HIV Prevention at CROI 2021. NATAP Report by Renee Heffron, PhD and Connie Celum, MD, University of Washington
CROI 2021 was held virtually and was highly successful in terms of the quality of the plenaries, oral abstract sessions, and the use of Science Spotlights to make the poster sessions interactive in a virtual context. The Young Investigator Workshop presentation by Dr. Molina about biomedical HIV prevention (https://www.vcroi2021.org/sessions/19762720/subsession/25640268/ADVANCES-IN-BIOMEDICAL-PREVENTION-OF-HIV) and the plenary by Dr. Bekker about long-acting PrEP were outstanding. In addition, Dr. Hildreth's plenary about health disparities is highly relevant to gaps in HIV prevention and PrEP access (https://www.vcroi2021.org/sessions/19762730/subsession/25640306/DISPARITIES-IN-HEALTH-FROM-HIV-TO-COVID-19-AND-BEYOND). A major focus of the prevention topics was on ongoing experience and lessons in the delivery of oral PrEP. A highly informative symposium discussed what PrEP delivers (https://www.vcroi2021.org/sessions/19762742/WHAT-DOES-PrEP-DELIVER). A great debate was held between Drs. Irungu and Dybul called "PrEP Scale-Up to Meet UNAIDS 2030 Goals: Is it Possible?" which highlighted some of the challenges and success with oral PrEP scale up. In addition, on the heels of exciting news of the high efficacy of injectable cabotegravir in cis-gender women and cis- and trans gender men, there were important new data presented on breakthrough infections with injectable cabotegravir. In addition, promising data were presented about the PK of islatravir dosed monthly or through an implant, and the new capsid inhibitor, lenacapavir. There were also exciting HIV prevention findings related to HIV epidemiology, PMTCT, and STIs, all of which are summarized in this report. |
Oral PrEP use and impact in France
Dr. Molina presented on the ANRS Prevenir study, which is an ongoing prospective cohort study enrolling individuals at high risk for HIV infection on PrEP. MSM could opt for either daily or on-demand PrEP with TDF/FTC. The main objective was to assess the overall HIV incidence in the study and per dosing regimen, as well as incidence of bacterial STIs (including syphilis, gonorrhoea, chlamydia and Mycoplasma genitalium) and viral hepatitis. From May 2017 to March 2019, 3067 subjects were enrolled across 22 sites in the Paris region, 44% being PrEP naïve with a median age of 36 years and 98.5% were MSM. At enrollment, PrEP was used daily and on demand by 50.5% and 49.5% of participants, respectively. The median number of partners in the prior 3 months was 10 and the median number of condomless sex events in the prior 4 weeks was 2. The median follow-up was 22 months with 5633 person-years of follow-up and an overall HIV incidence of 0.11 per 100 PY. Six participants (3 daily, 3 on demand) acquired HIV-infection during the study period (p=0.99). The STI incidence was 73 per 100 person year which remained stable during follow-up (except during the COVID-19 lockdown when it dropped to 32.4 per 100 PY). HCV incidence was 0.69 per 100 PY. Thus, in this PrEP cohort of mainly MSM at high risk of HIV-acquisition in Paris, HIV incidence was low whether participants used daily or on demand PrEP. There was a high incidence of bacterial STIs and HCV infection despite a drop in STI incidence during the COVID-19 lockdown.
In a Science Spotlight, Tassi presented on the nationwide roll-out of PrEP in France using the national database which included 9,893 individuals initiating PrEP, of which 99% were men with a median age of 36 years, and 15,313 person-years of follow-up. The median number of PrEP dispensations was 9, and 64% had HIV testing one month after initiation and 81% for quarterly HIV testing (https://www.vcroi2021.org/sessions/19764918/subsession/25642347/PrEP-EFFICACY-OVER-THE-FIRST-3-YEARS-OF-IMPLEMENTATION-IN-FRANCE-A-NATIONWIDE-STUDY). They identified 29 diagnoses of incident HIV infection for an HIV incidence rate of 0.19%. 18 HIV seroconverberters who used PrEP were identified more than 3 months after PrEP initiation at a median duration between last PrEP dispensation and HIV diagnosis of 180 days. Those who did not refill PrEP had a 4.7-fold higher risk of HIV acquisition.
PrEP disparities in the US
In the US, Rao reported on the uptake of PrEP among Black partners of persons living with HIV from 48 of 60 US health departments which reported data in 2019 on current PrEP use or referral to PrEP providers among HIV-negative partners of PWH (https://www.vcroi2021.org/sessions/19764918/subsession/25642351/PrEP-USE-AND-REFERRAL-BLACK-PARTNERS-OF-PEOPLE-WITH-HIV-IN-PARTNER-SERVICES-2019) . Partner serivice programs identified 710 HIV-negative Black partners of people with HIV, 52 (7.3%) reported taking PrEP at the time of contact with Partner Service programs. Notably, Black partners living in the South were much less likely (aPR=0.25) to have been referred to PrEP providers than in other regions. That observation and that only half of Black partners of PWH were on PrEP indicate that partner service programs need to identify and remove barriers to improve PrEP uptake among Blacks at risk for HIV infection.
