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1.
N Engl J Med ; 384(12): 1089-1100, 2021 03 25.
Artículo en Inglés | MEDLINE | ID: mdl-33761206

RESUMEN

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.).


Asunto(s)
Vacunas contra el SIDA , Adyuvantes Inmunológicos , Infecciones por VIH/prevención & control , VIH-1 , Inmunogenicidad Vacunal , Polisorbatos , Escualeno , Vacunas contra el SIDA/inmunología , Adolescente , Adulto , Virus de la Viruela de los Canarios , Método Doble Ciego , Femenino , Vectores Genéticos , VIH-1/genética , Humanos , Inmunización Secundaria , Masculino , Sudáfrica , Insuficiencia del Tratamiento , Adulto Joven
2.
Sex Transm Infect ; 99(7): 433-439, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-36889914

RESUMEN

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.


Asunto(s)
Gonorrea , Infecciones por VIH , Profilaxis Pre-Exposición , Enfermedades de Transmisión Sexual , Trichomonas vaginalis , Adolescente , Femenino , Humanos , Gonorrea/diagnóstico , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & control , Infecciones por VIH/tratamiento farmacológico , Sudáfrica/epidemiología , Zimbabwe/epidemiología , Incidencia , Estudios Prospectivos , Prevalencia , Enfermedades de Transmisión Sexual/epidemiología , Chlamydia trachomatis/genética
3.
J Infect Dis ; 226(2): 246-257, 2022 08 24.
Artículo en Inglés | MEDLINE | ID: mdl-35758878

RESUMEN

BACKGROUND: The ALVAC/gp120 + MF59 vaccines in the HIV Vaccine Trials Network (HVTN) 702 efficacy trial did not prevent human immunodeficiency virus-1 (HIV-1) acquisition. Vaccine-matched immunological endpoints that were correlates of HIV-1 acquisition risk in RV144 were measured in HVTN 702 and evaluated as correlates of HIV-1 acquisition. METHODS: Among 1893 HVTN 702 female vaccinees, 60 HIV-1-seropositive cases and 60 matched seronegative noncases were sampled. HIV-specific CD4+ T-cell and binding antibody responses were measured 2 weeks after fourth and fifth immunizations. Cox proportional hazards models assessed prespecified responses as predictors of HIV-1 acquisition. RESULTS: The HVTN 702 Env-specific CD4+ T-cell response rate was significantly higher than in RV144 (63% vs 40%, P = .03) with significantly lower IgG binding antibody response rate and magnitude to 1086.C V1V2 (67% vs 100%, P < .001; Pmag < .001). Although no significant univariate associations were observed between any T-cell or binding antibody response and HIV-1 acquisition, significant interactions were observed (multiplicity-adjusted P ≤.03). Among vaccinees with high IgG A244 V1V2 binding antibody responses, vaccine-matched CD4+ T-cell endpoints associated with decreased HIV-1 acquisition (estimated hazard ratios = 0.40-0.49 per 1-SD increase in CD4+ T-cell endpoint). CONCLUSIONS: HVTN 702 and RV144 had distinct immunogenicity profiles. However, both identified significant correlations (univariate or interaction) for IgG V1V2 and polyfunctional CD4+ T cells with HIV-1 acquisition. Clinical Trials Registration . NCT02968849.


Asunto(s)
Vacunas contra el SIDA , Infecciones por VIH , Seropositividad para VIH , VIH-1 , Femenino , Anticuerpos Anti-VIH , Proteína gp120 de Envoltorio del VIH , Infecciones por VIH/prevención & control , Humanos , Inmunoglobulina G , Masculino , Sudáfrica
4.
PLoS Med ; 18(6): e1003670, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-34143779

