icon-    folder.gif   Conference Reports for NATAP  
  Conference on Retroviruses
and Opportunistic Infections
February 12-16, 2022
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CROI 2022 and HIV prevention
  NATAP Report by Renee Heffron, PhD and Connie Celum, MD, University of Washington
Although many CROI participants were hoping for an in-person meeting in Denver, the surge in Omicron cases globally led the CROI Conference organizers to decide convert CROI 2022 to a virtual format. The virtual format did not detract from an outstanding set of plenaries, oral abstracts, poster discussions, and symposia with stimulating and robust discussions. HIV prevention was a major focus of CROI 2022 with In the opening session Dr. Beatriz Grinstein gave an outstanding N'Galy Mann lecture, entited "HIV prevention in vulnerable populations: Generating evidence to reduce inequalities." In the third plenary session Dr. Chloe Orkin gave an outstanding plenary, "New antiretrovirals and the future for HIV treatment and prevention" and Dr. Mark Feinberg gave an excellent plenary, "The past and future of HIV vaccines." Excellent and impactful oral abstracts were presented in session 4 (Evolvoing epidemiology of HIV SARS-CoV), session 7 (HIV prevention in vulnerable populations: Generating evidence to reduce inequalities), session 8 (Global perspectives on HIV testing, treatment and prevention), and session 13 (Shifting paradigms in HIV testing). Interactive sessions included lively discussions about PrEP (what will it take to increase PEP and PrEP use for adolescent girls and young women at risk?). Three exciting symposia included one about HIV prevention choices (Symposium 3, Bringing choice to HIV prevention), important priorities in STIs ( Symposium 6, Sexually transmitted infections: Reversing the Tide), and HIV prevention in special populations (Symposium 9).
As in past CROI meetings, exciting data about PrEP were presented at CROI 2022. In the late breaker abstract 88, Dr. Kenneth Ngure presented the new data in the choice period from the MTN 034/ REACH study, a cross-over trial of daily FTC-TDF and the monthly vaginal dapivirine ring among African adolescents and young women (AGYW). Of the 247 HIV-negative AGYW aged 16-21 enrolled from South Africa, Zimbabwe, and Uganda, participants were randomized to use the monthly ring or daily oral PrEP for each of the first 6 month period, then crossed over to the other product for 6 months. Ngure presented on findings from the third 6 month period in which participants were given a choice of ring, oral PrEP, or neither. Of the 92% AGYW participants who continued in the REACH choice period, 67% chose the ring, 31% oral PrEP, and 2% chose neither product. High adherence to oral PrEP in the initial 6 month period was strongly associated with participants' choice of oral PrEP, but not for the ring. Notably, adherence was much higher than has ever been reported in similar clinical trials among AGYW, who continue to have very high HIV incidence and had the lowest adherence with these daily oral PrEP and dapivirine ring in previous studies. The REACH study demonstrates that AGYW can make informed choices about HIV prevention products, can use products effectively with adherence support, and that AGYW benefit from HIV prevention options and the opportunity to make informed choice.
Dr. Sinead Delany-Moretlwe presented on safety and drug concentrations among women who became pregnant or breastfed during following in HPTN 084, an efficacy trial to evaluate the safety and efficacy of injectable long-acting cabotegravir (CAB-LA) compared to daily oral FTC/TDF for PrEP in HIV-uninfected African women, which was unblinded in 2020 due to clear evidence of superiority for long-acting CAB compared to oral PrEP. Resassuringly, very few adverse events were observed and were not related to the study product. Ongoing studies will examine the safety and pharmacology of CAB-LA in women who choose to continue CAB-LA through pregnancy. Thus, the safety data and drug concentrations provided reassurance about the safety, tolerability and pharmacokinetics during pregnancy and lactation, but more studies are needed to inform guidelines. Currently, data on CAB-LA are being reviewed by regulators and recommendations are being prepared particularly for its use in sub-Sharan Africa and globally.
