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The SARS-CoV-2 Omicron variant (B.1.1.529) has multiple spike protein mutations1,2 that contribute to viral escape from antibody neutralization3-6 and reduce vaccine protection from infection7,8. The extent to which other components of the adaptive response such as T cells may still target Omicron and contribute to protection from severe outcomes is unknown. Here we assessed the ability of T cells to react to Omicron spike protein in participants who were vaccinated with Ad26.CoV2.S or BNT162b2, or unvaccinated convalescent COVID-19 patients (n = 70). Between 70% and 80% of the CD4+ and CD8+ T cell response to spike was maintained across study groups. Moreover, the magnitude of Omicron cross-reactive T cells was similar for Beta (B.1.351) and Delta (B.1.617.2) variants, despite Omicron harbouring considerably more mutations. In patients who were hospitalized with Omicron infections (n = 19), there were comparable T cell responses to ancestral spike, nucleocapsid and membrane proteins to those in patients hospitalized in previous waves dominated by the ancestral, Beta or Delta variants (n = 49). Thus, despite extensive mutations and reduced susceptibility to neutralizing antibodies of Omicron, the majority of T cell responses induced by vaccination or infection cross-recognize the variant. It remains to be determined whether well-preserved T cell immunity to Omicron contributes to protection from severe COVID-19 and is linked to early clinical observations from South Africa and elsewhere9-12.
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COVID-19/imunologia , COVID-19/virologia , Reações Cruzadas/imunologia , Imunidade Celular , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Linfócitos T/imunologia , Adulto , Idoso , Vacinas contra COVID-19/imunologia , Convalescença , Hospitalização , Humanos , Pessoa de Meia-Idade , SARS-CoV-2/química , SARS-CoV-2/classificaçãoRESUMO
BACKGROUND: There are gaps in uptake of, adherence to, and persistence in the use of preexposure prophylaxis 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/TAF 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% confidence interval [CI], 0.00 to 0.19), 39 infections among 2136 participants in the F/TAF group (2.02 per 100 person-years; 95% 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 F/TAF 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) (34.9%); 4 participants in the lenacapavir group (0.2%) 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 number, NCT04994509.).
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The impact of previous SARS-CoV-2 infection on the durability of Ad26.COV2.S vaccine-elicited responses, and the effect of homologous boosting has not been well explored. We followed a cohort of healthcare workers for 6 months after receiving the Ad26.COV2.S vaccine and a further one month after they received an Ad26.COV2.S booster dose. We assessed longitudinal spike-specific antibody and T cell responses in individuals who had never had SARS-CoV-2 infection, compared to those who were infected with either the D614G or Beta variants prior to vaccination. Antibody and T cell responses elicited by the primary dose were durable against several variants of concern over the 6 month follow-up period, regardless of infection history. However, at 6 months after first vaccination, antibody binding, neutralization and ADCC were as much as 59-fold higher in individuals with hybrid immunity compared to those with no prior infection. Antibody cross-reactivity profiles of the previously infected groups were similar at 6 months, unlike at earlier time points, suggesting that the effect of immune imprinting diminishes by 6 months. Importantly, an Ad26.COV2.S booster dose increased the magnitude of the antibody response in individuals with no prior infection to similar levels as those with previous infection. The magnitude of spike T cell responses and proportion of T cell responders remained stable after homologous boosting, concomitant with a significant increase in long-lived early differentiated CD4 memory T cells. Thus, these data highlight that multiple antigen exposures, whether through infection and vaccination or vaccination alone, result in similar boosts after Ad26.COV2.S vaccination.
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Ad26COVS1 , COVID-19 , Humanos , COVID-19/prevenção & controle , SARS-CoV-2 , Anticorpos , Vacinação , Imunidade Adaptativa , Anticorpos Antivirais , Anticorpos Neutralizantes , Imunidade HumoralRESUMO
BACKGROUND: Confounding introduced by individuals' sexual risk behavior is potentially a significant source of bias in HIV-1 prevention intervention studies. To more completely account for sexual behaviors when assessing the efficacy of the monthly dapivirine ring, a new longer-acting HIV-1 prevention option for women, we estimated per-sex-act risk reduction associated with product use. METHODS: We conducted a secondary analysis of data from MTN-020/ASPIRE, a phase 3, randomized, placebo-controlled efficacy trial of the dapivirine ring that recruited HIV-uninfected, African women aged 18-45 years. With cumulative sex acts as the time scale, we used multivariable Cox regression with inverse probability of censoring weights to estimate HIV-1 risk reduction associated with a rate of dapivirine release indicative of consistent product use. RESULTS: Women in the dapivirine ring group (n = 1187) had an estimated incidence rate of 2.3 (95% confidence interval [CI], 1.8-3.1) HIV-1 acquisition events per 10 000 sex acts versus 3.6 (95% CI, 2.9-4.4) per 10 000 acts in the placebo group (n = 1187). Dapivirine release indicative of consistent ring use was associated with a 63% (95% CI, 33%-80%) per-sex-act HIV-1 risk reduction. CONCLUSIONS: These results support the efficacy of the dapivirine vaginal ring for HIV-1 prevention and help to inform decision-making for women, providers, and policymakers regarding product use. CLINICAL TRIALS REGISTRATION: NCT01617096.