RESUMEN

BACKGROUND: Pre-exposure prophylaxis (PrEP) is highly effective and an important prevention tool for African adolescent girls and young women (AGYW), but adherence and persistence are challenging. PrEP adherence support strategies for African AGYW were studied in an implementation study. METHODS AND FINDINGS: HIV Prevention Trials Network (HPTN) 082 was conducted in Cape Town, Johannesburg (South Africa) and Harare (Zimbabwe) from October 2016 to October 2018 to evaluate PrEP uptake, persistence, and the effect of drug level feedback on adherence. Sexually active HIV-negative women ages 16-25 were offered PrEP and followed for 12 months; women who accepted PrEP were randomized to standard adherence support (counseling, 2-way SMS, and adherence clubs) or enhanced adherence support with adherence feedback from intracellular tenofovir-diphosphate (TFV-DP) levels in dried blood spots (DBS). PrEP uptake, persistence through 12 months (no PrEP hold or missed visits), and adherence were assessed. The primary outcome was high adherence (TFV-DP ≥700 fmol/punch) at 6 months, compared by study arm. Of 451 women enrolled, median age was 21 years, and 39% had curable sexually transmitted infections (STIs). Most (95%) started PrEP, of whom 55% had uninterrupted PrEP refills through 12 months. Of those with DBS, 84% had detectable TFV-DP levels at month 3, 57% at month 6, and 31% at month 12. At 6 months, 36/179 (21%) of AGYW in the enhanced arm had high adherence and 40/184 (22%) in the standard adherence support arm (adjusted odds ratio [OR] of 0.92; 95% confidence interval [CI] 0.55, 1.34; p = 0.76). Four women acquired HIV (incidence 1.0/100 person-years), with low or undetectable TFV-DP levels at or prior to seroconversion, and none of whom had tenofovir or emtricitabine resistance mutations. The study had limited power to detect a modest effect of drug level feedback on adherence, and there was limited awareness of PrEP at the time the study was conducted. CONCLUSIONS: In this study, PrEP initiation was high, over half of study participants persisted with PrEP through month 12, and the majority of young African women had detectable TFV-DP levels through month 6 with one-fifth having high adherence. Drug level feedback in the first 3 months of PrEP use did not increase the proportion with high adherence at month 6. HIV incidence was 1% in this cohort with 39% prevalence of curable STIs and moderate PrEP adherence. Strategies to support PrEP use and less adherence-dependent formulations are needed for this population. TRIAL REGISTRATION: ClinicalTrials.gov NCT02732730.


Asunto(s)
Adenina/análogos & derivados , Fármacos Anti-VIH/uso terapéutico , Monitoreo de Drogas , Retroalimentación Psicológica , Infecciones por VIH/prevención & control , Cumplimiento de la Medicación , Organofosfatos/uso terapéutico , Profilaxis Pre-Exposición , Adenina/efectos adversos , Adenina/sangre , Adenina/uso terapéutico , Adolescente , Adulto , Fármacos Anti-VIH/efectos adversos , Fármacos Anti-VIH/sangre , Consejo , Pruebas con Sangre Seca , Femenino , Infecciones por VIH/diagnóstico , Infecciones por VIH/transmisión , Infecciones por VIH/virología , Conocimientos, Actitudes y Práctica en Salud , Humanos , Organofosfatos/efectos adversos , Organofosfatos/sangre , Factores Sexuales , Sudáfrica , Envío de Mensajes de Texto , Factores de Tiempo , Resultado del Tratamiento , Adulto Joven , Zimbabwe
5.
Vaccine ; 42(20): 125991, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-38772835

RESUMEN

BACKGROUND: Reactogenicity informs vaccine safety, and may influence vaccine uptake. We evaluated factors associated with reactogenicity in HVTN 702, a typical HIV vaccine efficacy trial with multiple doses and products. METHODS: HVTN 702, a phase 2b/3 double-blind placebo-controlled trial, randomized 5404 African participants aged 18-35 years without HIV to placebo, or ALVAC-HIV (vCP2438) at months 0, 1 and ALVAC-HIV (vCP2438) + Bivalent Subtype C gp120/MF59 at months 3, 6, 12 and 18. Using multivariate logistic regression, we evaluated associations between reactogenicity with clinical, sociodemographic and laboratory variables. RESULTS: More vaccine than placebo-recipients reported local symptoms (all p < 0.001), arthralgia (p = 0.008), chills (p = 0.012) and myalgia (p < 0.001). Reactogenicity was associated with female sex at birth (ORv = 2.50, ORp = 1.81, both p < 0.001) and geographic region. Amongst vaccine-recipients, each year of age was associated with 3 % increase in reactogenicity (OR = 1.03, p = 0.002). CONCLUSION: Vaccine receipt, female sex at birth, older age, and region may affect reactogenicity.


Asunto(s)
Vacunas contra el SIDA , Infecciones por VIH , Humanos , Vacunas contra el SIDA/efectos adversos , Vacunas contra el SIDA/administración & dosificación , Vacunas contra el SIDA/inmunología , Femenino , Masculino , Adulto , Adulto Joven , Infecciones por VIH/prevención & control , Adolescente , Método Doble Ciego , Eficacia de las Vacunas
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