapy in Taiwan. Journal of Infectious Disease. 2004;190(5):879–85. HH. [PubMed]
67. Castilla J, Del Romero J, Hernando V, Marincovich B, García S, Rodríguez C. Effectiveness of highly active antiretroviral therapy in reducing heterosexual transmission of HIV. Journal of Acquired Immune Deficiency Syndrome. 2005;40(1):96–101. [PubMed]
68. Health Prevention Trials Network [Accessed September 22, 2007];2007 at
69. Crepaz N, Hart TA, Marks G. Highly active antiretroviral therapy and sexual risk behavior: a meta-analytic review. Journal of the American Medical Association. 2004;292(2):224–36. [PubMed]
70. Hogben M, Liddon N. Disinhibition and risk compensation: scope, definitions, and perspective. Sexually Transmitted Diseases. 2008;35(12):1009–10. [PubMed]
71. Tun W, Gange SJ, Vlahov D, Strathdee SA, Celentano DD. Increase in sexual risk behavior associated with immunologic response to highly active antiretroviral therapy among HIV-infected injection drug users. Clinical Infectious Disease. 2004;38(8):1167–74. [PubMed]
72. Kennedy C, O’Reilly K, Medley A, Sweat M. The impact of HIV treatment on risk behaviour in developing countries: a systematic review. AIDS Care. 2007;19(6):707–20. [PubMed]
73. Fleming D, Wasserheit JN. From epidemiological synergy to public health policy and practice: the contribution of other sexually transmitted diseases to sexual transmission of HIV infection. Sexually Transmitted Infections. 1999;75(1):3–17. [PMC free article] [PubMed]
74. Cu-Uvin S, Hogan JW, Caliendo AM, Harwell J, Mayer KH, Carpenter CC. HIV Epidemiology Research Study. Association between bacterial vaginosis and expression of human immunodeficiency virus type 1 RNA in the female genital tract.1. Clinical Infectious Disease. 2001;33(6):894–6. [PubMed]
75. Mcclelland R, Wang CC, Mandaliya K, Overbaugh J, Reiner MT, Panteleeff DD, Lavreys L, Ndinya-Achola J, Bwayo JJ, Kreiss JK. Treatment of cervicitis is associated with decreased cervical shedding of HIV-1. AIDS. 2001;15(1):105–10. [PubMed]
76. Wang C, McClelland RS, Reilly M, Overbaugh J, Emery SR, Mandaliya K, Chohan B, Ndinya-Achola J, Bwayo J, Kreiss JK. The effect of treatment of vaginal infections on shedding of human immunodeficiency virus type 1. Journal of Infectious Disease. 2001;183(7):1017–22. [PubMed]
77. Dyer J, Eron JJ, Hoffman IF, Kazembe P, Vernazza PL, Nkata E, Costello Daly C, Fiscus SA, Cohen MS. Association of CD4 cell depletion and elevated blood and seminal plasma human immunodeficiency virus type 1 (HIV-1) RNA concentrations with genital ulcer disease in HIV-1-infected men in Malawi. Journal of Infectious Disease. 1998;177(1):224–7. [PubMed]
78. Wawer M, 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, Rakai Project Study Group Control of sexually transmitted diseases for AIDS prevention in Uganda: a randomised community trial. The Lancet. 1999;353(9152):525–35. [PubMed]
79. Wald A, Link K. Risk of human immunodeficiency virus infection in herpes simplex virus type 2-seropositive persons: a meta-analysis. Journal of Infectious Disease. 2002;185(1):45–52. [PubMed]
