HIV Prevention at CROI 2014
Conference on Retroviruses and Opportunistic Infections
Boston, MA, USA
March 3-6, 2014
Jared Baeten, MD PhD
Connie Celum, MD MPH
University of Washington
CROI 2014, held in chilly Boston, again brought together international researchers studying the pathogenesis, prevention, treatment, and cure of HIV and associated infections. The past years have seen tremendous enthusiasm regarding new HIV prevention and treatment strategies, which might signal a radical change in the global impact of the epidemic. As in previous years, oral sessions were recorded and are available online (www.croi2014.org; www.croiwebcasts.org), along with full copies of abstracts. We have cited specific links here for certain oral sessions - these contain both slides and video, but alternative links with slides with audio only are available.
Pre-exposure prophylaxis (PrEP) for HIV prevention
A major focus of the last four meetings of CROI has been the evidence and the role for PrEP for HIV prevention. In PrEP, an HIV-uninfected person uses an antiretroviral medication ahead of an HIV exposure in order to prevent infection. Four clinical trials have now demonstrated that daily oral PrEP, based on the antiretroviral agent tenofovir disoproxil fumarate (TDF), alone or in combination with emtricitabine (FTC), is efficacious for the prevention of HIV acquisition; one additional trial demonstrated efficacy for pericoital use of an intravaginal gel containing tenofovir. HIV protection ranged from 39% to 75% compared with placebo in these trials, and two additional trials found no HIV protection - the differences across trials have been attributed largely to adherence. Indeed, in multiple PrEP studies, adherence to PrEP appeared to be very strongly related to its HIV protection benefits, with evidence suggesting that those who took PrEP (e.g., based on detection of the study medication in blood samples) appeared to reduce their risk of HIV by ~90%. The US Food and Drug Administration (FDA) in 2012 approved daily oral FTC/TDF as the first PrEP agent with a formal label indication for prevention of sexual HIV acquisition. As part of a pre-conference symposium on clinical trials, a review of adherence measurement and lessons learned from PrEP trials related to adherence was presented (http://www.croiwebcasts.org/console/player/22017?mediaType=slideVideo&). In addition, an afternoon symposium on Tuesday was completely devoted to PrEP, with excellent review presentations on learning from pharmacology to understand PrEP efficacy (http://www.croiwebcasts.org/console/player/22132?mediaType=slideVideo&), implementing PrEP in resource-constrained settings (http://www.croiwebcasts.org/console/player/22133?mediaType=slideVideo&), prioritizing PrEP for those at greatest risk (and thus of greatest need, http://www.croiwebcasts.org/console/player/22135?mediaType=slideVideo&), and, finally, a community and patient perspective on taking PrEP for HIV prevention (http://www.croiwebcasts.org/console/player/22134?mediaType=slideVideo&). It is a session worth watching in full. What was most striking about this year's CROI was that the discussion on PrEP seems to have shifted - the presentations, questions, and chatter in the hallways are not about whether PrEP works for preventing HIV but instead they are about how to best implement this effective prevention intervention for maximal benefit and impact.
New research related to PrEP was presented in both oral and poster sessions. In 2011, the Partners PrEP Study, which was conducted among 4747 HIV serodiscordant couples from Uganda and Kenya, demonstrated that daily oral TDF and oral FTC/TDF as PrEP demonstrated that PrEP significantly reduced HIV incidence among heterosexual women and men who were at high risk of infection because of having a known HIV-infected partner. Compared to placebo, TDF reduced HIV risk by 67% (p<0.001) and FTC/TDF by 75% (p<0.001). At CROI 2014, updated results from the trial were presented, directly comparing single-agent TDF to combination FTC/TDF as PrEP (Baeten, abstract 43, http://www.croiwebcasts.org/console/player/22070?mediaType=slideVideo&). After 2011, the trial was continued, with those who had been initially assigned active PrEP continuing either TDF or FTC/TDF PrEP and those who had been assigned placebo re-randomized TDF or FTC/TDF. A total of 52 post-randomization HIV infection occurred among those assigned PrEP: 31 among those assigned TDF (incidence 0.7 per 100 person-years) and 21 among those assigned FTC/TDF (incidence 0.5 per 100 person-years), a difference that was not statistically significant (hazard ratio 0.67 for FTC/TDF compared to TDF alone, 95% confidence interval 0.39-1.17, p=0.16). For comparison, HIV incidence in the placebo arm prior to July 2011 was 2.0 per 100 person-years, emphasizing the substantial HIV protection PrEP (both TDF and FTC/TDF) offered in this population. Detection of tenofovir in plasma samples, measured in seroconverters and a subset of non-seroconverters, was associated with an 85% reduction in HIV risk for TDF and 93% reduction for FTC/TDF (both p<0.001).
