Incidence of Herpes Simplex Virus Type 2 Infection Among African Women Using Depot Medroxyprogesterone Acetate, a Copper Intrauterine Device, or a Levonorgestrel Implant for Contraception: A Nested Randomized Trial.

BACKGROUND: Globally, women have higher herpes simplex virus type 2 (HSV-2) prevalence than men; data from observational studies suggest a possible association of HSV-2 acquisition with use of intramuscular depot medroxyprogesterone acetate (DMPA-IM). METHODS: Within a randomized trial of the effect of 3 contraceptive methods-DMPA-IM, a copper intrauterine device (IUD), and a levonorgestrel (LNG) implant-on human immunodeficiency virus (HIV) acquisition, we assessed HSV-2 acquisition. HSV-2 and HIV seronegative women, aged 16-35 years, and seeking effective contraception were followed for 12-18 months at 12 sites in Eswatini, Kenya, South Africa, and Zambia from 2015 to 2018. HSV-2 serologic testing was done at enrollment and final study visits. Intention-to-treat analysis using Poisson regression with robust standard errors compared HSV-2 incidence by contraceptive method. RESULTS: At baseline, 4062 randomized women were HSV-2 seronegative, of whom 3898 (96.0%) had a conclusive HSV-2 result at their final study visit. Of these, 614 (15.8%) acquired HSV-2, at an incidence of 12.4/100 person-years (p-y): 10.9/100 p-y among women assigned DMPA-IM, 13.7/100 p-y the copper IUD, and 12.7/100 p-y the LNG implant. Incidence rate ratios (IRR) for HSV-2 acquisition were 0.80 (95% confidence interval [CI], .65-.97) for DMPA-IM compared with copper IUD, 0.86 (95% CI, .71-1.05) for DMPA-IM compared with LNG implant, and 1.08 (95% CI, .89-1.30) for copper IUD compared with LNG implant. HSV-2 acquisition risk was significantly increased among women who also acquired HIV during follow-up (IRR 3.55; 95% CI, 2.78-4.48). CONCLUSIONS: In a randomized trial, we found no association between HSV-2 acquisition and use of 3 contraceptive methods. TRIAL REGISTRATION: ClinicalTrials.gov number NCT02550067.

Sexual behaviour among women using intramuscular depot medroxyprogesterone acetate, a copper intrauterine device, or a levonorgestrel implant for contraception: Data from the ECHO randomized trial.

BACKGROUND: Contraceptive use has complex effects on sexual behaviour and mood, including those related to reduced concerns about unintended pregnancy, direct hormonal effects and effects on endogenous sex hormones. We set out to obtain robust evidence on the relative effects of three contraceptive methods on sex behaviours, which is important for guiding contraceptive choice and future contraceptive developments. METHODS: This is a secondary analysis of data from the Evidence for Contraceptive Options and HIV Outcomes (ECHO) randomized trial in which 7,829 HIV-uninfected women from 12 sites in Eswatini, Kenya, South Africa and Zambia seeking contraception were randomly assigned to intramuscular depot-medroxyprogesterone acetate (DMPA-IM), the copper intrauterine device (Cu-IUD) or the levonorgestrel (LNG) implant. Data collected for 12 to 18 months using 3-monthly behavioural questionnaires that relied on recall from the preceding 3 months, were used to estimate relative risk of post-baseline sex behaviours, as well as sexual desire and menstrual bleeding between randomized groups using modified Poisson regression. RESULTS: We observed small but generally consistent effects wherein DMPA-IM users reported lower prevalence of specified high risk sexual behaviours than implant users than Cu-IUD users (the '>' and '<' symbols indicate statistically significant differences): multiple sex partners 3.6% < 4.8% < 6.2% respectively; new sex partner 3.0% < 4.0% <5.3%; coital acts 16.45, 16.65, 17.12 (DMPA-IM < Cu-IUD); unprotected sex 65% < 68%, 70%; unprotected sex past 7 days 33% <36%, 37%; sex during vaginal bleeding 7.1%, 7.1% < 8.9%; no sex acts 4.1%, 3.8%, 3.4% (DMPA-IM > Cu-IUD); partner has sex with others 10% < 11%, 11%. The one exception was having any sex partner 96.5%, 96.9% < 97.4% (DMPA-IM < Cu-IUD). Decrease in sexual desire was reported by 1.6% > 1.1% >0.5%; amenorrhoea by 49% > 41% >12% and regular menstrual pattern by 26% <35% < 87% respectively. CONCLUSIONS: These findings suggest that women assigned to DMPA-IM may have a modest decrease in libido and sexual activity relative to the implant, and the implant relative to the Cu-IUD. We found more menstrual disturbance with DMPA-IM than with the implant (and as expected, both more than the Cu-IUD). These findings are important for informing the contraceptive choices of women and policymakers and highlight the need for robust comparison of the effects of other contraceptive methods as well.

Effects of Depot Medroxyprogesterone Acetate, Copper Intrauterine Devices, and Levonorgestrel Implants on Early HIV Disease Progression.

