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  IAS 2017: Conference on HIV Pathogenesis
Treatment and Prevention
Paris, France
July 23-26 2017
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HIV Prevention at IAS 2017
 
 
  9th IAS Conference on HIV Science
Paris, France 23-26 July 2017
 
Jared Baeten, MD PhD
Connie Celum, MD MPH
University of Washington

 
The IAS conference on HIV science alternates years with the larger International AIDS Conference (held last year in Durban, South Africa and to be held next year in Amsterdam). The smaller IAS meeting focuses on basic, clinical, and prevention science (and, increasingly, on implementation science as well). Like many recent IAS conferences, the meeting was shaped by an overarching vision statement - this year, very importantly, emphasizing that scientific knowledge and commitment to research matter for the global HIV response; the statement can be found at https://www.ias2017.org/The-Paris-Statement-HIV-Science-Matters. Much of the scientific program is available online, including abstracts, copies of slides, and webcasts of some session (searchable program available at http://programme.ias2017.org/ ).
 
Prevention was front and center at this year's meeting - indeed, it was arguably perhaps the dominant area of conversation. The world continues to move forward with implementing antiretroviral treatment (ART) for all persons living with HIV infection, regardless of disease stage, as a prevention intervention, and pre-exposure prophylaxis (PrEP) as an option for HIV uninfected but at-risk persons. Neither ART nor PrEP have achieved their full potential, however, and implementation and coverage remain insufficient globally. Other prevention interventions too are being delivered, in synergy with antiretroviral-based strategies, with opportunity still for more impact. Plenary talks related to prevention included ones on antiretrovirals for HIV prevention (http://programme.ias2017.org/Programme/Session/20 ), economic incentives to promote prevention (http://programme.ias2017.org/Programme/Session/21), and ending pediatric HIV (http://programme.ias2017.org/Programme/Session/21 ).
 
PrEP
 
Pre-exposure prophylaxis (or PrEP), in which an HIV uninfected person uses an antiretroviral as chemoprophylaxis against HIV received considerable attention at this year's IAS meeting - there were moments where the entire meeting felt like it was about PrEP. PrEP remains primarily oral tenofovir-based pills (mostly tenfovir disoproxil fumarate in combination with emtricitabine [FTC/TDF]), the only approach to date to have received regulatory approval in any country, although new PrEP agents are marching through clinical trials.
 
Oral PrEP clinical trials. A Tuesday morning oral abstract session (http://programme.ias2017.org/Programme/Session/139 ) presented fantastic updates from PrEP clinical trials; most focused on oral PrEP with FTC/TDF. A second session, on Wednesday (http://programme.ias2017.org/Programme/Session/145 ) addressed PrEP in more delivery settings. A third session, in prevention in adolescents (http://programme.ias2017.org/Programme/Session/143 ), included two important PrEP abstracts.
 
Updated results from the PROUD study were presented (abstract TUAC0101, McCormack). PROUD was a landmark study in the PrEP history - it randomized men who have sex with men (n=544) attending sexual health clinics in the UK to immediate or 12-month deferred access to PrEP, beginning in 2012 and stopping deferred PrEP access in 2014 because PrEP had reduced HIV incidence by 86% among those assigned to immediate use. PROUD was done after the clinical trials that first established that FTC/TDF PrEP was efficacious for HIV prevention, but questions about what its effectiveness might be in more real-world settings were the justification for PROUD. The data at IAS 2017 considered long-term follow-up of the PROUD cohort, through November 2016. In the deferred group, 206 of 269 eventually started PrEP and about 2/3 were still taking PREP at the end of following, which was for some 3 years after starting. Final HIV incidence was 1.6 vs. 9.4 per 100 person-years in the deferred phase of the trial, and then 1.2 vs. 0.3 in the post-deferred phase. 10 individuals received PrEP and later acquired HIV, but only 2 of these had any potential to be taking PrEP at the time of infection (given when they received prescriptions). STI rates were high throughout, as has been previously reported for PROUD. In sum, PrEP persistence was high (>60%), benefits were sustained, in spite of high STI rates in an important at risk population.
 