Thus, in this study, where PrEP was provided to African men and women whose primary HIV risk was heterosexual sex, once-daily oral TDF and FTC/TDF were safe and provided high and comparable risk reduction against HIV acquisition. For policymakers and others considering how best to implement PrEP, these findings suggest that TDF alone could be a viable PrEP agent, alongside FTC/TDF, which is currently the primary recommended PrEP strategy. As importantly, these findings also suggest that the paradigm for PrEP may be that a single effective agent is sufficient for high-level protection, in contrast to HIV treatment, where a combination of medications is essential. That bodes well for continued development of new PrEP agents (like those described below), many of which are being developed as single medications at this time.
At CROI 2013, the results of the VOICE study were presented. VOICE was a phase IIB, randomized, double-blind, placebo-controlled, five-arm trial of daily oral TDF and FTC/TDF and daily vaginal tenofovir gel as PrEP for the prevention of HIV acquisition by HIV seronegative women. 5029 women were enrolled at sites in South Africa, Zimbabwe, and Uganda. The results of VOICE were disappointing - PrEP adherence was very low (on the order of 30% or less, as measured by detection of tenofovir in blood samples) and the trial failed to demonstrate HIV protection as a result of any of the PrEP products studied. Adherence to study product was measured in multiple ways while the study was ongoing: monthly count of unused study product (pills/applicators), monthly self-report, and quarterly ACASI - all suggested ~90% adherence. At CROI 2014, an analysis of the behavioral measures of adherence was reported (van der Straten, abstract 44, http://www.croiwebcasts.org/console/player/22071?mediaType=slideVideo&). A total of 472 women were selected across the active oral and vaignal gel arms of the study. By tenofovir measurement in blood and vaginal swabs, adherence was similarly low for both those assigned pills and gel - on the order of 30%. None of the behavioral measures - clinic based pill counts, face-to-face interviews, audio computer-assisted self-interview - found anything near that level of non-adherence. Disappointingly, the predictive value of the self-reported data was suggested by the presenter to be "no better than flipping a coin." Perhaps not surprisingly, when non-adherence was self-reported, it was very strongly related to not detecting tenofovir in blood samples, but non-adherence was self-reported very infrequently. Thus, these data argue that new and better objective measures of adherence behavior are needed, particularly for clinical trial populations like that studied in VOICE. Continued work to understand the low adherence in VOICE as well as the potential for PrEP, now that it is demonstrated to be efficacious for HIV prevention (and thus no longer being evaluated in the same blinded, placebo-controlled trial way as it was in VOICE), to be implemented for women at risk.
Several posters reported early results for PrEP implementation in various populations. In a demonstration project conducted at sexually transmitted infection and community-based clinics in San Francisco, Washington DC, and Miami, interest in and uptake of PrEP has been high among men who have sex with men (Cohen, abstract 954), with >50% of those medically eligible choosing to initiate. Importantly, early data suggest high adherence as well, with tenofovir sampling in blood samples showing that 98% had any tenofovir detected and 77% had levels detected consistent with dosing at least 4 times per week, which has been the level previously associated with >90% HIV protection in men who have sex with men. In another project in Chicago (Hosek, abstract 951), PrEP uptake among at-risk young men who have sex with men, mostly men of color, has been similarly high. The authors concluded that young men who have sex with men appear willing and able to take PrEP when delivered in a community setting. A large internet-based survey of men who have sex with men from the US (>9000 respondents, Mayer, abstract 952), however, demonstrated that there is still a long way to go - although 30% of respondents reported a prior sexually transmitted infection and just over half reported anal sex without condoms at least once in the prior 3 months, only about 1% were using PrEP. Provider barriers may be an important problem; only half felt they could discuss sex with their primary care physician.
An analysis of a population-based longitudinal HIV seroincidece cohort in Swaziland, indicated that 28% of households had an HIV serodiscordant partnership and a substantial number of new HIV infections occurred in serodiscordant partnerships (Emerson, abstact 1027), and that PrEP could be an effective strategy to prevent new infections.