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Fármacos Anti-HIV , Dispositivos Anticoncepcionais Femininos , Infecções por HIV , Soropositividade para HIV , HIV-1 , Pirimidinas , Feminino , Humanos , Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/prevenção & controle , Infecções por HIV/epidemiologia , Comportamento de Redução do Risco , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Women in Africa disproportionately acquire HIV-1. Understanding which women are most likely to acquire HIV-1 can guide focused prevention with pre-exposure prophylaxis (PrEP). Our objective is to identify women at highest risk of HIV-1 and estimate PrEP efficiency at different sensitivity levels. METHODS: Nationally representative data were collected from 2015-2019 from 15 population-based household surveys. This analysis included women aged 15-49 who tested HIV-1 sero-negative or had recent HIV-1. Least absolute shrinkage and selection operator regression models were fit with 28 variables to predict recent HIV-1. Models were trained on the full population and internally cross-validated. Performance was evaluated using area under the receiver-operating-characteristic curve (AUC), sensitivity, and number needed to treat (NNT) with PrEP to avert one infection. RESULTS: Among 209,012 participants 248 had recent HIV-1 infection, representing 118 million women and 402,000 (95% CI: 309,000-495,000) new annual infections. Two variables were retained in the model: living in a subnational area with high HIV-1 viremia and having a sexual partner living outside the home. Full-population AUC was 0.80 (95% CI: 0.76-0.84); cross-validated AUC was 0.79 (95% CI: 0.75-0.84). At a sensitivity of 33%, up to 130,000 cases could be averted if 7.9 million women were perfectly adherent to PrEP; NNT would be 61. At a sensitivity of 67%, up to 260,000 cases could be averted if 25.1 million women were perfectly adherent to PrEP; the NNT would be 96. CONCLUSIONS: This risk assessment tool was generalizable, predictive, and parsimonious with tradeoffs between reach and efficiency.
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BACKGROUND: Oral pre-exposure prophylaxis (PrEP) with emtricitabine/tenofovir disoproxil fumarate (F/TDF) has high efficacy against HIV-1 acquisition. Seventy-two prospective studies of daily oral F/TDF PrEP were conducted to evaluate HIV-1 incidence, drug resistance, adherence, and bone and renal safety in diverse settings. METHODS: HIV-1 incidence was calculated from incident HIV-1 diagnoses after PrEP initiation and within 60 days of discontinuation. Tenofovir concentration in dried blood spots (DBS), drug resistance, and bone/renal safety indicators were evaluated in a subset of studies. RESULTS: Among 17,274 participants, there were 101 cases with new HIV-1 diagnosis (0.77 per 100 person-years; 95% CI 0.63-0.94). In 78 cases with resistance data, 18 (23%) had M184I or V, one (1.3%) had K65R, and three (3.8%) had both mutations. In 54 cases with tenofovir concentration data from DBS, 45 (83.3%), 2 (3.7%), 6 (11.1%), and 1 (1.9%) had average adherence of <2, 2-3, 4-6, and ≥7 doses/week, respectively, and the corresponding incidence was 3.9 (95% CI 2.9-5.3), 0.24 (0.060-0.95), 0.27 (0.12-0.60), and 0.054 (0.008-0.38) per 100 person-years. Adherence was low in younger participants, Hispanic/Latinx and Black participants, cisgender women, and transgender women. Bone and renal adverse event incidence rates were 0.69 and 11.8 per 100 person-years, respectively, consistent with previous reports. CONCLUSIONS: Leveraging the largest pooled analysis of global PrEP studies to date, we demonstrate that F/TDF is safe and highly effective, even with less than daily dosing, in diverse clinical settings, geographies, populations, and routes of HIV-1 exposure.
