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HIV Prevention at CROI 2019
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Conference on Retroviruses and Opportunistic Infections
Seattle, WA, USA
March 4-7, 2019
Jared Baeten, MD PhD
Connie Celum, MD MPH
University of Washington
CROI 2019 - held this year in a surprisingly sunny Seattle - 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 long been a major topic at CROI, with game-changing new options in prevention frequently being reported for the first time there. This year's CROI did not disappoint - there were important new prevention advances, many presentations on accelerating the prevention advances we have in our hands now, and then fantastic additional work addressing areas the relate to HIV prevention in the US and globally. 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.
HIV prevention in plenary sessions
CROI always has fantastic plenary sessions, and this year was no exception. Several this year were related to HIV prevention, including the opening session lectures: a special talk on the new Ending the HIV Epidemic plan for the US from the director of the National Institute of Allergy and Infectious Disease of the US National Institutes of Health (Fauci, http://www.croiwebcasts.org/console/player/41036?mediaType=slideVideo&), the Bernard Fields Lecture, which focused on broadly neutralizing antibodies as potential treatment and prevention tools (Nussenzweig, abstract 10, http://www.croiwebcasts.org/console/player/41037?mediaType=slideVideo&) and the N'Galy-Mann Lecture, which reflected on the HIV epidemic in Thailand (Phanuphak, abstract 11, http://www.croiwebcasts.org/console/player/41038?mediaType=slideVideo&). Morning plenary sessions that focused on HIV prevention included Tuesday's on sexually transmitted infections in the context of highly-effective HIV treatment and prevention (Marrazzo, abstract 12, http://www.croiwebcasts.org/console/player/41042?mediaType=slideVideo&) and Wednesday's on the use of phylogenetic methods for public health interventions (Oster, abstract 68, http://www.croiwebcasts.org/console/player/41159?mediaType=slideVideo&).
Pre-exposure prophylaxis (PrEP)
In PrEP, an HIV uninfected person uses an anti-HIV agent 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 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, and additional delivery approaches (e.g., implants) are in very early phase testing, all potentially heralding a future where multiple options exist for individuals to choose among for prevention.
A Wednesday morning oral abstract session addressed new options and opportunities for PrEP.
Three oral abstracts conducted evaluations of new PrEP agents in macaque challenge models. The first (Garber, abstract 100, http://www.croiwebcasts.org/console/player/41206?mediaType=slideVideo&) tested a combination of the broadly-neutralizing antibodies 10-1074 and 3BN117 in a penile and intravenous challenge model; these antibodies have previously been shown to provide protection in vaginal and rectal challenge studies in the macaque model. In this study, antibodies were provided as a single subcutaneous injection, and this injection provided protection against acquisition for a median of 15 weeks (penile challenge) and 5 weeks (intravenous challenge). Plasma levels associated with breakthrough infection were determined - i.e., as the single dose ran out - which should help determine target concentrations for human studies aimed at developing these antibodies for PrEP. The second (Dobard, abstract 101, http://www.croiwebcasts.org/console/player/41207?mediaType=slideVideo&) tested a rapidly-dissolving vaginal insert containing the antiretroviral combination of elvitegravir (EVG) and tenofovir alafenamide (TAF), inserted 4 hours prior to viral challenge. Animals receiving the active EVG/TAF insert, as opposed to a placebo insert, were highly protected against infection: 5/6 remained protected against HIV vs. only 1/8 (an estimated degree of protection of 92%). These results suggest that an on-demand, antiretroviral-containing vaginal insert could provide substantial HIV protection. Ongoing studies are testing whether the 4 hour window could be extended back to 24 hours prior to viral challenge or as late as 4 hours after challenge. The third abstract (Massud, abstract 102, http://www.croiwebcasts.org/console/player/41208?mediaType=slideVideo&) tested single-agent TAF against vaginal transmission, administered 24 hours prior and 2 hours after viral challenge. TAF alone was protective against HIV (estimated 73% compared to placebo); blood cell tenofovir concentrations were high and similar in animals that became versus did not become infected. These results highlight that TAF can provide moderate HIV protection but also the importance of defining HIV protection levels in blood samples and that emtricitabine (FTC) which is usually co-formulated with TAF for PrEP studies, appears to be important as well, perhaps boosting protection when TAF/tenofovir fails.