80. 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, Le Goff J, Belec L, Hayes R, HSV trial team. Steering and Data Monitoring Committees Effect of herpes simplex suppression on incidence of HIV among women in Tanzania. New England Journal of Medicine. 2008;358(15):1560–71. [PMC free article] [PubMed]
81. Celum C, Wald A, Hughes J, Sanchez J, Reid S, Delany-Moretlwe S, Cowan F, Casapia M, Ortiz A, Fuchs J, Buchbinder S, Koblin B, Zwerski S, Rose S, Wang J, Corey L, HPTN 039 Protocol Team 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. Lacet. 2008;371(9630):2109–19. [PMC free article] [PubMed]
82. Taylor S, Cane P, Workman J, Drake S, Shamanesh M, Pillay D. Identification of a Transmission Chain of HIV-1 Drug Resistant Virus. AIDS Research and Human Retroviruses. 2003;19(5):353–61. [PubMed]
83. Little S, Holte S, Routy JP, Daar ES, Markowitz M, Collier AC, Koup RA, Mellors JW, Connick E, Conway B, Kilby M, Wang L, Whitcomb JM, Hellmann NS, Richman DD. Antiretroviral-drug resistance among patients recently infected with HIV. New England Journal of Medicine. 2002;347(6):385–94. [PubMed]
84. Grant R, Hecht FM, Warmerdam M, Liu L, Liegler T, Petropoulos CJ, Hellmann NS, Chesney M, Busch MP, Kahn JO. Time trends in primary HIV-1 drug resistance among recently infected persons. Journal of the American Medical Association. 2002;288(2):181–8. [PubMed]
85. Turner D, Brenner B, Routy JP, Moisi D, Rosberger Z, Roger M, Wainberg MA. Diminished representation of HIV-1 variants containing select drug resistance-conferring mutations in primary HIV-1 infection. Journal of Acquired Immune Deficiency Syndrome. 2004;37(5):1627–31. [PubMed]
86. Connor EM, Sperling RS, Gelber R, Kiselev P, Scott G, O’Sullivan MJ, VanDyke R, Bey M, Shearer W, Jacobson RL, Pediatric AIDS Clinical Trials Group Protocol 076 Study Group Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment. New England Journal of Medicine. 1994;331(18):1173–80. [PubMed]
87. Tsai C, Follis KE, Sabo A, Beck TW, Grant RF, Bischofberger N, Benveniste RE, Black R. Prevention of SIV infection in macaques by (R)-9-(2-phosphonylmethoxypropyl)adenine. Science. 1995;270(5239):1197–9. [PubMed]
88. Tsai C, Emau P, Follis KE, Beck TW, Benveniste RE, Bischofberger N, Lifson JD, Morton WR. Effectiveness of postinoculation (R)-9-(2-phosphonylmethoxypropyl) adenine treatment for prevention of persistent simian immunodeficiency virus SIVmne infection depends critically on timing of initiation and duration of treatment. Journal of Virology. 1998;72(5):4265–73. [PMC free article] [PubMed]
89. Cardo D, Culver DH, Ciesielski CA, Srivastava PU, Marcus R, Abiteboul D, Heptonstall J, Ippolito G, Lot F, McKibben PS, Bell DM, Centers for Disease Control and Prevention Needlestick Surveillance Group A case-control study of HIV seroconversion in health care workers after percutaneous exposure. New England Journal of Medicine. 1997;337(21):1485–90. [PubMed]
90. Centers for Disease Control and Prevention Updated U.S. Public Health Service guidelines for the management of occupational exposure to HBV, HCV, and HIV and recommendations for postexposure prophylaxis. MMWR. 2001;50:1–42.