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BACKGROUND: Adjuvants are widely used to enhance and/or direct vaccine-induced immune responses yet rarely evaluated head-to-head. Our trial directly compared immune responses elicited by MF59 versus alum adjuvants in the RV144-like HIV vaccine regimen modified for the Southern African region. The RV144 trial of a recombinant canarypox vaccine vector expressing HIV env subtype B (ALVAC-HIV) prime followed by ALVAC-HIV plus a bivalent gp120 protein vaccine boost adjuvanted with alum is the only trial to have shown modest HIV vaccine efficacy. Data generated after RV144 suggested that use of MF59 adjuvant might allow lower protein doses to be used while maintaining robust immune responses. We evaluated safety and immunogenicity of an HIV recombinant canarypox vaccine vector expressing HIV env subtype C (ALVAC-HIV) prime followed by ALVAC-HIV plus a bivalent gp120 protein vaccine boost (gp120) adjuvanted with alum (ALVAC-HIV+gp120/alum) or MF59 (ALVAC-HIV+gp120/MF59) or unadjuvanted (ALVAC-HIV+gp120/no-adjuvant) and a regimen where ALVAC-HIV+gp120 adjuvanted with MF59 was used for the prime and boost (ALVAC-HIV+gp120/MF59 coadministration). METHODS AND FINDINGS: Between June 19, 2017 and June 14, 2018, 132 healthy adults without HIV in South Africa, Zimbabwe, and Mozambique were randomized to receive intramuscularly: (1) 2 priming doses of ALVAC-HIV (months 0 and 1) followed by 3 booster doses of ALVAC-HIV+gp120/MF59 (months 3, 6, and 12), n = 36; (2) 2 priming doses of ALVAC-HIV (months 0 and 1) followed by 3 booster doses of ALVAC-HIV+gp120/alum (months 3, 6, and 12), n = 36; (3) 4 doses of ALVAC-HIV+gp120/MF59 coadministered (months 0, 1, 6, and 12), n = 36; or (4) 2 priming doses of ALVAC-HIV (months 0 and 1) followed by 3 booster doses of ALVAC-HIV+gp120/no adjuvant (months 3, 6, and 12), n = 24. Primary outcomes were safety and occurrence and mean fluorescence intensity (MFI) of vaccine-induced gp120-specific IgG and IgA binding antibodies at month 6.5. All vaccinations were safe and well-tolerated; increased alanine aminotransferase was the most frequent related adverse event, occurring in 2 (1.5%) participants (1 severe, 1 mild). At month 6.5, vaccine-specific gp120 IgG binding antibodies were detected in 100% of vaccinees for all 4 vaccine groups. No significant differences were seen in the occurrence and net MFI of vaccine-specific IgA responses between the ALVAC-HIV+gp120/MF59-prime-boost and ALVAC-HIV+gp120/alum-prime-boost groups or between the ALVAC-HIV+gp120/MF59-prime-boost and ALVAC-HIV+gp120/MF59 coadministration groups. Limitations were the relatively small sample size per group and lack of evaluation of higher gp120 doses. CONCLUSIONS: Although MF59 was expected to enhance immune responses, alum induced similar responses to MF59, suggesting that the choice between these adjuvants may not be critical for the ALVAC+gp120 regimen. TRIAL REGISTRATION: HVTN 107 was registered with the South African National Clinical Trials Registry (DOH-27-0715-4894) and ClinicalTrials.gov (NCT03284710).
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Vacinas contra a AIDS , Compostos de Alúmen , Infecções por HIV , HIV-1 , Polissorbatos , Esqualeno , Adulto , Humanos , Adjuvantes Imunológicos , Vacinas contra a AIDS/efeitos adversos , Anticorpos Anti-HIV , Infecções por HIV/prevenção & controle , Imunogenicidade da Vacina , Imunoglobulina A , Imunoglobulina G , Vacinas Combinadas , Vacinas SintéticasRESUMO
In sub-Saharan Africa, adolescent girls and young women aged 15-24 (AGYW) experience high risk of early and unintended pregnancy. We assessed the impact of youth-friendly health services (YFHS) on pregnancy risk among AGYW who participated in the Girl Power study. In 2016, Girl Power randomly assigned four government-run health centers in Lilongwe, Malawi, to provide a standard (n=1) or youth-friendly (n=3) model of service delivery. At six and 12 months, study participants (n=250 at each health center) self-reported their current pregnancy status and received a urine pregnancy test. Because of missing pregnancy test results, we used multiple imputation to correct for outcome misclassification in self-reported pregnancy status, and applied the parametric g-formula on the corrected data to estimate the effect of YFHS on the 12-month risk of pregnancy. After correcting for outcome misclassification, the risk of pregnancy under the scenario where all health centers offered YFHS was 15.8% compared to 23.2% under the scenario where all health centers offered standard of care (risk difference: -7.3%, 95% CI: -15.5%, 0.8%). Access to a model of YFHS that integrates provider training with youth-friendly clinic modifications and community outreach activities may decrease risk of pregnancy among AGYW relative to standard of care.