New PrEP agents
Long-acting PrEP agents may avert some of the adherence challenges faced by daily oral/vaginal PrEP. GSK1265744 is a potent integrase inhibitor related to the treatment agent dolutegravir being formulated as a long-acting nanosuspension (GSK744LAP) for injectable use as PrEP and as treatment. In human volunteers, the half-life of GSK744LAP is on the order of ≥3 weeks, supporting the concept of monthly to quarterly injections for regular use. At CROI 2013, initial work on this novel PrEP agent was reported, with new data this year. Specifically, at CROI 2013, 100% protection was seen using GSK744LAP in a macaque challenge study (with 8 animals receiving active drug compared to a similar number receiving no PrEP, of which all became infected). This year, Andrews (abstract 39) correlated plasma concentrations of the medication with HIV protection. Twelve macaques were given GSK744LAP then challenged with virus each week for up to 18 weeks. Complete protection was seen for 5 weeks and then began to fade. Plasma concentrations above 3 times the protein-adjusted IC90 (the concentration that blocks 90% of viruses in the test tube) appeared fully protective and mostly so (estimated 97% protection) above 1 times the IC90. The authors argued that similar concentrations are expected with potentially quarterly injections in humans. The results were simultaneously published online (http://www.natap.org/2014/CROI/Science-2014-Andrews-science.1248707.pdf)......( http://www.natap.org/2014/CROI/croi_32.htm)
Two additional abstracts assessed vaginal challenge macaque models. In one (Radzio, abstract 40LB, presented by Garcia-Lerma), low-dose vaginal challenge (which had been used to predict tenofovir protection), 100% protection was achieved. In a second (Andrews, abstract 941LB), a somewhat less physiologic high-dose vaginal challenge model also demonstrated protection for 6 of 8 animals.
Further work on agents like GSK744LAP (another long-acting injectable, TMC-278 / injectable rilpivirine, is also moving into phase II studies in humans) will be important, as long-acting, user-independent PrEP agents offer opportunities to overcome adherence challenges seen in some of the trials of tenofovir-based daily oral PrEP. However, acceptability of 2 mL gluteal injections every 1-3 months will be an important factor to evaluate, as motivations to use PrEP and tolerability of monthly to every 3 monthly injections will likely be important determinants to adherence to injectable PrEP. It is also important to remember that these medications remain in early human testing and a viable product for clinics will be at least several years away, if further studies end up supporting these agents as effective for HIV prevention.
Intravaginal, slow-release rings containing antiretrovirals for PrEP offer a potentially powerful opportunity to prevent HIV while minimizing systemic medication exposure, and also overcome some challenges to PrEP adherence. The non-nucleoside reverse transcriptase inhibitor dapivirine (TMC-120, Janssen), formulated into a slow-release intravaginal ring, to be for a month, is in phase III clinical trials now; rings containing other medications, including tenofovir, are also under development.
Two abstracts reported new data for dapivirine. Chen (abstract 41; http://www.croiwebcasts.org/console/player/22068?mediaType=slideVideo&) reported on the final results of MTN-013/IPM 026, a multisite pharmacokinetics/pharmacodynamics study among 48 women of intravaginal rings containing dapivirine (25 mg), maraviroc (100 mg), both dapivirine and maraviroc, or placebo. The results were very encouraging for dapivirine - concentrations were high in cervicovaginal fluid, far about the IC90 for the drug. Importantly, ex vivo challenge of cervical biopsy samples strong a strong correlation between dapivirine concentrations and HIV protection, suggesting that, if in place, the dapivirine vaginal ring has high potential to block HIV. Unfortunately, the maraviroc data were not as encouraging - little of the drug out of the ring and into the relevant tissue. In the second study (Bunge, abstract 42LB; http://www.croiwebcasts.org/console/player/22069?mediaType=slideVideo&), dapivirine in gel and in film (like a breath freshener film) form were evaluated. Both formulations had high safety. The gel achieved very high concentrations of the medication (although some of the very highest concentrations might reflect gel still remaining in the genital track at the time of sampling), but the film still achieved concentrations comparable to the ring. In ex vivo laboratory viral challenge studies, both gel and film substantially blocked virus compared to placebo. These data provide proof of concept that films can deliver antiretrovirals at concentrations similar to sustained delivery tools like rings.