Breakthrough infections with current HIV diagnostic tests during FTC/TDF PrEP and injectable cabotegravir
The sensitivity of current HIV diagnostic tests during PrEP use and acute HIV infection was summarized by Colby (https://www.vcroi2021.org/live-stream/19762759/INNOVATIONS-AND-CHALLENGES-IN-TESTING-PREVENTION-AND-CARE) . The data came from the Thai Red Cross RV254 cohort with real-time pooled RNA testing of blood donors with Aptima testing and immediate ART offering, and the PrEP-15 program with monthly PrEP out of pocket for $15. Eight of 415 individuals were identified with acute HIV infection, of whom 6 were enrolled in the AHI cohort, and immediately switched to ART with triple drugs. In Week 0, three of these 6 had reactive 2nd or 3rd generation tests. At week 24, five of the 6 had reactive tests, and the most sensitive test was the 3rd generation test. One individual who only took PrEP for 2 days had a low RNA max of 276 and immediately started ART and never had a reactive test. Those who were on PrEP longer had higher reactivity on serologic tests. The 4th generation test was only reactive in 1 of 3. In summary, the 4th generation test was the least sensitive and the 3rd generation test was most sensitive among 5 of 6 who seroconverted by 24 weeks. These data highlight that standard serologic testing and algorithms may not confirm HIV infection when PrEP and/or ART is started early in acute HIV infection, and it is important to use nucleic acid testing to help identify acute HIV infection in such persons.
A highly publicized oral presentation by Landovitz featured breakthrough infections on the injectable cabotegravir (CAB-LA) and oral emtricitabine- tenofovir (FTC-TDF) arms in HPTN 083 (https://www.vcroi2021.org/sessions/19762746/subsession/25643425/LABORATORY-ANALYSIS-OF-HIV-INFECTIONS-IN-HPTN-083-INJECTABLE-CAB-FOR-P). HPTN 083 was a phase 2b/3 randomized, double-blind clinical trial that enrolled more than 4,500 transgender women and cisgender men who have sex with men (MSM) at 43 sites in Africa, Asia, Latin America and the United States. In the primary results of HPTN 083, 12 incident and four baseline infections occurred in the cabotegravir arm of the study (0.37 infections per 100 person-years) compared to 39 incident and three baseline infections in the FTC/TDF arm (1.22 infections per 100 person-years). In the CAB-LA arm, four incident HIV infections were delayed in detection using standard HIV testing; additional laboratory testing of samples identified their infections between 6 and 17 weeks earlier than by site testing with standard testing. Two of the four participants who acquired HIV despite on-time cabotegravir injections developed integrase inhibitor resistance-associated mutations, and the other two did not have samples with sufficient levels of virus for genotypic testing before they were started on ART. All four participants had expected concentrations of cabotegravir in their blood plasma. In contrast, 37 of 39 incident infections that occurred among participants taking FTC/TDF in HPTN 083 were attributed to nonadherence. The added testing resulted in minor updates to the primary results of the trial but no change in the overall interpretation that long-acting cabotegravir was superior to daily oral PrEP for HIV prevention. Reassuringly given the concerns about the long 'tail' of CAB-LA, none of the three participants infected during the tail phase of the study developed integrase inhibitor resistance. Notably, five of the 12 incident infections on CAB-LA demonstrated integrase inhibitor resistance with Q148K and E138K integrase strand transfer inhibitor (INSTI) mutations in one, Q148R, L74I, E138K and G140S INSTI mutations in the second; Q148R and E138A in the third; a R263K INSTI mutation in the fourth; and Q148R and G140A mutations in the fifth. Phenotypic susceptibility testing was performed on some of these breakthrough infections, and darunavir/ritonavir with two nucleoside/nucleotide reverse transcriptase inhibitors was used as the treatment for these breakthrough infections. The key implications of these findings are that diagnostic testing for CAB-LA users in implementation of this highly effective long-acting PrEP may require HIV RNA testing at initiation of cabotegravir (which will be examined in the open label extension to HPTN 083) and that evolution of INSTI resistance in breakthrough infections with cabotegravir occurs and must be carefully evaluated during rollout.