A second abstract from PROUD assessed the meaning of PrEP for men in the study, using qualitative methods (abstract TUAC0105, Gafos). 41 participants were interviewed. PrEP slotted into already-established behaviors, providing a "security blanket" or "safety net" and giving significant psychosocial benefits ("replaced fear" "removing worry" "relief after 25 years of weight"). Psychological benefits including more intimacy in relationships. Thus, added to men's existing lives, and their sexual "rules" and prevention strategies, rarely replacing things already there, but offering increased individual choice with great psychosocial benefits.
 
IPERGAY was a placebo-controlled trial of FTC/TDF PrEP, prescribed for "on-demand" use - i.e., 2 pills 2-24 hours before sex and 2 pills (one each day) for the 2 days after sex. Initial results for the trial were reported at CROI in 2015 and showed an 86% reduction in HIV risk (95% CI 50-98). After these results were demonstrated, the trial converted to an open-label extension phase, providing all men with active FTC/TDF PrEP; those results were presented at AIDS 2016 and were published during the week of IAS 2017 in Lancet HIV (http://www.thelancet.com/pdfs/journals/lanhiv/PIIS2352-3018(17)30089-9.pdf ). One important question from IPERGAY is whether the on-demand regimen would be effective among the subset of men who had infrequent sex, as the median sexual frequency in the IPERGAY population was such that pill use, even when taken on-demand, was approximately 4 or more pills per week, a level that has been associated with near-perfect HIV protection in other studies of PrEP. The subgroup analyses was presented at IAS 2017 (abstract TUAC0102, Antoni - http://natap.org/2017/IAS/IAS_77.htm ). Time segments with <15 pills/month per analyzed - a total of 134 person-years of follow-up in all, from 269 participants. They used detailed HIV testing methods to assign timing of infection. 6 infections occurred - all in the placebo arm, translating to a relative risk reduction of 100% (95% CI 39-100, p=0.013). Median pill use was 9.5 pills/month, covering 5 sex acts/month. These results suggest that on-demand PrEP is an effective alternative to daily PrEP for men with infrequent sexual exposures.
 
PrEP delivery. Fantastic oral abstracts were presented illustrating PrEP roll-out across the world. In a pre-conference session, experiences with roll-out were discussed from a variety of settings (http://programme.ias2017.org/Programme/Session/176). Oral abstracts discussed this further.
 
From Australia, >3000 individuals were enrolled in PrEP demonstration project in Melbourne in less than a year (abstract WEAC0104, Wright, PrEPX study). The project actually had to expand its sample size to accommodate interest. The work is being done at private practices and sexual health clinics, in a true demonstration of real-world delivery. HIV testing has increased. In the pre-conference session, similarly great interest in PrEP is being seen in Sydney and the surrounding area, and there is already suggestion of fewer new HIV infections being detected.
 
From Europe, an online survey of men who have sex with men illustrated that interest in PrEP is high, but access/availability is a key barrier (abstract WEAC0101, Bernier). From the Netherlands (abstract WEAC0106LB, Zimmermann), a really interesting abstract illustrated that men taking PrEP choose either a daily option or the IPERGAY on-demand regimen based on a variety of motives, including expectations about self in terms of adherence, anticipated sexual frequency, and confidence in the product. This was a great example of how different PrEP options appeal to different people and making sure options are available maximizes prevention use. From the US (abstract WEAC0105, Patel), adherence measurement using the medication possession ratio calculation approach was found to be strongly correlated with dried blood spot tenofovir levels - important information as people try to figure out adherence measurement in real-world settings.
 
In Kenya and Uganda, the ongoing SEARCH study, which is doing community-based ART for prevention and has added in PrEP, characteristics of early PrEP adopters were described (abstract WEAC0103, Ayieko). The SEARCH team used self-assessment of risk or an objective scoring tool (developed from prior analyses of seroconversions in the trial communities) to guide people to PrEP. A total of 739 early adopters were described, 78% started same-day as offered. 11% of those scored to be at high risk started PrEP; 39% of those with high self-assessment risk. More work is needed as PrEP rolls out to understand who starts, especially as PrEP uptake expands out of early adopters.
 
