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  Conference on Retroviruses
and Opportunistic Infections (CROI)
February 13-16, 2017, Seattle WA
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HIV Prevention at CROI 2017
Conference on Retroviruses and Opportunistic Infections
  Conference on Retroviruses and Opportunistic Infections
Seattle, WA, USA
February 13-16, 2017
Jared Baeten, MD PhD
Connie Celum, MD MPH
University of Washington
CROI 2017 again brought together researchers, clinicians, policymakers, advocates, funders and others to talk about the pathogenesis, prevention, treatment, and cure of HIV and associated infections. Prevention has been a major topic at CROI for many years now, with some of the game-changers in prevention first debuting there. In addition, the last few years have shown an increasing number of presentations on delivery of prevention strategies and assessment of impact at scale, the real measure of having an effect on the global epidemic. While this year's CROI did not have a single blockbuster prevention moment, there were a number of major advances in the prevention and implementation sphere.
As in previous years, oral sessions were recorded and are available online ( http://www.croiwebcasts.org/), along with full copies of abstracts ( http://www.croiconference.org/abstracts/search-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.
In addition to the abstract-driven sessions, there was a fantastic Thursday morning plenary on the efforts to end the HIV epidemic in New York City, an ambitious, multicomponent, public health intervention (Daskalakis, abstract 108, http://www.croiwebcasts.org/console/player/33560?mediaType=slideVideo&). It is very much worth watching.
Pre-exposure prophylaxis for HIV prevention
In PrEP, an HIV uninfected person uses an antiretroviral medication ahead of an HIV exposure in order to prevent infection. At each CROI since 2011, PrEP has been a major focal point, with major clinical trials, translational science, safety studies, and, most recently, implementation projects reporting findings. Large-scale efficacy clinical trials of PrEP - first as pills and then last year as an antiretroviral-containing vaginal ring - have demonstrated that PrEP is an effective and safe intervention for HIV prevention. Efficacy evaluations of injectable delivery of PrEP is ongoing, potentially heralding a future where multiple options exist for individuals to choose among for prevention.
From Atlanta, observational study of young black MSM explored challenges of translating interest in into uptake of PrEP (Rolle, abstract 90, http://www.croiwebcasts.org/console/player/33463?mediaType=slideVideo&). Of 184 men who were PrEP eligible and who were part of a larger study of prevention choices, 18 were not interested and 50 wanted to discuss it more at a later clinic visit. Of the remaining 116, all of whom were interested in PrEP, 53 didn't start. Overall, over 50% were interested but the median time to initiation visit was 16 weeks and then to medication start was an additional 4 weeks. The work points out there are substantial barriers between interest and uptake and efforts to diminish barriers (same-day PrEP start, for example) are desperately needed.
Two studies from Seattle described public health programs for PrEP services. In the first, STI partner services were discussed as a way to promote PrEP (Katz, abstract 89, http://www.croiwebcasts.org/console/player/33462?mediaType=slideVideo&). In brief, partners of MSM with STIs are contacted by partner services by public health specialists, which was enhanced with PrEP information/referral/appointments. 21% of partners offered PrEP attended an initial visit, with a higher percentage among white partners. These findings emphasize a novel opportunity to promote PrEP to high-risk MSM in the US. The second described a mobile health approach to continued engagement in a public health program PrEP public health program (Khosropour, abstract 964, http://www.croiwebcasts.org/console/player/33411?mediaType=slideVideo&). PrEP was offered to those at high risk (recent rectal GC or syhplis, methamphetamine use, HIV+ partner not on suppressive ART). An SMS [text messaging] program (provided by WelTel) included: automated weekly check-in (that moved to monthly with greater time on PrEP), automated reminders for appointments, and bi-directional open communication as an option. The program was monitored by two PrEP disease intervention specialists. In total 324 patients were offered SMS and 79% of those who willed a PrEP prescription opted in (218/275). SMS was associated with higher PrEP retention (∼75% vs. ∼50%). So a simple SMS adjunct to PrEP care was deliverable and was associated with better retention in care.