Limited data exist on the effects of contraceptives on HIV disease progression. We studied the association between intramuscular injectable depot medroxyprogesterone acetate (DMPA-IM), the copper intrauterine device (IUD), and the levonorgestrel (LNG) implant on markers of HIV disease progression at the time of HIV detection and 3 months postdetection and time from detection to CD4 count <350 cells/mm3. Among women initiating antiretroviral therapy (ART), we studied the effect of contraceptive group on time from ART initiation to viral load (VL) <40 copies/mL. We included women 16-35 years randomized to DMPA-IM, copper IUD, or LNG implant with incident HIV infection during the Evidence for Contraceptive Options and HIV Outcomes (ECHO) trial (n = 382). We analyzed HIV VL and CD4 cell count according to participants' randomized method and also conducted a "continuous use" analysis that excluded follow-up time after method discontinuation. We used adjusted linear models to compare mean VL and CD4 cell levels by contraceptive group up to the time of ART initiation. We compared time from HIV detection to CD4 count <350 cells/mm3 and, following ART initiation, time to viral suppression (VL <40 copies/mL) using Cox proportional hazards models. At HIV detection, women allocated to DMPA-IM had lower VL relative to copper IUD (-0.28 log10 copies/mL; 95% confidence interval [CI]: -0.55 to -0.01) and LNG implant (-0.27, CI: -0.55 to 0.02) and higher mean CD4 than copper IUD users by 66 cells/mm3 (CI: 11-121). In continuous use analyses women allocated to DMPA-IM progressed to CD4 < 350 cells/mm3 slower than copper IUD users (hazard ratio [HR] = 0.6, CI: 0.3-1.1), whereas copper IUD users progressed faster than LNG implant users (HR = 1.8, CI: 1.0-3.3). Time to viral suppression was faster for DMPA-IM than copper IUD (HR = 1.5, CI: 1.0-2.3) and LNG implant 1.4 (CI: 0.9-2.2) users. We found no evidence of more rapid early HIV disease progression among women using DMPA-IM than among women using copper IUD or LNG implant. Our finding of more rapid progression among copper IUD compared with DMPA-IM users should be interpreted cautiously.

Performance of serological and molecular tests within acute HIV infection.

BACKGROUND: Early diagnosis of acute HIV infection can be challenging and is critical in regards to early therapeutic decision making. OBJECTIVES: To evaluate the performance of different HIV tests in detecting early infections. STUDY DESIGN: A total of 83 leftover specimens of 61 study participants who seroconverted were used in this sub-study. 35 HIV RNA positive but still seronegative specimens (acute infections) were used for analysis of the sensitivity of the different assays in detecting early infections and 42 HIV RNA and antibody negative specimens were used for specificity analysis. RESULTS: Four (11%) specimens out of 35 acute infections were reactive with the Enzygnost® Anti-HIV 1/2 Plus and 12/35 (34%) with the Vironostika® HIV Ag/Ab. 16 (46%) specimens were confirmed as acute by the INNOTEST® HIV antigen mAb Antigen test. Only three (9%), 10 (29%) and 9 (27%) specimens were reactive with the Determine HIV-1/2 Ag/Ab Combo, SD Bioline HIV Ag/Ab Combo test and the HIV Combo test, respectively. The specificity of the different tests were 100%, 95%, 100%, 93%, 100% and 93% for Enzygnost® Anti-HIV 1/2 Plus, Vironostika® HIV Ag/Ab, INNO-Test HIV antigen mAb, Determine HIV-1/2 Ag/Ab Combo, SD Bioline HIV Ag/Ab Combo test and HIV Combo test respectively. CONCLUSION: RNA test, 4th generation ELISA and Single Ag test are the most sensitive tests for detection of an acute infection. As an alternative, the HIV Combo test is generally slightly more sensitive compared to its previous version, but the SD Bioline HIV Ag/Ab Combo tests has the best performance compared to the other simple rapid tests (SRTs) but none of them are precise in detecting Ag in the determination of acute infections.

Detection of new HIV infections in a multicentre HIV antiretroviral pre-exposure prophylaxis trial.

BACKGROUND: Monthly specimens collected from FEM-PrEP-a Phase III trial [1] were investigated for the detection of acute HIV (AHI) infection. OBJECTIVES: To evaluate the efficiency of the study-specific HIV algorithm in detecting AHI, and the performance of each of the serological and molecular tests used in diagnosing new infections, and their contribution to narrowing the window period. STUDY DESIGN: A total of 83 pre-seroconversion specimens from 61 seroconverters from the FEM-PrEP trial were further analyzed in a sub-study. During the trial, HIV seroconversion was diagnosed on site using a testing algorithm with simple/rapid tests (SRTs) and confirmed with a gold standard testing algorithm (see short communication: Fig. 1). The infection date was determined more accurately by the use of standard ELISAs and Nucleic Acid Amplification Tests (NAAT) in a look-back procedure. For this sub-study, the international central laboratory repeated the study algorithm using SRTs. RESULTS: A total of 83 pre-seroconversions specimens from 61 seroconverters were analyzed in a look-back procedure. RNA was detected in 35/61 seroconverters at the visit before the seroconversion visit as determined at the study sites. Four seroconversion dates were inaccurate at one study site as the international central laboratory detected the HIV infection one visit earlier using the same test algorithm. Using the gold standard, an additional seroconversion was detected at an earlier visit. The combined antigen/antibody and the single antigen test had a higher sensitivity compared to the SRTs in detecting acute infections. CONCLUSIONS: In the FEM-PrEP trial, the international central laboratory detected a small number of seroconversions one month earlier than the study sites using the same study algorithm. Standard tests are still the most sensitive tests in detecting pre-seroconversion or acute HIV infection, but they are costly, time consuming and not recommended for use on-site in a clinical trial.