From South Africa, an open-label study (Pluspills) assessed PrEP acceptability, safety, and use among adolescents aged 15-19 (abstract TUAC0207LB, Gill). 148 adolescents enrolled (99 women, 49 men). PrEP was well-tolerated, with no safety concerns. Adherence was reasonable (57% with detectable PrEP in blood at 12 weeks) but diminished with time. Only one HIV seroconversion occurred (incidence 0.76 per 100 person-years) in a 19 year-old woman who had stopped PrEP 24 weeks prior to testing positive for HIV. In summary, PrEP can be used by a segment of adolescents, but more work is needed to increase access and persistent use.
 
New PrEP agents. TDF-based pills are not likely to remain the only PrEP option for long. This is important - like for other prevention strategies (a strong analogy being contraception), choice is important and to have choice, one needs to have options. In 2016, two phase III trials among women in Africa demonstrated that an antiretroviral-containing vaginal ring (the dapivirine vaginal ring) was effective and safe for HIV prevention, and phase I-III studies of other potential options are ongoing. Long-acting injectable agents - that would work for a month, two, or more - offer substantial promise for becoming a PrEP option. Injectable agents have great appeal - they could be used discretely and could remove some adherence challenges (e.g., taking a daily pill, but not returning to a clinic to get HIV testing and a PrEP refill). Phase II and III studies are ongoing. One abstract (McGowan, TUAC0103) studied the pharmacokinetics and pharmacodynamics of the injectable TMC 278LA (long-acting injectable rilpivirine). There was a modest but significant accumulation in tissues; clade B and C explant replication was significantly suppressed in rectal samples (more C>B) but not in cervical/vaginal explants. This particular compound has not moved forward into later stage clinical trials at this time.
 
A second injectable, the integrase strand transfer inhibitor cabotegravir, was tested in the HPTN 077 trial a phase II safety and tolerability trial among 199 HIV uninfected men and women in Brazil, South Africa, Malawi, and the US assigned 3:1 to cabotegravir or placebo. (abstract Landovitz, TUAC0106LB - http://www.natap.org/2017/IAS/IAS_33.htm ).
 
There were two cohorts, one received study medication every 12 weeks (n=110, 800 mg of cabotegravir) and the second every 8 weeks (n=89, 600 mg of cabotegravir), because of emerging information from other studies suggesting more frequent dosing might be necessary to provide enough drug for HIV protection. Week 41 is primary endpoint, and ppts will be followed for 18 months after their last injection, to monitor how the drug declines over time (i.e., follow-up is through mid-2018). Retention in this phase II trial was good: 90% after an initial 4 week period of oral cabotegravir and then 72% in Cohort 1 & 80% in Cohort 2 completed all injections. Withdrawals because of reported adverse events were 7.9% vs. 2.1% (not statistically significant). Two adverse events were more common in the active arm compared to placebo: injection site pain and headache (p<0.001 and p=0.03). Injection site reactions were common: 92% in Cohort 1 & 88% in Cohort 2 vs. <40% in those assigned placebo. 1 seroconversion occurred - 48 weeks after last injection, and cabotegravir levels were not quantifiable in blood at that visit and at the visit 3 months prior. Pharmacokinetics analyses found that the 8 week injections kept most individuals above 4x the IC90, and pre-defined targets for drug levels were met. Thus, overall, cabotegravir was well-tolerated in men and men; the drug is moving into phase III evaluations. Points to watch for in those phase III trials will be the rate of discontinuation (which was fairly high in this phase II trial), trough levels and on-time return for follow-up injections (since the pharmacokinetics suggest that levels fall below potentially protective doses at or just beyond trough timing), and the joint effects of those on HIV incidence.
 