An interesting poster focused on STI screening in the context of PrEP delivery, using a mathematical modeling approach to consider data from the US (Jenness, abstract 1034). The authors found that STI screening, which CDC currently recommends to be done six-monthly for MSM on PrEP, would have important benefits for public health STI control - averting about 1/3 of new gonorrhea and chlamydia infections if ∼20% of MSM were taking PrEP. Moving testing to quarterly instead of six-monthly would detect (and avert) more infections but for less bang for the buck. Importantly, there would still be benefits even if risk behaviors increased on PrEP (and thus STI incidence increased) - so risky behaviors did not offset the benefits of screening. All in all, a great reminder that PrEP and STIs are linked but could be linked in a way that gains public health benefit for STI and HIV.
Two abstracts discussed pharmacies and PrEP delivery in the US. From Seattle (Tung, abstract 961, http://www.croiwebcasts.org/console/player/33408?mediaType=audio&), a pharmacy-driven model of PrEP delivery was presented. The approach used a Collaborative Drug Therapy Agreement (CDTA) that permits a pharmacist to provide a medication, under the remote oversight of a physician. The goal of the project (called One-Step PrEP) was to develop and implement a CDTA for PrEP in Seattle - that could serve as a model for PrEP delivery elsewhere. The work began in 2015 and allows a pharmacist to provide initial screening, counseling, prescribing and dispensing, as well as follow-up, all through a standardized, in-person protocol, with brief visits all done within the pharmacy itself. Between March 2015 and March 2016, 373 patients sought services and 245 initiated PrEP, only 57 had an existing primary care provider, suggesting that the program was providing a needed service. 98% were male, the age range was 18-64, and 84% were MSM. Two patients tested positive for HIV, one at initial screening and one during follow-up, in the context of nonadherence to PrEP. Retention was 75% and the most common reason for discontinuation was change of insurance. This revolutionary approach appears to provide a great option for patients and was financially sustainable for the pharmacy as well. From Nebraska and Iowa (Broekhuis, abstract 963, http://www.croiwebcasts.org/console/player/33410?mediaType=audio&), a survey of 140 pharmacists explored willingness to provide PrEP. Less than half (42%) were familiar with FTC/TDF as PrEP and only 25% were familiar with CDC guidelines for PrEP. However, just over half (54%) were potentially willing to provide PrEP services in the context of a CDTA. Having cared for HIV-infected patients, provided antiretrovirals, and having done HIV-related continuing education were related to greater willingness. These data thus are modestly encouraging and argue that continuing education can motivate even greater willingness.
A brief behavioral intervention was associated with increased PrEP use in a PrEP demonstration project among ∼300 MSM in New York (Golub, abstract 965, http://www.croiwebcasts.org/console/player/33412?mediaType=audio&). Two interventions were evaluated: a brief sexual health intervention that framed PrEP in terms of being a part of a healthy and fulfilling sex life, with men having the agency to choose PrEP and a brief adherence intervention that focused on empowerment and motivation, helping patients anticipate adherence challenges. Patients who received either intervention (or both) had high PrEP use (>90% had drug levels consistent with >4 pills/week), compared to 85% for those who received neither. High levels of adherence were maintained to 12 month, including in those who were younger (aged 18-24) or of color. The work suggests that small and simple shifts to treatment as usual can increase PrEP adherence. Work to integrate brief reframing messages into PrEP counseling in the real world may have great benefit.