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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 cellular 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 of ALVAC-HIV at months 0 and 1, followed by four booster injections of ALVAC-HIV plus bivalent subtype C gp120-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 follow-up, 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-gp120 regimen did not prevent HIV-1 infection among participants in South Africa despite previous evidence of immunogenicity. (HVTN 702 ClinicalTrials.gov number, NCT02968849.).
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Vacinas contra a AIDS , Adjuvantes Imunológicos , Infecções por HIV/prevenção & controle , HIV-1 , Imunogenicidade da Vacina , Polissorbatos , Esqualeno , Vacinas contra a AIDS/imunologia , Adolescente , Adulto , Vírus da Varíola dos Canários , Método Duplo-Cego , Feminino , Vetores Genéticos , HIV-1/genética , Humanos , Imunização Secundária , Masculino , África do Sul , Falha de Tratamento , Adulto JovemRESUMO
BACKGROUND: South Africa's first SARS-CoV-2 case was identified 5th March 2020 and national lockdown followed March 26th. Households are an important location for secondary SARS-CoV-2 infection. Physical distancing and sanitation - infection mitigation recommended by the World Health Organization (WHO) at the time - are difficult to implement in limited-resource settings because of overcrowded living conditions. METHODS: This study (ClinicalTrials.gov NCT05119348) was conducted from August 2020 to September 2021 in two densely populated, low socioeconomic Cape Town community sub-districts. New COVID-19 index cases (ICs) identified at public clinics were randomised to an infection mitigation intervention (STOPCOV) delivered by lay community health workers (CHWs) or standard of care group. STOPCOV mitigation measures included one initial household assessment conducted by a CHW in which face masks, sanitiser, bleach and written information on managing and preventing spread were provided. This was followed by regular telephonic follow-up from CHWs. SARS-CoV-2 PCR and IgM/IgG serology was performed at baseline, weeks 1, 2, 3 and 4 of follow-up. RESULTS: The study randomised 81 ICs with 245 HHCs. At baseline, no HHCs in the control and 7 (5%) in the intervention group had prevalent SARS-CoV-2. The secondary infection rate (SIR) based on SARS-CoV-2 PCR testing was 1.9% (n = 2) in control and 2.9% (n = 4) in intervention HHCs (p = 0.598). At baseline, SARS-CoV-2 antibodies were present in 15% (16/108) of control and 38% (52/137) of intervention participants. At study end incidence was 8.3% (9/108) and 8.03% (11/137) in the intervention and control groups respectively. Antibodies were present in 23% (25/108) of control HHCs over the course of the study vs. 46% (63/137) in the intervention arm. CHWs made twelve clinic and 47 food parcel referrals for individuals in intervention households in need. DISCUSSION: Participants had significant exposure to SARS-CoV-2 infections prior to the study. In this setting, household transmission mitigation was ineffective. However, CHWs may have facilitated other important healthcare and social referrals.
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COVID-19 , Características da Família , SARS-CoV-2 , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , COVID-19/transmissão , África do Sul/epidemiologia , Feminino , Masculino , Adulto , Estudos Prospectivos , Pessoa de Meia-Idade , Adulto Jovem , Adolescente , Aglomeração , Agentes Comunitários de Saúde , Criança , IdosoRESUMO
In Southern and Eastern Africa, initiation of daily oral pre-exposure prophylaxis (PrEP) for HIV prevention has been high among adolescent girls and young women (AGYW) offered PrEP. However, persistence and prevention-effective use of PrEP among this critical group continues to be a challenge. We conducted a qualitative sub-study of AGYW from the Community PrEP Study in Eastern Cape Province, South Africa who had high rates of pick up for monthly PrEP refills over two years, but differing levels of PrEP adherence based on tenofovir-diphosphate (TFV-DP) measurements in dried blood spots (DBS). Contrasting 22 AGYW with low versus high levels of TFV-DP in DBS, we qualitatively explored factors which influenced PrEP persistence vs. non-persistence, unique patterns of PrEP use (e.g., discarding or stockpiling), and participant recommendations for improving AGYW prevention-effective use of PrEP in the future. Results showed that PrEP misconceptions and mistrust among participants' social networks negatively influenced adherence. In comparison, supportive families and/or partners and personal trust that PrEP works positively influenced adherence. Those with low adherence described being motivated to come to the site for other study benefits (e.g., reimbursement money, snacks, sanitary pads) and discarding PrEP to avoid stigma associated with being seen with pills. Future PrEP implementation strategies should focus on involving families and partners in PrEP support for AGYW and minimizing PrEP stigma at a community level.Trial registration NCT03977181. Retrospectively registered on June 6, 2019.
