Featured Literature
Chappell CA, Kiser JJ, Brooks KM, et al. Sofosbuvir/velpatasvir pharmacokinetics, safety, and efficacy in pregnant people with hepatitis C virus. Clin Infect Dis. 2024 Dec 17:ciae595. doi: 10.1093/cid/ciae595.
Investigators evaluated plasma PK parameters of the pangenotypic regimen sofosbuvir/velatasvir (SOF/VEL) and assessed safety and efficacy in 11 participants. Participants were between 23 to 25 weeks’ gestation at enrollment and did not have HIV or hepatitis B co-infection, cirrhosis, or history of prior treatment with SOF or an NS5A inhibitor. Infants were followed for 12 months. One participant discontinued treatment due to pregnancy-related hyperemesis, and ten participants completed study medication and delivered (complete follow-up data were available for eight mother-baby pairs).
Upon SOF/VEL initiation, HCV viral load was undetectable by the third PK study visit for all (i.e., nine weeks after treatment initiation, or between 32-35 weeks’ gestation). All participants reported excellent adherence, defined as not missing more than one dose per week, except for one who missed greater than one dose per week in the last three weeks of treatment. All eight participants completing the SVR12 study visit had an undetectable viral load 12 weeks after completing SOF/VEL, and another participant who subsequently re-engaged in routine clinical care was found to have an undetectable viral load. The most common medication-related adverse events were nausea/vomiting, headache, and heartburn. None of the infants had a detectable viral load, and no medication-related safety concerns were identified.
Commentary
Along with other small studies, findings from this analysis support the tolerability, safety, and efficacy of SOF-based HCV treatment initiation during the second trimester. Further, findings from various PK measures suggest that SOF/VEL exposures were not clinically different in pregnancy. Investigators hope these data, along with results from other studies in the near future, will advance recommendations to support universal consideration and use of DAAs to treat HCV during pregnancy.
Featured Literature
Abdi B, Saliba S, Wirden M, et al. No virological failure in patients living with HIV with past NNRTI resistance-associated mutations switched to doravirine-containing regimens. J Antimicrob Chemother. 2025 Jan 15:dkae481. doi: 10.1093/jac/dkae481.
This observational, single-center study describes characteristics and virologic outcomes of 102 people with historical NNRTI associated mutations who were switched to doravirine (DOR)-containing regimens in routine clinical care. All were DOR-naïve with viral load of 50 copies/mL or less pre-switch, and had previously documented NNRTI mutations in RNA and/or DNA based genotypes. For people with historical mutations affecting DOR susceptibility, DNA genotype was performed at switch to assess for mutation persistence. Median age was 59 years, with 22 years on ART, and seven years viral suppression. Sixty-three were switched to a three-drug regimen (of this group, 89% switched to DOR/TDF/3TC) and 39 to a two-drug regimen (of this group, 51% to DOR/RAL and 44% to DOR/DTG).
Reasons for switch were primarily pill burden and long-term toxicity prevention, however several switched due to adverse effects attributed to current ART (e.g., weight gain, dyspepsia, CNS side effects, arthralgias, drug interactions). Twenty-five percent had historical DOR mutations; at time of switch, DNA GRT revealed that archived mutations were no longer detected in 72 percent of this sub-group. Eighty-six people had complete 96-week follow-up on DOR, and no virologic failures were detected.
Commentary
Findings from this real-world analysis help shed light on how often DOR is being considered for virologically suppressed people seeking ART modification, and virologic outcomes after switching to DOR-inclusive regimens. The additional details regarding drug resistance mutations in this population (both historically documented and mutations identified on DNA genotype at time of switch) help provide information on DOR efficacy even among people with a history of NNRTI failure and emergence of select mutations. As authors note, further analyses on NNRTI mutation clearance need to be confirmed and may help inform whether NNRTI “recycling” could be a viable option for some individuals.