A pharmacokinetics study, this time in humans, explored tenofovir disoproxil fumarate (TDF) vs. TAF concentrations of tenofovir in lymph nodes, the primary site of HIV replication (Fletcher, abstract 103, http://www.croiwebcasts.org/console/player/41209?mediaType=slideVideo&). Tenofovir diphosphate (TFV-DP) concentrations in blood cells with TAF were 7-fold higher than with TDF; in lymph nodes 6-fold higher; and lower in the ileum and rectum, perhaps reflecting better absorption in the gut for TAF compared to TDF. These results provide interesting information about where in the body to target PrEP drugs for best effects.
The much-anticipated primary results of the DISCOVER trial - a very large clinical trial among MSM and transgender women which tested daily oral tenofovir alafenamide (TAF) in combination with FTC as PrEP - were presented (Hare, abstract 104LB, http://www.croiwebcasts.org/console/player/41210?mediaType=slideVideo&). TAF, which is used widely now for HIV treatment, achieves more rapid and higher intracellular levels of tenofovir in its phosphorylated form compared to TDF and has some evidence (through blood biomarkers) of better renal and bone effects than TDF. The design of DISCOVER was a randomized, non-inferiority trial - 5387 randomized from the US, Canada and Europe: 2693 to F/TDF and 2694 F/TAF. The primary endpoint was HIV acquisition, measured at the time of 100% completing 48 weeks of follow-up and 50% completing 96 weeks. The trial aimed to enroll MSM and transgender women at high risk for HIV, and the size of the trial was gauged based on HIV incidence in prior studies of PrEP among MSM. Overall, 83% remained on drug at the time of primary analysis. The median age was 34 years, and 74 transgender women participated; 24% were Latino and 16% were nonwhite. Only 22 infections occurred over 8756 person-years of follow-up: 7 among those on FTC/TAF (0.16% per year) and 15 among those on FTC/TDF (0.34% per year). The effect did establish noninferiority (but not superiority) of TAF compared to TDF. All 22 infections occurred in MSM: 5 occurred at the very first follow-up visit (likely occurring prior to study start), most of the rest had low PrEP drug levels, only 2 had medium/high drug levels. Resistance testing was available for 19 seroconversions - 4 had resistance to FTC, none to TDF/TAF. Tolerability was very high to both drugs. Bone density results showed a statistically significant effect - a slight increase in those on TAF and a slight decrease of those on TDF; similarly renal biomarkers showed better results for TAF - both of these are consistent with data already known for TAF from HIV treatment studies. Together, these results suggest that FTC/TAF is similarly effective to FTC/TDF (and maybe, just maybe, a tinge more so - perhaps because its intracellular concentrations persist longer than TDF, allowing it to potentially be more forgiving to missed dosing) as well as equally safe (if not a bit more so, in the long run). The HIV protection finding, however, is based on just 22 infections - the smallest number of any PrEP trial - nearly all of which seem to be failures to take the medication rather than failures of the medication itself. The very low HIV incidence in both arms of DISCOVER testifies to the protective power of oral PrEP with tenofovir-type medications, but it is essential for interpreting the findings to feel that HIV incidence would have been higher in the absence of PrEP. Along these lines, the DISCOVER investigators presented two pieces of additional data, suggesting HIV should have been higher if PrEP was not in the picture. First, STI rates were very high: gonorrhea at ~45% per year, chlamydia at 42% per year, and syphilis at 10% per year; these extraordinarily high rates were comparable between the two arms and suggest there should have been HIV exposures going on frequently. Second, due to a lack of a placebo arm, a counterfactual estimate, using CDC surveillance data, was done to try to explore what HIV incidence would have been in the US sites in the absence of PrEP - it was >4% per year, compared to the observed <0.4% per year. Like all models, this one has limitations - there are likely many characteristics that differ somewhat between persons who enrolled in DISCOVER and the general population of the cities where they come from, a model is never the same as true data, and importantly the model did not account for race or try to make equivalent the racial distribution of the DISCOVER and modeled groups - but nevertheless the model provides a broad picture that HIV transmission was still occurring in in the cities where the trial was done, but essentially not in the trial population itself. Overall, the results of DISCOVER provide compelling data that FTC/TAF can be an alternative to FTC/TDF as PrEP. In addition, the use of STI incidence and the counterfactual estimate provide ideas about novel and data-driven ways forward for evaluation of new PrEP agents in future PrEP trials.
