Featured Literature
McCrary LM, Curtis MR, Kelly JC, et al. Real-world experience of hepatitis C treatment with glecaprevir-pibrentasvir during pregnancy. Clin Inf Dis. 2026 August 11:ciag422. doi:10.1093/cid/ciag422
This brief report describes a retrospective case series evaluating treatment outcomes in 14 patients with HCV mono-infection who initiated glecaprevir/pibrentasvir between 14 and 32 weeks’ gestation. In March 2024, infectious diseases and maternal-fetal medicine physicians at a single tertiary care center adopted IDSA/AASLD guidance on shared decision-making, and began offering patients the option of prenatal treatment after the first trimester or postpartum deferral. Demographic and clinical information, HCV treatment data, as well as maternal, delivery, and neonatal outcomes were collected from electronic medical record review. No patients had cirrhosis, one had pre-existing intrahepatic cholestasis of pregnancy, two had pre-existing gestational diabetes, and four had pre-treatment substance use during pregnancy.
Treatment was initiated at an average GA of 25 weeks, and 10/14 (71%) women completed treatment. Among the four who did not, three discontinued within the first week (reasons included lost medications and anxiety/concern for fetal well-being) and one subsequently elected to defer treatment until after delivery. There were no reported safety concerns. For the 10 who completed therapy, all had an undetectable viral load by delivery; among eight with on-treatment monitoring, no AST/ALT/total bilirubin elevations were observed. Early post-treatment virologic data were available for nine, and all achieved SVR4: there were no known treatment failures, although follow-up SVR testing was not completed for all. No preterm deliveries and no neonatal safety concerns were observed; among six infants with available screening results, no perinatal transmissions were identified.
Commentary
Data on HCV treatment in pregnancy are lacking and prior studies have focused on sofosbuvir-based combinations. Despite the small number cases and retrospective nature of this analysis, these real-world data offer important information that supports offering HCV treatment during pregnancy as well as reassuring data on maternal safety and tolerability and infant outcomes.
Featured Literature
Pennetzdorfer N, Naik V, Montezuma-Rusca JM, Sklar P, Callebaut C, and Margot NA. Baseline and week 48 resistance analysis in participants receiving bictegravir + lenacapavir in the phase 2 ARTISTRY-1 study. AIDS. 2026 August 1;40(8):1140-1145.
Investigators described baseline resistance among 128 participants in the phase 2 portion of ARTISTRY-1 who switched to BIC+LEN from a suppressive complex ART regimen and characterized emergent BIC and/or LEN resistance after 48 weeks. Baseline analyses included historical genotypes and retrospective proviral DNA (Day 1 collection). Postbaseline testing was performed in participants with confirmed virologic rebound, with analysis at the confirmation visit if VL ≥ 200 copies/mL. Phenotypic susceptibility to LEN was assessed by calculating EC50 fold-change relative to wild-type reference virus. Baseline resistance to NRTIs, NNRTIs, and PIs was detected in 81 percent, 65 percent, and 46 percent of participants, respectively. Primary INSTI mutations were identified in 10 participants (11%) by proviral DNA only (presence of INSTI mutations on historical reports was exclusionary for enrollment): nine individuals were in the BIC 75mg/LEN 25mg group and one was in the complex ART continuation group. N155 and Q148 substitutions (all mixtures with WT) were the most common baseline INSTI mutations.
Virologic suppression was maintained across all groups, and baseline proviral RAMs did not impact Week 48 treatment outcomes. One participant with multi-class resistance who switched to BIC 75mg/LEN 50mg [from twice-daily DRV/r, twice-daily DTG, and MVC] experienced confirmed virologic rebound: although no emergent INSTI RAMs were identified, a new capsid substitution (N74T) was identified on next-generation sequencing. Phenotypic analyses indicated this mutation did not substantially impair LEN susceptibility.
Commentary
In late April, the FDA accepted a New Drug Application submission for bictegravir 75mg/lenacapavir 50mg as a once-daily, single-tablet switch option based on ARTISTRY 1 and 2 findings. Although people with historical INSTI resistance were not enrolled in the trials, these analyses describe a small number (10) of participants with baseline mutations identified via retrospective DNA testing: most were associated with older INSTIs and not anticipated to have major impact on BIC susceptibility, and all remained suppressed at 48 weeks with no emergent mutations.
Featured Literature
Hou J, Lim SG, Buti M, et al. Phase 3 results of bepirovirsen treatment for chronic hepatitis B virus infection. N Engl J Med. 2026 May 28. doi: 10.1056/NEJMoa2515131.