From France, the results of a nested trial of STI prophylaxis within a PrEP study drew great attention (Molina, abstract 91LB, http://www.croiwebcasts.org/console/player/33464?mediaType=slideVideo&). In brief, STI rates are high among MSM who are eligible for PrEP and who are on PrEP. Indeed, these high rates are a conundrum for PrEP - men on PrEP have very low HIV rates but high STI rates and strategies to prevent STIs are needed. Post-exposure prophylaxis has been used against several infectious diseases, with mixed effects for prevention of STIs. Within the open-label phase of the IPERGAY study (which had demonstrated the efficacy of on-demand PrEP for HIV prevention in MSM), men were randomized to open-label doxycycline 200 mg orally within 24 h after sex vs no doxycycline. The outcomes were gonorrhea, chlamydia, and syphilis. 232 men were randomized, half to receive doxycycline, and retention was 91%. 14-19% had an STI at baseline. The results were striking: the incidence of a first STI was 37.7 per 100 person-years for those receiving doxycycline (28 cases) versus 69.7 per 100 person-years for those who did not receive doxycline (45 cases), a 47% reduction (95% CI 15-67, p=0.008). Most STIs were asymptomatic. There was no effect on gonorrhea prevention, which was expected since most in France in resistant to doxycycline already, but strong effects on chlamydia (70% reduction, p=0.006, 21 vs. 7 cases) and syphilis (HR 73% reduction, p<0.05, 10 vs. 3 cases). Doxycycline prophylaxis was safe and tolerated. Antibiotic resistance studies are ongoing and the longer-term benefits are yet unknown but these results were striking and suggest a new era for STI prevention in the context of PrEP.
Two abstracts focused on prevention of HIV among women with abnormal vaginal flora, the etiology of bacterial vaginosis (BV). At the Durban IAS meeting in July 2016, a secondary analysis of data from the CAPRISA 004 clinical trial of tenofovir 1% vaginal gel found reasonably high HIV protection from the gel among those who did not have abnormal flora but no protection when flora were abnormal, and a possitlbe mechanism was suggested, specifically that Gardnerella vaginalis (which is commonly found in the vagina when flora are abnormal) metabolized topically-delivered tenofovir. In contrast, beneficial Lactobacillus species, which are dominant in a vagina with healthy flora, did not metabolize tenofovir.
A pharmacokinetics study seemed to confirm these findings about vaginal flora and topically-delivered tenofovir (Hillier, abstract 86LB, http://www.croiwebcasts.org/console/player/33459?mediaType=slideVideo&). This analysis presented data from a study topically delivered tenofovir, as a film, which was used daily for a week. The authors found that with higher quantitative levels of Gardnerella vaginalis in the vagina that cervicovaginal fluid, cervical tissue, and plasma concentrations of tenofovir were reduced, and the reverse was true when concentrations of beneficial Lactobacillus species were higher. The findings were even true during one of the visits in the study, when a high dose (40 mg) of tenofovir was directly applied in the vaginal and concentrations were measured two hours later. These results are thus in agreement with the CAPRISA 004 findings - topically delivered tenofovir has its concentrations reduced, rapidly, when vaginal flora are abnormal. The results, however, did not directly speak to whether that reduction is enough to substantially reduce protection from HIV (because there was still tenofovir around). Nevertheless, they remind us, again, that HIV prevention products can be influenced by biology - and delivery approach, choice of antiretroviral, genital infections and other factors might impact the efficacy of topical and systemically-delivered prevention products. In contrast, an analysis of the effect of abnormal vaginal flora on oral PrEP efficacy found different results (Heffron, abstract 85, http://www.croiwebcasts.org/console/player/33458?mediaType=slideVideo&). Like the CAPRISA 004 analysis, this analysis used data from another large, randomized, placebo-controlled, efficacy trial of PrEP, the Partners PrEP Study, which evaluated FTC/TDF and TDF alone, definitively demonstrating in 2011 the efficacy of daily oral PrEP for HIV prevention in heterosexual men and women. The analysis presented at CROI 2017 assessed whether bacterial vaginosis, which was measured by Gram stain of vaginal fluid at baseline and throughout the trial, reduced the efficacy of PrEP for HIV prevention - it did not. A total of 1470 women were followed in the trial - 1/3 received placebo and the remainder PrEP (FTC/TDF or TDF). At entry into the study, 24% of women had bacterial vaginosis and another 12% had abnormal flora but not meeting full bacterial vaginosis criteria. Compared to placebo, PrEP protection against HIV was 73% (p=0.001) for women with normal flora and 77% (p=0.04) for women with bacterial vaginosis. A number of subanalyses - including for women with Lactobacillus-dominant flora and those with Gram stain evidence of Garnerella vaginalis - showed similar findings, i.e., no effect of abnormal flora to decrease PrEP's benefits. These data are extremely reassuring that oral PrEP has efficacy in women with (and without) abnormal flora, and that providing PrEP need to be predicated on testing or treatment for bacterial vaginosis. The results perhaps are not surprising, given that oral PrEP is absorbed systemically and thus shouldn't be massively compromised by the flora of the vagina, but they are important findings, given the global effort to increase PrEP access for women at risk, particularly in Africa where HIV risk is high in many settings and bacterial vaginosis is often common.