PrEP in pregnancy and postpartum
PrEP is an important intervention for pregnant and postpartum periods during which the risk of HIV acquisition is increased several fold. Joseph-Davies presented on the important topic of PrEP during PrEP in pregnant and postpartum women and findings from the PrEP-PP study, an ongoing prospective cohort of 759 pregnant, HIV-uninfected women at their first antenatal care (ANC) visit in Cape Town. South Africa (https://www.vcroi2021.org/sessions/19762746/subsession/25640406/IMPACT-OF-COMMON-SIDE-EFFECTS-ON-PrEP-PERSISTENCE-DURING-PREGNANCY-IN-SOUTH-AFRICA). In this cohort of pregnant women with a median age of 26 years and median gestation of 21 weeks at enrollment, 91% initiated PrEP at their first antenatal visit, and 73% of women on PrEP returned for a repeat prescription at 1 month, and 62% returned at 3 months. Among those returning at 3 months, 85% reported adhering to PrEP. Adherence was poorer with women who came in later in their pregnancy (>20 weeks) for their first ANC visit, or had lower education (completed primary vs. secondary school) (p<0.05). Almost one-third of women on PrEP reported side effects at their 1 month follow-up, primarily nausea and/or vomiting (22%), dizziness (25%), and headache (8%). Women on PrEP in the 1st or 2nd trimester had a 2.6 higher likelihood (odds) of reporting side effects compared to postpartum women, after adjusting for age, gestation and time in study. Women who reported side effects at 1 month were half as likely to persist with PrEP and report high adherence at 3 months, compared to women who did not report side effects (aOR=0.50), adjusting for age, gestational age, and the time in study. In a study which focused on pregnant and postpartum women that was presented by Pintye in a Science Spotlight, similar proportions of Kenyan women had TFV-levels indicating >4 PrEP doses/week use based on measurements of tenofovir in hair during pregnancy and postpartum periods. The analyses indicate that hair measurement for PrEP use may not need to be adjusted for PK differences in the perinatal period. Abstract 710. https://www.vcroi2021.org/sessions/19764938/subsession/25642458/TENOFOVIR-HAIR-LEVELS-SIMILAR-AMONG-PREGNANT-AND-POSTPARTUM-PrEP-USERS
PrEP and transgender populations
Given small numbers of transgender women and men who have participated in oral PrEP trials, more information about potential interactions between PrEP and gender-affirming hormone therapy is needed (GAHT) (https://www.vcroi2021.org/sessions/19764889/subsession/25642170/EXOGENOUS-HORMONE-PHARMACOKINETICS-IN-TRANSGENDER-ADOLESCENTS-RECEIVING-ORAL-TDFFTC). Yager presented data from two studies which enrolled young trans people aged 16+ who had been on GAHT for at least a month, half of whom were trans-women taking estrogen and half of whom were trans-men taking testosterone, who took directly observed daily oral FTC/TDF PrEP. The findings provided reassurance that levels of GAHT are not significantly lower in young transgender men and women once they start taking PrEP. The first study focused on hormone levels, and in the second, PrEP levels were compared between the women and men in the study, and were also compared with PrEP levels in studies that established typical PrEP levels in cisgender people. The same 24 trans men and 26 trans women took part in both studies. In the first study, while the levels of estradiol and testosterone were both slightly lower after PrEP was started, the difference in levels was not statistically significant and would not have any clinical effect. Estradiol levels were collected at baseline (i..e, before taking PrEP) and after 2-3 weeks on PrEP, and did not differ after starting PrEP in either gender. The Cmax of estradiol in the women was 334 pg/ml off PrEP and 284 pg/ml on PrEP, and the 15% difference was not statistically significant. In the men, the Cmax levels of testosterone were 813 ng/ml before PrEP and 739 ng/ml on PrEP, a 10% difference which was also not significant. The intracellular levels of tenofovir were 34% higher in the men than the women, and the emtricitabine levels 56% higher, which was statistically significant (p = 0.05 for TDF and p = 0.003 for FTC) but was no longer significant for TDF once the rate of elimination via the kidneys was taken into account (p = 0.15). The absolute values for intracellular TDF levels were 75 fmols per million cells (fmols/106 cells) in men and 56 fmols/106 cells in women., which is reassuringly similar to levels seen in prior studies of cisgender participants controls (typical levels to range from 36 to 71 fmols/106 cells). TDF and FTC levels were both 42% lower in women who took their estrogen via a weekly or every two week intramuscular injection than in women who took oral pills. The differences seen in intracellular drug levels were not reflected in plasma levels, where there was no difference between men and women. Although intracellular levels of TDF-DP and FTC-TP were lower in trans women than in trans men, they were still well within the range of levels seen in similar studies of directly observed PrEP conducted in cisgender people.
