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

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

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

Associations Between Genital Tract Infections, Genital Tract Inflammation, and Cervical Cytobrush HIV-1 DNA in US Versus Kenyan Women

Cervical shedding of HIV-1 DNA may influence HIV-1 sexual transmission. HIV-1 DNA was detected in 250 (80%) of 316 and 207 (79%) of 259 cervical cytobrush specimens from 56 US and 80 Kenyan women, respectively. Plasma HIV-1 RNA concentration was associated with increased HIV-1 DNA shedding among US and Kenyan women. Kenyan women had higher cervicovaginal concentrations of proinflammatory interleukins (IL)-1β, IL-6, IL-8, and anti-inflammatory secretory leukocyte protease inhibitor compared with US women (all P < 0.01). HIV-1 DNA shedding was associated with increased concentrations of IL-1β and IL-6 and lower secretory leukocyte protease inhibitor among US women but not Kenyan women

Interaction Between Lactobacilli, Bacterial Vaginosis-Associated Bacteria, and HIV Type 1 RNA and DNA Genital Shedding in U.S. and Kenyan Women

Bacterial vaginosis has been associated with genital HIV-1 shedding; however, the effect of specific vaginal bacterial species has not been assessed. We tested cervicovaginal lavage from HIV-1-seropositive women for common Lactobacillus species: L. crispatus, L. jensenii, and seven BV-associated species: BVAB1, BVAB2, BVAB3, Leptotrichia, Sneathia, Megasphaera, and Atopobium spp. using quantitative PCR. We used linear and Poisson regression to evaluate associations between vaginal bacteria and genital HIV-1 RNA and DNA. Specimens from 54 U.S. (310 visits) and 50 Kenyan women (137 visits) were evaluated. Controlling for plasma viral load, U.S. and Kenyan women had similar rates of HIV-1 RNA (19% of visits vs. 24%; IRR=0.95; 95% CI 0.61, 1.49) and DNA shedding (79% vs. 76%; IRR=0.90; 0.78, 1.05). At visits during antiretroviral therapy (ART), the likelihood of detection of HIV-1 RNA shedding was greater with BVAB3 (IRR=3.16; 95% CI 1.36, 7.32), Leptotrichia, or Sneathia (IRR=2.13; 1.02, 4.72), and less with L. jensenii (IRR=0.39; 0.18, 0.84). At visits without ART, only L. crispatus was associated with a lower likelihood of HIV-1 RNA detection (IRR=0.6; 0.40, 0.91). Vaginal Lactobacillus species were associated with lower risk of genital HIV-1 shedding, while the presence of certain BV-associated species may increase that risk

Complex decisions: correlates of injectable contraceptive discontinuation following HIV-1 seroconversion in an HIV prevention trial.

Contraceptive adherence during acute and recent HIV-1 infection is important to maternal and child health given the elevated risk of vertical HIV-1 transmission and additional complications of pregnancy. Injectable contraception (IC) is the most common non-barrier modern contraception method used in sub-Saharan Africa (SSA). Adherence to IC after HIV-1 seroconversion is not well understood. We examined factors associated with IC discontinuation among women in SSA diagnosed with HIV-1 infection while participating in a clinical trial of biomedical HIV-1 prevention. After diagnosis with HIV-1 infection in the VOICE trial, 255 women from South Africa, Uganda, and Zimbabwe enrolled in a longitudinal observational study (MTN-015). Contraceptive method was assessed at MTN-015 baseline and at 3, 12, and 24 months post-seroconversion. Correlates of IC discontinuation were examined by Cox proportional hazard modeling. IC use was reported at baseline by 78% of women enrolled (198/255), of which 92% (182/198) completed at least one follow-up visit. Two-thirds of women (66%, 121/182) continued on IC during the follow-up period (median 24 months). Lower rates of IC discontinuation were observed in women who reported having had at least one child (HR 0.39, 95% CI 0.20-0.82) or earning a personal income (HR 0.51, 95% CI 0.30-0.87) at baseline. These findings suggest that many women with HIV-1 infection face complex decision-making regarding family planning in the years that follow seroconversion and highlight that some women may discontinue IC use despite on-site provision of family planning services. Understanding the broader context of family planning choices in recently seroconverted women may be key to more effective linkages between family planning services and HIV-1 testing and care