Understanding how to identify good individuals at risk for HIV for prioritizing for PrEP is a priority. From California, data from a large heath care system's electronic health record were used to create a risk scoring prediction to flag individuals at risk for HIV who might be good candidates for PrEP (Marcus, abstract 105, http://www.croiwebcasts.org/console/player/41211?mediaType=slideVideo&). The approach incorporated a diversity of regularly-available data from clinical databases - demographics, social history, medications prescribed, diagnosis codes, laboratory orders and results, etc. Rigorous analytic techniques generated models which then were used to predict the probability of HIV diagnosis within 3 years for each patient. The final model contained 44 variables and had high predictive capacity (C-statistic of 0.86, which is quite excellent). The full model flagged 2.2% of the patient population as PrEP candidates and identified 46% of new HIV cases in men and performed much better than more simple flags (e.g., just based on having an STI). The model performed poorly for women. Overall, this kind of electronic health record approach can flag individuals at high risk for HIV who might be good candidates for PrEP - exactly what busy primary care providers might need to increase PrEP access and use.
The CDC presented data on PrEP persistence using data from 2012-2016 (Huang, abstract 106, http://www.croiwebcasts.org/console/player/41212?mediaType=slideVideo&). Data came from two large databases, one commercial (>100 large companies) and a second from Medicaid (just a small subset of the national Medicaid program). Individuals were restricted to those enrolled in the health plan for at least 6 months before and after their first prescription date. Persistence was assessment from first prescription until a break of 30 days. A total of 7250 commercial users were included and 349 Medicaid users. Median persistence was 14.5 months for the commercial users and 7.6 months for the Medicaid users; 56% and 34% at 12 months respectively. Men had higher persistence than women, in both groups. Persistence was higher for older persons (20.5 months for those aged 45-54). In the Medicaid cohort, white users had greater persistence than black users. Of course, risk behavior data were not available for this pharmacy refill database - undoubtedly some individuals who stopped PrEP did so because of a change in risk behavior. In any case, these results give one approach and result to understand continuous persistence with PrEP refills.
A Thursday themed poster discussion called "PrEP in fits and starts" focused on different aspects of PrEP delivery.
Two abstracts looked at kidney function in the context of TDF-based PrEP. The first (Liegeon, abstract 960, http://www.croiwebcasts.org/console/player/41342?mediaType=slideVideo&) reported on the mean decline in kidney function with on-demand PrEP in the IPERGAY study. The mean estimated glomerular filtration rate at enrollment was 106 ml/min. The median number of FTC-TDF or placebo tablets was 15 per month. The mean decline in eGFR in the TDF-FTC group was -01.53 compared to -0.88 ml/min in the placebo arm and was not statistically significant (p=0.27). The slope of decline in eGFR was not greater in MSM >40 years or those with eGFR <90 ml/min at enrollment. There was a dose response with tenofovir exposure and eGFR, based on taking >15 FTC/TDF tablets per month in the prior 2 months as well as with a higher plasma tenovoir level. The authors concluded that the renal safety of on-demand PrEP was excellent and that the relative decrease in eGFR was not clinically significant and only 2 men had persistent declines in eGFR. The second (Pintye, abstract 961, http://www.croiwebcasts.org/console/player/41343?mediaType=slideVideo&) reported on the use of a point of care creatinine test which facilitated PrEP delivery within maternal child health and antenatal care settings in Kenya. Only 8 of 4007 women had an estimated creatinine clearance <50 mL/min, strongly suggesting that creatinine testing may not really be mandatory for large public health PrEP delivery programs. The cost of the point of care creatinine testing was $4.50 per test.