91. Schechter M, do Lago RF, Mendelsohn AB, Moreira RI, Moulton LH, Harrison LH, Praca Onze Study Team Behavioral impact, acceptability, and HIV incidence among homosexual men with access to postexposure chemoprophylaxis for HIV. Journal of Acquired Immune Deficiency Syndrome. 2004;35(5):519–25. [PubMed]
92. Buchbinder S, Vittinghoff E, Heagerty PJ, Celum CL, Seage GR, 3rd, Judson FN, McKirnan D, Mayer KH, Koblin BA. Sexual risk, nitrite inhalant use, and lack of circumcision associated with HIV seroconversion in men who have sex with men in the United States. Journal of Acquired Immune Deficiency Syndrome. 2005;39(1):82–9. [PubMed]
93. Roland M, Neilands TB, Krone MR, Katz MH, Franses K, Grant RM, Busch MP, Hecht FM, Shacklett BL, Kahn JO, Bamberger JD, Coates TJ, Chesney MA, Martin JN. Seroconversion following nonoccupational postexposure prophylaxis against HIV. Clinical Infectious Disease. 2007;41(10):1507–13. [PubMed]
94. Guest G, Shattuck D, Johnson L, Akumatey B, Clarke EE, Chen PL, MacQueen KM. Changes in sexual risk behavior among participants in a PrEP HIV prevention trial. Sexually Transmitted Diseases. 2008;35(12):1002–8. [PubMed]
95. Smith D, Grohskopf LA, Black RJ, Auerbach JD, Veronese F, Struble KA, Cheever L, Johnson M, Paxton LA, Onorato IM, Greenberg AE, U.S. Department of Health and Human Services Antiretroviral postexposure prophylaxis after sexual, injection-drug use, or other nonoccupational exposure to HIV in the United States: recommendations from the U.S. Department of Health and Human Services. MMWR. 2005;54:1–20. [PubMed]
96. Vourvahis M, Tappouni HL, Patterson KB, Chen YC, Rezk NL, Fiscus SA, Kearney BP, Rooney JF, Hui J, Cohen MS, Kashuba AD. The pharmacokinetics and viral activity of tenofovir in the male genital tract. Journal of Acquired Immune Deficiency Syndrome. 2008;47(3):329–33. [PMC free article] [PubMed]
97. Mayer K, Mimiaga MJ, Cohen D, Grasso C, Bill R, Van Derwarker R, Fisher A. Tenofovir DF plus lamivudine or emtricitabine for nonoccupational postexposure prophylaxis (NPEP) in a Boston Community Health Center. Journal of Acquired Immune Deficiency Syndrome. 2008;47(4):494–9. [PubMed]
98. Bassett I, Freedberg KA, Walensky RP. Two drugs or three? Balancing efficacy, toxicity, and resistance in postexposure prophylaxis for occupational exposure to HIV. Clinical Infectious Disease. 2004;39(3):395–401. [PubMed]
99. Mayer K, Mimiaga M, Gelman M, Trufant J, Maynard S, McMorrow P. Tenofovir DF/Emtricitabine/Raltegravir (TDF/FTD/RAL) Appears Safe and Well-Tolerated for Non-Occupational Post-Exposure Prophylaxis (NPEP); 5th IAS Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2009) 2009 July 19-22; Cape Town, South Africa. 2009.2009.
100. Dumond J. Maraviroc (MRV) genital tract (GT) fluid and tissue pharmacokinetics (PK) in healthy female volunteers: implications for pre- or post-exposure prophylaxis (PrEP or PEP); Conference on retroviruses and opportunistic infections; 2007; Boston, MA. 2007; ea.
101. Dobard C, Parikh U, Sharma S, Cong ME, Smith J, Garcia-Lerma G, Novembre F, Otten R, Folks T, Heneine W. Retrovirus. Montreal: 2009. Complete Protection against Repeated Vaginal Simian HIV Exposures in Macaques by a Topical Gel Containing Tenofovir Alone or with Emtricitabine. 2009. 2009. [PMC free article] [PubMed]
102. Garcia-Lerma G, Cong ME, Mitchell J, Youngpairoj A, Martin A, Hanson D, Otten R, Paxton L, Folks T, Heneine W. Retrovirus. Montreal: 2009. Prevention of Rectal Simian HIV Transmission in Macaques by Intermittent Pre-exposure Prophylaxis with Oral Truvada. 2009. 2009.