The integrase strand transfer inhibitor cabotegravir has been formulated as a long-acting injectable nanosuspension (CAB-LA) for potential use as both treatment and PrEP. This injectable formulation was protective in the macaque-challenge model and is currently being evaluated in an ongoing phase III trial in men who have sex with men (MSM). For all PrEP agents, the potential for resistance is a concern; in trials of oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for PrEP, resistance was rare and essentially exclusively related to initiation during undiagnosed HIV infection or infection occurring when drug concentrations dropped below protective levels. A macaque model of cabotegravir was evaluated for resistance to that putative PrEP agent, using an approach that mimicked PrEP initiation during acute infection (Gracia-Lerma, abstract 84, http://www.croiwebcasts.org/console/player/33457?mediaType=slideVideo&). In this study, CAB-LA was initiated in macaques who had been recently infected with SHIV but who had not yet seroconverted - a situation analogous to initiation of CAB-LA PrEP during acute HIV infection. Plasma, rectal, and vaginal viral replication was reduced while CAB-LA was present, not surprisingly. As cabotegravir levels dimished over time, the emergence of virus resistant to integrase inhibitors was observed with mutations including I72T, E92Q & G, A122T, Q124R, S135A, G140R, G188R, across different animals, some of which previously known to be associated with integrase resistance (G118R, E92Q, E92G). Some of these mutations were detected in virus isolated from rectal and vaginal fluid virus as well. These results are thus in line with FTC/TDF PrEP trial findings, where resistance can emerge in individuals initiated on PrEP during acute infection.
The dapivirine vaginal ring demonstrated efficacy for HIV prevention in two clinical trials at CROI in 2016. This year, a follow-on analysis from one of those studies (MTN-020/ASPIRE), assessed an important safety question, specifically the effect of ring use on contraceptive efficacy for pregnancy prevention (Balkus, abstract 88, http://www.croiwebcasts.org/console/player/33461?mediaType=slideVideo&). The analysis was motivated by analyses from HIV treatment populations that have suggested antagonistic drug-drug interactions between certain antiretrovirals (specifically, the NNRTI efavirenz) and certain contraceptives (particularly hormonal implants), with substantially reduced pregnancy prevention effects when the two are used together. Dapivirine is an NNRTI as well, and, while its topical delivery as a ring results in minimal systemic concentrations, it was important to assess whether any adverse effects occurred. In total, 2310 women were included in the analysis of this trial -half assigned to placebo and half to the active dapivirine ring. There were no substantial differences in pregnancy rates between those assigned placebo and those assigned the active ring, across a variety of contraceptives. Notably, for both active and placebo ring recipients, oral contraceptive pills provided substantially less pregnancy protection than other longer-acting methods, like implants. These results support the use of the dapivirine vaginal ring for women, including those choosing to contracept. This study, and others in the same vein - in women using and not using contraception, women who become pregnant or who are breastfeeding a child - are essential for demonstrating whether a new prevention tool, like the ring, can be safely used in populations. These kinds of studies must a priority for new PrEP interventions.