The dapivirine vaginal ring is the PrEP agent that is furthest along towards becoming an alternative to oral TDF-based pills, after the results of the two trials last year. At IAS 2017, data from a safety study of the dapivirine vaginal ring in US adolescent women (trial MTN-023/IPM 030) were presented (abstract TUAC0206LB, Bunge). http://natap.org/2017/IAS/IAS_98.htm This study involved 99 young women aged 15-17 who were randomized 3:1 dapivirine:placebo from 6 sites in the US. They used the dapivirine ring continuously for 24 weeks, replacing a new ring every 4 weeks. Overall, the ring was extremely safe and was well used: 87% of blood samples had dapivirine detected and 95% of returned, used rings had levels depleted to a degree to suggest use. 95% of women said it was easy to use the ring and 93% said they liked using it. These results are very encouraging - young women can safely use the dapivirine ring, with high adherence.
 
A second dapivirine abstract assessed vaginal microbiota in women using investigational dapivirine vaginal films or gels (abstract TUAC0104, Hillier). http://natap.org/2017/IAS/IAS_70.htm . At the IAS 2016 meeting data from the CAPRISA 004 trial (which tested tenofovir gel) were presented that suggested that women who had abnormal vaginal flora or bacterial vaginosis had lower levels of tenofovir and lesser HIV protection, suggesting that topical delivery of antiretrovirals could be influenced by vaginal flora. [Note, this may not be the case for systemic antiretrovirals - results from an oral PrEP trial found no effect of vaginal flora on HIV protection, results presented at CROI 2017 and published just before IAS 2017 http://www.thelancet.com/journals/lanhiv/article/PIIS2352-3018(17)30110-8/abstract .] The IAS 2017 abstract found that dapivirine concentrations were not decreased by vaginal bacteria associated with bacterial vaginosis, suggested that the effect might be tenofovir-specific and not relevant to all topical PrEP approaches.
 
An interesting preferences study from Canada assessed characteristics of potential new PrEP agents for men who have sex with men, including pills, injections, on-demand rectal gels, etc. (abstract WEAC0102, Tan). Notably, attitudes were heterogeneous - the most preferred option was an ideal pill to use on demand and with perfect protection but some men favored multiple options or specific alternatives. Multiple options will probably be needed to cover all individuals and have the greatest prevention impact.
 
Finally, a new medication (MK-8591), a nucleoside reverse transcriptase translocation inhibitor, formulated as a weekly pill was found to be completely protective against low-dose rectal SHIV challenge in macaques (abstract MOAX0203LB, Markowitz). http://natap.org/2017/IAS/IAS_03.htm Weekly or other less-frequent oral dosing approaches may be in the future for PrEP.
 
Combination HIV prevention
 
Antiretroviral treatment is a potent HIV prevention strategy. Like PrEP, the ultimate impact of TasP for HIV prevention depends on its coverage in a population (i.e., how many people who have HIV infection actually are receiving ART) and adherence (i.e., how well those receiving ART take it). Other prevention strategies - testing, voluntary medical male circumcision, behavior change, treatment of sexually transmitted infections, economic empowerment, and others - come together for maximum impact.
 
Swaziland, a country with a 32% national HIV prevalence in 2011, has implemented a combination prevention package for HIV (abstract MOAX0204LB, Nkambule). From 2011 to 2016, annual HIV testing increased from 180,000 to >400,000, people starting ART from 14,000 to >22,000, and VMMCs from 38,000 to >93,000. The Swaziland HIV Incidence Measurement Survey (SHIMS) 2 was done in 2016 as a nationally representative assessment of HIV in the country. Overall HIV prevalence was 27%. 73% of HIV infected persons had a suppressed viral load. Overall, the country was near 90-90-90 goals (85-87-92). Estimated HIV incidence, based on HIV assays to estimate recent infection, was 1.4% per year (1.7 in women, 1.0 in men), down 44% from estimates in 2011 (2.5% per year then). While the HIV testing assays do leave some room for question of the magnitude of these results, they nevertheless illustrate that scale up of testing, treatment, and other prevention interventions can have really encouraging effects on an important country for the epidemic.
 
An oral abstract session on other prevention interventions covered the gamut of important tools (http://programme.ias2017.org/Programme/Session/148). The HPTN 068 trial tested conditional cash transfer among young women in rural South Africa; results, presented at IAS 2015, found no decrease in incident HIV, but there was a decrease in intimate partner violence. An abstract at IAS 2017 dissected the mechanism for that decrease (abstract TUAC0401, Kilburn), finding both fewer partnerships (and thus less opportunity for violence from a partner) and also less violence within partnerships (perhaps from financial empowerment).
 
