Search

The delivery of comprehensive sexuality education to adolescents at school is recognized as a long-term strategy to support adolescent health. Suboptimal sexual and reproductive health (SRH) outcomes among South African adolescents necessitate the ongoing development and optimization of SRH education and promotion models. We conducted a cluster-randomized controlled trial amongst secondary schools (n = 38) in Cape Town, South Africa, to evaluate a sport-based, near-peer-led SRH curriculum, SKILLZ, amongst female learners (n = 2791). Biomedical (sexually transmitted infections [STIs], human immunodeficiency virus [HIV] and pregnancy) and socio-behavioural (social support, gender norms and self-concept) outcomes were assessed pre and post intervention. Attendance at SKILLZ was low and intervention participants did not show an improvement in SRH outcomes, with HIV and pregnancy incidence remaining stable and STI prevalence remaining high and increasing in both control and intervention arms. Although evidence of positive socio-behavioural measures was present at baseline, participants with high attendance showed further improvement in positive gender norms. SKILLZ did not demonstrate the capacity to significantly impact clinical SRH outcomes. Modest improvements in outcomes amongst high attenders suggest that the impact may be possible with improved attendance; however, in the absence of optimal attendance, alternative intervention strategies may be required to improve SRH outcomes amongst adolescents.

BACKGROUND There are gaps in uptake of adherence to, and persistence in the use of preexposure pro-dephylaxis for human immunodeficiency virus (HIV) prevention among cisgender women. METHODS We conducted a phase 3, double-blind, randomized, controlled trial involving adolescent girls and young women in South Africa and Uganda. Participants were assigned in a 2:2:1 ratio to receive subcutaneous lenacapavir every 26 weeks, daily oral emtricitabine-tenofovir alafenamide (F/TAF), or daily oral emtricitabine-tenofovir disoproxil fumarate (F/TDF; active control); all participants also received the alternate subcutaneous or oral placebo. We assessed the efficacy of lenacapavir and F/TAP by comparing the incidence of HIV infection with the estimated background incidence in the screened population and evaluated relative efficacy as compared with F/TDF. RESULTS Among 5338 participants who were initially HIV-negative, 55 incident HIV infections were observed: 0 infections among 2134 participants in the lenacapavir group (0 per 100 person-years; 95°/0 confidence interval [CI], 0.00 to 0.19), 39 infections among 2136 participants in the F/TAP group (2.02 per 100 person-years; 95°/0 CI, 1.44 to 2.76), and 16 infections among 1068 participants in the F/TDF group (1.69 per 100 person-years; 95% CI, 0.96 to 2.74). Background HIV incidence in the screened population (8094 participants) was 2.41 per 100 person-years (95% CI, 1.82 to 3.19). HIV incidence with lenacapavir was significantly lower than background HIV incidence (incidence rate ratio, 0.00; 95% CI, 0.00 to 0.04; P<0.001) and than HIV incidence with F/TDF (incidence rate ratio, 0.00; 95% CI, 0.00 to 0.10; P<0.001). HIV incidence with F/TAF did not differ significantly from background HIV incidence (incidence rate ratio, 0.84; 95% CI, 0.55 to 1.28; P=0.21), and no evidence of a meaningful difference in HIV incidence was observed between FITAF and F/TDF (incidence rate ratio, 1.20; 95% CI, 0.67 to 2.14). Adherence to F/TAF and F/TDF was low. No safety concerns were found. Injection-site reactions were more common in the lenacapavir group (68.8%) than in the placebo injection group (F/TAF and F/TDF combined) (34.996); 4 participants in the lenacapavir group (0.296) discontinued the trial regimen owing to injection-site reactions. CONCLUSIONS No participants receiving twice-yearly lenacapavir acquired HIV infection. HIV incidence with lenacapavir was significantly lower than background HIV incidence and HIV incidence with F/TDF. (Funded by Gilead Sciences; PURPOSE 1 ClinicalTrials.gov numben NCT04994509.). [ABSTRACT FROM AUTHOR]

Background: Islatravir (ISL) is a nucleoside reverse transcriptase translocation inhibitor in development for prevention of HIV-1. Phase 3 trials of oral ISL 60 mg once monthly (QM) are enrolling. We [...]