Finally, a fantastic Tuesday symposium focused on the intersection of STIs and HIV prevention, including the vaginal microbiome (http://www.croiwebcasts.org/console/player/33430?mediaType=slideVideo&), antibiotic prophylaxis (http://www.croiwebcasts.org/console/player/33431?mediaType=slideVideo&), syphilis control (http://www.croiwebcasts.org/console/player/33432?mediaType=slideVideo&), and point-of-care diagnostics (http://www.croiwebcasts.org/console/player/33433?mediaType=slideVideo&). Populations / Epidemiology and HIV Transmission
In the Tuesday oral abstract session, entitled "Hiding in plain sight: Discovering the undiagnosed and undertreated fraction," several presentations from the US CDC highlighted recent trends in HIV incidence and viral suppression in the US. Singh (abstract 30, http://www.croiwebcasts.org/console/player/33364?mediaType=slideVideo&) used a recently developed methodĀ for estimating HIV incidence between 2008 and 2014. Overall, incidence declined by 18%. There was a 36% decrease in heterosexuals and a 56% decline in people who inject drugs. MSM accounted for approximately 70% of new HIV infections; incidence did not decline for black MSM over this time frame, and increased among Latino MSM and among MSM aged 25-34 years, The overall 18% reduction in HIV incidence was substantially less than the national target of 25% reduction so work remains to reach HIV prevention and care efforts in the U.S. and to address health disparities, especially for gay and bisexual men of color and gay and bisexual men in young adulthood. A second presention (Crepasz, abstract 31, http://www.croiwebcasts.org/console/player/33365?mediaType=slideVideo&) reported on data among 630,965 people diagnosed with HIV in 2014 from 33 US jurisdictions. Three quarters of those with only one viral load measure in 2014 had viral suppression, and of the 54% who had two or more viral load tests in 2014, only half had durable viral suppression. Rates of durable viral suppression in 2014 were higher in males, whites than in Hispanics or blacks, and higher in MSM than other risk groups. 8% of people diagnosed with HIV in 2014 never achieved viral suppression, and an additional 32% with no viral load test in 2014 - probably did not have viral suppression. A third abstract (Buchacz, abstract 32, http://www.croiwebcasts.org/console/player/33366?mediaType=slideVideo&) reported a steady drop in the time HIV-infected persons spent above 1500 copies in the US, from 37% in 2000 to 10% in 2014. The analysis was from the HIV Outpatient Study (HOPS), and involved 5873 people with a median follow-up of 5.4 years. The group spent 86% of observation time on ART. Overall, the study group spent 24% of the observation period with a viral load above 1500. In addition to calendar year, the other factors that were independently associated with viral load >1500 were baseline viral load above 1500, baseline CD4 count below 350 (vs 500+), not on ART, age <50, public insurance, and black race. The decline in the proportion of time HIV-infected persons are viremic reflect improving antiretroviral regimens and fewer treatment interruptions.
From Uganda, data from the Rakai community cohort project assessed rollout of combination HIV prevention and its effects on HIV incidence (Grabowski, abstract 34LB, http://www.croiwebcasts.org/console/player/33368?mediaType=slideVideo&). Data were from 12 surveys in 30 communities from 1999 to 2016. Over the analysis period, 33,937 individuals participated in the cohort, including 17,870 HIV negative persons who contributed 94,427 person-years of follow-up and 931 incident HIV cases. ART was introduced in 2004 and by 2016 coverage was 69%. Increasing ART coverage was accompanied by significant changes in HIV viral load suppression, rising from 42% in 2009 to 75% by 2016 among all HIV positive persons. Scale-up of male circumcision was initiated in 2007, and coverage increased from 15% in 1999 to 60% in 2016, including an increase among non-Muslim men from 3.5% to 53%. The only substantive change in sexual behavior over the time period was in a delay sexual debut: the proportion of late adolescents (ages 15 to 19 years) who reported never having sex rose from 30% in 1999 to 55% in 2016. Self-reported condom use with non-marital partners remained steady at around 40% in men and 30% in women. Notably, HIV incidence significantly declined by 42% (from 1.16 to 0.66 per 100 person-years). HIV incidence declined more among males (54% reduction) than females (32% reduction), likely because of the direct benefit of circumcision and an indirect result of ART in HIV positive female partners. These results provide empiric evidence that HIV control efforts utilizing combination interventions can have a substantial population-level impact but that additional prevention interventions, such as PrEP, are needed to further drive down HIV incidence. From Namibia, data on HIV incidence from a surveillance study were presented (Nakanyala, presented by Patel, abstract 35, http://www.croiwebcasts.org/console/player/33369?mediaType=slideVideo&). Data were from home-based HIV testing in the Zambezi region, where HIV prevalence is high. From December 2014 to July 2015, 1,004 households were enrolled with 2,218 adults (66% participation), among whom 60% were female, 37% were ages 15-24 years, and 22% were HIV positive (63.9% previously diagnosed). HIV incidence among baseline-negative adults was measured by repeat rapid testing. One year later, repeat HIV testing of the 1,742 HIV negative identified 26 seroconversions in 1,970 person-years for a cluster-adjusted HIV incidence of 1.3% per year. Notably, the incidence was almost 3% in young women, again highlighting the need for primary prevention among young women in sub-Saharan Africa. Viral suppression at follow-up was 71% among HIV positive adults.