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Adenina/análogos & derivados , Fármacos Anti-HIV , Infecções por HIV , Organofosfatos , Humanos , Adolescente , Feminino , África do Sul , Cognição , Pesquisa Qualitativa , Infecções por HIV/prevenção & controle , Fármacos Anti-HIV/uso terapêuticoRESUMO
BACKGROUND: Poor psychological well-being is both prevalent among South Africans living with HIV and has been associated with poor HIV clinical outcomes. However, the relationship between disclosure and psychological well-being remains unclear. This analysis sought to examine the relationship between two disclosure-related variables, disclosure status and reaction received, and psychosocial well-being among a sample of young adults living with HIV (YALWH) in urban South Africa. METHOD: This was a secondary analysis using observational data from Standing Tall, a randomized controlled trial that recruited 100 participants ages 18-24 who tested positive for HIV after initially presenting to two well-established mobile clinics for HIV testing. Interviews investigating primary and secondary outcomes of interest were done at baseline and 6 months following recruitment. RESULTS: About half (51%) of participants disclosed their HIV status within 6 months after recruitment. Simple linear regression analyses revealed that disclosure of HIV status within 6 months after study enrollment predicted significantly lower levels of disclosure concerns and internalized stigma (p < 0.05). Reactions to disclosure were not significantly associated with any of the measures of psychosocial well-being considered in this analysis (p > 0.05). CONCLUSION: The results suggest that the act of disclosure among newly diagnosed YALWH may be associated with reductions in internalized stigma. In addition, the finding that the act of disclosure may be a more important determinant of psychosocial well-being than the reaction to disclosure has important implications for interventions designed to promote disclosure and psychosocial well-being in YALWH.
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Importance: Emtricitabine and tenofovir disoproxil fumarate (F/TDF) for HIV preexposure prophylaxis (PrEP) is highly effective in cisgender men who have sex with men (MSM) when adherence is high (>4 doses/week). Real-world effectiveness and adherence with F/TDF for PrEP in cisgender women is less well characterized. Objective: To characterize the effectiveness of F/TDF for PrEP and its relationship with adherence in cisgender women. Design, Setting, and Participants: Data were pooled from 11 F/TDF PrEP postapproval studies conducted in 6 countries that included 6296 cisgender women aged 15 to 69 years conducted from 2012 to 2020. HIV incidence was evaluated according to adherence level measured objectively (tenofovir diphosphate concentration in dried blood spots or tenofovir concentration in plasma; n = 288) and subjectively (electronic pill cap monitoring, pill counts, self-report, and study-reported adherence scale; n = 2954) using group-based trajectory modeling. Exposures: F/TDF prescribed orally once a day. HIV incidence was analyzed in subgroups based on adherence trajectory. Main Outcomes and Measures: HIV incidence. Results: Of the 6296 participants, 46% were from Kenya, 28% were from South Africa, 21% were from India, 2.9% were from Uganda, 1.6% were from Botswana, and 0.8% were from the US. The mean (SD) age at PrEP initiation across all studies was 25 (7) years, with 61% of participants being younger than 25 years. The overall HIV incidence was 0.72 per 100 person-years (95% CI, 0.51-1.01; 32 incident HIV diagnoses among 6296 participants). Four distinct groups of adherence trajectories were identified: consistently daily (7 doses/week), consistently high (4-6 doses/week), high but declining (from a mean of 4-6 doses/week and then declining), and consistently low (less than 2 doses/week). None of the 498 women with consistently daily adherence acquired HIV. Only 1 of the 658 women with consistently high adherence acquired HIV (incidence rate, 0.13/100 person-years [95% CI, 0.02-0.92]). The incidence rate was 0.49 per 100 person-years (95% CI, 0.22-1.08) in the high but declining adherence group (n = 1166) and 1.27 per 100 person-years (95% CI, 0.53-3.04) in the consistently low adherence group (n = 632). Conclusions and Relevance: In a pooled analysis of 11 postapproval studies of F/TDF for PrEP among cisgender women, overall HIV incidence was 0.72 per 100 person-years; individuals with consistently daily or consistently high adherence (4-6 doses/week) to PrEP experienced very low HIV incidence.
