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Background To explore the association between concomitant hormonal contraceptive and antiretroviral therapy (ART) use and (1) plasma viral suppression and (2) genital HIV shedding among HIV-positive women initiating ART. Methods We analyzed plasma viral load and genital viral RNA shedding from 1079 HIV-positive women initiating ART who were followed prospectively in 3 sub-Saharan African HIV prevention studies. Plasma and endocervical swab samples were collected every 6 months. Self-reported contraceptive use was categorized into injectable, implant, oral, or nonhormonal/no contraception. We used multivariate Cox regression to assess time to plasma viral suppression and logistic regression with generalized estimating equations to assess genital viral shedding for each contraceptive method. Results At the time of ART initiation, there were 211 (20%) injectable, 69 (6%) implant, 50 (5%) oral, and 749 (69%) nonhormonal or no method users. Plasma viral suppression was high (90% by 6 months) and hormonal contraceptives did not diminish time to plasma viral suppression as compared to nonhormonal/no methods [adjusted hazard ratios: injectables 0.89 (95% confidence interval: 0.75 to 1.07), implants 0.91 (0.68 to 1.23), and oral methods 1.33 (1.06 to 1.66)]. Genital viral shedding was uncommon any time after ART initiation (only 9% of samples had detectable viral shedding) and hormonal contraceptives were not associated with an increased detection of genital viral shedding [adjusted odds ratios: injectables 1.07 (0.69 to 1.65), implants 0.67 (0.31 to 1.49), and oral methods 0.56 (0.19 to 1.69)]. Conclusions The hormonal contraceptives assessed were not associated with reduced ART effectiveness among HIV-positive women initiating ART. HIV-positive women should continue to be offered contraceptive options, including hormonal ones that best meet their needs.

We recently reported that risk of sexually-acquired HIV-1 infection is significantly increased by variants in the gene encoding CD101, a protein thought to modify inflammatory responses. Using blood samples from individuals with versus without these variants, we now demonstrate that CD101 variants modify the prevalence of diverse circulating inflammatory cell types, and show that CD101 variants are associated with increased proinflammatory cytokine production by circulating T-cells. Further, one category of CD101 variants was associated with a reduced capacity of regulatory T-cells to suppress CD4+ T-cell cytokine production, resulting in a hypothesized loss of baseline immune quiescence. These data were supported by transcriptomic data revealing alterations in the intrinsic regulation of antiviral pathways and HIV-resistance genes in individauls with CD101 variants. Our data support the hypothesis that CD101 regulates bystander inflammation, with CD101 variants altering heterosexual acquisition of HIV-1 by allowing for increased prevalence and altered function of specific T-cell subsets.

BackgroundUnderstanding the absolute and relative risk of human immunodeficiency virus type 1 (HIV) acquisition during pregnancy and the postpartum period can inform HIV prevention strategies for women.MethodsWe used a complementary log-log model and data from 2751 HIV-serodiscordant couples to compare the probability of HIV acquisition among women per sex act during early pregnancy, late pregnancy, the postpartum period, and the nonpregnant period.ResultsAt total of 686 pregnancies were identified, and 82 incident HIV infections occurred. After adjustment for condom use, age, preexposure prophylaxis (PrEP) use, and HIV viral load, the per-act probability of HIV acquisition was higher in late pregnancy (adjusted relative risk [aRR], 2.82; P = .01) and the postpartum period (aRR, 3.97; P = .01) as compared to that during nonpregnant period. For a 25-year-old woman not taking PrEP, the HIV acquisition probability per condomless sex act with an HIV-infected male partner with a viral load of 10 000 copies/mL was 0.0011 (95% confidence interval [CI] 0.005-0.0019), 0.0022 (95% CI, 0.0004-0.0093), 0.0030 (95% CI, 0.0007-0.0108), and 0.0042 (95% CI, 0.0007-0.0177) during the nonpregnant period, early pregnancy, late pregnancy, and the postpartum period, respectively.ConclusionThe HIV acquisition probability per condomless sex act steadily increased during pregnancy and was highest during the postpartum period, suggesting that biological changes during pregnancy and the postpartum period increase HIV susceptibility among women.

Background Understanding the absolute and relative risk of human immunodeficiency virus type 1 (HIV) acquisition during pregnancy and the postpartum period can inform HIV prevention strategies for women. Methods We used a complementary log-log model and data from 2751 HIV-serodiscordant couples to compare the probability of HIV acquisition among women per sex act during early pregnancy, late pregnancy, the postpartum period, and the nonpregnant period. Results At total of 686 pregnancies were identified, and 82 incident HIV infections occurred. After adjustment for condom use, age, preexposure prophylaxis (PrEP) use, and HIV viral load, the per-act probability of HIV acquisition was higher in late pregnancy (adjusted relative risk [aRR], 2.82; P = .01) and the postpartum period (aRR, 3.97; P = .01) as compared to that during nonpregnant period. For a 25-year-old woman not taking PrEP, the HIV acquisition probability per condomless sex act with an HIV-infected male partner with a viral load of 10 000 copies/mL was 0.0011 (95% confidence interval [CI] 0.005-0.0019), 0.0022 (95% CI, 0.0004-0.0093), 0.0030 (95% CI, 0.0007-0.0108), and 0.0042 (95% CI, 0.0007-0.0177) during the nonpregnant period, early pregnancy, late pregnancy, and the postpartum period, respectively. Conclusion The HIV acquisition probability per condomless sex act steadily increased during pregnancy and was highest during the postpartum period, suggesting that biological changes during pregnancy and the postpartum period increase HIV susceptibility among women.