HIV Testing and Linkage to Care and Treatment as Prevention
HIV testing, linkage to care, initiation of ART, continued engagement in care, and viral suppression define the continuum that is key to maximizing the benefits of treatment as prevention. A number of studies were presented that suggest ways to improve the steps in this continuum.
A randomized trial of novel strategies to incentivize HIV testing among men in Uganda was presented (Chamie, abstract 33, http://www.croiwebcasts.org/console/player/33367?mediaType=slideVideo&). Four rural Ugandan parishes and enrolled men aged ≥18 years. Participants were randomized to 6 groups that received incentives of varying type and amount for HIV testing at a 13-day community health campaign in 2016. Incentive types were 1) gain-framed incentives (control) in which participants were told they would receive a small prize if they came for HIV testing; 2) loss-framed incentives in which participants were told they had won a small prize, shown the prize, and told they would lose the prize if they did not come for HIV testing; or 3) lotteries in which those who came for HIV testing had a chance to instantly win large prizes. Each incentive type had a low and high amount with a program cost per participant of about US$1 and $5. The primary outcome was HIV testing uptake at the community health campaign. Of the 2,530 men enrolled, a high proportion (76%) were tested for HIV with HIV prevalence of 7.6%. HIV testing uptake ranged from 72% in the low-cost, gain-framed incentive group to 80% in the low-cost, lottery incentive group. Although HIV testing uptake was higher in the two lottery groups (78%; p=0.08) and the two loss-framed groups (77%; p=0.22) than in the two gain-framed groups (74%), these differences were not statistically significant. Across incentive types, there was no significant difference in testing uptake in high- vs. low-cost groups. However, among participants in the low-cost groups, testing uptake was significantly higher in the lottery than the gain-framed incentive group (80% vs. 72%). Thus, low-cost, lottery-based incentives were significantly more effective in increasing HIV testing uptake among men than standard gain-framed incentives of comparable cost. Offering lottery-based rewards that have a low per-person cost is a promising way to achieve high HIV testing coverage among men. In a themed discussion on Wednesday ("HIV self-testing: Know thyself" http://www.croiwebcasts.org/console/player/33505?mediaType=slideVideo&), several abstracts on self-testing worldwide were presented.
From New York, data on the continuum of HIV self-test (HIVST) awareness, exposure and use in 2015-16 were presented, from prior to launch of an HIVST give-away program (Salcuni, abstract 891, http://www.croiwebcasts.org/console/player/33506?mediaType=slideVideo&). Of 1151 MSM surveyed, 85% were aware of HIVST but only half had seen one in a pharmacy and only 23% had used one. Persons with higher income and who had recently tested were more likely to be aware and to have used HIVST. From Kenya, data on a peer-led oral HIV self-testing program among MSM were presented (Saunders, abstract 893, http://www.croiwebcasts.org/console/player/33507?mediaType=slideVideo&). They compared the HIV prevalence and time to immediate ART initiation among newly diagnosed MSM during a 6-month period of clinic-based HIV testing and 3 months of oral HIVST led by trained lay counselors through a CBO through peer distribution. The rate of undiagnosed HIV infection was significantly higher (8.7% among the 337 MSM tested through the peer oral HIVST program compared to 3.5% among 690 MSM tested through the clinic. Encouragingly, they found high rates of MSM coming for confirmatory testing in the HIVST group and a trend towards higher same day ART initiation.
