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Introduction: Initiation of NNRTI therapy has been associated with an increased risk of diabetes among people living with HIV (PLHIV) who have never received antiretroviral therapy. We examined the effect of switching to NNRTIs on the incidence of diabetes among PLHIV already on ARVs.

Methods: A simulated targeted clinical trial conducted within longitudinal cohorts of PLHIV in the United States and Canada. Non-diabetic participants who had used NNRTI or PI for at least 180 days (2016–2022) were followed for up to 5 years, starting from the clinic visits during which they continued their NNRTI or PI treatment or switched to an NNRTI. The effect of this treatment change on the incidence of diabetes was estimated using a robust variance- weighted Cox regression. We also assessed whether this effect (i) varied according to the time elapsed since the treatment change and (ii) was explained by weight gain during the first year.

Results: 13,071 participants were followed during 2,702 visits in which they switched from an NNRTI to an NNRTI, 54,766 visits in which they continued on an NNRTI, 1,714 visits in which they switched from a PI to an NNRTI, and 26,599 visits in which they continued on a PI. Switching from a PIP to an INI was associated with an adjusted relative risk (HR) of 1.38 (95% CI, 1.06–1.80) for incident diabetes, whereas switching from an NNRTI to an INI was associated with an HR of 1.10 (95% CI, 0.87–1.39). The risk of diabetes was higher during the first two years following the switch from PIs to NIs (HR: 1.67; 95% CI: 1.21–2.30), but not thereafter (HR: 1.08; 95% CI: 0.75–1.57; p for interaction = 0.06). The effect of switching from PIs to NIs on diabetes does not appear to be related to weight gain.

Conclusion: The increased risk of diabetes following the switch from PPIs to INIs highlights the metabolic impact of this treatment change and may warrant close monitoring early in the post-treatment period, regardless of any weight gain.

Background: One in three people living with HIV is anti-HBc-positive and HBsAg-negative, suggesting prior exposure. HBV reactivation can occur in this group if antiretroviral therapy with nucleos(t)ide reverse transcriptase inhibitors — which are active against both HIV and HBV— is discontinued. We describe HBV reactivation in people living with HIV who are anti-HBc+/HBsAg− following a switch from an HBV-active ARV to an HBV-inactive ARV.

Methods: We identified a high-risk cohort of 5,986 anti-HBc+ participants who switched from an HBV-active ARV to an HBV-inactive ARV no later than December 31, 2023, and were HBsAg− at the last test prior to this switch. HBV reactivation was defined as the detection of HBV DNA or HBsAg positivity at any time after the treatment switch. ARVs active against HBV included 3TC, FTC, or tenofovir.

Results: Forty (0.67%) HBc-antibody-positive and HBsAg-negative patients experienced HBV reactivation after switching to an ARV regimen that was not active against HBV. The median time to reactivation was 8.9 months (IQR: 5.5–26.7). The HBV reactivation rate was 25.1 per 10,000 person-years (95% CI %: 18.4–34.3). Predefined subgroup analyses revealed higher rates of HBV reactivation (per 10,000 person-years) among those who had been HBsAg- positive in the distant past and had never seroconverted to anti-HBs (321; 95% CI, 120–855) compared with those who had never been HBsAg-positive or anti-HBs-positive (38.0; 95% CI, 22.9–63), or who were anti-HBs antibody-positive but had never been HBsAg-positive (17.4; 95% CI, 11.2–27.0).

Conclusion: The overall risk of HBV reactivation appears to be low after switching from an ARV active against HBV to an ARV inactive against HBV in PLWHIV who are anti-HBc-positive but HBsAg-negative.

Background: Type 2 diabetes is common among people living with HIV (PLHIV), although studies comparing diabetes-related complications in people with and without HIV remain limited. This issue was evaluated using data from the Swedish Cohort Study on Morbidity and HIV (COSMOHS).

Method: A national study including Swedish residents born between 1930 and 2006 who were diagnosed with type 2 diabetes between 2010 and 2019 and followed through December 31, 2024, using data from seven national registries, including the national HIV and diabetes registries. Follow-up began at the time of diagnosis of type 2 diabetes. Outcomes included renal events, cardiovascular events, and all-cause mortality. A proportional-hazards Cox regression was used to estimate adjusted hazard ratios (aHRs) by HIV status, stratified by propensity score quintiles for age, sex, immigration status, comorbidities, and socioeconomic status.

Results: 350 people living with HIV (PLHIV) and 311,668 HIV-negative patients (PWOH) were included, with similar median follow-up durations (7.8 years; 8.8 years). PLHIV had a higher risk of renal events than PWOH (major adverse renal event: adjusted HR 2.04; 95% CI: 1.57–2.65), but no significantly increased risk of cardiovascular events (major adverse cardiovascular event: adjusted HR 1.18; 0.87–1.60) or all-cause mortality. These results were consistent across sensitivity analyses, including competing risks models for mortality and the exclusion of PLHIV receiving TDF at enrollment. After accounting for the physiological increase in serum creatinine with bictegravir, cobicistat, dolutegravir, and rilpivirine, the increased renal risk persisted, although it was not statistically significant. The renal risk was more pronounced among PLWHIV with a BMI ≥ 30 kg/m².

