OBJECTIVE: To assess the effect of oral and injectable contraceptive use compared to nonhormonal contraceptive use on HIV acquisition among Southern African women enrolled in a microbicide trial. STUDY DESIGN: This is a prospective cohort study using data from women enrolled in HIV Prevention Trials Network protocol 035. At each quarterly visit, participants were interviewed about self-reported contraceptive use and sexual behaviors and underwent HIV testing. Cox proportional hazards regression was used to assess the effect of injectable and oral hormonal contraceptive use on HIV acquisition. RESULTS: The analysis included 2830 participants, of whom 106 became HIV infected (4.07 per 100 person-years). At baseline, 1546 (51%) participants reported using injectable contraceptives and 595 (21%) reported using oral contraceptives. HIV incidence among injectable, oral and nonhormonal contraceptive method users was 4.72, 2.68 and 3.83 per 100 person-years, respectively. Injectable contraceptive use was associated with a nonstatistically significant increased risk of HIV acquisition [adjusted hazard ratio (aHR)=1.17; 95% confidence interval (CI) 0.70, 1.96], while oral contraceptive use was associated with a nonstatistically significant decreased risk of HIV acquisition (aHR=0.76; 95% CI 0.37,1.55). CONCLUSION: In this secondary analysis of randomized trial data, a marginal, but nonstatistically significant, increase in HIV risk among women using injectable hormonal contraceptives was observed. No increased HIV risk was observed among women using oral contraceptives. Our findings support the World Health Organizations recommendation that women at high risk for acquiring HIV, including those using progestogen-only injectable contraception, should be strongly advised to always use condoms and other HIV prevention measures. IMPLICATIONS: Among Southern African women participating in an HIV prevention trial, women using injectable hormonal contraceptives had a modest increased risk of HIV acquisition; however, this association was not statistically significant. Continued research on the relationship between widely used hormonal contraceptive methods and HIV acquisition is essential.

Background

Recent HIV prevention trials required use of effective contraceptive methods to fulfill eligibility for enrollment. We compared pregnancy rates in a subset of participants enrolled in the Microbicide Trials Network protocol (MTN-003), a randomized trial of chemoprophylaxis to prevent HIV acquisition among women aged 18-45 years who initiated depot medroxyprogesterone acetate (DMPA) or combined oral contraceptives (COCs) at enrollment, relative to those already using DMPA or COCs.

Methods

Data were analyzed from MTN-003 participants from Uganda. Before enrollment, information on contraceptive type and initiation date was obtained. Urine pregnancy tests were performed at monthly follow-up visits. Cox proportional hazards models were used to compare pregnancy incidence among new users (initiated ≤60 days before enrollment) and established users (initiated >60 days before enrollment).

Results

Of 322 women enrolled, 296 were COC or DMPA users, 82 (28%) were new users, and 214 (72%) were established users. Pregnancy incidence was higher among new contraceptive users compared to established users (20.70% vs. 10.55%; adjusted hazard ratio [HR] = 1.66; 95% confidence interval [95% CI] 0.93-2.96). Among DMPA users, pregnancy incidence was 10.20% in new users versus 3.48% in established users (HR = 2.56; 95% CI 0.86-7.65). Among new COC users, pregnancy incidence was 42.67% in new users versus 23.67% in established COC users (adjusted HR = 1.74; 95% CI 0.87-3.48).

Conclusions

New contraceptive users, regardless of method, at the Uganda MTN-003 site had an increased pregnancy risk compared to established users, which may be due to contraceptive initiation primarily for trial eligibility. New users may benefit from intensive contraceptive counseling and additional contraceptive options, including longer acting reversible contraceptives.

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.

The effect of the levonorgestrel-releasing intrauterine device (LNG-IUD) on genital HIV-1 RNA shedding and inflammation among 25 HIV-infected women was evaluated. Blood, endocervical, and cervicovaginal lavage samples were collected from HIV-infected women not taking antiretrovirals before LNG-IUD insertion and 1 month, 3 month, and 6 months thereafter. HIV-1 RNA was quantitated by real-time reverse transcriptase-polymerase chain reaction. Inflammatory markers were measured by enzyme immunoassay. Genital HIV-1 RNA shedding and inflammatory markers did not differ between LNG-IUD placement and month 6, with the exception of interleukin 1β that increased (0.42 log10; 95% confidence interval: 0.10 to 0.75). The LNG-IUD did not increase genital HIV-1 RNA shedding after 6 months of use.

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.

Objective

To develop and validate an HIV risk assessment tool to predict HIV acquisition among African women.

Design

Data were analyzed from 3 randomized trials of biomedical HIV prevention interventions among African women (VOICE, HPTN 035, and FEM-PrEP).

Methods

We implemented standard methods for the development of clinical prediction rules to generate a risk-scoring tool to predict HIV acquisition over the course of 1 year. Performance of the score was assessed through internal and external validations.