A second study from Kenya assessed the role of partner violence in women's ability to distribute self-tests to male partners (Schaffer, abstract 894, http://www.croiwebcasts.org/console/player/33508?mediaType=slideVideo&). Overall, 21% of 160 women reported a history of IPV in the prior 12 months, and women who experienced IPV were significantly less likely to report that their partner used HIVST and that couples self-testing occurred (90% and 87%, respectively). They recommend further research on secondary distribution of HIVST to reach male partners.
Finally, from Malawi, two abstracts informed HIVST services (Indravudh, abstract 895 and 896, http://www.croiwebcasts.org/console/player/33509?mediaType=slideVideo& and http://www.croiwebcasts.org/console/player/33510?mediaType=slideVideo&). The first was a in a discrete choice experiment were which indicated a preference for home access and low cost distribution by lay counselors with some level of post-test support beyond the instruction leaflet, and a preference for linkage services at home with a short waiting time. Men and those who had never tested were less averse to price, and those who had never tested had a stronger preference for home access and comprehensive linkage services. The second assessed user support for HIVST beyond instructions for use, which indicated high acceptability (86% self-tested), high accuracy (with a sensitivity of 93% and specificity of 99%), and feasibility (95% reported HIVST was easy to use), with the most common error of reading the results before the specified time in a small number of participants.
Linkage to and Engagement in Care
Lamb (abstract 110, http://www.croiwebcasts.org/console/player/33586?mediaType=slideVideo&) reported on a combination intervention strategy to address multiple barriers in HIV linkage and retention in Mozambique. The combination intervention included same day CD4 counts at the day of HIV diagnosis, point of diagnosis ART counseling with fast tracking for ART initiation, SMS messages to encourage linkage and retention, and appointment reminders. They also had a subset who also received financial incentives for linkage and retention with up to three $5 prepaid cell phone cards. The combination intervention increased linkage after diagnosis and retention at 12 months by 50-60% with the combination intervention. The improvement was primarily driven by significantly enhanced linkage rather than changes in retention. There was no additional benefit due to financial incentives.
In abstract 111, Steward http://www.croiwebcasts.org/console/player/33587?mediaType=slideVideo& reported on a RCT of peer navigation called I-CARE in South African primary clinics. The cluster RCT of I-CARE evaluated automated 2-way SMS reminders and peer navigators. SMS are simpler to implement but less flexible & less personal, whereas peer navigators are more complex to implement but more flexible and are a more personal source of support. The SMS message was "how are you?" and reminder messages and health promotion messages were also sent with biweekly phone and SMS contact. Peer navigators had a minimum of monthly in-person meetings, and accompanied patients to clinic appointments as needed. A total of 752 newly diagnosed HIV patients were enrolled and randomized to the SMS, peer navigator or standard of care arm. Half of the sample were recruited within 7 days of HIV diagnosis. Those who were in the peer navigator arm had increased retention at 12 months as well as being on ART. In analyses stratified by gender, the OR was 2.13 for women and 1.48 for men for retention at 12 months.
In (abstract 113, Hermanshttp://www.croiwebcasts.org/console/player/33589?mediaType=slideVideo&) presented on the increased risk of ART failure among a large cohort of South African patients based on low-level viremia. The threshold for virologic suppression depends on guidelines and sensitivity of assays; WHO guidelines use <1000 copies as viral suppression, and the concern is that persons with viral levels 50-1000 are kept on first line regimens, such as 2 NRTI and a NNRTI which has a low genetic barrier to resistance. In an observational cohort of almost 133,000 HIV patients in South Africa, low level viremia occurred in 12% of patients per year. In 60,000 patients that achieved VL<1000 on first line regimen, 27% achieved low level viremia and 14% developed virologic failure. The 26% of patients with low level viremia account for 38% of patients with subsequent virologic failure. The hazard ratio for subsequent virologic failure was associated with level of low level viremia: HR 2.2 for 50-199, copies, 3.8 for 200-399 copies, and 5.7 for those with 400-999 copies. In addition, the risk of subsequent virologic failure is higher for those with persistent low level viremia. In terms of considering implications for the sensitivity of point of care viral load assays which are being developed for low resource settings, clinical outcomes are also needed to determine whether this should inform WHO and other guidelines.