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Fármacos Anti-HIV , Infecções por HIV , Profilaxia Pré-Exposição , Minorias Sexuais e de Gênero , Masculino , Humanos , Feminino , Tenofovir/uso terapêutico , Emtricitabina/uso terapêutico , Homossexualidade Masculina , Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Infecções por HIV/tratamento farmacológico , AconselhamentoRESUMO
BACKGROUND: Alternative approaches to syndromic management are needed to reduce rates of sexually transmitted infections (STIs) in resource-limited settings. We investigated the impact of point-of-care (POC) versus central laboratory-based testing on STI treatment initiation and STI adverse event (STI-AE) reporting. METHODS: We used Kaplan-Meier and Cox regression models to compare times to treatment initiation and STI-AE reporting among HVTN702 trial participants in South Africa. Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) were diagnosed POC at eThekwini clinic and in a central laboratory at Verulam/Isipingo clinics. All clinics used POC assays for Trichomonas vaginalis (TV) testing. RESULTS: Among 959 women (median age, 23 [interquartile range, 21-26] years), median days (95% confidence interval [95%CI]) to NG/CT treatment initiation and NG/CT-AE reporting were 0.20 (.16-.25) and 0.24 (.19-.27) at eThekwini versus 14.22 (14.12-15.09) and 15.12 (13.22-21.24) at Verulam/Isipingo (all P < .001). Median days (95%CI) to TV treatment initiation and TV-AE reporting were 0.17 (.12-.27) and 0.25 (.20-.99) at eThekwini versus 0.18 (.15-.2) and 0.24 (.15-.99) at Verulam/Isipingo (all P > .05). Cox regression analysis revealed that NG/CT treatment initiation (adjusted hazard ratio [aHR], 39.62 [95%CI, 15.13-103.74]) and NG/CT-AE reporting (aHR, 3.38 [95%CI, 2.23-5.13]) occurred faster at eThekwini versus Verulam/Isipingo, while times to TV treatment initiation (aHR, 0.93 [95%CI, .59-1.48]) and TV-AE reporting (aHR, 1.38 [95%CI, .86-2.21]) were similar. CONCLUSIONS: POC testing led to prompt STI management with potential therapeutic and prevention benefits, highlighting its utility as a diagnostic tool in resource-limited settings.
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Infecções por Chlamydia , Gonorreia , Infecções por HIV , Infecções Sexualmente Transmissíveis , Trichomonas vaginalis , Vacinas , Adulto , Feminino , Humanos , Adulto Jovem , Infecções por Chlamydia/diagnóstico , Infecções por Chlamydia/tratamento farmacológico , Infecções por Chlamydia/epidemiologia , Chlamydia trachomatis , Gonorreia/diagnóstico , Gonorreia/tratamento farmacológico , Gonorreia/epidemiologia , HIV , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Neisseria gonorrhoeae , Testes Imediatos , Infecções Sexualmente Transmissíveis/diagnóstico , Infecções Sexualmente Transmissíveis/tratamento farmacológico , Infecções Sexualmente Transmissíveis/epidemiologia , África do Sul/epidemiologiaRESUMO
BACKGROUND: We aimed to assess the effectiveness of a single dose of the Ad26.COV2.S vaccine (Johnson & Johnson) in health-care workers in South Africa during two waves of the South African COVID-19 epidemic. METHODS: In the single-arm, open-label, phase 3B implementation Sisonke study, health-care workers aged 18 years and older were invited for vaccination at one of 122 vaccination sites nationally. Participants received a single dose of 5â×â1010 viral particles of the Ad26.COV2.S vaccine. Vaccinated participants were linked with their person-level data from one of two national medical insurance schemes (scheme A and scheme B) and matched for COVID-19 risk with an unvaccinated member of the general population. The primary outcome was vaccine effectiveness against severe COVID-19, defined as COVID-19-related admission to hospital, hospitalisation requiring critical or intensive care, or death, in health-care workers compared with the general population, ascertained 28 days or more after vaccination or matching, up to data cutoff. This study is registered with the South African National Clinical Trial Registry, DOH-27-022021-6844, ClinicalTrials.gov, NCT04838795, and the Pan African Clinical Trials Registry, PACTR202102855526180, and is closed to accrual. FINDINGS: Between Feb 17 and May 17, 2021, 477â102 health-care workers were enrolled and vaccinated, of whom 357â401 (74·9%) were female and 119â701 (25·1%) were male, with a median age of 42·0 years (33·0-51·0). 215â813 vaccinated individuals were matched with 215â813 unvaccinated individuals. As of data cutoff (July 17, 2021), vaccine effectiveness derived from the total matched cohort was 83% (95% CI 75-89) to prevent COVID-19-related deaths, 75% (69-82) to prevent COVID-19-related hospital admissions requiring critical or intensive care, and 67% (62-71) to prevent COVID-19-related hospitalisations. The vaccine effectiveness for all three outcomes were consistent across scheme A and scheme B. The vaccine effectiveness was maintained in older health-care workers and those with comorbidities including HIV infection. During the course of the study, the beta (B.1.351) and then the delta (B.1.617.2) SARS-CoV-2 variants of concerns were dominant, and vaccine effectiveness remained consistent (for scheme A plus B vaccine effectiveness against COVID-19-related hospital admission during beta wave was 62% [95% CI 42-76] and during delta wave was 67% [62-71], and vaccine effectiveness against COVID-19-related death during beta wave was 86% [57-100] and during delta wave was 82% [74-89]). INTERPRETATION: The single-dose Ad26.COV2.S vaccine shows effectiveness against severe COVID-19 disease and COVID-19-related death after vaccination, and against both beta and delta variants, providing real-world evidence for its use globally. FUNDING: National Treasury of South Africa, the National Department of Health, Solidarity Response Fund NPC, The Michael & Susan Dell Foundation, The Elma Vaccines and Immunization Foundation, and the Bill & Melinda Gates Foundation.