Pharmacokinetics and tolerability of new agents
Patel summarized the mechanism of action and pharmacokinetics of oral islatravir (ISL), a translocation inhibitor with immediate chain termination as well as delayed chain termination, which has robust activity against drug-resistant variants, favorable tolerability and safety in persons with HIV (PHI) and HIV- individuals (https://www.vcroi2021.org/sessions/19762731/subsession/25640308/ISLATRAVIR-PK-THRESHOLD--DOSE-SELECTION-FOR-MONTHLY-ORAL-HIV-1-PrEP) . The active moiety of ISL is islatravir triphosphate, ISL-TP, which has a long intracellular half-life of 190 hours. Patel described key pharmacokinetic parameters, specifically the threshold and dose selection for monthly oral ISL dosing for phase 3 HIV prevention trials. He described that the in vitro IC50 of ISL is substantially lower than currently marketed nonnucleoside transcriptase inhibitors. The inhibitory quotient scale as the ratio of trough concentration and in vitro concentration. The PK threshold established for ISL is 0.05 pmol/106 (or 0.05 pmol per million cells), which were found to be associated with effectiveness in previous rhesus macaque challenge studies with IV challenge with weekly ISL. The monthly oral dose of ISL 60 mg is expected to maintain systemic ISL-TP concentrations >0.05 pmol per million cells based on modeling from the multi-dosing phase 2 study, MK 016, which was presented at R4P 2021. The tissue levels are also greater than the threshold of 0.05 pmol per million cells. The levels of ISL-TP exceed the PK threshold within a couple of hours and are maintained above the PK threshold from the first dose of administration. Matthews presented on the islatravir implant which was evaluated among 36 participants who received either one of three doses of ISL in an implant (doses of 48 mg, 52 mg, or 56 mg of ISL) or placebo (https://www.vcroi2021.org/sessions/19762731/subsession/25643416/NEXT-GENERATION-ISLATRAVIR-IMPLANTS-PROJECTED-TO-PROVIDE-YEARLY-HIV-PROPHYLAXIS). This presentation follows the promising PK data Matthews presented at IAS 2019, in this presentation based on the reformulated implant that contains polymer and islatravir. The implants also included barium to locate the implant (e.g., in the event that it slips or migrates under a muscle). Participants were followed for 12 weeks with the implant and for 8 weeks after implant removal. The ISL implants evaluated in this study used the same applicator as Nexplanon applicator, and the prototype ISL implants which would be advanced into clinical trials need to be evaluated for safety and PK. Using PK modeling, the 56 mg ISL implant is projected to lead to concentrations above the 0.05 pmol per million cells threshold for 52 weeks. After removal of the implant the effective half-life was about 198 hours, which is similar to oral dosing. Mild local reactions were observed in 22/36 (61%) and the most common systemic AE was headache which is consistent with AEs observed with other implants. No dose-relationship was observed. There were no serious adverse events or early discontinuation and no lab abnormalities. These PK and tolerability results support the development of the ISL-eluting implant for 1 year dosing, and that the "long tail" problem which was an initial concern in studies of injectable cabotegravir for PrEP would likely not be an issue for people who discontinue the islatravir implant.
Lutz, evaluated drug-drug interactions with lenacapavir, a novel capsid inhibitor which is being evaluated for six month subcutaneous dosing for PrEP, and has been shown to achieve up to 2.3 log10 decline in HIV RNA in phase 1b trials (https://www.vcroi2021.org/sessions/19762731/subsession/25640309/CLINICAL-EVALUATION-OF-DRUG-INTERACTIONS-WITH-ORAL-LENACAPAVIR-AND-PROBE-DRUGS). Rifampin and efavirenz were dosed to steady state after single dose famotidine, which showed no significant interactions. To evaluate CYP3A substrates, midazolam was evaluated and which demonstrated that lenacapavir is a minor CYP3A inhibitor. Overall, the results of these drug-drug interaction studies showed that lenacapavir has limited drug interaction potential and can be used with strong inhibitors of the CYP3A and P-glycoprotein drug metabolism pathways, but should not be used with potent CYP3A and P-glycoprotein inducers or UGT1A1 inhibitors. Twice-yearly lenacapavir injections for PrEP will be evaluated in two clinical trials, through adding a lenacapavir arm to the Women's HIV Prevention Study, which is evaluating daily oral PrEP using FTC/TDF or F/TAF for adolescent girls and young African women and daily oral PrEP versus six-monthly lenacapavir injections in cisgender men, transgender women and trans men who have sex with men in the US and South Africa. Bekerman reported that a single injection of GS-CA1, a drug similar to lenacapavir which is active against both HIV and its simian cousin SIV, partially protected macaques which were repeatedly exposed to SHIV (https://www.vcroi2021.org/sessions/19764930/subsession/25643391/LONG-ACTING-HIV-CAPSID-INHIBITOR-EFFECTIVE-AS-PrEP-IN-A-SHIV-RHESUS-MACAQUE-MODEL) . While all eight monkeys in the placebo group were infected after 15 SHIV exposures, five of the eight animals that received a higher GS-CA1 dose were protected, representing a 96% risk reduction. Notably, the infections in the GS-CA1-dosed groups occurred only after marked compound washout (9+ weeks post dose).