In abstract 114LB, Justman http://www.croiwebcasts.org/console/player/33590?mediaType=slideVideo& presented on the population HIV estimates (PHIA) from Zimbabwe, Malawi and Zambia. The primary objectives of these large national surveys were to estimate national HIV incidence among adults 15 years old and higher, and to estimate national and subnational prevalence of viral suppression. The teams conducted cross-sectional two-stage cluster samples to achieve nationally representative cohorts with about 30,000 adults and between 5,000-15,000 children. Blood was obtained to measure HIV RNA and DNA, LAg avidity EIA with recent infections defined as LAg <1.5 and viral load >1000. Of the almost 77000 participants from Zimbabwe, Malawi and Zambia, the combined HIV prevalence was 12% (9.8% in men and 14.4% in women). There was heterogeneity in the HIV epidemic within each country, and higher HIV prevalence of up to 22% in southern regions. 1.4% 0-10 yo prevalence and 1.8 in 10-14 year olds. The HIV incidence was 0.5 among 15-59 year-olds and was lower in men (0.3) than women (0.7). Viral load suppression was 62% (56% in men and 65% in women) with significant differences by gender in Zimbabwe and Malawi. 90-90-90 targets were 70%, 87% and 89% overall with a similar pattern across 3 countries. Awareness of HIV status (i.e., the 'first 90") remains a challenge with 30% of persons living with HIV unaware of status, and almost half of HIV-infected adolescents not aware of their status. These results highlight the need to keep the 'foot on the pedal' and targeted testing young adults and adolescents.
Voluntary medical male circumcision
The presentations about VMMC at CROI 2017 focused on uptake and risk compensation. In poster 982, Agot presented results from a cluster randomized controlled trial (cRCT) to evaluate tailored interventions to improve uptake of VMMC, we conducted a survey of men from the Luo, traditionally non-circumcising ethnic community who were aged 25-39 years to determine their circumcision status, estimated VMMC prevalence and predictors of being circumcised. Of the 5,639 in this analysis, 51% self-reported being circumcised. men aged 35-39 years with post-primary education, non-Christians and employed are more likely to be circumcised. The authors recommend that VMMC providers seeking to improve uptake among men aged 25-34 years should target men who are or were married, less educated and unemployed. In poster 983, Ortblad evaluated risk compensation using data from a population-based cohort study in KwaZulu-Natal, South Africa longitudinally from 2003 to 2014.
Self-reported circumcision status and sexual behavior was collected for all individuals annually, 2009-2014. Sexual behavior was measured as condom use at last sex, regular condom use, number of partners in the last 12 months, and number of concurrent partners. Of the 14,997 men who reported their circumcision status with a median age of 25, they found no evidence for risk compensation following circumcision and concluded that risk compensation is unlikely to reduce the impact of VMMC campaigns on population HIV incidence in real-world settings.
Similarly, in poster 984, Montano evaluated risk compensation as part of the Zimbabwean national VMMC campaign of a cohort of 2,379 HIV-negative men aged 18-40 in 2 urban areas in Zimbabwe, approximately half of whom were circumcised near recruitment time, and 1,183 were eligible for VMMC but declined it. Study group was significant for only 3 measures: circumcised men were more likely to have had a partner in past 6 and 12 months, and less likely to drink alcohol before sex. Over time, risk behavior increased in both groups including in the number of partners, multiple non-spousal partners, suspected partner had other partners, a partner of unknown HIV status, concurrent partners, lack of condom use with concurrent partners, and being drunk in the past 30 days. There was a significant decrease in using a condom at last sex, consistent condom use with their spouse, and recent STI diagnosis. Although no risk compensation was seen among circumcised men compared to uncircumcised men, this study coincided with increased availability of ART in Zimbabwe, and the increased risk behaviors over 12 months in both groups could be related to men viewing HIV as a chronic treatable condition.