A systematic review from the World Health Organization was presented in support of its new guidelines on partner notification services (abstract TUAC0403, Dalal), available at http://www.who.int/hiv/pub/vct/hiv-self-testing-guidelines/en/ ).
 
HIV self-testing
 
There were several symposia and oral sessions focused on HIV self-testing, including one on Sun called 'Evidence for Action: Key findings from the HIV self-testing (STAR) project in Malawi, Zambia and Zimbabwe (http://programme.ias2017.org/Programme/Session/76 ). The STAR project aims to increase access, informed demand, reduce policy and regulatory barriers, and remove structural barriers to HIV self-testing (HIVST) in Africa. Their conservative estimate is a market of 3.3-5.5 million users through community channels by 2020 and 11-15 million with moderate investment and expansion to pharmacies and facilities. Mutseta reported that in the first year of test kits distribution in Zimbabwe, Zambia and Malawi, almost half were men, 28-50% were young people (16-24 years) and about 25% were first time testers. Men were more likely to take up VMMC if they self- tested, compared to men who took up VMMC without the HIVST option (57% vs 42%). In a session on the cost-effectiveness of the STAR program, Maheswaran presented that although the cost-effectiveness is uncertain at a country level, HIVST can be delivered at comparable costs to facility-based HIV testing services, that community-based HIVST may be cost-effective in settings of low HIV testing coverage, and that linkage to HIV prevention is critical, given that the majority of men will test HIV-negative.
 
Choko presented on a multi-arm adaptive cluster RCT in Malawi (SUSA2011) to improve linkage to prevention, specifically voluntary medical male circumcision, (VMMC) and ART among male partners of antenatal care attendees. They randomized ANC attendees to standard of care, HIV ST kits only, HIV ST kits and either a $3 or $10 incentive for the man, a lottery with a low value, or a phone reminder. The primary outcome was the proportion of male partners of ANC attendees who tested and either linked to care/initiated ART or VMMC within 28 days. They conducted the study in 2 phases with approximately 2300 women in 71 clusters with 6 arms. The proportion of men who had never tested ranged from 40-64% in the 6 arms. Notably 87% of women reported their partners had tested by 28 days, 7% of whom tested HIV-positive. Male partners were 2 to 2.5 fold more likely to test and link to care in the HIVST and incentive arms: RR 2.6 in the self-testing and $10 incentive arm, 2.0 the self-testing and $3 incentive arm. While significant compared to clinic invitation letters, a minority of men were on ART or booked for VMMC by 28 days - the highest rate was 19% in the HIVST and $10 incentive arm, highlight that more research is needed on strategies to efficiently link men into ART or prevention services.
 
Wanyenze presented on HIV ST for partners of women attending antenatal care in Uganda (MOSA1204). Her team conducted a 2 arm cluster randomized trial (the cluster was clinic day) among 1514 antenatal clinic attendees in 3 clinics in central Uganda, half were randomized to provide HIVST to their partner and family members and half to standard of care education messages about partner testing. Follow-up of women was conducted at 1 and 3 months with qualitative interviews among 70 male partners. The HIVST arm was significantly better in the proportion of male partners who were tested (74% among women randomized to HIVST compared to 36% among the control arm (p<0.0001); couple testing (70% vs 21%), and HIV disclosure (23% vs 13%). The HIVST intervention was cost-effective and acceptable with rare social harms (2 in couples who learned that they were HIV serodiscordant). In the subset of 70 men interviewed, linkage to HIV care was greater in the HIVST arm.
 
An oral abstract session on Monday was focused on self-testing (http://programme.ias2017.org/Programme/Session/123 ).
 
