Evidence of HIV-1 Genital Shedding after One Year of Antiretroviral Therapy in Females Recently Diagnosed in Bamako, Mali

Little is known about the dynamic of HIV-1 shedding and resistance profiles in the female genital reservoir after antiretroviral therapy (ART) initiation in resource-limited countries (RLCs), which is critical for evaluating the residual sexual HIV-1 transmission risk. The present study aimed to evaluate the efficacy of 1 year duration ART at blood and genital levels in females newly diagnosed for HIV-1 from three centers in Bamako, Mali. Seventy-eight consenting females were enrolled at the time of their HIV-1 infection diagnosis. HIV-1 RNA loads (Abbott Real-Time HIV-1 assay) were tested in blood and cervicovaginal fluids (CVF) before and 12 months after ART initiation. Primary and acquired resistances to ART were evaluated by ViroseqTM HIV-1 genotyping assay. The vaginal microbiota was analyzed using IonTorrentTM NGS technology (Thermo Fisher Scientific). Proportions of primary drug resistance mutations in blood and CVF were 13.4% and 25%, respectively. Discrepant profiles were observed in 25% of paired blood/CVF samples. The acquired resistance rate was 3.1% in blood. At month 12, undetectable HIV-1 RNA load was reached in 84.6% and 75% of blood and CVF samples, respectively. A vaginal dysbiosis was associated with HIV RNA shedding. Our findings emphasize the need of reinforcing education to improve retention in care system, as well as the necessity of regular virological monitoring before and during ART and of implementing vaginal dysbiosis diagnosis and treatment in RLCs.

Genital Shedding of Human Immunodeficiency Virus Type-1 (HIV) When Antiretroviral Therapy Suppresses HIV Replication in the Plasma

Background During antiretroviral treatment (ART) with plasma HIV RNA below the limit of quantification, HIV RNA can be detected in genital or rectal secretions, termed discordant shedding (DS). We hypothesized that proliferating cells produce virions without HIV replication. Methods ART-naive Peruvians initiating ART were observed for DS over 2 years. HIV env and pol genomes were amplified from DS. Antiretrovirals and cytokines/chemokines concentrations were compared at DS and control time points. Results Eighty-two participants had ART suppression. DS was detected in 24/82 (29%) participants: 13/253 (5%) cervicovaginal lavages, 20/322 (6%) seminal plasmas, and 6/85 (7%) rectal secretions. HIV RNA in DS specimens was near the limit of quantification and not reproducible. HIV DNA was detected in 6/13 (46%) DS cervicovaginal lavages at low levels. Following DNase treatment, 5/39 DS specimens yielded HIV sequences, all without increased genetic distances. Women with and without DS had similar plasma antiretroviral levels and DS in 1 woman was associated with inflammation. Conclusions HIV RNA and DNA sequences and therapeutic antiretroviral plasma levels did not support HIV replication as the cause of DS from the genital tract. Rather, our findings infer that HIV RNA is shed due to proliferation of infected cells with virion production.

417. Cytomegalovirus (CMV) and Sexually Transmitted infections (STIs) During Pregnancy

Background Congenital cytomegalovirus infection (cCMV) is a leading cause of hearing loss and neurodevelopmental disabilities. Although higher rates of CMV acquisition and reinfections with new virus strains are seen in women with STIs, the significance of CMV-STI co-infections during pregnancy and whether co-infections increase intrauterine transmission of CMV remains unclear. Higher rates of CMV genital shedding were seen in mothers of infants with cCMV compared with those with uninfected infants. The objective of this study was to determine the association between CMV seroprevalence and STIs and whether STIs during pregnancy influences CMV genital shedding. Methods Vaginal swabs from a cohort of CMV seropositive women in labor from a multi-center study were analyzed. After DNA extraction from vaginal swabs, PCR was performed for detection of CMV, Neisseria gonorrhoeae (GC), Chlamydia trachomatis (CT), Trichomonas vaginalis (TV) and Mycoplasma genitalium (MG). The prevalence of STIs in CMV seropositive pregnant women was determined in this cohort and CMV genital shedding rates were compared between groups with and without STIs. Results In this cohort, CMV genital shedding in late pregnancy was detectable in 13% (21/160) of women while rates of detection for MG, GC, CT and TV were 3%, 0.6%, 1.2% and 8%, respectively. CMV-STI co-infections were noted in 2.5% (4/160) of women. CMV genital shedding was documented in only one woman with STIs, compared with 12.5% (20/160) without STIs. Among women shedding CMV in the genital tract, CMV viral load levels ranged from 1.1 × 102 IU/mL to 2.2 × 104 IU/mL. Conclusion In a cohort of CMV seropositive women, the presence of STIs in late pregnancy did not increase CMV genital shedding. Our preliminary findings suggest CMV shedding is not associated with STIs detected late in pregnancy. Disclosures All authors: No reported disclosures.

