High prevalence and incidence of gonorrhoea and chlamydia in young women eligible for HIV pre-exposure prophylaxis in South Africa and Zimbabwe: results from the HPTN 082 trial.

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.

PrEP uptake, persistence, adherence, and effect of retrospective drug level feedback on PrEP adherence among young women in southern Africa: Results from HPTN 082, a randomized controlled trial.

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.

Feasibility and Safety of IUD Insertion by Mid-Level Providers in Sub-Saharan Africa.

CONTEXT: The copper IUD is safe and effective, but underutilized in Sub-Saharan Africa, in part because of a lack of trained providers. The World Health Organization recommends training mid-level providers-including nurses and midwives-to insert IUDs; however, the safety of such task shifting has not been evaluated in Sub-Saharan Africa. METHODS: Data were drawn from baseline surveys and study charts of 535 sexually active women aged 18-45 who used a copper IUD while participating in an HIV-prevention clinical trial conducted from August 2012 through June 2015 in Malawi, South Africa, Uganda and Zimbabwe. IUDs were inserted by study physicians, nurses and midwives trained as part of the trial, and by local nonstudy providers. Chi-square and Fisher's exact tests were used to compare women's experiences of adverse events-such as irregular bleeding, pelvic pain or device expulsion-by provider type. RESULTS: Half (54%) of women reported experiencing an adverse event; the most common were irregular bleeding and pelvic pain (45% and 25%, respectively). Compared with women who had received an IUD from a study physician or study nurse, greater proportions of women who had received one from a nonstudy provider reported any adverse event (76% vs. 49% and 51%, respectively), irregular bleeding (57% vs. 41% and 45%) and pelvic pain (35% vs. 15% and 32%); the difference between study physicians and nurses was significant only for pelvic pain. Expulsion rates were comparable for study nurses and nonstudy providers (12.3 and 11.9 per 100 woman-years, respectively), but lower for study physicians (7.3 per 100 woman-years). CONCLUSIONS: The findings support task shifting of IUD insertion to mid-level providers to improve IUD access in Sub-Saharan Africa.

RESUMEN Contexto: Aunque el DIU de cobre es seguro y efectivo, está subutilizado en África subsahariana, en parte debido a la falta de proveedores de servicios de salud capacitados. La Organización Mundial de la Salud recomienda capacitar a los proveedores de nivel medio ­incluidas las enfermeras y parteras­ para insertar los DIU; sin embargo, la seguridad de tal cambio de tareas ha sido evaluada en África subsahariana. Métodos: Se obtuvieron datos de encuestas de línea de base y cuadros de un estudio de 535 mujeres sexualmente activas, de 18 a 45 años, que usaron un DIU de cobre en un ensayo clínico de prevención del VIH realizado entre agosto de 2012 y junio de 2015 en Malaui, Sudáfrica, Uganda y Zimbabue. Los DIU fueron insertados por médicos participantes en el estudio, enfermeras y parteras capacitadas como parte del ensayo, así como por proveedores de servicios de salud locales no relacionados con el estudio. Las pruebas exactas de Chi-cuadrado y Fisher se usaron para comparar las experiencias de las mujeres con eventos adversos ­como sangrado irregular, dolor pélvico o expulsión del dispositivo­ por tipo de proveedor. Resultados: La mitad (54%) de las mujeres reportaron haber experimentado algún evento adverso; los eventos más comunes fueron sangrado irregular y dolor pélvico (45% y 25%, respectivamente). En comparación con las mujeres que habían recibido un DIU de un médico o de una enfermera del estudio, una gran parte de las mujeres que lo habían recibido de un proveedor no relacionado con el estudio reportaron algún tipo de evento adverso (76% vs. 49% y 51%, respectivamente), sangrado irregular (57 % vs. 41% y 45%) y dolor pélvico (35% vs. 15% y 32%); La diferencia entre los médicos y las enfermeras del estudio fue significativa solo para el dolor pélvico. Las tasas de expulsión fueron comparables para las enfermeras del estudio y los proveedores no relacionados con el estudio (12.3 y 11.9 por 100 años-mujer, respectivamente), pero más bajas para los médicos del estudio (7.3 por 100 años-mujer). Conclusiones: Los hallazgos respaldan el cambio de tareas de inserción del DIU a proveedores de nivel medio para mejorar el acceso al DIU en África Subsahariana.

RÉSUMÉ Contexte: Bien qu'il soit sûr et efficace, le DIU au cuivre est sous-utilisé en Afrique subsaharienne, faute, en partie, de prestataires formés. L'Organisation mondiale de la Santé recommande la formation de prestataires de niveau intermédiaire ­ personnel infirmier et sages-femmes ­ pour la pose du DIU. La sécurité de cette délégation de tâches n'a cependant pas été évaluée en Afrique subsaharienne. Méthodes: Les données proviennent d'enquêtes de base et de graphiques d'étude concernant 535 femmes sexuellement actives âgées de 18 à 45 ans qui utilisaient un DIU au cuivre dans le cadre d'un essai clinique de prévention du VIH réalisé d'août 2012 à juin 2015 en Afrique du Sud, au Malawi, en Ouganda et au Zimbabwe. Les DIU avaient été posés par les médecins, infirmières et sages-femmes de l'étude, formés dans le cadre de l'essai, ainsi que par des prestataires locaux extérieurs à l'étude. Le test chi carré et la méthode exacte de Fisher ont servi à comparer l'expérience d'effets indésirables ­ tels que saignements irréguliers, douleurs pelviennes ou expulsion du DIU ­ vécus par les femmes suivant le type de prestataire. Résultats: La moitié (54%) des femmes ont signalé un effet indésirable, les plus courants étant les saignements irréguliers et les douleurs pelviennes (45% et 25%, respectivement). Par rapport aux femmes dont le DIU avait été posé par un médecin ou une infirmière de l'étude, de plus grandes proportions de celles qui avaient obtenu leur dispositif d'un prestataire extérieur à l'étude ont signalé un effet indésirable quelconque (76% contre 49% et 51%, respectivement), des saignements irréguliers (57% contre 41% et 45%) et des douleurs pelviennes (35% contre 15% et 32%). La différence entre les médecins et le personnel infirmier de l'étude n'est significative que pour les douleurs pelviennes. Les taux d'expulsion sont comparables pour les infirmières de l'étude et les prestataires extérieurs (12,3 et 11,9 pour 100 femmes-années, respectivement), mais il est moindre pour les médecins de l'étude (7,3 pour 100 femmes-années). Conclusions: Les résultats sont favorables à la délégation de la pose du DIU aux prestataires de niveau intermédiaire pour améliorer l'accès au DIU en Afrique subsaharienne.