Effects of Urethritis on Human Immunodeficiency Virus (HIV) in Semen: Implications for HIV Prevention and Cure

Abstract

Background Prior to the widespread availability of antiretroviral therapy (ART), Men living with HIV with urethritis had increased concentration of HIV in semen. This study aims to better evaluate HIV shedding in men with urethritis receiving ART, and implications for the cure of HIV. Methods Men living with HIV with urethritis taking ART ≥12 weeks were enrolled at a sexually transmitted infections clinic in Lilongwe, Malawi. Study follow-up included visits 1, 2, 4, 8, 12, 24, 36, and 48 weeks post urethritis diagnosis and treatment. Matched blood and semen samples were collected at all visits, and all additional episodes of urethritis were followed with extra visits 1, 2, and 4 weeks after treatment. Results 111 men enrolled in the study between January 2017 – March 2019, and 77 (69%) were suppressed in the blood (<400 copies/mL). Among the 77 men, 87 episodes of urethritis were evaluated during follow-up. Of the 87 episodes, 15 episodes (17%) had instances of seminal viral shedding ≥400 copies/mL despite viral suppression in the blood. At follow-up of non-urethritis episodes, ≤6% of men at each visit had a viral load ≥400 copies/mL in the semen while maintaining viral suppression in the blood. Conclusions An HIV cure requires the elimination of HIV from every body compartment, but available ART does not currently accomplish this. Our study highlights the male genital tract as a local source of HIV that can be reversibly activated. A better understanding of this phenomenon is important to advance the HIV cure field.

Gentamicin Susceptibility in Neisseria gonorrhoeae and Treatment Outcomes for Urogenital Gonorrhea After 25 Years of Sustained Gentamicin Use in Malawi

“…Men with acute urethritis were recruited for study participation at the Bwaila District Hospital STI Clinic in Lilongwe, Malawi. Participants were originally recruited as part of a parent study of men living with HIV who had acute urethritis 27 ; after enrollment for that study closed, an additional cohort of consecutive men with acute urethritis was recruited to increase sample size, regardless of HIV status. All participants, in both cohorts, were at least 18 years of age; lived in Lilongwe District; and provided written informed consent before study participation.…”

Brief Report: Blood and Genital Fluid Viral Load Trajectories Among Treated and Untreated Persons With Acute HIV Infection in Malawi

“…12 Among HIV-infected Malawian men virally suppressed on ART, nearly 20% of urethritis episodes were associated with genital VL “blipping” despite sustained viremic control. 22 In our cohort, both participants who started ART and had a co-occurring STI at week 12 maintained undetectable genital VLs. Nonetheless, frequent STIs following AHI diagnosis underscores the importance of combined biomedical and BIs.…”

High level of HIV viral suppression in a cross-sectional study of Ugandan men with urethritis and bacterial STI

“…Paired plasma viral loads were undetectable. 21 Modern integrase inhibitor-based ART regimens have been shown to rapidly decrease blood and seminal plasma to <40 cpm; this was achieved in 4 weeks in plasma compared with 12 weeks in seminal plasma. 22 Assuming people with VL <1000 copies are relatively unlikely to transmit, these data suggest that a minority of participants were at greater risk for onward transmission.…”

“…The synergistic effect of UDS, however, may potentiate HIV transmission risk even in the presence of relatively low-level viremia. 21 Therefore, efforts should focus on ensuring VLS in the minority of those with detectable plasma viral loads and developing targeted interventions to decrease STI coinfections. Further work is required to investigate predictors of VLS in Ugandan men and to examine the feasibility and added value of POC HIV RNA assays to increase diagnostic yield when screening men with UDS for HIV, particularly in those at risk with a negative POC antibody assay.…”