From New York, an abstract (Mikati, abstract 962, http://www.croiwebcasts.org/console/player/41344?mediaType=slideVideo&) described immediate initiation of PrEP (iPrEP) versus delaying start of PrEP for acute HIV symptoms, history of acute hepatitis B or renal disease (dPrEP); reasons for dPrEP were. Of 1437 persons in NYC sexual health clinics evaluated for PrEP, the median age was 28 and 1387 (97%) qualified for iPrEP and 50 (3%) for dPrEP. Those in the dPrEP were less likely to start (35%) and more likely to discontinue PrEP. Notably, only 4 iPrEP ppts were subsequently stopped due to contraindications (e.g., discovered by laboratory testing that returned after immediate PrEP was started). Another presentation assessed PrEP uptake and persistence among young black MSM (Serota, abstract 963, http://www.croiwebcasts.org/console/player/41345?mediaType=slideVideo&) in Atlanta. 298 HIV-negative black MSM ages 16-20 were offered PrEP at each visit, although PrEP was not advertised as a feature of study. Of 125 BMSM who started PrEP, 69% of their follow up time (person-time) was on PrEP. The median time to first PrEP discontinuation was 219 days. Most men who discontinued PrEP restarted, sometimes multiple times. Factors associated with increased risk of PrEP discontinuation included young age (<22), marijuana use, an STI diagnosis, and <3 anal sex partners. The authors suggested that on-demand PrEP may be a good option for MSM who discontinue PrEP. Lastly, from Kenya (Oluoch, abstract 964, http://www.croiwebcasts.org/console/player/41346?mediaType=slideVideo&), a report about low (5.4%) PrEP uptake among a cohort of adolescent girls with a median age of 18 who were either sexual naïve or only had 1 lifetime partner. Girls were offered PrEP based on a risk score that indicated 168 of 400 AGYW were eligible for PrEP, of whom 26 (15%) had an STI and 9 (5.4%) accepted PrEP. The authors recommended greater PrEP awareness campaigns for young African women.
Two Thursday symposia addressed PrEP issues. One talk focused on challenging cases in PrEP - including resistance, false negative and false positive HIV test results (Molina, abstract 160, http://www.croiwebcasts.org/console/player/41366?mediaType=slideVideo&). Other talks addressed the prevention challenges for young African women (Delany-Moretlwe, abstract 163, http://www.croiwebcasts.org/console/player/41372?mediaType=slideVideo&) and young transgender persons (Radix, abstract 162, http://www.croiwebcasts.org/console/player/41371?mediaType=slideVideo&).
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 sessions focused on HIV testing: including strategies to improve the steps in the testing-to-viral suppression continuum and understanding the impact of universal testing and treatment on population-level HIV incidence.
The long-awaited PopART trial results were reported at this year's CROI (Hayes, abstract 92LB, http://www.croiwebcasts.org/console/player/41195?mediaType=slideVideo&). PopART looked at universal testing and treatment (UTT) on HIV incidence in South Africa and Zambia. The trial used a community-randomized design, with communities assigned to one of three groups: Arm A was the full PopART intervention which focused on house-to-house HIV testing of the community, immediate linkage to treatment, and ART regardless of CD4 count; Arm B was similar to Arm A except ART was provided according to national guidelines (which were to delay initiation until CD4 decline early in the PopART trial but then expanded to ART at all CD4 counts fairly early in the trial), and Arm C was standard of care HIV testing and ART provision. To measure the impact of the intervention, a random sample from each community was enrolled into a parallel cohort, and HIV incidence was measured between Month 12 and Month 36 of follow-up (which was between 2015 and 2018). The total population of the communities was about 1 million persons. While PopART focused principally on UTT, the door-to-door intervention (in Arms A and B) included referral for medical male circumcision, services for prevention of mother-to-child transmission of HIV, and treatment of sexually transmitted infections and tuberculosis. The cohorts were heavily (~70%) weighted towards women and follow-up in the cohorts was about 70%. The intervention was successful in delivering ART: treatment coverage was about 80% in Arms A and B by the end of follow-up and viral suppression was about 70% in Arms A and B, a bit higher than Arm C (60%). However, HIV incidence did not exactly map to the intervention delivery - when Arm B was compared to Arm C, HIV incidence was lower, by about 30% (1.06% incidence per year versus 1.55%, p=0.006), but Arm A, the full intervention of the trial, was not statistically different than Arm C (7% incidence difference, 1.45% versus 1.55%, p=0.5). In summary, PopART was able to achieve the first two 90s of the UNAIDS 90:90:90 and came close in the third 90. Arm B had a modest effect on HIV incidence, but not the more robust Arm A package, a finding that is perplexing. Four UTT trials have now been done, with varying results - two found no difference between UTT and standard HIV testing and treatment, one found a modest effect, and PopART found something between. The take-away from these studies seems to be that good access to HIV testing, indeed universal, with linkage to ART is absolutely necessary but also sadly insufficient to substantially drive down HIV incidence. For all trials, HIV incidence in all arms, including the intervention arms, was much, much higher than needed for HIV epidemic control, emphasizing how UTT needs to be combined with other prevention strategies to achieve the prevention impact globally needed.