103. Cohen M, Kashuba AD. Antiretroviral therapy for prevention of HIV infection: new clues from an animal model. PLoS Medicine. 2006;5(2):e30. [PMC free article] [PubMed]
104. Grant RM, Cates W, Jr, Clarke E, Coates T, Cohen MS, Delaney M, Flores G, Goicochea P, Gonsalves G, Harrington M, Lama JR, MacQueen KM, Moore JP, Peterson L, Sanchez J, Thompson M, Wainberg MA. AIDS. Promote HIV chemoprophylaxis research, don’t prevent it. Science. 2005;309(5744):2170–1. BS. [PubMed]
105. Peterson L, Taylor D, Roddy R, Belai G, Phillips P, Nanda K, Grant R, Clarke EE, Doh AS, Ridzon R, Jaffe HS, Cates W. Tenofovir disoproxil fumarate for prevention of HIV infection in women: a phase 2, double-blind, randomized, placebo-controlled trial. PloS Clinical Trials. 2007;2(5):e27. [PMC free article] [PubMed]
106. Peterson L, Taylor D, Clarke EEK. Findings from a double-blind, randomized, placebo-controlled trial of tenofovir disoproxil fumarate (TDF) for prevention of HIV infection in women; XVI International AIDS Conference; 2006 August 13-18; Toronto, Ontario, Canada. 2006.2006.
107. Mayer K, Maslankowski LA, Gai F, El-Sadr WM, Justman J, Kwiecien A, Mâsse B, Eshleman SH, Hendrix C, Morrow K, Rooney JF, Soto-Torres L, HPTN 050 Protocol Team Safety and tolerability of tenofovir vaginal gel in abstinent and sexually active HIV-infected and uninfected women. AIDS. 2006;20(4):543–51. [PubMed]
108. Ayudhya U, Hopkins N, Cost M, Billitto N, Rooney J, Dezzutti C. Retrovirus. Montreal: 2009. Microbicide, Tenofovir 1% Gel, Efficacy Determined for Pre- and Post-Coital. 2009. 2009.
109. Hillier S. Retrovirus. Montreal: 2009. Pre-Exposure Prophylaxis: Could It Work? 2009. 2009.
110. Abdool Karim S, Coletti A, Richardson B, Ramjee G, Hoffman I, Chirenje M, Taha T, Kapina M, Maslankowski L, Soto-Torres L. Retrovirus. Montreal: 2009. Safety and Effectiveness of Vaginal Microbicides BufferGel and 0.5% PRO 2000/5 Gel for the Prevention of HIV Infection in Women: Results of the HPTN 035 Trial. 2009. 2009.
111. Barditch-Crovo P, Deeks SG, Collier A, Safrin S, Coakley DF, Miller M, Kearney BP, Coleman RL, Lamy PD, Kahn JO, McGowan I, Lietman PS. Phase i/ii trial of the pharmacokinetics, safety, and antiretroviral activity of tenofovir disoproxil fumarate in human immunodeficiency virus-infected adults. Antimicorbial agents and chemotherapy. 2001;45(10):2733–9. [PMC free article] [PubMed]
112. Van Rompay K, Johnson JA, Blackwood EJ, Singh RP, Lipscomb J, Matthews TB, Marthas ML, Pedersen NC, Bischofberger N, Heneine W, North TW. Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. Retrovirology. 2007;6(4):25. [PMC free article] [PubMed]
113. Subbarao S, Otten RA, Ramos A, Kim C, Jackson E, Monsour M, Adams DR, Bashirian S, Johnson J, Soriano V, Rendon A, Hudgens MG, Butera S, Janssen R, Paxton L, Greenberg AE, Folks TM. Chemoprophylaxis with tenofovir disoproxil fumarate provided partial protection against infection with simian human immunodeficiency virus in macaques given multiple virus challenges. Journal of Infectious Disease. 2006;194(7):904–11. [PubMed]
114. Garcia-Lerma J. Prevention of rectal SHIV tranmission in macaques by tenofovir/FTC combination; 13th Annual Conference on Retroviruses and Opportunistic Infections; 2006 February 5-8; Denver, CO. 2006.2006.