Featured Literature
Baxter A, Gopalappa C, Islam MH, et al. Updates to HIV transmission rate estimates along the HIV care continuum in the United States, 2019. J Acquir Immune Defic Syndr. 2025 Jan 23. doi: 10.1097/QAI.0000000000003623.
Investigators sought to update HIV transmission rates and distribution by care continuum status, race/ethnicity, transmission group, and age to help inform HIV prevention and care intervention goals, refine current strategies, and reduce health disparities. The Progression and Transmission of HIV (PATH) 3.0 model was updated to cover a simulation period from 2006-2019 and aligned with National HIV Surveillance System data and new elements related to race/ethnicity and age group. The model also used data from the National Survey of Sexual Health and Behaviors and National HIV Behavioral Surveillance System.
Overall HIV transmission rate in 2019 was estimated at 2.94 new infections per 100 person-years: of new infections (n=35,100), 4.1 percent were associated with persons with acute infection and unaware of their status; 41.7 percent persons with chronic infection and unaware of their status; 41.0 percent persons aware of their status but not in care; and 13.2 percent persons in care on ART but not virally suppressed. Among estimated transmissions, 71.6 percent were associated with MSM, 11.6 percent heterosexual men and women, 11.4 percent injection drug use, and 5.4 percent MSM who inject drugs. Regarding age group, the largest percentage of overall transmissions (32.9%) was associated with persons aged 25-34, and persons aged 55 and older represented the largest proportion of PWH (35.5%).
Commentary
Although this analysis suggests an overall increased percentage of PWH taking ART with viral suppression since 2016, with associated decrease in transmission rate over time, high rates of transmission still occur among persons with undiagnosed infection and persons aware of their status but not engaged in ongoing care. Authors call for continued focus on routine HIV screening/testing and increased HIV testing for priority populations, and rapid linkage to care strategies that can effectively remove barriers to engaging in care and durable ART suppression, especially for key populations. This research highlights the importance of federal funding and support for HIV screening, testing, and treatment for priority populations.
Featured Literature
Vodstrcil LA, Plummer EL, Fairley CK, et al. for the StepUp Team. Male-partner treatment to prevent recurrence of bacterial vaginosis. N Engl J Med. 2025 Mar 6:392(10):947-957. doi: 10.1056/NEJMoa2405404.
This study describes results of a randomized open-label trial assessing whether partner therapy using concurrent oral and topical antimicrobial treatment decreased three-month bacterial vaginosis (BV) recurrence compared to standard of care. Symptomatic premenopausal women (with a single regular male partner) who met diagnostic criteria and were receiving first-line treatment (e.g., metronidazole twice daily for seven days, intravaginal clindamycin for seven nights, or intravaginal metronidazole for five nights) were enrolled from sexual health and family planning clinics in Australia. Male partners in the intervention group received metronidazole 400mg (taken 2x/day for 7 days) and 2% clindamycin cream (applied 2x/day for 7 days).
BV recurrence was observed in 24/69 (35%) in the intervention group compared with 43/68 (63%) in the control group, with a recurrence rate of 1.6 versus 4.2 per person-year. When stratified by IUD use and circumcision status, there was no evidence of different treatment effects. Sensitivity analyses indicated that recurrence was lowest among partners of men who were 100 percent adherent to treatment medications. Adverse events were reported among 26/56 (46%) men who received treatment and provided complete data: these included nausea, headache, and metallic taste (four participants reported redness or irritation of penile skin).
Commentary
Findings of this trial indicate that one week of oral and topical antimicrobial therapy which alters penile microbiota may subsequently reduce the rate of BV recurrence among women who also receive standard of care treatment. This intervention appears effective for partners of women with an IUD as well as uncircumcised partners (although it should be noted the trial was not powered to specifically explore these associations). Given that some studies have noted a higher frequency of BV recurrence among women with HIV, ongoing questions about the microbiome and HIV transmission, and association between BV and certain gynecologic-obstetric outcomes, these results may help inform changes in clinical recommendations and practice for HIV and sexual health providers.