Background: RV144 demonstrated modest HIV preventive vaccine efficacy in Thailand. Amongst multiple identified correlates, IgG V1V2 antibodies were associated with 43% HIV risk reduction. The P5 aimed to further this by investigating subtype C vaccine regimens with different vectors (canarypox, DNA plasmid), adjuvants (alum, MF59, AS01.sub.B], or none), gp120 protein doses (40mcg, 200mcg, 600mcg), dosing strategies (prime-boost, co-administration) and administration methods (needle-syringe, Biojector). We compare IgG V1V2 responses across P5 trials with available data. Methods: In the HVTN100, HVTN107, HVTN108, and HVTN111 trials, serum specimens were obtained two weeks after the fourth vaccination. We measured the frequency and, amongst positive responders, the magnitude (MFI*: background-subtracted mean fluorescence intensity minus blank responses) of HIV-1-specific IgG (1:50 dilution) responses against V1V2 antigens for subtype C, gp70-TV1.GSKvacV1V2/293F (matched to subtype C protein vaccine), or subtype CRF01_AE, AE.A244 V1V2 Tags/293F (matched to subtype B/E protein vaccine), depending on protein administered. Responses were measured on Bio-Rad using a standardized custom Luminex HIV-1 binding antibody multiplex assay. Results: Amongst these subtype C regimens, the lowest response rate was induced by a regimen of two subtype C ALVAC primes followed by three boosts of subtype C ALVAC +200 mcg unadjuvanted gp120 (4/17 = 23.5%, CI 9.6%-47.3%); median magnitude 727.1MFI* (IQR 430.1 to 1152.1). The highest response rates were in co-administration groups of adjuvanted protein plus DNA or ALVAC at all timepoints). Rates, median magnitudes were 93.8%, 12124.8MFI* (DNA +40 mcg gp120 + [AS01.sub.B] at 3 timepoints); 91.4%, 21756.9MFI* (DNA + 200 mcg gp120 + [AS01.sub.B] at 3 timepoints); 89.1%, 7147.25MFI* (DNA + 200 mcg gp120 + MF59 by needle-syringe at 3 timepoints); 88.5%, 7745MFI* (DNA by Biojector + 200 mcg gp120 + MF59 by needle-syringe at 3 timepoints); 86.7%, 6205.1MFI* (subtype C ALVAC + 200 mcg gp120 + MF59 at 4 timepoints). For subtype C regimens, pooled response rates were higher for: (i) co-administration regimens versus regimens omitting protein in the first two doses (152/169 = 89.9% versus 233/374 = 62.3%, p < 0.00,001) and (ii) groups with DNA vaccines versus those with ALVAC (202/253 = 79.8% versus 187/299 = 62.5%, p < 0.00,001). Conclusions: Strategies which optimized IgG V1V2 responses in P5 subtype C vaccine trials included adjuvanted protein, and co-administration of adjuvanted protein + DNA or ALVAC vaccination. Responses to DNA administration by needle and syringe or Biojector were equivalent., OA18.01 F. Laher (1); C. DiazGranados (2); C. Innes (3); E. Andersen-Nissen (4); G.E. Gray (5); H. Lu (6); J. Hutter (7); K. Mngadi (3); K. Marshall (6); L. Polakowski [...]