115. Gupta R, Hill A, Sawyer AW, Pillay D. Emergence of drug resistance in HIV type 1-infected patients after receipt of first-line highly active antiretroviral therapy: a systematic review of clinical trials. Clinical Infectious Disease. 2008;47(5):712–22. [PubMed]
116. Brenner B, Oliveira M, Doualla-Bell F, Moisi DD, Ntemgwa M, Frankel F, Essex M, Wainberg MA. HIV-1 subtype C viruses rapidly develop K65R resistance to tenofovir in cell culture. AIDS. 2006;20(9):F9–F13. [PubMed]
117. Smith D. Antiretroviral resistance is not an important risk of the oral tenofovir prophylaxis trial in Botswana: a simple mathematical modelling approach; XVI International AIDS Conference; 2006 August 13-18; Toronto, Canada. 2006; 2006. ea.
118. Buchbinder S. Retrovirus. Montreal: 2009. HIV Prevention. 2009.
119. Gallant J. Drug resistance after failure of initial antiretroviral therapy in resource-limited countries. Clinical Infectious Disease. 2007;44(3):453–5. [PubMed]
120. Van Rompay K, Matthews TB, Higgins J, Canfield DR, Tarara RP, Wainberg MA, Schinazi RF, Pedersen NC, North TW. Virulence and reduced fitness of simian immunodeficiency virus with the M184V mutation in reverse transcriptase. Journal of Virology. 2002;76(12):6083–92. [PMC free article] [PubMed]
121. Kellerman S, Hutchinson AB, Begley EB, Boyett BC, Clark HA, Sullivan P. Knowledge and use of HIV pre-exposure prophylaxis among attendees of minority gay pride events, 2004. Journal of Acquired Immune Deficiency Syndrome. 2006;43(3):376–7. [PubMed]
122. Mimiaga M, Case P, Johnson CV, Safren SA, Mayer KH. Preexposure antiretroviral prophylaxis attitudes in high-risk Boston area men who report having sex with men: limited knowledge and experience but potential for increased utilization after education. Journal of Acquired Immune Deficiency Syndrome. 2009;50(1):77–83. [PMC free article] [PubMed]
123. Liu A, Kittredge PV, Vittinghoff E, Raymond HF, Ahrens K, Matheson T, Hecht J, Klausner JD, Buchbinder SP. Limited knowledge and use of HIV post- and pre-exposure prophylaxis among gay and bisexual men. Journal of Acquired Immune Deficiency Syndrome. 2008;47(2):241–7. [PubMed]
124. [Accessed December 26, 2009];Part of the Solution: Setting expectations for WHO and UNAIDS. 2009 at
125. Bennett D, Bertagnolio S, Sutherland D, Gilks CF. The World Health Organization’s global strategy for prevention and assessment of HIV drug resistance. Antiviral Therapy. 2008;13(Supplement 2):1–13. [PubMed]
126. World Health Organization . Rapid advice: Antiretroviral therapy for HIV infection in adults and adolescents. 2009.
127. Walensky R, Kuritzkes DR. The Impact of The President’s Emergency Plan for AIDS Relief (PEPfAR) beyond HIV and Why It Remains Essential. Clinical Infectious Disease. 2010;50(2):272–5. [PubMed]
128. Law M, Prestage G, Grulich A, Van de Ven P, Kippax S. Modelling the effect of combination antiretroviral treatments on HIV incidence. AIDS. 2001;15(10):1287–94. [PubMed]
129. Abbas U, Anderson RM, Mellors JW. Potential impact of antiretroviral chemoprophylaxis on HIV-1 transmission in resource-limited settings. PLos ONE. 2007;2(9):e875. [PMC free article] [PubMed]
130. Coates T, Richter L, Caceres C. Behavioural strategies to reduce HIV transmission: how to make them work better. Lancet. 2008;372(9639):669–84. [PMC free article] [PubMed]