Genital Human Immunodeficiency Virus–1 RNA and DNA Shedding in Virologically Suppressed Individuals Switching From Triple- to Dual- or Monotherapy: Pooled Results From 2 Randomized, Controlled Trials

Background Increasingly, people living with human immunodeficiency virus (HIV) benefit from lower drug regimens (LDRs). Exploring viral genital shedding during LDRs is crucial to ensure their safety. Methods We pooled genital sub-studies from 2 clinical trials in this area. Patients were randomized 1:1 to continue abacavir/lamivudine/dolutegravir or switch to dolutegravir (MONCAY trial), or to continue tenofovir/emtricitabine + a third agent or switch to tenofovir/emtricitabine (TRULIGHT trial). Participants whose plasma HIV-RNA remained <50 copies/mL had sperm or cervicovaginal lavage collected between Weeks 24 and 48. HIV-RNA and HIV-DNA were amplified by ultrasensitive polymerase chain reaction. The main objective was to measure the proportion of participants who had no detectable HIV in genital fluids, both according to each strategy and then in an aggregated analysis (LDR versus triple therapies). Results There were 64 participants (35 males, 29 females) included: 16 received dual therapies and 16 received triple therapies in TRULIGHT; and 16 received monotherapies and 16 received triple therapies in MONCAY. In TRULIGHT, 13/15 (87%) of evaluable participants on dual therapy had no detectable HIV in their genital fluid, versus 14/15 (93%) under triple therapy (P = 1.0). In MONCAY, these figures were 12/15 (80%) on monotherapy versus 13/16 (81%) on triple therapy (P = 1.0). In the pooled analysis, a similar proportion of participants in the LDR and triple therapy groups had no detectable HIV: 25/30 (83%) and 27/31 (87%), respectively (P = .73). Conclusions There was no evidence of increased HIV-RNA and/or -DNA shedding in the genital fluids of people who maintained undetectable plasma HIV-RNA during LDRs. Clinical Trials Registration NCT02302547 and NCT02596334

Genital Shedding of Resistant Human Immunodeficiency Virus-1 Among Women Diagnosed With Treatment Failure by Clinical and Immunologic Monitoring

Background. The accumulation of human immunodeficiency virus (HIV) resistance mutations can compromise treatment outcomes and promote transmission of drug-resistant virus. We conducted a study to determine the duration and evolution of genotypic drug resistance in the female genital tract among HIV-1-infected women failing first-line therapy. Methods. Treatment failure was diagnosed based on World Health Organization (WHO) clinical or immunologic criteria, and second-line therapy was initiated. Stored plasma and genital samples were tested to determine the presence and timing of virologic failure and emergence of drug resistance. The median duration of genital shedding of genotypically resistant virus prior to regimen switch was estimated. Results. Nineteen of 184 women were diagnosed with treatment failure, of whom 12 (63.2%) had confirmed virologic failure at the switch date. All 12 women with virologic failure (viral load, 5855–1 086 500 copies/mL) had dual-class resistance in plasma. Seven of the 12 (58.3%) had genital HIV-1 RNA levels high enough to amplify (673–116 494 copies/swab), all with dual-class resistance. The median time from detection of resistance in stored samples to regimen switch was 895 days (95% confidence interval [CI], 130–1414 days) for plasma and 629 days (95% CI, 341–984 days) for genital tract secretions. Conclusions. Among women diagnosed with treatment failure using WHO clinical or immunologic criteria, over half had virologic failure confirmed in stored samples. Resistant HIV-1 RNA was shed in the genital tract at detectable levels for ≈1.7 years before failure diagnosis, with steady accumulation of mutations. These findings add urgency to the ongoing scale-up of viral load testing in resource-limited settings.

Low prevalences of HIV infection and HSV genital shedding in the general adult female population in Senegal

Introduction: Herpes simplex virus (HSV) is the main co-factor for heterosexual transmission of the human immunodeficiency virus (HIV) in sub-Saharan Africa, and could be involved in the dynamics of the HIV epidemic in Senegal. Methodology: Genital shedding of HSV was evaluated in adult females who had visited the provincial healthcare centres in Diass, Louga, and Kebemer in Senegal. Study subjects were interviewed by a healthcare worker for sociodemographic characteristics and sexual behavior, and HIV serology was offered. In addition, cervical secretion lavage samples were evaluated for HSV DNA by real-time polymerase chain reaction (PCR), the melting curve analysis of which permitted distinction between HSV type 1 (HSV-1) and HSV type 2 (HSV-2). Results: Among 302 women (mean age, 40 years) enrolled, none were infected by HIV. The mean age at first sexual intercourse was 20 years, and the mean number of sexual partners in the previous year was 1.3 (range, 1–7). Only 6 of 302 (1.9%) women had cervico-vaginal secretions positive for HSV DNA. No association between HSV DNA shedding and any sociodemographic or biological variables was found. Surprisingly, genital shedding of HSV-1 was found in two (0.7%) women, representing 33% of herpes-shedding women, and HSV-2 in four (1.5%) women. Conclusions: Taken together, our observations indicate a low prevalence of HSV DNA genital shedding in adult Senegalese women.