Liu reported on a phase 1 study of the 3 month dapivirine ring
(https://www.vcroi2021.org/sessions/19762746/subsession/25640404/PHASE-1-PK-SAFETY-AND-ACCEPTABILITY-STUDY-OF-3-MONTH-DAPIVIRINE-VAGINAL-RINGS). The monthly dapivirine vaginal ring has received a positive review by the European Medicines Agency and is recommended by the World Health Organization as one of several options for HIV prevention. The phase I study involved 49 healthy HIV-negative women and individuals assigned female sex at birth in the U.S. who were randomized (1:1:1) trial comparing 2 extended duration (100 or 200 mg dapivirine) vaginal used continuously for 13 weeks to a monthly 25 mg DPV VR. Across timepoints, plasma and cervicovaginal fluid (CVF) DPV concentrations were higher in the 100 and 200 mg VR arms compared with the 25 mg arm and the peak concentration (Cmax) and Area Under the Concentration-Time Curve (AUC) for 0-28 days were 1.5 to 2 times higher for the extended duration VRs vs. monthly VR. All three rings showed no safety concerns and were well-tolerated by study participants. When comparing dapivirine concentrations those using the 90 day rings had 1.3 – 1.9 times more dapivirine in blood plasma, and 1.5 to 2.9 times more in vaginal fluids. There were also higher concentrations noted in cervical tissues. Eighty-two percent reported being fully adherent, and no statistically significant differences were found between groups. These findings support further evaluation of 3-month DPV VRs for HIV prevention in women.
Multiple studies presented new data related to prevention of HIV transmission perinatally, including a study of differentiated care for postpartum women with increasing levels of TFV-DP and a study of the rollout of dolutegravir in Kenya. In a nested case-control study within a trial of differentiated care for postpartum ART, women who initiated ART during pregnancy and were <10 weeks postpartum had DBS drawn periodically during followup. These DBS were paired with plasma viral load measurements taken 3-6 months later. The study found a dose-response relationship between increasing TFV-DP concentrations and future VL <20 copies/mL. The use of TFV-DP had high sensitivity for predicting viremia but low specificity. Odayar concluded that TFV-DP levels could help to distinguish non-adherence from virologic failure.
https://www.vcroi2021.org/live-stream/19762731/HIV-TREATMENT-AND-PREVENTION-NEW-OPPORTUNITIES-TO-OPTIMIZE-DRUG-DOSING-ADHERENCE-AND-ANTIRETROVIRAL-THERAPY Abstract #93).
Romo presented findings regarding the uptake and use of dolutegravir (DTG) among 15,793 treatment-naïve and 74,788 treatment-experienced adults ≥16 years) in Kenya using data from the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium. DTG was rapidly implemented among treatment-naïve and experienced male patients and female patients not of reproductive potential. Among treatment-naïve patients, the quarterly proportion starting ART with a DTG-containing regimen was greatest among men and females ≥50 years. This trend began in 2018 and the discrepancy has grown over time despite a recommendation in July 2019 by WHO of DTG for all and a recommendation by the Kenyan MOH of DTG to all with caution about exposure to DTG at conception and first trimester. Quarterly incidence proportions for DTG uptake were statistically lower among women of reproductive potential (age <50 years) relative to men before and after the 2019 change in recommendations. There were no differences in DTG use in women ≥50 years relative to men. Findings in treatment-experienced patients were very similar. Abstract 109. https://www.vcroi2021.org/live-stream/19762734/IDENTIFYING-DISPARITIES-AND-OPPORTUNITIES-IN-HIV
Data from the US were presented to better characterize the HIV epidemic among American Indian/Alaska Native populations. Using data from the US CDC National HIV Surveillance System, Sembajwe and colleagues evaluated trends in HIV diagnoses and mortality among people identified as single-race American Indian/Alaska Native (AI/AN). Results demonstrate stable or declining rates of HIV diagnosis from 2014-18 except for the age groups of 13-24 and 35-44 years which have experienced an increase in diagnosis. Mortality declined overall and remained highest in the age group of 45-54 years. 63% of newly diagnosed infections were among people reporting male-to-male sexual contact. The highest rates of diagnosis were observed in the Navajo and Albuquerque jurisdictions with rates of 13.9 and 13.3 per 100,000, respectively. Abstract 108. https://www.vcroi2021.org/live-stream/19762734/IDENTIFYING-DISPARITIES-AND-OPPORTUNITIES-IN-HIV
HIV testing, including self-testing
Numerous studies presented data on HIV testing, including HIV self-testing, novel strategies to promote HIV testing, and the impact of COVID-19 regulations and lockdown on HIV testing and diagnosis. Using data from PEPFAR, Drammeh presented an analysis that compared the percentage change in the number of people aged >15 years with an HIV-positive diagnosis who initiated ART before (January-June 2019) and during the pandemic (January-June 2020). Index HIV testing (inclusive of community-based testing) decreased in 7 countries and increased in 5 countries during the pandemic. Provider-initiated HIV testing decreased in all but 1 country (Cameroon). HIV treatment initiation decreased in 7 countries and increased in 4 countries, highlighting the need to continue efforts to strengthen HIV case finding and linkage to care. Abstract 143. https://www.vcroi2021.org/live-stream/19762745/COVID-EPIDEMIOLOGY-AND-ITS-IMPACT-ON-HIV-CARE-AND-PREVENTION