Assuntos
COVID-19 , Infecções por HIV , Vacinas , Ad26COVS1 , Adolescente , Adulto , Idoso , COVID-19/epidemiologia , COVID-19/prevenção & controle , Feminino , Humanos , Masculino , SARS-CoV-2 , África do Sul/epidemiologiaRESUMO
The pox-protein regimen tested in the RV144 trial is the only vaccine strategy demonstrated to prevent HIV-1 infection. Subsequent analyses identified antibody and cellular immune responses as correlates of risk (CoRs) for HIV infection. Early predictors of these CoRs could provide insight into vaccine-induced protection and guide efforts to enhance vaccine efficacy. Using specimens from a phase 1b trial of the RV144 regimen in HIV-1-uninfected South Africans (HVTN 097), we profiled innate responses to the first ALVAC-HIV immunization. PBMC transcriptional responses peaked 1 day post-vaccination. Type I and II interferon signaling pathways were activated, as were innate pathways critical for adaptive immune priming. We then identified two innate immune transcriptional signatures strongly associated with adaptive immune CoR after completion of the 4-dose regimen. Day 1 signatures were positively associated with antibody-dependent cellular cytotoxicity and phagocytosis activity at Month 6.5. Conversely, a signature present on Days 3 and 7 was inversely associated with Env-specific CD4+ T cell responses at Months 6.5 and 12; rapid resolution of this signature was associated with higher Env-specific CD4+ T-cell responses. These are the first-reported early immune biomarkers of vaccine-induced responses associated with HIV-1 acquisition risk in humans and suggest hypotheses to improve HIV-1 vaccine regimens.
Assuntos
Vacinas contra a AIDS/imunologia , Infecções por HIV/prevenção & controle , HIV-1/imunologia , Imunidade Inata/imunologia , Anticorpos Neutralizantes/imunologia , Citotoxicidade Celular Dependente de Anticorpos/imunologia , Linfócitos T CD4-Positivos/imunologia , Anticorpos Anti-HIV/imunologia , Antígenos HIV/imunologia , Infecções por HIV/imunologia , Humanos , Leucócitos Mononucleares/imunologia , RiscoRESUMO
INTRODUCTION: We investigated the prevalence, incidence and factors associated with sexually transmitted infections (STIs) among young African women seeking HIV pre-exposure prophylaxis (PrEP). METHODS: HPTN 082 was a prospective, open-label PrEP study enrolling HIV-negative sexually active women aged 16-25 years in Cape Town and Johannesburg, South Africa, and Harare, Zimbabwe. Endocervical swabs from enrolment, months 6 and 12 were tested for Neisseria gonorrhoeae (GC) and Chlamydia trachomatis (CT) by nucleic acid amplification, and Trichomonas vaginalis (TV) by a rapid test. Intracellular tenofovir-diphosphate (TFV-DP) concentrations in dried blood spots were measured at months 6 and 12. Associations between risk characteristics and STI outcomes were assessed using Poisson regression. RESULTS: Of 451 enrolled participants, 55% had an STI detected at least once. CT incidence was 27.8 per 100 person-years (py) (95% CI 23.1, 33.2), GC incidence was 11.4 per 100 py (95% CI 8.5, 15.0) and TV incidence was 6.7 per 100 py (95% CI 4.5, 9.5). 66% of incident infections were diagnosed in women uninfected at baseline. Baseline cervical infection (GC or CT) risk was highest in Cape Town (relative risk (RR) 2.38, 95% CI 1.35, 4.19) and in those not living with family (RR 1.87, 95% 1.13, 3.08); condom use was protective (RR 0.67, 95% CI 0.45, 0.99). Incident CT was associated with baseline CT (RR 2.01; 95% CI 1.28, 3.15) and increasing depression score (RR 1.05; 95% CI 1.01, 1.09). Incident GC was higher in Cape Town (RR 2.40; 95% CI 1.18, 4.90) and in participants with high PrEP adherence (TFV-DP concentrations ≥700 fmol/punch) (RR 2.04 95% CI 1.02, 4.08). CONCLUSION: Adolescent girls and young women seeking PrEP have a high prevalence and incidence of curable STIs. Alternatives to syndromic management for diagnosis and treatment are needed to reduce the burden of STIs in this population. TRIAL REGISTRATION NUMBER: NCT02732730.