The feasibility of HIVST among female sex workers (FSWs) attending a clinic in Zimbabwe over a 6 month period was assessed (abstract MOAX0104, Mavedzenge). Almost half of the 607 women presenting for HIV testing opted for HIVST, and 96% used the HIVST at the clinic site. 98 (39%) tested positive, almost all of whom reported seeking post-test services. Notably, all 325 trusted that the HIVST was correct and 99% were comfortable learning their test result without a provider present. Their willingness to pay for HIVST was sensitive to price with a dramatic reduction in willingness if the test cost more than $5. Almost 40% were concerned about forced testing. In abstract MOAX0105LB, Oldenburg presented on a RCT of HIVST for FSWs in which 965 peer educators were enrolled who were asked to recruit 6 FSWs, either through standard of care, direct delivery of HIV ST to FSWs or delivering coupons for HIV ST to SWs. Over a 4 month follow-up period, HIVST was highly used by participants (84% by coupons) and 95% by direct delivery, but did not increase HIV testing rates relative to standard of care in which 89% of FSW reported testing. However, linkage to care and ART initiation rates were lower in the HIV ST direct delivery and coupon arms than the standard testing arm. This study showed that both facility-based HIV testing and HIV ST were acceptable, that HIV self-testing did not lead to elevated rates of intimate partner violence, and that linkage to care may be delayed in Zambian FSWs who use HIVST.
 
A pilot of HIVST in the UK through a mobile app ordering portal that was trying to reach MSM was presented (abstract MOAX0102, James). Almost 5000 tests were ordered over 6 weeks, 91% of whom were from urban settings. 19% had never been tested for HIV, and 37% had tested more than a year ago. 81% reported 2 or more partners in the past year, and 47% reported sex with alcohol or drugs. Text reminders were sent at days 7 and 10. 62% reported their results, of which 0.92% were positive, and 92% of those with HIV positive results had accessed services. User satisfaction was high, and most men reported they would use the service again and 57% would be willing to pay for it.
 
A 12 month RCT of HIV self-testing among MSM (eSTAMP) in the US, who were recruited online in 2015 was presented (abstract MOAX0103, McGowan). 1325 MSM were randomized to the intervention arm (men were mailed 4 rapid HIV tests at baseline with the option of replenishing the ones used) and 1340 to the control arm. The mean age was 30 years, 58% were white, and 17% had never been tested for HIV. Of the 72% who completed at least one follow-up survey, HIV testing and number of newly identified HIV cases were significantly higher in the intervention arm; 79% reporting that they used 3 HIV tests compared to 22% in the control arm and the number and proportion of newly identified HIV cases was double (25, 2.6% vs 11, 1.2%). Thus, internet-based HIV screening programs with free HIV rapid tests increased HIV testing and diagnosis among MSM, including those who have not previously accessed traditional HIV testing services.
 
Ayles presented an evaluation of oral HIV self-testing which was nested with the cluster randomized study of universal ART treatment, HPTN071/POPART (abstract TUAC0406LB). Four of the Zambian HPTN071 intervention communities were randomized by community health intervention worker zones, with an average of 471 households per zone. In HIVST zones, individuals aged >16 years who did not self-report being HIV-positive, were offered a choice of HIVST or HIVFP. Secondary distribution of HIVST was offered for absent partners. The overall increase in the proportion of adults enumerated in the HIVST arm who knew their HIV status was modestly higher in the HIVST than the non-HIVST arm (63% vs 61%, adjusted OR 1.25, p=0.04). The increase in knowledge of HIV status was greater among men (55.0% in HIVST compared to 50.2% in the non-HIVST arm (adj OR 1.30, p=0.01), In summary, HIV self-testing was a major innovation featured at IAS 2017, and the presentations indicate substantial evidence of feasibility and high acceptability of HIVST among hard to reach populations. Specifically, HIVST increased testing uptake, testing frequency and 'yield' of reactive results and did not cause social harm. Additional research is needed to ensure linkage to care and prevention in order to optimize the long-term benefit of knowledge of serostatus as well as the cost-effectiveness of HIVST strategies. Mobile health technologies could support HIVST demand creation and access or results.
 