Background: Daily Pre-Exposure Prophylaxis (PrEP) is highly effective when adhered to, but its personal and public health benefits it limited by cost, user-acceptability and uptake. The Combined HIV Adolescent PrEP and Prevention Study (CHAPS) is a three-country study to investigate the acceptability of different PrEP regimens amongst young people in sub-Saharan Africa. We describe preferences for daily and on-demand PrEP in Cape Town and Johannesburg (South Africa), Entebbe (Uganda) and Harare (Zimbabwe). Methods: Trained interviewers conducted cross-sectional, structured online surveys capturing socio-demographics, HIV risk behaviours, preferences for daily and on-demand PrEP (three dosing options; (1) two pills before and after sex, (2) two pills a few hours before sex, (3) two pills a few hours after sex). Data were analysed by site and gender using STATA. Results: Of 1339 participants aged 13 to 24 years enrolled, 49.7% were female, with most (70.7%) aged 18 to 24 years. The majority (78.9%) had sex, 83.3% a current partner, and 38.3% knew to have sex two hours in advance. Overall, 22.2% reported first sex aged 14 years or younger and 50.8% weekly sexual activity. About half (51.4%) reported using a condom at last sex (55.6% females; 47.6% males). Twenty-five percent had ever heard of PrEP before the study (11.8% in Entebbe) and willingness to use PrEP was 95.8%. Overall, on-demand PrEP was the preferred option (59.5%) except for Cape Town, where 68.2% preferred daily PrEP. Males (65.2% vs 53.8%) preferred on-demand while females (46.3% vs 34.8%) preferred daily use. Despite an overall preference (59.5%) across sites for on-demand PrEP versus daily PrEP, more participants (36.8%) reported that taking daily PrEP would be the easiest compared to the on-demand regimen options (26.2% (1), 27.5% (2) and 9.5% (3)). Conclusions: Awareness of PrEP was low, despite high willingness to use PrEP. PrEP demand creation needs to be reviewed, optimised and tailored to socio-demographic differences and designed in conjunction with young people. Additionally, although overall more participants in our sample preferred on-demand options, their sexual behaviour patterns may not support its use (e.g. sex events are unplanned for many). Strategies in sexual health education and promotion particularly around assessing and understanding sexual risk behaviour needs further exploration., OA11.02 J. Dietrich (1); N. Ahmed (2); S. Nash (3); G. Tshabalala (1); T. Nematadzira (4); S. Hornschuh (1); M. Atujuna (2); M. Mulaudzi (1); R. Muhumuza (5); A. Ssemata [...]

Background: Prevention effectiveness of oral PrEP is directly associated with levels of adherence. To improve the prevention-effective-use of PrEP, we explored behavioral, social and community factors associated with PrEP disclosure and use among adolescent girls and young women (AGYW). Methods: Individual in-depth interviews (IDI) were conducted with 40 AGYW (aged 16 to 25 years) participating in the Community PrEP study in Eastern Cape Province, South Africa. IDI guides were developed using Social Practice Theory (SPT). IDI domains included: PrEP knowledge and use, study site experiences, PrEP actions plans and influences, and PrEP discussions in social spaces. AGYW with [greater than or equal to] 12 months of study participation were interviewed, with equal representation of AGYW with high and low PrEP adherence measured via tenofovir-diphosphate (TFV-DP) blood concentrations. IDIs were conducted in isiXhosa, audio-recorded, transcribed and translated for analysis using an iterative process guided by SPT to assess factors influencing PrEP disclosure and adherence. Results: Most participants (78.4%) were enrolled in high school, lived with family (97.3%), had a current partner (51.4%), and were sexually active (64.9%) within the last year. All participants considered their high HIV risk and future goals as primary PrEP motivators. Participants described PrEP disclosure events to family members, friends and boyfriend/partners, with 91.7% of those with high TFV-DP blood concentrations disclosing to all three categories, while only 57.9% of those with low TFV-DP blood concentrations disclosed to all three. Receiving PrEP support from multiple individuals helped in navigating PrEP disinterest from others, lack of PrEP education within the community, and mistrust in relationships. After disclosure, gossip and PrEP myths were not influential for those with multiple disclosures and sources of support. All participants described taking PrEP as an independent journey, but with support from different people in their lives. Conclusions: PrEP initiation was strongly influenced by one's future goals, while PrEP adherence was seen as an independent journey influenced by disclosures to key individuals in different social spaces. AGYW with high TFV-DP blood concentrations described larger circles of assembled support. Prevention-effective-use of oral PrEP among AGYW may be dependent on building disclosure skills to develop a PrEP support system., OA07.04 J. Daniels (1); D. Bresenham (2); L. de Vos (2); R. Mawarire (2); M. Atujuna (3); S. Hosek (4); C. Celum (5); L.-G. Bekker (3) and A. Medina-Marino (2) [...]