Objectives Studies that rely on self-report to investigate the relationship between hormonal contraceptive use and HIV acquisition and transmission, as well as other health outcomes, could have compromised results due to misreporting. We determined the frequency of misreported hormonal contraceptive use among African women with and at risk for HIV. Study design We tested 1102 archived serum samples from 664 African women who had participated in prospective HIV prevention studies. Using a novel high-performance liquid chromatography–mass spectrometry assay, we quantified exogenous hormones for injectables (medroxyprogesterone acetate or norethisterone), oral contraceptives (OC) (levonorgestrel or ethinyl estradiol) and implants (levonorgestrel or etonogestrel) and compared them to self-reported use. Results Among women reporting hormonal contraceptive use, 258/358 (72%) of samples were fully concordant with self-report, as were 642/744 (86%) of samples from women reporting no hormonal contraceptive use. However, 42/253 (17%) of samples from women reporting injectable use, 41/66 (62%) of samples from self-reported OC users and 3/39 (8%) of samples from self-reported implant users had no quantifiable hormones. Among self-reported nonusers, 102/744 (14%) had ≥1 hormone present. Concordance between self-reported method and exogenous hormones did not differ by HIV status. Conclusion Among African women with and at risk for HIV, testing of exogenous hormones revealed agreement with self-reported contraceptive use for most women. However, unexpected exogenous hormones were identified among self-reported hormonal contraceptive users and nonusers, and an important fraction of women reporting hormonal contraceptive use had no hormones detected; absence of oral contraceptive hormones could be due, at least in part, to samples taken during the hormone-free interval. Misreporting of hormonal contraceptive use could lead to biased results in observational studies of the relationship between contraceptive use and health outcomes. Implications Research studies investigating associations between hormonal contraceptive use and HIV should consider validating self-reported use by objective measures; because both overreporting and underreporting of use occur, potential misclassification based on self-report could lead to biased results in directions that cannot be easily predicted.

Background Genital human immunodeficiency virus (HIV) RNA shedding can continue despite HIV being undetectable in blood, and can be associated with transmission. Methods We included African women on antiretroviral therapy (ART). Linear and generalized linear mixed models were used to compare the magnitude and prevalence of genital shedding, respectively, by time since ART initiation. Multivariable logistic regression with generalized estimating equations was used to assess predictors of genital shedding among women with undetectable plasma viral load (VL). Results Among 1114 women, 5.8% of visits with undetectable plasma VL and 23.6% of visits with detectable VL had genital shedding. The proportion of visits with genital shedding decreased with time since ART initiation but the magnitude of shedding remained unchanged when plasma VL was undetectable (P = .032). Prevalence of shedding did not vary by time since ART initiation when plasma VL was detectable (P = .195), though the magnitude of shedding significantly increased (P = .04). Predictors of genital shedding were HIV disease stage, antiretroviral regimen, and genital ulcers or cervical tenderness. Discussion In addition to ART, reducing immune activation through prevention and treatment of HIV-related conditions and genital tract infections may decrease the risk of HIV-1 shedding and potential transmission.

ObjectiveThe objective of this study is to assess whether antiretroviral therapy (ART) may diminish the effectiveness of hormonal contraceptive methods.MethodsUsing data from 5153 HIV-infected women followed prospectively for 1-3 years in three HIV prevention studies in Africa, we compared incident pregnancy rates by contraceptive method (implant, injectable, oral or none) and ART use. Multivariable Cox regression models were used to determine adjusted hazard ratios (aHRs) and test interactions between each method and ART use.ResultsDuring follow-up, 9% of women ever used implants, 40% used injectables and 14% used oral contraceptives; 31% of women ever used ART, mostly nevirapine (75% of ART users) or efavirenz-based (15%). Among women not using contraception, pregnancy rates were 13.2 and 22.5 per 100 women-years for those on and not on ART, respectively. Implants greatly reduced the incidence of pregnancy among both women on ART [aHR 0.06, 95% confidence interval (95% CI) 0.01-0.45] and not on ART (aHR 0.05, 95% CI 0.02-0.11). Injectables (aHR 0.18 on ART and aHR 0.20 not on ART) and oral contraceptives (aHR 0.37 on ART and aHR 0.36 not on ART) also reduced pregnancy risk, though by lesser degrees. ART use did not significantly diminish contraceptive effectiveness, although all methods showed nonstatistically significant reduced effectiveness when concurrently using efavirenz.ConclusionHormonal contraceptive methods are highly effective in reducing pregnancy risk in HIV-infected women, including those concurrently using ART. Studies of potential interactions between ART and contraceptives should evaluate real-world effectiveness of contraceptive methods; in this study, implants were the most effective method to prevent pregnancy, even during ART use.