The incidence of HIV among women recruited during late pregnancy and followed up for six years after childbirth in Zimbabwe.

BACKGROUND: HIV incidence is a useful tool for improving the targeting of populations for interventions and assessing the effectiveness of prevention strategies. A study in Harare, Zimbabwe reported cumulative incidences of 3.4% (3.0-3.8) and 6.5% (5.7-7.4) among post-partum women followed for 12 and 24 months respectively between 1997 and 2001. According to a Government report on HIV the prevalence of HIV fell from about 30% in 1999 to 14% in 2008. The purpose of this study was to determine the incidence of HIV-1 among women enrolled during late pregnancy and followed for six years after childbirth and to identify risk factors associated with acquisition of HIV. METHODS: HIV-uninfected pregnant women around 36 weeks gestation were enrolled from primary health care clinics in peri-urban settlements around Harare and followed-up for up to six years after childbirth. At every visit a questionnaire was interview-administered to obtain socio-demographic data and sexual history since the previous visit. A genital examination was performed followed by the collection of biological samples. RESULTS: Of the 552 HIV-uninfected women 444 (80.4%) were seen at least twice during the six years follow-up and 39 acquired HIV, resulting in an incidence (95% CI) of 2.3/100 woman-years-at-risk (wyar) (1.1-4.1). The incidence over the first nine months post-partum was 5.7/100 wyar (3.3-8.1). A greater proportion of teenagers (15.3%) contributed to a high incidence rate of 2.9/100 (0.6-8.7) wyar. In multivariate analysis lower education of participant, RR 2.1 (1.1-4.3) remained significantly associated with HIV acquisition. Other risk factors associated with acquisition of HIV-1 in univariate analysis were young age at sexual debut, RR 2.3, (1.0-5.6) and having children with different fathers, RR 2.7(1.3-5.8). Women that knew that their partners had other sexual partners were about four times more likely to acquire HIV, RR 3.8 (1.3-11.2). CONCLUSION: The incidence of HIV was high during the first nine months after childbirth. Time of seroconversion, age and educational level of seroconverter are important factors that must be considered when designing HIV intervention strategies.

Zim CHIC: A cohort study of immune changes in the female genital tract associated with initiation and use of contraceptives.

PROBLEM: Contraceptive hormones are systemically active, potent, and likely to invoke biological responses other than known fertility regulation impacts. We hypothesized that initiation of depot medroxyprogesterone acetate (DMPA) would increase genital HIV-target-cells and soluble immune mediators compared with baseline and initiation of other contraceptive methods. METHOD OF STUDY: We collected cervical cytobrushes and cervicovaginal fluid from healthy Zimbabwean women aged 18-34 to assess immune cell populations, cytokines, and innate anti-HIV activity at baseline and after 30, 90, and 180 days use of DMPA (n = 38), norethisterone enanthate (n = 41), medroxyprogesterone acetate/estradiol cypionate (n = 36), levonorgestrel implant (n = 43), etonogestrel implant (n = 47), or copper intrauterine device (Cu-IUD) (n = 45). Cells were quantified by flow cytometry, cytokines were detected by multiplex assays, and innate anti-HIV activity was assessed by in vitro HIV challenge. RESULTS: Compared to baseline, the number of cervical HIV target cells (#CD4 cells P < .04 and #CD11c cells P < .04), the concentration of the inflammatory cytokine IL-1ß (P < .01), and the innate in vitro anti-HIV activity (P < .001) significantly decreased following DMPA initiation. In Cu-IUD users, genital HIV target cells increased (#CD4 cells P < .001, #CD4CCR5 cells P = .02, #CD4CD69 cells P < .001, #CD8CD69 P = .01, and #CD11c cells P = .003) at day 30 and resolved by day 180. IFN-γ (P < .001), IL-1ß (P < .001), IL-6 (P < .001), IL-8 (P < .001), IL-10 (P < .01), and RANTES (P < .001) were also significantly increased at day 30. Minimal alterations were observed following initiation of subdermal implantable contraceptives. CONCLUSIONS: This head-to-head study compared six contraceptives and found increased HIV target cells and cervical inflammation temporally associated with Cu-IUD initiation. Use of hormonal contraception, including DMPA, did not increase cervical HIV target cells or inflammation. Clinical Trial Number: NCT02038335.

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.

Misreporting of contraceptive hormone use in clinical research participants.

OBJECTIVE: Researchers traditionally rely on participant self-report for contraceptive use. We hypothesized that self-reported contraceptive use by clinical research participants may disagree with objectively measured hormonal status. STUDY DESIGN: We enrolled women in Harare, Zimbabwe, aged 18-34, who by self-report had not used hormonal or intrauterine contraception for >30 days, or depot medroxyprogesterone acetate for >10 months, into a study designed to assess biologic changes with contraceptive initiation and use. Blood samples obtained at enrollment and each follow-up visit (N=1630 from 447 participants) were evaluated by mass spectrometry for exogenous hormones. We individually interviewed a subset of participants (n=20) with discrepant self-reported and measured serum hormones to better understand nondisclosure of contraceptive use. RESULTS: Discrepant with self-reported nonuse of hormonal contraception, synthetic progestogens were detectable in 120/447 (27%, 95% confidence interval 23%-31%) enrolled women. Measured exogenous hormones consistent with use of contraceptive pills (n=102), injectables (n=20) and implants (n=3) were detected at enrollment, with 7 women likely using >1 contraceptive. In-depth interviews revealed that participants understood the requirement to be hormone free at enrollment (100%). Most (85%) cited partner noncooperation with condoms/withdrawal and/or pregnancy concerns as major reasons for nondisclosed contraceptive use. All interviewed women (100%) cited access to health care as a primary motivation for study participation. Of participants who accurately reported nonuse of hormonal contraception at enrollment, 41/327 (12.5%) had objective evidence of nonstudy progestin use at follow-up that disagreed with self-reported nonuse. CONCLUSIONS: Women joining contraceptive research studies may misrepresent their use of nonstudy contraceptive hormones at baseline and follow-up. Objective measures of hormone use are needed to ensure that study population exposures are accurately categorized. IMPLICATIONS STATEMENT: Among Zimbabwean women participating in a contraceptive research study, 27% had objective evidence of use of nonstudy contraceptives at enrollment that disagreed with self-report. Studies that rely on self-report to identify contraceptive hormone exposure could suffer from significant misclassification.

Implementation of a prospective pregnancy registry for antiretroviral based HIV prevention trials.

BACKGROUND: Safety data on pregnancy and fetal outcomes among women in HIV prevention trials are urgently needed to inform use of effective antiretroviral agents for HIV prevention. We describe an effective, efficient, and novel method to prospectively collect perinatal safety data concurrent with on-going parent clinical trials. METHODS: The Microbicide Trials Network (MTN)-016 study is a multinational prospective pregnancy exposure registry designed to capture pregnancy and neonatal outcomes. Studies currently contributing data to this registry included phase I and II safety trials with planned exposures to candidate HIV prevention agents, as well as phase IIB and III efficacy trials capturing data on pregnancy and infant outcomes following inadvertent fetal exposure during study participation. RESULTS: To date, participants from two phase I studies and two effectiveness trials have participated in MTN-016, resulting in 420 pregnant women and 381 infants enrolled. Infant retention has been high, with 329 of 381 (86%) infants completing the 12-month follow-up visit. CONCLUSION: In a research setting context, it is feasible to establish and implement a prospective, multinational HIV chemoprophylaxis pregnancy registry that will generate pregnancy exposure data in a robust fashion.