Assessing the effect of hormonal contraception on HIV acquisition in observational data: challenges and recommended analytic approaches

Determining whether hormonal contraception (HC), particularly the injectable contraceptive depot-medroxyprogesterone acetate (DMPA), increases a woman's risk of HIV acquisition is a priority question for public health. However, assessing the relationship between various HC methods and HIV acquisition with observational data involves substantial analytic design issues and challenges. Studies to date have used inconsistent approaches and generated a body of evidence that is complex and challenging to interpret

Effects of Pregnancy and Bacterial Vaginosis on Proinflammatory Cytokine and Secretory Leukocyte Protease Inhibitor Concentrations in Vaginal Secretions

We compared vaginal proinflammatory cytokine and secretory leukocyte protease inhibitor (SLPI) concentrations among pregnant and nonpregnant women according to bacterial vaginosis (BV) status. One-hundred and twenty-two women at 12–20 weeks' gestation and 133 nonpregnant controls had vaginal concentrations of interleukin (IL)-1β, IL-6, IL-8, and SLPI measured by enzyme immunoassay. Multivariable linear regression was used to evaluate factors independently associated with vaginal cytokine and SLPI response. Pregnancy and BV were both independently associated with increased vaginal concentrations of IL-1β and IL-8; pregnant women had increased concentrations of SLPI, while women with BV had decreased SLPI concentrations

Bacterial vaginosis and the risk of trichomonas vaginalis acquisition among HIV-1 negative women.

Centre for the AIDS Programme of Research In South Africa.Background: The vaginal microbiota may play a role in mediating susceptibility to sexually transmitted infections, including Trichomonas vaginalis (TV). Methods: Data were analyzed from HIV-1-seronegative women participating in HIV Prevention Trials Network Protocol 035. At quarterly visits for up to 30 months, participants completed structured interviews and specimens were collected for genital tract infection testing. T. vaginalis was detected by saline microscopy. Bacterial vaginosis (BV) was characterized by Gram stain using the Nugent score (BV = 7Y10; intermediate = 4Y6; normal = 0Y3 [reference group]). Cox proportional hazards models stratified by study site were used to assess the association between Nugent score category at the prior quarterly visit and TV acquisition. Results: In this secondary analysis, 2920 participants from Malawi, South Africa, United States, Zambia, and Zimbabwe contributed 16,259 follow-up visits. Bacterial vaginosis was detected at 5680 (35%) visits,and TV was detected at 400 (2.5%) visits. Adjusting for age, marital status, hormonal contraceptive use, unprotected sex in the last week and TV at baseline, intermediate Nugent score, and BVat the prior visit were associated with an increased risk of TV (intermediate score: adjusted hazard ratio [aHR], 1.73; 95% confidence interval [CI], 1.21Y2.19; BV: aHR, 2.40; 95% CI, 1.92Y3.00). Sensitivity analyses excluding 211 participants with TV at baseline were similar to those from the full study population (intermediate score: aHR, 1.54; 95% CI, 1.10Y2.14; BV: aHR, 2.23; 95% CI, 1.75Y2.84). Conclusions: Women with a Nugent score higher than 3 were at an increased risk for acquiring TV. If this relationship is causal, interventions that improve the vaginal microbiota could contribute to reductions in TV incidence

Oral and injectable contraceptive use and HIV acquisition risk among women in four African countries : a secondary analysis of data from a microbicide trial.

CAPRISA, 2016.Abstract available in pdf

Expanding contraceptive options for PMTCT clients: a mixed methods implementation study in Cape Town, South Africa

Abstract Background Clients of prevention of mother-to-child transmission (PMTCT) services in South Africa who use contraception following childbirth rely primarily on short-acting methods like condoms, pills, and injectables, even when they desire no future pregnancies. Evidence is needed on strategies for expanding contraceptive options for postpartum PMTCT clients to include long-acting and permanent methods. Methods We examined the process of expanding contraceptive options in five health centers in Cape Town providing services to HIV-positive women. Maternal/child health service providers received training and coaching to strengthen contraceptive counseling for postpartum women, including PMTCT clients. Training and supplies were introduced to strengthen intrauterine device (IUD) services, and referral mechanisms for female sterilization were reinforced. We conducted interviews with separate samples of postpartum PMTCT clients (265 pre-intervention and 266 post-intervention) to assess knowledge and behaviors regarding postpartum contraception. The process of implementing the intervention was evaluated through systematic documentation and interpretation using an intervention tracking tool. In-depth interviews with providers who participated in study-sponsored training were conducted to assess their attitudes toward and experiences with promoting voluntary contraceptive services to HIV-positive clients. Results Following the intervention, 6% of interviewed PMTCT clients had the desired knowledge about the IUD and 23% had the desired knowledge about female sterilization. At both pre- and post-intervention, 7% of clients were sterilized and IUD use was negligible; by comparison, 75% of clients used injectables. Intervention tracking and in-depth interviews with providers revealed intervention shortcomings and health system constraints explaining the failure to produce intended effects. Conclusions The intervention failed to improve PMTCT clients’ knowledge about the IUD and sterilization or to increase use of those methods. To address the family planning needs of postpartum PMTCT clients in a way that is consistent with their fertility desires, services must expand the range of contraceptive options to include long-acting and permanent methods. In turn, to ensure consistent access to high quality family planning services that are effectively linked to HIV services, attention must also be focused on resolving underlying health system constraints weakening health service delivery more generally