In a late breaker abstract 96, Dr. Raphy Landowicz presented on updated efficacy, safety and breakthrough infections in HPTN 083, an ongoing Phase 2b/3 randomized controlled trial that demonstrated superior efficacy with 66% reduced risk of HIV acquisition for long-acting injectable cabotegravir (CAB-LA) vs. daily oral TDF/FTC in the prespecified primary analysis. After unblinding in May 2020, participants continued on their original randomized study treatment until the protocol was amended and operationalized to offer eligible participants open-label CAB-LA. Fifty-one incident HIV infections were identified in the blinded trial (12 CAB, 39 TDF/FTC), and the investigators reported on an additional year of additional follow-up, in which 46 additional incident HIV infections were identified in the pre-planned analysis period (13 CAB, 33 TDF/FTC); 4 occurred during the blinded phase (2 CAB, 2 TDF/FTC), 42 after unblinding (11 CAB, 31 TDF/FTC). Reduction in risk for CAB-LA vs. FTC/TDF remained similar in blinded and unblinded phases (HR=0.33 95%CI (0.18-0.62) and HR=0.34 95%CI (0.17-0.67), Table). HIV incidence was higher in both arms in the unblinded phase, likely attributable to decreased TDF/FTC adherence, reduced CAB injection coverage, and increased relative contributions to overall person-time from high incidence regions. The 2 newly-identified blinded CAB arm infections were both in the setting of on-time injections; the 11 newly-identified unblinded CAB arm infections included 1 with on-time injections, 3 with delayed injections, and 7 that occurred ≥6 months after the last CAB exposure (2 of these 7 never received a CAB injection). Six additional new CAB arm infections were identified ≥3 years on study (all ≥6 months after the last CAB exposure). Thus, the relative reduction in HIV incidence for CAB-LA compared to daily oral FTC/TDF were consistent during one year of additional unblinded study follow-up and no new safety concerns were identified.
The question of what testing strategy should be used (such as viral load testing) for long-acting PrEP in which diagnosis of incident HIV infections may be delayed is a central question. The role of viral load monitoring with CAB-LA implementation is being weighed for earlier detection of HIV infection in order to reduce selection of resistance to integrase inhibitors which are the backbone of most HIV treatment regimens. In abstract 95, Eshelman with colleagues from HPTN 083 and HPTN 084 presented a late breaker abstract which summarized the use of viral RNA in persons who acquired HIV in HPTN 083 and HPTN 084. Inhibitor (INSTI) resistance-associated mutations (RAMs) were detected in 5 CAB-exposed participants with HIV infection using the GenoSure PRIME assay, which has a limit of detection of 500 c/mL. Two other participants with breakthrough infection did not have genotyping results since all VLs were <500 c/mL. In all 7 participants, detection of infection at study sites using rapid tests and antigen/antibody tests was delayed by a median 60 days (range 35-117) and all 7 participants received CAB-LA injections after infection occurred. The investigators used a single-genome sequencing (SGS) INSTI genotyping assay to assess whether earlier detection of these HIV infections would have provided an opportunity to start ARTbefore INSTI resistance emerged. The SGS assay was successful for 18/21 samples tested and detected INSTI RAMs in 6/7 participants (4/5 with prior genotyping results, 2/2 with no prior genotyping results). The authors concluded that earlier detection of HIV infection using an HIV RNA assay in the setting of CAB-LA PrEP would allow for earlier ART initiation in order to reduce the risk of INSTI resistance, but would require highly sensitive assays. Given the high efficacy of CAB-LA, observations that breakthrough infections are rare, and the limited availability and additional costs of every 2 month VL assays in low and middle income countries, it is not clear that this is needed for CAB-LA PrEP implementation if HIV RNA screening is not available or the costs are unaffordable.
A poster presented by Cambiano estimated a 75% drop in new HIV infections in a decade will continue if current prevention measures are maintained, leading to new cases of HIV in gay and bisexual men becoming rare by 2040. During 2020, 976 gay or bisexual men tested HIV positive and 1067 heterosexuals. But this includes people diagnosed with a low CD4 count who may have had HIV for years and people who caught it outside the UK. The model used 'counterfactual' scenarios to tease out the contribution of each of these changes, including:
1) condom use in gay men never rose far beyond the levels seen in 1980. If HIV testing rates, the proportion on ART and PrEP use were all at today's levels, but condom use was only 10%, there would be 1496 new infections in 2021.
2) if the number of gay men testing for HIV was still the same as in 2012, even though condom use, the proportion of men with HIV on treatment and PrEP use were at present levels, this would lead to 1271 infections.
3) condom use, testing and PrEP stay at current levels, but people only starting HIV treatment when their CD4 counts fall below 350, as in 2012. This would lead to 853 infections in 2021.
4) PrEP had never been introduced (currently with >25000 MSM on PrEP), then even if condom use, testing and treatment were all at 2021 levels, then there would be 1433 new infections in 2021.