Assuntos
Gonorreia , Infecções por HIV , Profilaxia Pré-Exposição , Infecções Sexualmente Transmissíveis , Trichomonas vaginalis , Adolescente , Feminino , Humanos , Gonorreia/diagnóstico , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Infecções por HIV/tratamento farmacológico , África do Sul/epidemiologia , Zimbábue/epidemiologia , Incidência , Estudos Prospectivos , Prevalência , Infecções Sexualmente Transmissíveis/epidemiologia , Chlamydia trachomatis/genéticaRESUMO
Many early phase HIV prevention studies define HIV risk-related eligibility criteria. We conducted a retrospective review of HIV Vaccine Trials Network (HVTN) Phase 1 and 2 HIV vaccine clinical trials completed in South Africa from 2003 to 2020, evaluating HIV incidence by protocol-defined risk criteria. Comparisons between groups controlled for age, gender and year of trial initiation. Across 12 trials, 1 did not specify risk criteria, and 11 specified various low risk criteria thematically categorized under sexual behaviors, clinical characteristics, and/or drug use behavior. Of the 11 trials, 6 used low sexual risk eligibility criteria standardized by the HVTN in 2009. Of the 1249 participants, median age 23.0 years, 66% were enrolled with the HVTN 2009 standardized low risk criteria, 15% using other sets of low risk criteria, and 19% using no risk criteria. Compared with the standardized low risk criteria group [2.3], HIV incidence per 100 person-years was significantly higher in the non-standardized low risk criteria group [5.0] and in the no risk criteria group [4.8]. In South Africa, cohorts with low HIV incidence can be identified primarily through sexual behavior and clinical characteristics.
Assuntos
Vacinas contra a AIDS , Infecções por HIV , HIV-1 , Adulto , Humanos , Adulto Jovem , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Incidência , África do Sul/epidemiologiaRESUMO
Eliminating adolescent HIV in high-burden African countries depends on the success of implementing evidence-based interventions to reduce transmission and improve treatment outcomes. The Adolescent HIV Prevention and Treatment Implementation Science Alliance (AHISA) takes a collaborative approach to addressing key challenges and identifying and developing new areas of investigation to advance the adolescent HIV agenda. This special supplement represents the collective learning of the Alliance related to implementation science in the context of the adolescent HIV continuum of care from multiple African countries. Specifically, this series describes the current academic landscape of adolescent HIV and implementation science, such as the methodological use and utility of implementation measures and frameworks; addresses timely topics such as the use of innovative technologies for study adaptations in the context of the global COVID-19 pandemic; and explores opportunities to enhance adolescent-responsive approaches to HIV prevention and treatment using implementation science.
Assuntos
Síndrome da Imunodeficiência Adquirida , COVID-19 , Infecções por HIV , Adolescente , Humanos , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Ciência da Implementação , PandemiasRESUMO
We examined oral PrEP interest among adolescents and its association with perceived parental support and PrEP stigma. Cross-sectional data were collected during baseline procedures of the "Our Family Our Future" intervention trial in South Africa. Adolescents (14-16 years) at elevated risk for acquiring HIV and their parents or caregivers were dyadically enrolled from 2018 to 2021. There were 879 complete adolescent-parent dyads. Among adolescents, 27% had heard about PrEP, 67% reported they would want to use PrEP, and 58% thought their parent would want them to use PrEP. Among parents, 33% had heard about PrEP and 85% reported they would want their adolescent to use PrEP. Adolescents who thought their parent would want them to use PrEP were more likely to be interested in PrEP than adolescents who thought their parent would not want them to use PrEP (adjusted prevalence ratio (aPR) = 2.11, 95% CI 1.82, 2.44). Further, adolescents with higher average PrEP stigma scores above the adolescent sample median were less likely to be interested in PrEP than adolescents with lower average PrEP stigma scores (aPR = 0.81, 95% CI 0.72, 0.91). In conclusion, parents were more supportive of their adolescent taking PrEP than adolescents perceived they would be, and perceptions of low parental support and greater PrEP stigma were associated with reduced PrEP interest among adolescents. Interventions should aim to improve adolescent-parent communication around sexual health and effective HIV prevention tools.