Background: HIV incidence is high during pregnancy and postpartum in many settings. PrEP is safe and effective but requires adherence during potential HIV exposure, yet the facilitators of high maternal adherence are not well understood in high HIV burden settings. Methods: We conducted semi-structured interviews with women who reported high adherence (PrEP use [greater than or equal to]25 days in last 30-days) within a PrEP service for pregnant and postpartum women located in a large primary care facility in a high-HIV burden township. Topics for interviews included: individual and interpersonal risk, disclosure, anticipated PrEP stigma, safety, side-effects, and facility-level factors effecting adherence. A thematic approach guided an iterative process of coding (reviewed to ensure intercoder reliability) and analysis using NVivo 12. Results: We interviewed 25 postpartum women with high PrEP adherence who were on PrEP for a median of nine-months, median age 26-years, and median baseline gestational age 24-weeks. Themes identified as key drivers of optimal PrEP use were HIV risk perception --primarily due to partner's perceived risky sexual behaviors and unknown serosatus and a strong desire to have a baby free of HIV. Reported disclosure of PrEP use to family, partners and friends facilitated PrEP adherence. Women continued PrEP postpartum because they felt empowered by PrEP and did not want to 'go backwards' and increase their HIV risk as before PrEP. Women who reported high adherence all discussed having community support and reminders to take PrEP on time. The primary barriers were anticipated or experienced stigma, which most overcame through education of partners/family about PrEP. Pregnant women experienced transient side effects, but found ways to continue, including taking PrEP at night. Women believed PrEP education and counselling were accessible when integrated into antenatal care which contributed to high PrEP adherence. Conclusions: Facilitators of optimal PrEP use through pregnancy and postpartum included fear of HIV acquisition for self and infant, mostly due to partner sexual behaviors and unknown serostatus, along with PrEP disclosure, and encouragement from partners and family. PrEP programs for pregnant and postpartum women should integrate strategies to assist women with realistic appraisals of risk and teach skills for securing support for significant others., OA21.05LB D. Joseph Davey (1); L. Knight (2); K. Dovel (3); N. Tsawe (4); N. Mashele (4); J. Markt-Maloney (1); Y. Gomba (4); P. Gorbach (1); L.-G. Bekker (5); T. [...]

Background: Oral PrEP is a safe and effective prevention strategy to reduce women's risk of HIV in pregnancy and postpartum. Successful PrEP outcomes require PrEP adherence at the time of potential HIV exposure, especially in pregnancy when tenofovir plasma concentrations are lower than postpartum. Methods: The PrEP in pregnancy and postpartum (PrEP-PP) study is an ongoing prospective cohort which enrolls consenting pregnant, HIV-uninfected women (>15-years) at first antenatal care visit, followed through 12-months postpartum. Interviewers collect data on participant socio-demographics, relationships, HIV risk factors including: partner's serostatus, intimate partner violence, substance use and depression. At baseline we provided point-of-care STI testing/treatment of chlamydia, gonorrhea and trichomonas (GeneXpert). We evaluate factors associated with: PrEP initiation, PrEP persistence (returning for PrEP repeat prescription) and PrEP adherence (reporting taking PrEP [greater than or equal to] 5 of last seven-days) at three-months after PrEP start using multivariable logistic regression controlling for baseline age and gestational age. Results: Between Aug'19 and Oct'20 we enrolled 712 pregnant women (median gestation = 21w; median age = 26y). Following counseling, 91% of women initiated PrEP at their first antenatal visit (n = 649). Women who were married had lowest odds of taking PrEP compared to unmarried women (aOR = 0.11; 95% CI = 0.02 to 0.73), though over one-fourth didn't know her partner's serostatus (27%). Thirty-five percent of women were diagnosed with a STI. Those with a STI had a nonsignificant greater odds of initiating PrEP (aOR = 1.60; 95% CI = 0.89 to 2.89). Pregnant women who reported high internalized PrEP stigma had lower odds of initiating PrEP (aOR = 0.06; 95% CI = 0.03 to 0.12). At 1 m, 72% women returned for a repeat prescription; at 3 m, 60% returned. Among those returning at 3 m, 87% reported adhering to PrEP in past seven-days. Being postpartum was associated with lower odds of PrEP persistence and adherence (aOR = 0.31; 95% CI = 0.16 to 0.61) adjusting for follow-up study, maternal and gestational age. Retention was lower in women who reported side-effects (22% of women reported nausea, dizziness and vomiting). Conclusions: PrEP uptake was high especially in high-risk women. PrEP persistence and adherence were higher than other SA populations. Anticipated stigma, side effects and the postpartum period presented challenges to optimal PrEP use, pointing to potential targets for interventions to improve PrEP adherence in pregnant/postpartum women., OA07.05LB D. Joseph Davey (1); R. Mvududu (2); N. Mashele (2); M. Lesosky (2); L.-G. Bekker (3); P. Gorbach (1); T. Coates (4); L. Myer (2) and PrEP-PP study (1) [...]