Using state-level surveillance data from Oregon, USA, Menza presented a study designed to determine the impact of SARS-CoV-2 on public sector testing for HIV and bacterial STI (monthly CT/NG and syphilis testing). Monthly testing rates for HIV declined at a statistically significant level by 50% during and 28% after the stay-at-home order, dramatic declines that did not recover by September 2020. For NG/CG, monthly testing declined 58% during and 44% after the stay-at-home order. Syphilis tests declined 58% during and 38% after the stay-at-home order. HIV diagnoses declined during the stay-at-home order and were elevated 12% (but not statistically significantly) after the order. After the stay-at-home order, primary syphilis diagnoses increased by 45% relative to before the order. Abstract 144. https://www.vcroi2021.org/live-stream/19762745/COVID-EPIDEMIOLOGY-AND-ITS-IMPACT-ON-HIV-CARE-AND-PREVENTION
Using data from PEPFAR-funded HIV testing at 48 facilities and 7 community sites in 2 states in India that bear the greatest burden of the HIV epidemic in India, Enugu and colleagues compared index HIV testing before (January-March 2020), during (April-June 2020), and after lockdown (July-September 2020). There was a 93% decline in newly diagnosed HIV positive during lockdown and 71% decline after lockdown. The absolute number of contacts of index cases also declined (84% during and 47% after lockdown). The number of contacts elicited per index case increased during lockdown and post-lockdown and HIV-positivity among contacts was 13% greater during lockdown and similar to pre-lockdown frequency in the post-lockdown period. This may reflect greater time available for staff to support people newly diagnosed and to test their contacts. With respect to linkage of people diagnosed to HIV care and ART initiation, linkage improved (with 81% more people being linked) during lockdown and the average time to ART initiation decreased by 1 day during and 3 days post lockdown. Abstract 145. https://www.vcroi2021.org/live-stream/19762745/COVID-EPIDEMIOLOGY-AND-ITS-IMPACT-ON-HIV-CARE-AND-PREVENTION
Using data from the PEPFAR monitoring, evaluation, and reporting database, Gross and colleagues compared 2020 levels of pediatric HIV testing in outpatient, index, and community settings to the same calendar time period in the prior year in 14 PEPFAR countries in sub-Saharan Africa. Overall, pediatric testing declined by 34% during COVID-19 and there has been a 26% decline in pediatric HIV diagnoses. Outpatient HIV testing declined 30% and diagnoses declined by 28% and pediatric HIV index testing declined by 21% and diagnoses declined by 22%. Some countries have begun to experience a recovery in testing to the frequencies seen pre-COVID. Community testing declined by 30% and diagnoses declined by 26%. Adolescent HIV testing declined overall by 17% and diagnoses declined by 24% - and this was seen in all testing modalities and particularly in outpatient and index testing. Abstract 173. https://www.vcroi2021.org/live-stream/19762760/MATERNAL-AND-CHILD-HIV-AND-SARS-CoV-2
New testing strategies
Sundararajan presented on a cluster RCT of traditional healers delivering HIV testing in Uganda, given the low uptake of HIV testing in rural areas, where traditional healers are often first line of health care (https://www.vcroi2021.org/live-stream/19762759/INNOVATIONS-AND-CHALLENGES-IN-TESTING-PREVENTION-AND-CARE). Prior research had shown that 34% of adults visiting traditional healers in rural Uganda had not tested for HIV in the prior 12 months. This cluster RCT was done in southwestern Uganda in the Mbarara township where the HIV prevalence is 7.9%. The study was designed as a parallel arm, unblinded cluster RCT with the primary outcome of receipt of an HIV within 90 days, and the secondary outcomes of linkage to care within 90 days, assessed by 90-day telephone follow-up. Healers were trained to deliver HIV education, pre and post HIV test counseling and how to use Oraquick POC HIV tests and provide local clinic for linkage to care for those testing HIV+. Between Aug 2019-Feb 2020, 17 of 25 healers in Mbarara township were randomized and 500 individuals screened per arm, with 250 enrolled per arm, of whom 88% had ever tested for HIV but the majority had not tested within the past 2 years. In the intervention arm, 250 (100%) received an HIV test compared to 57 of 250 (22%). Thus, traditional healer delivery of HIV self-testing increased the proportion of clients who tested for HIV by 4.4 fold. None of the control arm participants and 10 (4%) of all persons tested in the intervention arm had new HIV diagnoses; 7 of the 10 newly identified HIV infections in the intervention arm were linked to care within 90 days. Both of these findings were highly significant.