Without these interventions, there would have been 7646 new infections in 2021, which is 11 times more than the 669 that occurred. The four interventions were synergistic. The model found that annual HIV incidence in gay men in the UK has fallen to 0.12% in 2021 (i.e., one new infection in 833 people). The model forecasts that incidence will continue to fall, to one new infection in 2500 gay men in 2030 and just over one in 5000 in 2040, a situation the researchers call 'virtual elimination'.
Prevention of Mother to Child transmission (PMTCT)
Data related to prevention of mother to child transmission of HIV focused on safety of novel ARVs for infants when used by mothers and early treatment options for children perinatally infected. Data presented by Dr. Lynda Stranix-Chibanda (Abstract 30) from a secondary analysis of the IMPAACT 2010 randomized trial of EFV/FTC/TDF, DTG/FTC/TDF, and DTG/FTC/TAF found that predominantly breastfed infants (N=479) who were exposed to EFV were statistically smaller in length at 26 and 50 weeks of age, compared to infants exposed to either DTG-containing regimen. The prevalence of stunting was 16.4% at week 26 and 16.8% at week 50 overall and greater in infants exposed to EFV. The authors conclude that infant growth should be an additional factor considered in the selection of optimal maternal ART regimen.
Data presented by Dr. Deborah Persaud (Abstract 31) from the IMPAACT P1115 study examined the 2-year impact of very early ART provision to infants born with in utero HIV infection to achieve restricted levels of cell-associated DNA and HIV reservoirs. Two cohorts of infants (N=54 in total) were initiated on ART within 48 hours of birth and the estimated probability of remaining virally suppressed at 2 years was 33% in Cohort 1 and 57% in Cohort 2. In addition, having higher earlier cell-associated HIV DNA was associated with greater risk of virologic failure at 2 years. These data provide evidence supporting the conclusion that infants who suppress virus with very early ART can achieve restricted HIV reservoirs by 2 years of age. Two-year virologic outcomes of very early art for infants in the IMPAACT P1115 study
Dr. Roger Shapiro (Abstract 32) presented data from a proof-of-concept study of infant treatment with broadly neutralizing antibodies (bNAbs, VRC01LS and 10-1074 ) as an alternative to ART treatment in virally suppressed children who had initiated ART within 7 days after birth. In 25 children switched from ART to bNAbs, 11 maintained viral suppression though 24 weeks of bNAb-only treatment, while 14 experienced viral rebound. This does demonstrate proof-of-concept however, newer bNAb combinations may be needed to result in more favorable treatment outcomes. Treatment with Broadly Neutralizing Antibodies in Children with HIV in Botswana (The Tatelo Study)
Relevant to application of the principle of U=U to vertical transmission through breastfeeding, in abstract 684, Sibiude presented data from the French National Perinatal Cohort collected from 2000-2017 with 15,959 live births to mothers living with HIV-1 in mainland France and with follow-up data up to two years of age. Importantly, the HIV transmission rate of 0% among 5482 infants born to mothers who were taking HIV treatment at the time of conception, had an undetectable viral load at childbirth (<50 c/ml) and did not breastfeed. In addition, there was a 0% transmission rate for 2358 infants whose mothers were undetectable during the first trimester of pregnancy. The authors also presented predictors of perinatal transmission: 8.3% transmission rate among mothers who did not receive ART; timing of ART initiation (0.1% before conception, 0.5% in the first trimester, 0.8% in the second trimester and 1.7% in the third trimester), maternal viral load (0 if maternal VL was <50 copies, 0.2% with a viral load between 50 and 400, and 2.4% above 400), and premature delivery (1.3% for babies delivered between 32 and 36 weeks and 2.1% for those delivered before 32 weeks).
In addition to presenting original data, in his plenary talk on day 2, Dr. Andrew Prendergast provided an excellent overview of what is known and unknown about morbidity in children who are were exposed to HIV in utero and uninfected.
A number of oral presentations provide new or updated data on the epidemiology of HIV infection in the US and global locations, including in the oral abstract session 4. Three talks highlight epidemic trends in the US.