One of the prior UTT trials (Makhema et al., AIDS2018), the Ya Tsie study done in Botswana (which showed a modest 30% reduction in HIV with UTT compared to standard of care), reported intervention coverage at CROI 2019 (Wirth, abstract 95, http://www.croiwebcasts.org/console/player/41198?mediaType=slideVideo&). The trial found that HIV diagnoses, ART coverage, and viral suppression all were very high in both arms, higher in the intervention arm; modest levels of male circumcision also occurred. In the end of the trial, 88% of all HIV-infected persons were on ART and virally suppressed. These results emphasize that it is possible to achieve very high levels of treatment coverage.
From Mozambique, a demographic surveillance population study found declining HIV incidence in recent years with increasing ART use (MacKellar, abstract 98, http://www.croiwebcasts.org/console/player/41201?mediaType=slideVideo&). The work began in 2014 and follow-up was reported through 2017; in 2016, ART guidelines recommended universal treatment. The intervention included home-based HIV testing and linkage, done by lay counselors, and improvement in ART services. Each year, a random 10-20% household survey was done to explore viral suppression in persons with HIV and recent HIV infection through a laboratory assay that has been correlated with new infection (LAg-Avidity). Across the surveys, 55-60% participated. HIV diagnoses improved over time, from 67% in 2014 to 88% in 2017; younger persons (under 30) were less likely to be HIV diagnosed. ART use also increased, from 60% to 79% overall - lower in men and younger persons. Viral suppression was 66% in 2017. By the LAg-Avidity assay, HIV incidence appeared to have declined by ~50% over the follow-up period. These encouraging, population-based results, although not from a rigorous trial, emphasize that access to testing and treatment services does make a difference.
Index HIV self-testing (HIVST) of partners of ART clients may be a high yield way to identify persons who are not aware they are HIV-positive or in an HIV serodiscordant partnership. HIVST may help with barriers to disclosure and stigma. A non-blinded randomized trial of secondary distribution of HIVST or referral slips from HIV positive persons in ART programs was done in 3 district hospitals in Malawi from March 2018-Jan 2019 (Dovel, abstract 93, http://www.croiwebcasts.org/console/player/41196?mediaType=slideVideo&). The primary outcome was known HIV status and secondary outcomes were HIV positivity rates in partners, ART initiation at 6 months, and social harms and AEs. 365 ART clients completed the follow-up survey (75% retention), and 161 partners completed a follow up survey (62% response). Over 90% of index ART cases reported distributing HIVST or the referral slips. The HIV positivity rate was 16% in the SOC and 19% in the HIVST arm; however only 20% of persons with a reactive HIVST had confirmatory testing. Although no social harms were reported, linkage to care was low (3 of 4 HIV positive male partners in SOC and 6 of 27 in the HIVST arm initiated ART). A majority indicated that they needed help from their partner (the index ART client) to use HIVST and had difficulty with interpretation.
It has been challenging to reach the UNAIDS 90:90:90 targets for HIV positive men; encouragingly, a study from Kenya and Uganda (Kamya, abstract 138, http://www.croiwebcasts.org/console/player/41307?mediaType=slideVideo&) reported a faster initiation of ART among HIV positive persons with CD4 <350 and a 40% greater mortality benefit among HIV positive men. Data were from the SEARCH trial, which was a multi-disease community health fair and home testing intervention in western Kenya and eastern Uganda. However, a poster from SEARCH (Chamie, abstract 896) reported that coverage of HIV testing was low (16%) among key populations, of whom 19-28% of HIV positive key populations were out of care and required additional outreach.
From South Africa, a 2x2 factorial design trial randomized men to financial incentives and/or an a tablet-based decision-support application to assess HIV testing uptake (Kim, abstract 54LB, http://www.croiwebcasts.org/console/player/41098?mediaType=slideVideo&). The financial incentive was a R50/$30 food voucher conditional on home-based HIV testing; the EPIC-HIV decision support application was developed for a tablet format and offered only to men, exploring reasons why men might / might not want to be tested and seek care. Individuals were 15+ years of age (median 29 years), from rural KwaZulu-Natal. In total, financial incentives increased (by 55%) the likelihood of home-based HIV testing (from ~17-18% to ~27-28% at the population level but closer to 70% among those with whom the study actually made direct contact). The decision-support app did not increase HIV testing. In sum, a micro-incentive can increase HIV testing for men.