HIV testing and linkages to care, and treatment as prevention
HIV testing is the starting point for all subsequent steps in the HIV treatment and prevention cascades, particularly initiation of antiretroviral therapy (ART) for those found to be HIV infected. Two abstracts related to HIV testing were presented as part of the Monday oral session.
On of the Thursday morning plenaries was devoted to understanding costs and how to better quantify and extract benefits from PEPFAR (http://www.croiwebcasts.org/console/player/22261?mediaType=slideVideo&). PEPFAR has been a tremendous success, but thinking forward in an era of constrained resources, how best to demand treatment and prevention impact from PEPFAR must be a priority.
At CROI 2013 an extremely innovative study of HIV self-testing and home initiation of ART was reported. In 14 urban neighborhoods in Blantyre (total population 16,660), HIV self-testing kits were made available through community counselors; 7 neighborhoods were randomized to facility-based HIV care alone (control arm) and 7 were randomized to facility-based HIV care plus the option for home-based initial HIV assessment and ART initiation (intervention arm). At 6 months, overall uptake of self-testing was 58% of adults and ART initiation was substantially higher with optional home initiation of ART. At CROI 2014, one year follow-up was reported (Choko, abstract 147, http://www.croiwebcasts.org/console/player/22287?mediaType=slideVideo&). Uptake of self testing was nearly 100% by 12 months for those 16-19 years of age, reducing with older persons. In addition, linkage to care was assessed - with an estimated 78% linkage. Monitoring of negative outcomes of testing found no evidence of substantial gender based violence or suicide related to testing. These results continue the encouraging work of this team. A poster about cost-effectiveness of self-testing in Zimbabwe indicated that introduction of self-testing would be cost-effective under most scenarios considered, but more information is needed about uptake of testing through self-testing vs available HIV testing programs with linkages to care and ART uptake are needed (Cambiano, abstract 1045).
Another presentation (Barnabas, abstract 148, http://www.croiwebcasts.org/console/player/22288?mediaType=slideVideo&) assessed a program of home-based HIV counseling and testing and facilitated linkage to care, using point-of-care CD4 counts and lay counselor follow-up to encourage linkage. The program tested >3500 adults in rural South Africa and Uganda, finding 636 HIV infected persons. Linkage to care was very high (>90%). Initiation of ART was also high, although lower in those with higher CD4 counts (200-350 cells/μL). Still, population viral load decreased substantially - by 0.5 log10 copies/mL overall and by nearly 2 log10 copies/mL for those with CD4 counts ≤350 cells/μL (who were thus eligible to initiate ART). In sum, these data suggest that community-based programs with relatively low intensity testing and linkage to HIV care can achieve high community impact. A poster describing another household based HIV testing program, this one in Botswana, noted an important challenge - the majority of women in the community were tested but only 50% of men (Novitsky, abstract 1043).
One abstract that received considerable media attention was one describing HIV transmission risk in a prospective cohort of European HIV serodiscordant couples on ART (Roger, abstract 153LB, http://www.croiwebcasts.org/console/player/22072?mediaType=slideVideo&. All couples selected for the analysis reported at least some amount of condomless sex; in total 767 couples contributed 894 person-years of follow-up: 282 men who have sex with men couples, 245 heterosexual couples with HIV uninfected male partners, and 240 heterosexual couples with HIV uninfected female partners. ART adherence was high. There were no HIV transmissions within the partnerships during the study. This translated into an upper 95% confidence interval of the risk estimate of 0.4% per year, and 1% per year for those practicing anal sex. While the findings thus cannot establish zero risk of HIV transmission on ART, they suggest an upper limit of risk for policymakers and clinicians to use in messaging to patients. More data will come in the next few years to continue to quantify the risk of transmitting HIV for persons on effective ART.
Epidemiology and prevention
Several abstracts presented new epidemiologic data, or data using epidemiologic methods combined with virologic methods.
A European study assessed temporal trends in CD4 count and plasma HIV viral load set point from data from 1980 through 2012 (Pantazis, abstract 36, http://www.croiwebcasts.org/console/player/22063?mediaType=slideVideo&). There was suggestion that HIV is evolving to greater virulence and transmissibility - with a 50% decrease in the estimated time to decline to a CD4 count ≤350 cells/μL and a 0.4 log10 copies/mL increase in viral set point (translating to an estimated 44% increase in transmissibility). These findings mirror theoretical work that had hypothesized that, as HIV became globally established, it would evolve in this direction.