This study describes efficacy and safety of the antisense oligonucleotide bepirovirsen given to adults with NA-suppressed HBV mono-infection and no cirrhosis in the B-Well 1 and B-Well 2 trials. The analysis included 1834 participants in Europe, the Asia-Pacific region, and Americas on at least six months of stable NA therapy (HBsAg range: 100 to 3000 IU/mL; ALT ≤ 2x ULN) who were randomized 2:1 to bepirovirsen or placebo. Weekly subcutaneous bepirovirsen 300mg was given from weeks one to 24 with a loading dose on days four and 11; participants continued background NA therapy during this period. NA therapy was then continued between weeks 24 and 48 (NA-only stage); subsequently, participants with HBV DNA < LLOQ and no HBsAg detection (from week 24 to week 46), ALT ≤ 2x ULN, and negative HBeAg were eligible for NA discontinuation at week 48.
Response was assessed at week 72 (i.e., 24 weeks after discontinuation of all treatment) in eligible participants. At week 48, NA therapy was discontinued in 24 percent of the B-Well 1 and 24 percent of the B-Well 2 bepirovirsen groups versus none in the placebo groups. Twenty percent of B-Well 1 and 19 percent of B-Well 2 bepirovirsen participants achieved functional cure at week 72, compared with none in the placebo groups. Overall, severe adverse events were reported in seven percent of participants receiving bepirovirsen versus four percent placebo; during the treatment period, injection site reactions were noted in 53 percent of participants receiving bepirovirsen versus 14 percent placebo. Events leading to permanent treatment discontinuation occurred in three percent of participants receiving bepirovirsen.
Commentary
Current therapies for chronic hepatitis B virus are limited by low rates of functional cure even after extended treatment periods, and novel agents are greatly needed. In this B-Well study, the percentage of participants with a functional cure in the bepirovirsen groups was significantly higher than those in the placebo groups (especially for people with lower baseline HBsAg levels). Bepirovirsen is currently under priority review with Breakthrough Designation, and the FDA decision is expected in the fall of 2026. Studies including people with HIV co-infection and people with cirrhosis will help further define the broader potential impact of this agent on key global health priorities.
Featured Literature
Short WR, Ogle MC, Farmer E, et al. Implementation of long-acting cabotegravir/rilpivirine in U.S. HIV care settings: results from a national survey of front-line clinicians. Open Forum Inf Dis. 2026 May 6. https://doi.org/10.1093/ofid/ofag281.
This study describes results of a cross-sectional, web-based survey of AAHIVM members and credentialed clinicians which was distributed late July 2024. The primary outcome of interest was proportion of clinicians adopting LA-CAB/RPV (secondary outcomes included reported barriers and prescribing patterns across various scenarios). Out of 325 respondents across diverse practice settings (37% physicians, 29% pharmacists, 24% nurse practitioners, and 10% physician associates), 91 percent reported at least one LA-CAB/RPV prescription—most (76%) used a direct-to-inject approach.
Operational barriers affected 59 percent: specific challenges included appointment scheduling, coordination between clinic staff and pharmacies, and management of missed doses. Of the respondents, 41 percent reported financial barriers such as insurance denials, navigating prior authorizations, and high co-pays. As well, 38 percent experienced administrative challenges related to leadership/institutional buy-in and investment in infrastructure. Staffing shortages (28%) and medication storage challenges (24%) were prevalent. Prescribing practices for case scenarios varied: although over 91 percent were willing to prescribe LA-CAB for people with BMI > 30 kg/m2, only 42 percent would for BMI > 50 kg/m2. Out of respondents, 63 percent were comfortable using LA-CAB/RPV for people with viremia and adherence challenges and 54 percent for people with isolated anti-HBc reactivity. As well, 51 percent were willing to prescribe LA-CAB/RPV for women of reproductive potential not using contraception. For respondents who provided care to youth/young adults, half had prescribed LA-CAB/RPV. Finally, 54 percent considered two consecutive HIV RNA measurements > 200 copies/mL as treatment failure (vs. 11% who considered a lower threshold of 51-199 copies/mL as indicating failure).
Commentary
Thank you to Academy community members who participated in this survey, which resulted in one of the first studies describing broad national experiences with LA-CAB/RPV to date, and reflected a diverse range of health care professionals at multiple practice settings, including academic medical centers, federally qualified health centers, and other contexts. Similar to findings from other analyses, operational and financial challenges were the most common and significant barriers cited by providers – authors note these challenges may exacerbate ongoing disparities in access to long-acting ART. The study also reveals a number of clinical scenarios where provider practices vary, highlighting uncertainty and opportunities for future training efforts.