HIV disease progression among women following seroconversion during a tenofovir-based HIV prevention trial.

CAPRISA, 2017.Abstract available in pdf

COVID-19 in pregnancy in South Africa : tracking the epidemic and defining the natural history

South Africa (SA) has seen a rapid increase in COVID-19 infections in recent weeks, with cases exceeding 40 000 in early June and anticipated to escalate rapidly as lockdown is eased. The country also has the largest HIV burden globally, and poor maternal and child health indices in many parts. Although early indications were that COVID-19 infection does not worsen pregnancy and birth outcomes, recent reports have raised fresh concerns. Preterm birth, neonatal pneumonia[9-11] and cases of vertical transmission and postpartum infections have been reported, including in SA. Some maternal deaths related to COVID-19 have occurred, possibly linked to haemodynamic changes immediately postpartum and/or to the thrombogenic nature of both pregnancy and COVID- 19. Maternal wellbeing in pregnant women with COVID-19 infection is a major concern, as these women often have high anxiety about infecting their newborn child, and may experience challenging interactions with healthcare providers and community stigma. Most evidence on COVID-19 and pregnancy to date is limited to case series, involves only symptomatic women without HIV, and is almost exclusively from high-income countries. Cohort data across a range of settings and population groups are the only means of fully understanding the natural history, clinical disease spectrum and risks of COVID-19 in pregnant women, fetuses and infants.http://www.samj.org.zaam2021Obstetrics and Gynaecolog

Interventions to Improve Vaginal Health in Kenyan Women

Thesis (Ph.D.)--University of Washington, 2012 Introduction : Vaginal infections, including bacterial vaginosis (BV), vulvovaginal candidiasis (VVC) and Trichomonas vaginalis (TV), are highly prevalent among reproductive-aged women and are associated with a number of adverse reproductive health outcomes. Interventions that improve vaginal health could have a substantial impact on reproductive health. Methods : Data from women enrolled in a randomized trial of periodic presumptive treatment (PPT) for vaginal infections were used to assess the effect of PPT on: (1) establishing and sustaining a healthy vaginal environment; and (2) BV and Lactobacillus colonization in the 3-month interval following completion of the trial. Data from women enrolled in an open cohort study of female sex workers were used to compare the effect of single-dose 2g oral metronidazole on TV infection in HIV-1-seropositive versus HIV-1-seronegative women. Results : The incidence of a healthy vaginal environment was 608 per 100 person-years in the intervention arm and 454 per 100 person-years in the placebo arm (hazard ratio [HR]=1.36; 95% confidence interval [CI] 1.17-1.58). Sustained vaginal health (healthy vaginal environment for ≥ 3 consecutive visits) was also more frequent in the intervention arm (HR=1.69; 95% CI 1.23-2.33). The post-trial incidence of BV was 260 per 100 person-years in the intervention arm versus 358 per 100 person-years in the placebo arm (HR=0.76; 95% CI 0.51-1.12). The post-trial incidence of Lactobacillus colonization was 180 per 100 person-years in the intervention arm versus 127 per 100 person-years in the placebo arm (HR=1.42; 95% CI 0.85-2.71). There were 42 of 282 (15%) persistent infections among HIV-seropositive women versus 35 of 288 (12%) among HIV-seronegative women (adjusted odds ratio [aOR]=1.26; 95% CI 0.75-2.12). TV infection with concurrent BV by Gram stain was associated with an increased likelihood of persistent TV (aOR=1.82; 95% CI 1.11-2.99). Conclusions : Periodic presumptive treatment is effective at establishing and sustaining a healthy vaginal environment. However, its effect on BV and Lactobacillus colonization was not sustained after cessation of the intervention. The frequency of persistent TV following treatment with single-dose metronidazole was similar by HIV-1 status. Alternative regimens may be necessary to improve cure rates for women with TV and concurrent BV