An abstract from San Francisco (Truong, abstract 37, http://www.croiwebcasts.org/console/player/22064?mediaType=slideVideo&) described transmission clustering in new infection. A total of 1300 new infections between 2005 and 2011 were studied, 86% in men (most of those in men who have sex with me). 27% were linked to a cluster of 2-3 other new infections and 18% were linked to a cluster of ≥4 new infections. Thus, half of new infections were associated with a cluster, suggesting grouping and onward transmission of acute infection. Notably, a recent sexually transmitted infection was common, suggesting one entry point for prevention (i.e., men presenting for treatment of a sexually transmitted infection are a prime population for prevention services, before they acquire HIV).
Another US abstract (Rosenberg, abstract 38, http://www.croiwebcasts.org/console/player/22065?mediaType=slideVideo&) described work in a prospective cohort of men who have sex with men in Atlanta. A total of 562 men contributed 832 person-years of follow-up during a maximum of 24 months of follow-up. What was particularly concerning was HIV incidence in the men who were black: cumulative HIV incidence over 24 months was 11.3% and 16.6% in those less than age 25. Factors associated with HIV acquisition included black race, lack of health insurance, anal sex without condoms, and having partners who were either older or black. Thus, individual factors, social factors, and sexual partner networks contribute to risk. The results were sobering - more than 1 in 10 young black men in Atlanta will acquire HIV each year. After this abstract, and the one prior, there was significant discussion in the audience of prevention interventions, particularly targeted PrEP factoring in location, age, race, recent syphilis infection, multiple partners, and drug use, to mitigate this staggering risk.
In a study from rural Uganda, HIV risk in coupled relationship was described (Grabowski, abstract 146, http://www.croiwebcasts.org/console/player/22286?mediaType=slideVideo&). In couples who were established to be both HIV seronegative (total 4570 couples), 135 HIV infections were observed in prospective follow-up. HIV incidence was 0.39 per 100 couple-years for HIV introduction into the relationship by the male partner and 0.24 per 100 couple-years for introduction into the relationship by the female partner. There was a strong relationship between self-reporting an extra couple relationship (i.e., multiple partners) and HIV risk, but self-reporting of extra-couple relationships in demographic surveys was limited, particularly by women. Encouragingly, there was some suggestion that scale-up of male circumcision ART in the region was associated with decreasing HIV incidence.
Data from a national serosurvey in Kenya were encouraging (Maina, abstract 149, http://www.croiwebcasts.org/console/player/22289?mediaType=slideVideo&). The Kenya AIDS Indicator Survey (KAIS) was conducted in 2012, following a similar survey in 2007. HIV prevalence fell during that period: from 7.2% to 5.6%, and in both men and women. The proportion who had tested for HIV increased from 34% to 72%; still, even in 2012, 53% of HIV infected persons were unaware of their HIV status. Male circumcision increased in the areas of the country with the lowest practice of male circumcision. Of those on ART, 75% were virally suppressed. These findings are very encouraging for Kenya, where strong actions in treatment and prevention appear to be having benefit.
An interesting and unexpected report from the Africa Centre in rural KwaZulu-Natal was the lack of association between having an older partner did not predict higher risk of HIV acquisition among younger women and was protective among older women (Harling, abstract 145, http://www.croiwebcasts.org/console/player/22285?mediaType=slideVideo&). The study had strong statistical power with 458 HIV seroconversions; the risk analysis evaluated most recent partner which may not have represented the source of HIV exposure if women had multiple partners between the annual HIV testing campaigns.
Poster presentations highlighted the potential of virologic phylogenetic studies to understand active HIV transmission networks, based on viral linkage studies of recently infected persons in the US and Netherlands (abstracts 205, 207, 211, 212, 214). The San Diego group have shown a model of how phylogenetic analyses can provide a means of delivering targeted interventions, such as targeted contact tracing (abstract 210) and early ART (abstract 206), based on real-time phylogenetic analyses to identify social networks of recently infected persons.
Finally, an excellent plenary on Tuesday morning described current knowledge of HIV risk and prevention globally in persons who inject drugs (http://www.croiwebcasts.org/console/player/22039?mediaType=podiumVideo&).