In a cluster randomized trial in Malawi, 9 mid-level public health centers were randomized to either optimized provider initiated testing and counseling, passive HIVST, or active HIVST. Using a difference in difference analysis, Dovel and colleagues estimated that the each strategy resulted in an increase in HIV testing above the standard of care (18% greater frequency of testing for the PITC arm, 33% for the passive HIVST, and 220% increase for facilities conducting active HIVST). In addition, facilities randomized to passive or active HIVST saw major reductions in the time that healthcare workers spent per HIV test completed. Abstract 181. https://www.vcroi2021.org/live-stream/19762759/INNOVATIONS-AND-CHALLENGES-IN-TESTING-PREVENTION-AND-CARE
At 3 Kenyan MCH clinics, 798 HIV negative pregnant women were offered a choice of HIV testing using self-test kits in their home or rapid testing in the clinic. Women who chose the at-home HIV self test approach were further offered the choice of taking an HIV self-test kit to their partner or referring him to the MCH clinic for testing. At 14 weeks postpartum, the women self-reported whether their partner had received an HIV test. Results showed that fewer women selected the home HIVST option but among those that did, 60% reported that their partner received an HIV test (relative to 38% among women who opted for in-clinic rapid HIV testing). Partner testing was more commonly done via home-based self-testing kits than clinic-based testing. Abstract 674. https://www.vcroi2021.org/sessions/19764939/subsession/25642462/PARTNER-TESTING-AMONG-PREGNANT-WOMEN-OFFERED-HIV-RETESTING-IN-KENYA
In a Science Spotlight presented by Karidia Diallo, 690 facilities in South Africa were evaluated in 2017 and 2020 according to 7 domains within a quality insurance tool and each facility was ranked for each domain. The percentage of facilities meeting eligibility criteria for national certification increased from 5.1% in 2017 to 43.5% in 2020. Major domains seeing improvements were related to activities implemented by providers, enhanced stocks and consumables management, increased uptake of internal quality control measures, and increase use of HIV testing registers and proper documentation. Abstract 675. https://www.vcroi2021.org/sessions/19764939/subsession/25642463/INNOVATIVE-QUALITY-APPROACH-TO-IMPROVE-HIV-RAPID-TESTING-IN-SOUTH-AFRICA
In a Science Spotlight presented by Bien-Gund, 7.7% of 6, 563 HIV-negative or unknown status MSM in the 2017 CDC NHBS survey who had at least 1 HIV test in the past 12 months had used HIVST. Self-testing was associated with increased test frequency and more recent testing. Abstract 677. https://www.vcroi2021.org/sessions/19764939/subsession/25642465/HIV-SELF-TESTING-AND-RISK-BEHAVIORS-AMONG-MEN-WHO-HAVE-SEX-WITH-MEN-IN-23-US-CITIES
In addition to studies of pregnancy summarized earlier, one additional study in the realm of reproductive health and HIV treatment was presented by Scarsi. As a primary exogenous hormone present in numerous contraceptives, levonorgesterol (LNG) is subject to drug-drug interactions but safety and PK studies of strategies to double LNG doses have not been conducted. She presented data from women using EFV in ACTG 5375 in which 52 women were randomized in 1:2 ratio to receive either standard or double dose of LNG emergency contraception dosing. Women receiving the double dose achieved 51-133% greater PK levels of LNG that were above the threshold for contraceptive efficacy while women receiving the single dose had numerous PK parameters below previous thresholds for contraceptive efficacy. She concluded that EFV-based ART acted to decrease the half-life of LNG and using a double dose of levonorgesterel for emergency contraception will increase measures of LNG PK by 51-133% in individuals receiving EFV ART. https://www.vcroi2021.org/live-stream/19762731/HIV-TREATMENT-AND-PREVENTION-NEW-OPPORTUNITIES-TO-OPTIMIZE-DRUG-DOSING-ADHERENCE-AND-ANTIRETROVIRAL-THERAPY Abstract #91
Sexually Transmitted Infections