First, Sonia Singh (Abstract 43) presented data from the US National HIV Surveillance System that was used to estimate lifetime risk of HIV diagnosis and compare risk among different populations. Based on recent data, lifetime risk overall was 1 in 120. Males (1 in 76) had higher risk than females (1 in 309) with black males at highest risk (1 in 27) among all gender and racial groups presented. The highest lifetime risk was 1 in 39 in Washington, DC and there were improvements in risk in all groups except for males who are American Indian/Alaska Native, Hispanic/Latino, and Native Hawaiian/other Pacific Islander and white females, which highlights continued disparities in HIV prevention and treatment. Estimating the Lifetime Risk of a Diagnosis of HIV Infection in the United States, Blacks have highest risk
Second, Stephen Perez (Abstract 44) presented additional data from the US National HIV Surveillance System highlighting transmission clusters first detected in 2018-19 that were identified through molecular network analysis. Of 144 clusters identified, people identifying as primarily men who have sex with men comprised 68% and people who inject drugs were 24%. Additional characteristics of clusters included diversity in race/ethnicity and gender identity.
Third, Shuntai Zhou (Abstract 45) presented data showcasing the use of a state-wide platform (assay and methods) for conducting surveillance of HIV recency and drug resistant mutations. Using data from all new infections diagnosed in North Carolina in 2018-21, the team found that 39.2% of samples from 743 individuals with newly diagnosed infection were infections recently acquired during the past 9 months. In addition, testing found increases in the frequency of any NNRTI mutation and decreases in any NRTI mutation from 2018-2021.
In a multi-country analysis, Suzue Saito (Abstract 90) presented data demonstrating detection of recent HIV infections determined using the recent infection testing algorithm with data collected via public health facilities in Democratic Republic of Congo, Eswatini, and Lesotho from 2018-21 (with some variance in the years by country). Among people tested from DRC, Eswatini, and Lesotho, 4%, 5%, and 18% were classified as recent infections, respectively. Outpatient department settings yielded the largest frequency of diagnoses that were classified as recent.
An oral abstract (Abstract 91) was presented by Isabella Young, a new investigator awardee, with data on the prevalence of HIV and viremia in migrant households in Uganda. Relative to households with no migrant participants, households with a recent in- or out-migrant had similar HIV prevalence and viremia. In subgroup analyses, individuals with migrating spouses, the prevalence of HIV was higher, supporting calls for couple-centric sexual health interventions to encourage engagement in HIV prevention and treatment. LONG-ACTING INJECTABLE FOR PREVENTION OF HIV AND UNPLANNED PREGNANCY
HIV testing, including self-testing
Multiple oral abstract sessions presented data related to HIV testing, including self-testing and other novel testing strategies. In a large study using data gathered from routine PEPFAR systems, Barkary Drammeh presented data regarding recently updated HIV testing strategies (Abstract 89). The analysis included data from 41 countries and 443 million HIV tests and found that the number of tests conducted peaked in 2018 and has since decreased by 45% annually. Despite decreases, the analysis found that the more recent and efficient HIV testing strategies resulted in stable percent positivity among people tested. The presentation concluded by discussing the importance of maintaining this balance - making testing more efficient, in terms of diagnosing new individuals living with HIV, without compromising the number of people who are diagnosed.
There has been considerable interest in estimated HIV incidence through cross-sectional samples by the recency assay and testing algorithm to identify persons who acquired HIV in the past 12 months. In abstract 90, Dr. Suzie Saito presented a multi-country analysis of the proportion of PLWH who had apparent recent infections in outpatient departments and estimated the HIV incidence. The team analyzed data from 268 health facilities offering recency testing in Democratic Republic of Congo, DRC (from November 2020–September 2021), Eswatini (from July 2019–September 2021), and Lesotho (August 2019–April 2020). In DRC and Eswatini, RITA was used to identify recent cases defined as those newly diagnosed HTS clients ≥15 years (Eswatini) or ≥18 years (DRC) with a recent result on a rapid test for recent infection (RTRI) assay and a viral load of ≥1000 HIV RNA copies/mL. In Lesotho, we used RTRI assay results only in HTS clients ≥18 years. They examined the share and yield of RITA or RTRI recent cases by testing modality stratified by age (<30, ≥30 years) and sex. Of 18,170 (63% female) PLHIV with an RTRI result in the 3 countries, 4% were RITA recent in DRC, 5% were RITA recent in Eswatini, and 18% were RTRI recent in Lesotho. In all countries, OPD accounted for the largest share of newly diagnosed HIV cases identified. In Eswatini, VCT and index testing were additionally significantly associated with recent infections, and ANC/L&D/PNC/CWC clinics were additionally significantly associated with recent infections for women <30 yearrs of age. Yield of recent infections were highest in FP and STI clinics in Eswatini, VCT clinics in DRC and ANC/L&D/PNC/CWC clinics in Lesotho. Testing volume was low in these modalities compared to OPD. Thus, OPD is an effective testing approach to identify new infections. FP, STI, VCT, ANC/L&D/PNC/CWC had higher yield in some settings, suggesting that OPD could improve efficiency with more targeted testing. HIV recent infection surveillance can help inform testing interventions.