PMTCT
 
ART is central to prevention of mother-to-child transmission of HIV (PMTCT) but numerous challenges impede perfect implementation of PMTCT services. There were a number of excellent PMTCT-focused sessions at IAS 2017, covering new science in reducing infant HIV infections. One oral abstract session on Wednesday had a few highlights: http://programme.ias2017.org/Programme/Session/146.
 
From Western Kenya, a spatial-temporal analysis of data from multiple facilities provided excellent information on the evolving delivery program there (abstract WEAC0203, Waruru). Overall, MTCT rates have decreased (17% in 2007, 7% in 2013) and infant testing has increased. The visualization of data with spatial-temporal analysis illustrated specific geographic areas for ongoing optimization.
 
In Swaziland, a community-based survey was done to assess impact of Option A prevention (abstract WEAC0205, Chouraya). Multistage sampling was used, covering all areas of the country - ultimate sample was n=724. Overall, HIV-free survival at 18-24 months was 95% with a ∼3.6-4.1% (depending on assumptions) MTCT rate. Encouraging news.
 
HIV vaccines
 
IAS 2017 had a number of presentations and symposiums about HIV vaccines. A symposium on Sunday, entitled "Future Perfect: Opportunities and Obstacles for HIV Vaccines" (http://programme.ias2017.org/Programme/Session/187 ) and included three interesting talks, including one by Dr. Anthony Fauci who directs the NIAID at the US NIH about whether we can end the HIV pandemic and strategies to find an effective HIV vaccine. Louis Picker spoke about exploiting novel cellular immunity in HIV prevention through cytomegalovirus vectors, and Rogier Sanders spoke about novel envelop proteins to induce neutralizing antibodies. These talks and slides are available at http://www.vaccineenterprise.org/content/future-perfect-opportunities-and-obstacles-hiv-vaccines/presentations .
 
In a Tuesday symposium called "Correlates of Reduced HIV Acquisition in Vector Prime Protein Boost HIV Vaccine Regimens" (TUSA02, http://programme.ias2017.org/Programme/Session/183), presentations highlighted how correlates of HIV infection in humans from the Thai RV144 trial and from non-human primates are guiding design and evaluation of candidate HIV vaccines. The results of the APPROACH trial results were presented of the first-in-human trial of immunogens mosaic vaccines developed by Janssen. http://natap.org/2017/IAS/IAS_22.htm . The immunogens were created with genes from different subtypes of HIV-1delivered through viral vectors, including an engineered version of adenovirus serotype 26 (Ad26). The APPROACH trial included 393 adults from the US, Rwanda, Uganda, South Africa and Thailand, in which approximately 50 participants each were randomized to a regimen containing two prime doses of Ad26.Mosaic.HIV and two boosts with either Ad26.Mosaic.HIV or MVA-Mosaic and/or two different doses of Clade C gp 140 administered over 48 weeks. All of the vaccine regimens were well-tolerated and after the third vaccination, most active vaccine regimens elicited antibody responses in 100% of participants. Notably, the regimen that elicited the greatest immune responses in humans was the same regimen that also showed the greatest protection against an HIV-like virus in nonhuman primates during preclinical studies. The Ad26 mosaic vaccine will be tested for efficacy in the HVTN 705 trial, which will start later in 2017. The mixture of four Ad26 mosaic immunogens will be combined with a clade C gp140 boost in a placebo-controlled trial in 2600 South African women, to begin in late 2017. In the same session, Dr. Glenda Gray presented about the ongoing HVTN 702 trial, which is a phase 2b/3 multi-site, randomized, double-blind, placebo-controlled clinical trial among 5400 adults to evaluate the safety and efficacy of ALVAC-HIV (vCP2438) and subtype C in South Africa. HVTN 702 is a follow-up to the Thai RV144 trial, which had approximately 30% efficacy from which correlates of HIV protection were identified. An 18 month booster was included based on the results of the phase 2 HVTN 100 trial. Given similarities and differences in correlates between the human RV144 trial with an ALVAC-based regimen and non-human primate studies with the Ad26 mosaic immunogens, samples will be collected at the same schedule to conduct parallel immune correlate analyses in HVTN 702 and 705, which will increase the power to compare correlates within and between these trials.