Reproductive health and HIV
Hormonal contraception is used widely and plays an important role in preventing unintended pregnancies and reducing maternal morbidity and mortality. To the great distress of researchers and policymakers, however, some (but, importantly, not all) prospective observational studies have found an increased risk for women to acquire HIV infection when they are using hormonal contraception, especially injectable depot medroxyprogesterone acetate (DMPA, otherwise known as branded Depo-Provera). This injectable contraceptive is a popular contraceptive method, with high use in southern and East Africa, where HIV is prevalent; it is also easy to use, fast to administer, and can be used discretely. Limited data also suggest that HIV infected women using DMPA might be more infectious to sexual partners. At CROI 2013, this topic was prominent, and a poster discussion at CROI 2014 brought in new information that will further the conversation.
The first abstract assessed SHIV replication (in plasma, rectal, and vaginal compartments) of pigtail macaques receiving DMPA (Radzio, abstract 884, http://www.croiwebcasts.org/console/player/22184?mediaType=slideVideo&). In this animal model, there was no suggestion that DMPA increased HIV infectiousness.
The second abstract (Guthrie, abstract 885, presented by Roxby, http://www.croiwebcasts.org/console/player/22185?mediaType=slideVideo&) presented a cross-sectional study of innate immune markers in cervicovaginal swabs from 288 HIV uninfected women from Kenya: 165 not using contraception, 41 using DMPA, 6 using the progestin implant Jadelle, and 16 using oral contraceptives. DMPA users had significantly higher concentrations of the markers HNP1-3, LL-37, and lactoferrin compared to women not using contraception; even with just 6 women sampled, those using implants also had higher concentrations of LL-37 and lactoferrin. HNP1-3 and LL-37 have been associated with HIV acquisition in prior studies and lactoferrin is broadly recognized as important in innate immunity. These results add to the discussion of potential biologic mechanisms by which hormonal contraception could influence HIV risk.
The third presentation (Noguchi, abstract 886, http://www.croiwebcasts.org/console/player/22186?mediaType=slideVideo&) presented data from the VOICE study, mentioned above. In that study, the vast majority of study particiapnts were from South Africa, where two types of injectable contraception are on the market, DMPA and a different progestin NET-EN. This abstract compared HIV acquisition for DMPA compared to NET-EN, a direct assessment of whether different progestins could carry different risks.
In total, 3163 women were followed prospectively, 2055 used DMPA and the remainder NET-EN. In multivariate analyses, DMPA use was associated with a statistically significant increased risk of HIV compared to NET-EN use (adjusted HR 1.42, 95% CI 1.03-1.97, p=0.03). In subgroup analyses, the effect was greater among women with HSV-2 (adjusted HR 2.02, 95% CI 1.11-3.66, p=0.02). Limitations of the study included the observational nature of the data (always a concern that uncontrolled confounding may explain the results) and the fact that there were several demographic and behavioral characteristics that were different between NET-EN and DMPA users. The HSV-2 interaction was interesting and requires additional studies; interestingly, previous studies of DMPA compared to no contraception have suggested HSV-2 uninfected women had greater HIV risk associated with DMPA use. Thus, the HSV-2 finding in the prior observational analysis was exactly the opposite of these findings, but subgroup findings should always be considered carefully. Nevertheless, these data add to the growing amount of high quality findings assessing contraception and HIV risk, and they remind us again that not all hormonal contraception is the same - that some methods may carry different biologic risks.
Medical male circumcision
The presentations on medical male circumcision (MMC) included a poster presentation about acceptability related to adverse effects with the PrePex device (Musiige, abstract 964). Encouragingly, a study of PrePex device in Botswana indicated that although 37% reported odor 2 days after medical male circumcision, a minority reported significant disruption in daily activity and 95% who reported odor indicated they would still recommend the PrePex to others. A study of MMC among HIV-infected men in Rakai, Uganda (Tobian, abstract 966) indicated that HIV shedding from the circumcision wound increased from 10% to 60% immediately post-circumcision which decreased by week one and returned to baseline within 4 weeks. A cross-sectional study of prevalence of HIV among circumcised and uncircumcised men who have sex with men in China found a 54% lower odds of being HIV uninfected among men who were circumcised (Qian, abstract 963). This is not definitive evidence of a causal relationship between circumcision and susceptibility to HIV but is prompting consideration of a RCT of MMC among HIV negative MSM.