A fantastic symposium on U=U (undetectable=untransmittable) on Wednesday afternoon covered the scientific underpinnings (http://www.croiwebcasts.org/console/player/41273?mediaType=slideVideo&), clinical aspects (http://www.croiwebcasts.org/console/player/41274?mediaType=slideVideo&), community perceptions (http://www.croiwebcasts.org/console/player/41275?mediaType=slideVideo&), and public health implications http://www.croiwebcasts.org/console/player/41276?mediaType=slideVideo&). The session was great and the world cannot amplify enough the important U=U message.
Adherence monitoring
Adherence is essential to the efficacy of both PrEP ART. In a Tuesday themed poster discussion on ART and PrEP monitoring, several studies were presented about tenofovir-based assays to monitor PrEP and ART adherence. A directly-observed therapy study of escalating FTC/TAF dosing to determine the corresponding thresholds for tenofovir diphosphate intracellular levels in dried blood spots (DBS) corresponding to previously established levels with TDF-FTC dosing (Yager, abstract 483, http://www.croiwebcasts.org/console/player/41117?mediaType=slideVideo&). DBS showed dose-proportional concentrations with TAF-FTC dosing, suggesting that DBS could be useful for the interpretation of the DISCOVER trial results of TDF-FTC and TAF-FTC for PrEP. There has been a call for point-of care assays for monitoring tenofovir-based PrEP, data on an urine-based antibody assay to tenofovir were presented (Gandhi. abstract 0464, http://www.croiwebcasts.org/console/player/41118?mediaType=slideVideo&). The assay was developed using urine samples from a directly-observed therapy study with 30 HIV- patients taking TDF/FTC DOT 2, 4 or 7 doses per week. A cut-off of 1500 ng/ml correctly classified 98% of persons who took a dose 24 hrs previously as adherent. In comparing the urine TFV level by tandem LC-MS to ELISA, the urine assay was found to be 99% sensitive and 94% specific. The urine antibody is being developed into a lateral flow immunoassay in collaboration with Alere, with results available in 5 minutes. Clinical studies of a POC assay of recent TDF use are needed to determine the utility of counseling about recent PrEP and ART adherence. Lastly, another urine assay to evaluate adherence to ART (TAF/FTC/CBOI/EVG) or PrEP with TAF or TDF/FTC based on single dose PK followed by 4 and 10 days of daily oral dosing was reported (Haaland, abstract 0465, http://www.croiwebcasts.org/console/player/41119?mediaType=slideVideo&). Urine FTC correlated with plasma FTC levels but urine TFV concentrations did not correlate with plasma TFV and need to be further evaluated.
Sexually transmitted infections
A number of talks addressed the intersection of HIV and STIs. An excellent plenary session (Marrazzo, noted above) covered the challenges and opportunities for addressing rising STI rates in the US (and globally) that have been seen in recent years, coincident with the roll-out of effective antiretroviral treatment and prevention.
One abstract (Dionne-Odom, abstract 47, http://www.croiwebcasts.org/console/player/41091?mediaType=slideVideo&) used data from a national consortium of HIV care clinics based at several Centers for AIDS Research (CFARs, and specifically the CNICS cohort) to assess syphilis incidence in HIV-infected women, between 2005 and 2016. While there have been a considerable amount of data demonstrating rising syphilis rates in men who have sex with men in various cities in the US and globally, data for women have been more limited; in addition, of course, syphilis in women risks the potential for congenital syphilis if they become pregnant. This analysis among women found that incident syphilis occurred at a rate of 760 cases per 100,000 person-years, compared to an expected 2.3 cases per 100,000 in the general population of women in the US. Syphilis was associated with black race (OR 2.2, p<0.01), injection drug use (OR 2.2, p<0.01), and hepatitis C coinfection (OR 1.9, p=0.02). Thus from this nationally representative sample of women seeking HIV care, syphilis incidence was high and there was high intersectionality with the US drug use epidemic.
