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Background: Women living with HIV (WLHIV) have lower rates of contraceptive use than noninfected peers, yet concerns regarding contraceptive efficacy and interaction with antiretroviral therapy (ART) complicate counseling. Hormonal contraceptives may increase genital tract HIV viral load (gVL) and sexual transmission risk to male partners. We compared gVL, plasma VL (pVL), and intrauterine contraceptive (IUC) continuation between the levonorgestrel intrauterine system (LNG-IUS) and copper intrauterine device (C-IUD) in Cape Town, South Africa. Methods and findings: In this double-masked, randomized controlled noninferiority trial, eligible WLHIV were ages 18–40, not pregnant or desiring pregnancy within 30 months, screened and treated (as indicated) for reproductive tract infections (RTIs) within 1 month of enrollment, and virologically suppressed using ART or above treatment threshold at enrollment (non-ART). Between October 2013, and December 2016, we randomized consenting women within ART groups, using 1:1 permuted block randomization stratified by ART use, age (18–23, 24–31, 32–40), and recent injectable progestin contraceptive (IPC) exposure, and provided the allocated IUC. At all visits, participants provided specimens for gVL (primary outcome), pVL, RTI, and pregnancy testing. We assessed gVL and pVL across 6 and 24 months controlling for enrollment measures, ART group, age, and RTI using generalized estimating equation and generalized linear models (non-ART group pVL and hemoglobin) in as-treated analyses. We measured IUC discontinuation rates with Kaplan-Meier estimates and Cox proportional hazards models. We enrolled 71 non-ART (36 LNG-IUS, 31 C-IUD; 2 declined and 2 were ineligible) and 134 ART-using (65 LNG-IUS, 67 C-IUD; 1 declined and 1 could not complete IUC insertion) women. Participant median age was 31 years, and 95% had 1 or more prior pregnancies. Proportions of women with detectable gVL were not significantly different comparing LNG-IUS to C-IUD across 6 (adjusted odds ratio [AOR]: 0.78, 95% confidence interval [CI] 0.44–1.38, p = 0.39) and 24 months (AOR: 1.03, 95% CI: 0.68–1.57, p = 0.88). Among ART users, proportions with detectable pVL were not significantly different at 6 (AOR = 0.83, 95% CI 0.37–1.86, p = 0.65) and 24 months (AOR = 0.94, 95% CI 0.49–1.81, p = 0.85), whereas among non-ART women, mean pVL was not significantly different at 6 months (−0.10 log10 copies/mL, 95% CI −0.29 to 0.10, p = 0.50) between LNG-IUS and C-IUD users. IUC continuation was 78% overall; C-IUD users experienced significantly higher expulsion (8% versus 1%, p = 0.02) and elective discontinuation (adjusted hazard ratio: 8.75, 95% CI 3.08–24.8, p < 0.001) rates. Sensitivity analysis adjusted for differential IUC discontinuation found similar gVL results. There were 39 serious adverse events (SAEs); SAEs believed to be directly related to IUC use (n = 7) comprised 3 pelvic inflammatory disease (PID) cases and 4 pregnancies with IUC in place with no discernible trend by IUC arm. Mean hemoglobin change was significantly higher among LNG-IUS users across 6 (0.57 g/dL, 95% CI 0.24–0.90; p < 0.001) and 24 months (0.71 g/dL, 95% CI 0.47–0.95; p < 0.001). Limitations included not achieving non-ART group sample size following change in ART treatment guidelines and truncated 24 months' outcome data, as 17 women were not yet eligible for their 24-month visit at study closure. Also, a change in VL assay during the study may have caused some discrepancy in VL values because of different limits of detection. Conclusions: In this study, we found that the LNG-IUS did not increase gVL or pVL and had low levels of contraceptive failure and associated PID compared with the C-IUD among WLHIV. LNG-IUS users were significantly more likely to continue IUC use and had higher hemoglobin levels over time. The LNG-IUS appears to be a safe contraceptive with regard to HIV disease and may be a highly acceptable option for WLHIV. Trial registration: ClinicalTrials.gov NCT01721798. Catherine Todd and colleagues study an intrauterine contraceptive device in women with HIV infection. Author summary: Why was this study done?: Women living with HIV (WLHIV) infection must consider their contraceptive options in tandem with and complicated by potential interactions between hormonal contraception and HIV disease. These issues potentially contribute to lower use of highly effective hormonal contraceptive methods among WLHIV. Global use of intrauterine contraception (IUC), specifically the levonorgestrel intrauterine system (LNG-IUS), has increased across the last decade. However, there are few trials comparing safety of the LNG-IUS with that of the copper intrauterine device (C-IUD) among