Oral and poster presentations detailed the priorities for STIs as risk factors for HIV acquisition, including a symposium presentation on the potential role of bacterial vaginosis and HIV acquisition (http://www.croiwebcasts.org/console/player/22358?mediaType=slideVideo&), which highlighted the need for improved understanding of microbiologic understanding of bacterial vaginosis which could inform our understanding of interventions to treat BV. A poster presentation of microbiome studies of male partners of women with BV indicated that uncircumcised men are a reservoir for BV organisms (Liu, abstract 1017), suggesting that interventions to reduce BV may need to also target men. An analysis of HPV and HIV shedding in Senagalese women and Seattle MSM, indicated no association between HPV and cervical or anorectal HIV shedding (Hood, abstract 1020), suggesting that HPV vaccination in HIV infected persons may not reduce HIV shedding or infectiousness.
Prevention of mother-to-child transmission of HIV
Prevention of mother-to-child transmission (PMTCT) of HIV is a tremendous public health achievement. An oral abstract session devoted to PMTCT presented new data.
Data from Kenya assessed HIV incidence during pregnancy in a prospective cohort study in two health facilities in the western part of the country, where prevalence is highest (Kinuthia, abstract 68, http://www.croiwebcasts.org/console/player/22142?mediaType=slideVideo&). Women were recruited if they had had a negative rapid HIV test within the prior 3 months. Of 1304 women enrolled, 24 acquired HIV: 10 with new infection at enrollment and 14 during follow-up, for an overall incidence of 2.34%. Very few had a known HIV infected partner. These findings reinforce the need for repeat HIV testing in late pregnancy for areas with high HIV prevalence, as well as consideration for prevention strategies (PrEP, partner testing, etc) in pregnancy.
From Uganda, a randomized trial assessed the effectiveness of efavirenz (EFV) compared to lopinavir/ritonavir (LPV/r), both plus a nucleoside backbone (usually zidovudine/lamivudine), in 389 pregnant women (Cohan, abstract 69, http://www.croiwebcasts.org/console/player/22143?mediaType=slideVideo&).
Virologic suppression was very high but was higher at delivery in those receiving EFV (98% vs. 86%, p<0.001), although not ante or postpartum. There were more GI symptoms for LPV/r, but all grade 1/2. Birth outcomes were similar (Kass, poster abstract 867), and there were only 2 HIV transmissions (both to women receiving LPV/r. In summary, both EFV and LPV/r based ART during pregnancy and breastfeeding achieved high virologic suppression, with some advantage to EFV in viral suppression and low-grade side effects. Importantly, these results demonstrate high levels of viral suppression can be achieved, and HIV transmission to infants can be very low.
Another randomized trial assessed post-natal prophylaxis to breastfed infants using either LPV/r or lamivudine (3TC) (Kankasa, abstract 70, http://www.croiwebcasts.org/console/player/22144?mediaType=slideVideo&). The trial was conducted among 1273 women and infants in Burkina Faso, South Africa, Uganda, and Zambia. Women had CD4 counts >350 cells/μL and received standard perinatal prophylaxis. Post-natal transmission rates at 50 weeks were 1.4% LPV/r and 1.5% for 3TC (p=0.83). LPV/r and 3TC had similar safety and relatively similar adherence (perhaps slightly lower in LPV/r, which may have less palatability). Thus, LPV/r is non-inferior to 3TC for postnatal prophylaxis.
A big challenge has been increasing uptake of HIV testing among men, which would enhance uptake of prevention of mother to child transmission as well as identify HIV serodiscordant couples. A poster presentation of a randomized trial of home-based vs antenatal clinic-based male partner testing among 300 pregnant women in Kenya indicated that both pregnant women and their male partners (Osoti, abstract 884) preferred home-based testing to ANC testing. Innovative strategies, including home-based testing, are needed to increase uptake of men who know their HIV serostatus, are in an HIV serodiscordant or seroconcordant partnership, and are and are linked to HIV care and prevention including prevention of mother to child transmission.
Finally, a second infant seemingly without evidence of HIV infection after very early initiation of antiretroviral therapy received considerable media attention (Persaud, abstract 75LB, http://www.croiwebcasts.org/console/player/22149?mediaType=slideVideo&). A randomized trial to assess whether early initiation of combination ART immediately after birth in infants infected in utero is planned to start later this year.
CROI: Second Swiftly Treated Baby Seems to Have Cleared HIV - written by Mark Mascolini - (03/06/14)
CROI: Very Early Combination Antiretroviral Therapy in Perinatal HIV Infection: Two Case Studies - "Mississippi" baby followup & 2nd case of infant that appears to have cleared HIV/remains on cART - (03/06/14)