From London, data on STI rates over the past decade were presented, based on national surveillance data from men who have sex with men attending sexual health clinics (Ogaz, abstract 48, http://www.croiwebcasts.org/console/player/41092?mediaType=slideVideo&). Since 2012, gonorrhea and chlamydia diagnoses have risen nearly two-fold, with syphilis more than doubling. Of 128,000 men attending sexual health clinics in 2017, 12% had gonorrhea, 9% chlamydia, and 2% syphilis. PrEP use has also increased, somewhat lagging the start of the increase in STIs. Thus, in spite of STI increases, new HIV diagnoses have fallen starting in 2014 and continuing further into 2017: with an estimated HIV incidence of 1.9% per year in 2012/13, 1.8% per year in 2014/5, and 0.8% per year in 2016/7; similar magnitude of decrease was seen when restricting to higher-risk MSM. In summary, in the UK, there has been an increasing number of bacterial STIs since 2012 and sharp decrease in HIV, coincident with expanding PrEP use. These data serve as an important baseline as PrEP use continues to expand.
From Paris, a project using postal delivery of STI (and HIV) tests was reported (Delagreverie, abstract 49, http://www.croiwebcasts.org/console/player/41093?mediaType=slideVideo&). This novel idea was advertised by banners on dating apps and social media, then sent, by routine post, testing kits that included HIV, HCV, HBV, syphilis, gonorrhea, and chlamydia (the last two from urine, rectal swab, and throat swab). The target group was HIV-negative MSM aged 18 and older. In just 7 weeks, 2051 people ordered a kit, 1188 (58%) returned samples, nearly all of whom sent complete samples. The average age was 30 years with a median of 10 partners in the prior year and 48% of men had been tested for STIs in the past year. Positive results were present for 1.3% of HIV samples (n=13, 7 of whom were unaware of their HIV status), 0.5% for HCV, 0.4% for HBV, 1.7% for syphilis, 9.6% for chlamydia (the majority rectal infections), and 11.7% for gonorrhea (majority throat or rectal). Most individuals preferred email, phone call, or text communication of results. In summary, STI home self-testing was very attractive to young, educated men who were at high risk for STIs, and sampling was very feasible.
Contraception
The interface of contraceptive use with HIV, both from a treatment and a prevention perspective.
A randomized, safety trial of two different intrauterine devices among women living with HIV was reported (Todd, abstract 50, http://www.croiwebcasts.org/console/player/41094?mediaType=slideVideo&). For women with HIV, contraceptive coverage is often much lower than desired, and contraceptive choices can be limited by provider perceptions about what is safe for women living with HIV. The trial was a double-blind, randomized trial, done between 2015 and 2017. Following screening, women were randomized in a 1:1 fashion to copper or levonorgestrel IUDs. In total, 199 women were enrolled and followed, of whom 132 were using ART at the time of study initiation, although 20% had detectable plasma viral load at the time of enrollment. During follow-up (at 6 months and then up to 24 months), there was no difference in safety between the arms, nor in plasma viral load levels. Approximately 75% used their IUD through 24 months, greater for the hormonal IUD compared to the copper version, with more dysmenorrhea side effects for the copper group. There were very low rates of pregnancies or complications, as expected. In summary, both copper and levonorgestrel IUDs were safe in women with HIV, impacting neither genital nor plasma viral levels, high continuation rates, and very low complication frequencies.
For women living with HIV, one tricky issue in the last few years has been evidence of a drug-drug interaction between levonorgestrel (LNG) implants for contraception and concurrent use of efavirenz for HIV treatment, with efavirenz resulting in lowering LNG levels, sometimes below levels needed for contraception. Trying to overcome this interaction, a double-dose LNG implant trial was done (i.e., rather than one set of implants, two, one in each arm), among women taking stable efavirenz treatment (Scarsi, abstract 51, http://www.croiwebcasts.org/console/player/41095?mediaType=slideVideo&). Follow-up was through 48 weeks. Notably, the double-dose LNG improved but did not fully correct the lower LNG blood levels among women taking efavirenz: overall, LNG blood levels were 33-44% lower in women receiving double-dose LNG implants who were also taking efavirenz, when compared to women on a single implant and not on efavirenz; this effect was less than the single implant plus efavirenz (57% lower). Using an LNG blood cut-off of ≤303 pg/mL, which has been associated with contraceptive efficacy, fewer women in the double- vs standard-dose group (46% vs 90%, respectively; p=0.002) were impacted. This drug-drug interaction will continue to be a topic of pharmacology and public health research going forward.
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