Dr. Jennifer Chang (Abstract 142) presented data from a retrospective study of Kaiser Permanente Southern California system showing changes in HIV and STI testing during the COVID-19 pandemic. Similar to findings from Drammeh, Chang found that there were lower rates of testing for chlamydia, gonorrhea, syphilis, and HIV. Diagnosis rates for chlamydia, gonorrhea, and HIV were also lower but higher for syphilis.
Dr. Pollyanna Chavez presented descriptive data on the US CDC's first direct-to-consumer HIV self-test program following the launch of a marketing campaign and opening of an online portal where individuals could order HIV self-test kits (Abstract 141). In the first 8 months of the program, >56,000 people ordered >100,000 tests and more than half of the orders were from locations targeted by the US Ending the HIV Epidemic initiative.
Dr. Jalpa Thakker (Abstract 144) presented data from a study of HIV self-testing conducted in India where outreach workers contacted potential testers via social media, conducted counseling, and facilitated testers to receive self-test kits via home delivery or pick up at a community site. Among the 2,234 people registered, 61% ordered an HIV self-test kit and 90% of those uploaded results from their test. Four percent (4%) of those with uploaded test results were HIV-positive and none had previously tested for HIV.
Dr. Dvora Joseph Davey (Abstract 145) presented data from a randomized trial of women living with HIV in rural South Africa who were assigned to promote HIV testing with their male partners either through 1) provision of an HIV self-test kit or 2) standard of care referral letter for facility-based testing. Among 176 women living with HIV who were recruited from high-density peri-urban and rural health facilities, women randomized to the HIV self-testing arm were 41% more likely to report that their male partner had tested for HIV (relative risk=1.41, 95% confidence interval 1.14-1.76). There was one report of intimate partner violence from a woman in the self-testing arm and women reported that testing was easily and accepted by their partners.
Dr. Kenneth Ngure (abstract xx) presented data from a randomized trial of HIV self-testing to improve 6-month PrEP use in Kenya, which showed that there was no difference in 6-month HIV testing, PrEP refill, or PrEP adherence in members of HIV serodiscordant couples in the trial (60% of participants) and that women singly-enrolled had 19.8% higher PrEP adherence compared to the standard of care. These data support calls to reduce the burden of 3-monthly clinic visits by providing PrEP users with a 6-month supply of PrEP and an HIV self-test kit to use for interim testing at 3 months.
Reproductive Health
Data related to reproductive health and HIV prevention were less prominent at CROI 2022 than recent years. The most notable presentation was a satellite talk from Dr. Dominica Seidman (Abstract 59) that laid out experiences with contraceptive counseling in order to suggest counseling strategies for HIV prevention that align with the core value of "choice". The contraceptive field has often used an efficacy-driven strategy to counseling and advise women on contraceptive choice but this results in a tiered approach to offering products, rather than a person-centered approach that considers all options as possibilities and works with individuals to find the optimal tool for them.
Medical male circumcision
in Abstract 87 by New Investigator Awardee, Kidist Zewdie, on the effectiveness of voluntary medical male circumcision (MMC) and traditional male circumcision, she presented data that VMMC reduces HIV incidence but not traditional circumcision which leaves part of the foreskin. Using data from the HPTN 071/PopART cluster-randomized trial with 10,831 HIV-negative men, the team reported that HIV incidence rates were 0.31 and 0.94 person years among those undergoing MMC and traditional circumcision, respectively, and 0.97 person years in uncircumcised men. Compared to uncircumcised men, men with MMC experienced an HIV incidence rate that was 70% lower (95% CI 0.16-0.55, <0.0001) without circumcision. Importantaly, there was no difference in HIV incidence in those with traditional circumcision compared to those without circumcision. This is an important finding that supports the widescale implementation of VMMC through PEPFAR and other programs. In addition, this finding underscores the need to work with traditional circumcision providers to convey the importance of removing the entire foreskin, and to train lay providers in safe and effective MMC procedures.