Studies related to STI and HIV prevention included novel data about the association between contraceptives and HSV-2 acquisition, doxycycline used alongside PrEP to treat and prevent syphilis and chlamydia, and presence of bacterial vaginosis immediately after sexual debut. HSV-2 acquisition was evaluated in an RCT of contraceptive methods among Kenyan women and presented by Dr. Mugo, in a secondary analysis that compared HSV-2 rates incidence among 3,898 women who were randomized to copper intrauterine device (IUD), levonorgesterel (LNG) implant, and intramuscular depo medroxyprogesterone acetate (DMPA-IM). Rates of HSV-2 incidence were 10.9. 13.7, and 12.7 per 100 person years among women randomized to DMPA-IM, copper IUD and LNG implant, respectively. The rate among women randomized to DMPA-IM were marginally statistically lower (0.67-0.99, p=0.04) but there was little difference in HSV-2 incidence rates across the three contraceptive arms. Being an HIV seroconverter, having infection with C. trachomatis or N. gonorrhoeae, having multiple partners, and living with a partner were associated with being an HSV-2 seroconverter during the trial. Abstract 152. https://www.vcroi2021.org/live-stream/19762746/PREVENTION-2021. HSV-2 also was estimated to account for a substantial proportion of new HIV infections, as presented by Silhol in a Science Spotlight. Mathematical modeling using data on HSV-2 prevalence, HIV incidence, ART coverage and empirical HIV incidence rate ratios by HSV-2 status suggests that HSV-2 could be responsible for 37% of new HIV infections if it only increases HIV acquisition. If HSV-2 also increases HIV acquisition and transmission, HSV-2 is estimated to be responsible for 51% of new HIV infections. Abstract 708. https://www.vcroi2021.org/sessions/19764938/subsession/25642456/GLOBAL-AND-REGIONAL-ESTIMATES-OF-THE-CONTRIBUTION-OF-HSV-2-TO-INCIDENT-HIV-INFECTIONS. Effective HSV-2 prevention methods remain a high priority for HIV prevention.
Effective interventions for bacterial STIs are also needed, given the continuing epidemic of bacterial STIs among persons who are also at risk for HIV. Presented by Grennan in a Science Spotlight, a 48-week pilot study of daily 100mg doxycycline starting immediately or delayed until week 24 taken alongside PrEP among 52 MSM or transgender women with prior syphilis diagnosis. Relative to participants randomized to delay use of doxycycline until 24 weeks, participants initiating doxycycline immediately experienced a 82% reduction in incident STIs (95% CI 0.05-0.68, p=0.011). This was driven by differences in chlamydia (0 cases in the immediate doxycycline group versus 0 cases in the group that began immediately). Abstract 709. https://www.vcroi2021.org/sessions/19764938/subsession/25642457/DAILY-DOXYCYCLINE-IN-MSM-ON-PrEP-FOR--PREVENTION-OF-SEXUALLY-TRANSMITTED-INFECTIONS
Observational data indicate that bacterial vaginosis is a risk factor for HIV acquisition. Presented by Roxby in a Science Spotlight, 400 Kenyan adolescent girls and young women (80% with no sexual activity at enrollment) had BV prevalence of 2.8% pre-sex and 13.7% in visits post sexual activity. 43% of participants had had at least 1 episode of BV during the 48-month follow up period. Abstract 722. https://www.vcroi2021.org/sessions/19764942/subsession/25642474/BACTERIAL-VAGINOSIS-TRENDS-AMONG-ADOLESCENTS-BEFORE-AND-AFTER-SEXUAL-ACTIVITY In the same study of 400 Kenyan adolescent girls and young women (80% with no sexual activity at enrollment), Wang presented that 163/292 sexually active AGYW experienced any STI event and 70 had a subsequent STI event. The most common type of event was infection with CT (81% of events) followed by GC (11%) and TV (7%). Abstract 721. https://www.vcroi2021.org/sessions/19764942/subsession/25642473/RISK-FOR-REPEAT-STI-EPISODES-AMONG-KENYAN-ADOLESCENT-GIRLS-AND-YOUNG-WOMEN
Prevention for people who inject drugs
One study is summarized that presented data on frequency of HIV testing among people receiving syringe services and medication for opioid use disorder. In this study, Menezes and colleagues posited that injection networks may inform HIV prevention service utilization among PWID in India. In a cross-sectional analysis of 11,745 people who inject drugs to characterize their use of HIV prevention services. 15% of the sample had had an HIV testing the last 6 months, 20% engaged with MOUD in the prior month, and 27% used syringe services in the prior month. Recent HIV testing was more frequent among people who reported sharing injection equipment with people known to be living with HIV (AOR=2.54, p=0.4). Abstract 719. https://www.vcroi2021.org/sessions/19764909/subsession/25642296/INJECTION-NETWORKS-AND-HIV-PREVENTION-SERVICES-AMONG-PEOPLE-WHO-INJECT-DRUGS-IN-INDIA