Results

The final risk score resulting from multivariable modeling included age, married/living with a partner, partner provides financial or material support, partner has other partners, alcohol use, detection of a curable sexually transmitted infection, and herpes simplex virus 2 serostatus. Point values for each factor ranged from 0 to 2, with a maximum possible total score of 11. Scores ≥5 were associated with HIV incidence >5 per 100 person-years and identified 91% of incident HIV infections from among only 64% of women. The area under the curve (AUC) for predictive ability of the score was 0.71 (95% confidence interval [CI]: 0.68 to 0.74), indicating good predictive ability. Risk score performance was generally similar with internal cross-validation (AUC = 0.69; 95% CI: 0.66 to 0.73) and external validation in HPTN 035 (AUC = 0.70; 95% CI: 0.65 to 0.75) and FEM-PrEP (AUC = 0.58; 95% CI: 0.51 to 0.65).

Conclusions

A discrete set of characteristics that can be easily assessed in clinical and research settings was predictive of HIV acquisition over 1 year. The use of a validated risk score could improve efficiency of recruitment into HIV prevention research and inform scale-up of HIV prevention strategies in women at highest risk.

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.

Depression worsens HIV outcomes in populations treated with antiretroviral therapy (ART) medications. Data are limited on the relationship between depression and HIV in untreated populations in sub-Saharan Africa. We aimed to identify associations between likely clinical depression, alcohol use, social support by partners, and HIV viral load (VL) among ART untreated women who recently became HIV positive and enrolled in the Microbicide Trials Network (MTN)-015 study. Analyses used cross-sectional data collected at baseline in MTN-015. Participants in this analysis (N = 190) enrolled from other MTN trials were not receiving ART and provided data on their HIV disclosure status to their husband or male partner and alcohol use behavior. The dependent variable, VL, was categorized as: low (≤400 RNA copies/mL; 9.1% of participants), medium (401-20,000 RNA copies/mL; 48.8%), and high (>20,000 RNA copies/mL; 42.0%). Depression was assessed using eight items from Hopkins Symptom Checklist; a cutoff of ≥1.75 indicated likely clinical depression. Independent variables with a significance of p ≤ 0.05 in unadjusted regressions were included in a regression adjusted for age, education, and time since seroconversion. Depressive symptoms were positively associated with high VL, in the adjusted regression (OR = 1.80; 95% CI = 1.07-3.01). Results suggest that likely having clinical depression may have a biological relationship with HIV disease progression.

Research suggests that womens experience of intimate partner violence (IPV) is associated with poor engagement in HIV care and treatment. However, most studies have been cross-sectional and conducted in North America. We examined the association between physical IPV and HIV care outcomes in a prospective cohort study of women living with HIV (WLHIV) in Malawi, South Africa, Uganda, and Zimbabwe. At enrollment, 15% of the 351 participants self-reported physical IPV. IPV experience was not associated with time to first engagement in HIV care or the proportion virally suppressed after 6 months on ART. Women reporting physical IPV were less likely to initiate ART within 6 months of becoming eligible (adjusted RR 0.74, 95% CI 0.53-1.03). IPV screening is critical to identify survivors and link them to appropriate services. However, addressing IPV may not increase engagement in HIV care or viral load suppression among WLHIV in sub-Saharan Africa.

Background

As the effect of biomedical prevention interventions on the natural history of HIV-1 infection in participants who seroconvert is unknown, the Microbicide Trials Network (MTN) established a longitudinal study (MTN-015) to monitor virologic, immunological, and clinical outcomes, as well as behavioral changes among women who become HIV-infected during MTN trials. We describe the rationale, study design, implementation, and enrollment of the initial group of participants in the MTN seroconverter cohort.

Methods

Initiated in 2008, MTN-015 is an ongoing observational cohort study enrolling participants who acquire HIV-1 infection during effectiveness studies of candidate microbicides. Eligible participants from recently completed and ongoing MTN trials are enrolled after seroconversion and return for regular follow-up visits with clinical and behavioral data collection. Biologic samples including blood and genital fluids are stored for future testing.

Results

MTN-015 was implemented initially at six African sites and enrolled 100/139 (72%) of eligible women who seroconverted in HIV Prevention Trials Network protocol 035 (HPTN 035, conducted by the MTN). The median time from seroconversion in HPTN 035 to enrollment in MTN-015 was 18 months. Retention was good with >70% of visits completed. Implementation challenges included regulatory reviews, translation, and testing of questionnaires, and site readiness.

Conclusions

Enrollment of HIV-seroconverters into a longitudinal observational follow-up study is feasible and acceptable to participants. Data and samples collected in this protocol will be used to assess safety of investigational HIV microbicides and answer other important public health questions for HIV infected women.