Background: South Africa has the highest HIV incidence globally. HIV risk has been extensively studied in South African cisgender women; however, less is known about risk drivers in cisgender men and transgender women (TGW). We characterised HIV incidence, and sexual behaviours and clinical characteristics associated with HIV acquisition, amongst cisgender men and TGW in two South African HIV vaccine efficacy trials. Methods: We included data from heterosexual cisgender men (HCM), men who have sex with men (MSM) and TGW who participated in Uhambo (N = 1611 randomised to vaccine/placebo, 2016 to 2020) and Phambili (N = 219 randomised to placebo, 2007 to 2011; vaccinees excluded due to potential vaccine-increased risk). Cox proportional hazards models were used to associate baseline variables--self-reported last thirty-days (Uhambo) or six-months (Phambili) sexual behaviours and laboratory-confirmed STIs--with HIV acquisition. Results: Median age was 25 (IQR: 22 to 30). Most identified as heterosexual or reported no male partner (1636/1830 [89.40%]). More MSM and TGW versus HCM reported anal sex (90.21% vs. 5.01%), transactional sex (41.75% vs. 11.37%), [greater than or equal to]2 partners (82.99% vs. 65.28%), sex with alcohol/drugs (67.53% vs. 55.50%) or sex with an HIV-positive partner (71.65% vs. 44.74%). Overall HIV incidence was 1.32% annually (95% CI: 0.99 to 1.74) and higher in MSM and TGW (8.84%, 95% CI: 5.40 to 13.65) or those with an STI (2.99%, 95% CI: 1.63 to 5.01). Based on multiplicity-adjusted univariate analyses, anal sex (HR 6.34, 95% CI: 3.45 to 11.66), transactional sex (HR 3.42, 95% CI: 1.80 to 6.51), and MSM or homosexual identity (HR 15.62, 95% CI: 7.82 to 31.81) were significantly associated with HIV acquisition. In a multivariate model of published HIV risk factors, only MSM and homosexual identity (HR 12.90, 95% CI: 4.03 to 41.29; p < 0.001) was significantly associated with HIV acquisition. Conclusions: Identifying as MSM or homosexual is a strong predictor of HIV acquisition in South African men and TGW. While overall incidence in cisgender men and TGW is low relative to women, subpopulations of cis-gender men and TGW experience exceptionally high incidence., OA02.05LB M. Malahleha (1); H. Janes (2); F. Laher (3); L.-G. Bekker (4); B. S. Prigmore (5); D. Grove (5); J.J. Kee (5); M. Allen (6); M. Andrasik (2); M. [...]

BACKGROUND A safe, effective vaccine is essential to eradicating human immunodeficiency virus (HIV) infection. A canarypox-protein HIV vaccine regimen (ALVAC-HIV plus AIDSVAX B/E) showed modest efficacy in reducing infection in Thailand. An analogous regimen using HIV-1 subtype C virus showed potent humoral and cel-lular responses in a phase 1-2a trial in South Africa. Efficacy data and additional safety data were needed for this regimen in a larger population in South Africa. METHODS In this phase 2b-3 trial, we randomly assigned 5404 adults without HIV-1 infection to receive the vaccine (2704 participants) or placebo (2700 participants). The vaccine regimen consisted of injections ofALVAC-HIV at months 0 and 1, followed by four booster injections of ALVAC-HIV plus bivalent subtype C gpl20-MF59 adjuvant at months 3, 6, 12, and 18. The primary efficacy outcome was the occurrence of HIV-1 infection from randomization to 24 months. RESULTS In January 2020, prespecified criteria for nonefficacy were met at an interim analysis; further vaccinations were subsequently halted. The median age of the trial participants was 24 years; 70% of the participants were women. The incidence of adverse events was similar in the vaccine and placebo groups. During the 24-month followup, HIV-1 infection was diagnosed in 138 participants in the vaccine group and in 133 in the placebo group (hazard ratio, 1.02; 95% confidence interval, 0.81 to 1.30; P=0.84). CONCLUSIONS The ALVAC-gpl20 regimen did not prevent HIV-1 infection among participants in South Africa despite previous evidence ofimmunogenicity. (HVTN 702 ClinicalTrials .gov number, NCT02968849.). [ABSTRACT FROM AUTHOR]