WLHIV and none focusing specifically on impact on HIV disease. What did the researchers do and find?: In a randomized controlled trial in Cape Town, South Africa, 199 women with confirmed HIV seropositivity and not desiring pregnancy in the next 30 months were recruited and allocated, with 98 receiving the C-IUD and 101 the LNG-IUS. Participants had genital tract samples collected by menstrual cup and blood taken for genital and plasma viral load levels at enrollment and at 3-, 6-, 12-, 18-, and 24-month visits. Women could return at any time for unscheduled visits and remained in the study even if the IUC was removed on request. Women receiving the LNG-IUS did not have any significant difference in change in detectable genital tract viral load compared with C-IUD users, regardless of ART status. However, women receiving the C-IUD were more likely to have the IUC removed than those receiving the LNG-IUS through the study period. What do these findings mean?: This study is among the first comparing a hormonal to nonhormonal long-acting reversible contraceptive method with genital tract HIV RNA as the primary outcome among WLHIV. These data suggest that LNG-IUS is as safe as the C-IUD for WLHIV and will strengthen international medical eligibility guidelines. The high continuation rates of the LNG-IUS, critically important for a device with a 5-year duration of use, should prompt including this method in the available method mix to promote the ability of WLHIV to meet their fertility goals. [ABSTRACT FROM AUTHOR]

Background: Reproductive tract infections (RTIs) are a major cause of morbidity and mortality, yet RTI testing remains limited in resource-constrained settings. We assessed performance of an existing RTI risk assessment screening tool among women living with HIV (WLHIV) considering intrauterine contraceptive (IUC) use., Methods: We conducted a cross-sectional analysis among WLHIV screened for participation in an IUC trial in Cape Town, South Africa (NCT01721798). RTI testing included Neisseria gonorrhoeae , Chlamydia trachomatis , Trichomonas vaginalis and bacterial vaginosis. Tool scoring was based on five separately scored criteria: (1) age under 25 years, (2) cohabitation with a partner, (3) secondary education, (4) self-reported intermenstrual bleeding and (5) number of current sexual partners and condom use frequency (score 0-5). We assessed tool performance in detecting RTI at 0 vs 1-5, 0-1 vs 2-5 and 0-2 vs 3-5 score thresholds., Results: Of 303 women, 52% (n=157) reported antiretroviral therapy use and median age was 31 years. The prevalence of any RTI was 38% (gonorrhoea=7%, chlamydia=11%, trichomoniasis=12% and bacterial vaginosis=18%) and 8% of women had multiple RTIs. Overall, 4%, 27% and 69% of women had screening tool scores of 0, 1 or 2+, respectively. At a threshold of at least one scored criterion, the tool demonstrated high sensitivities (95%-97%) but low specificities (3%-4%) for detecting any RTI. Increasing the score threshold and/or inclusion of abnormal vaginal discharge marginally improved specificity., Conclusion: The prevalence of RTIs observed in this population was high, and the screening tool had no discriminatory power to detect prevalent RTIs., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Measurement of cytokines in the lower female genital tract offer insight into risk for HIV infection and reproductive complications. However, few studies have systematically compared mucosal collection methods or whether collection order matters. We compared longitudinal cytokine profiles in matched genital samples collected from women living with HIV using menstrual cup (MC), endocervical swabs (ECS) and swab-enriched cervicovaginal lavage (eCVL). Samples were collected at enrollment [MC:ECS:eCVL], 3-months (ECS:eCVL:MC) and 6-months (eCVL:MC:ECS) and concentrations of 28 cytokines determined by Luminex. Cytokine clustering was assessed using Principle Component Analysis (PCA), Partial Least Squares Discriminant Analysis (PLSDA) and factor analysis. Generally, higher cytokine concentrations were detected in MC samples, followed by ECS and eCVL, irrespective of study visit or sampling order. Factor analysis and PCA identified ECS to be inferior for measuring regulatory cytokines and IP-10 than eCVL or MC. Although concentrations differed, the majority of cytokines correlated between methods. Sampling order influenced cytokine concentrations marginally, and cytokines clustered more strongly by method than study visit. Variance in profiles was lowest in MC, suggesting greater consistency of sampling compared to other methods. We conclude that MC sampling offered advantages over other methods for detecting cytokines in women, with order marginally influencing profiles.