Conclusion: In this national cohort, PLWHIV with type 2 diabetes had a higher risk of renal complications than people not living with HIV, suggesting that enhanced renal monitoring may be warranted. Further research should explore the underlying mechanisms, particularly antiretroviral therapy, to guide clinical management.

Background: To assess HBV serological profiles and the risk of reactivation or incident infection among people living with HIV (PLHIV) switching to CAB/RPV-LA therapy.

Methods: A prospective cohort of PLWHIV initiating treatment with CAB/RPV-LA at Hospital Clínic in Barcelona between February 2023 and February 2025. HBV serology, vaccination status, and liver function tests were assessed at enrollment. Transaminase levels were routinely monitored (at weeks 12 and 28, then every 6 months), and HBV serology/DNA testing was performed in cases of abnormal transaminase levels, acute hepatitis, or clinical suspicion of reactivation. HBV reactivation was defined as a conversion from a negative HBsAg result to a positive result or the presence of detectable HBV DNA in anti-HBc-positive/HBsAg-negative individuals, or as an increase in HBV DNA of ≥ 1 log or ≥ 100 IU/mL in participants with chronic hepatitis B (HBsAg-positive). HBV infection was defined as HBsAg seroconversion in individuals not previously exposed to HBV.

Results: Among the 741 participants (92% men, median age 43 years, 61% had vaccine-induced immunity, and 25% had previously been exposed to HBV [anti-HBc-positive], of whom 3% had isolated anti-HBc antibodies), the median follow-up was 54 weeks. No HBV reactivation or HBV infection was observed in individuals without chronic hepatitis at enrollment. Among the 4 individuals (0.5%) with undiagnosed chronic HBV infection (HBsAg-positive), 2 developed clinical HBV reactivation and 2 remained stable after a treatment change; all 4 subsequently returned to a tenofovir-containing regimen. Elevated transaminases occurred in 17% of the cohort during follow-up, regardless of HBV serostatus.

Conclusions: LA-CAB/RPV therapy appears safe in individuals previously exposed to HBV, including those with isolated anti-HBc antibodies. Comprehensive hepatitis B screening, vaccination, and liver monitoring are essential.

Objective: To analyze the dynamics of liver stiffness in people living with HIV (PLHIV) with advanced liver fibrosis who achieved a sustained virologic response to HCV treatment and to evaluate the factors associated with the normalization or progression of liver stiffness after long-term follow-up.

Methods: A prospective, multicenter cohort study that included individuals coinfected with HIV and HCV from the Spanish GEHEP-011 cohort who met the following criteria: pretreatment liver stiffness ≥ 9.5 kPa; sustained virologic response to direct-acting antiviral therapy; a measurement of liver stiffness available at the time of sustained virologic response. Factors associated with normalization of liver stiffness (≤ 7.2 kPa on two consecutive measurements) and its progression (an increase in liver stiffness > 20% on the last available measurement) were analyzed.

Results: A total of 678 patients were included. The median follow-up duration was 40 (17–71) months. Repeated-measures analysis of variance revealed a significant main effect of time on the liver stiffness score. Overall, 221 patients (32.6%) achieved normalization. A lower probability of normalization was associated with advanced liver disease [baseline liver elasticity score: sHR = 0.26 (95% CI, 0.19–0.37), p < 0.001; hepatic decompensation prior to sustained virologic response: sHR = 0.22 (0.05–0.97), p < 0.001; baseline MELD score: sHR = 0.81 (0.69– 0.94), p = 0.006]. An increase in the liver stiffness score occurred in 50 patients (7.4%). The increase was associated with higher baseline liver stiffness [sHR = 1.04 (1.01–1.07), p = 0.007], a higher controlled attenuation parameter [CAP ≥ 280 dB/m: sHR = 2.94 (1.16–7.44)], and older age [sHR = 1.06 (1.00–1.13) per year, p = 0.04].

Conclusion: In people living with HIV, liver elasticity decreases significantly over the long term following HCV cure, reaching values ≤ 7.2 kPa. In a significant proportion of patients, liver elasticity remains stable or even increases. Advanced age and the concomitant presence of hepatic steatosis are associated with progression.

Background: Although tuberculosis is a major concern among patients with advanced HIV infection, the STATIS trial, which focused on its management, revealed high mortality rates. Histoplasmosis, a fungal infection endemic to sub-Saharan Africa, presents with clinical manifestations similar to those of tuberculosis. It may therefore be common and potentially responsible for deaths among patients with advanced HIV infection in this region. We conducted a satellite study of the ANRS STATIS trial to establish preliminary estimates of the prevalence of histoplasmosis among people with advanced HIV infection in Côte d’Ivoire.

Methods: We analyzed urine samples from patients previously enrolled in the STATIS trial in Côte d’Ivoire. These outpatient patients, who were newly diagnosed as HIV-positive, had a CD4+ T-cell count < 100/µL, and were eligible for antiretroviral therapy, were randomized to receive either routine antituberculosis treatment or test-guided antituberculosis treatment. We performed an enzyme-linked immunosorbent assay (ELISA) for Histoplasma antigen on their urine samples.

Results: The prevalence of Histoplasma antigenuria was 68/280 (24.3%; 95% CI: 19.5% –29.8%), of whom 52/280 (18.6%; 14.3% –23.7%) were symptomatic. Among the 22 cases of tuberculosis documented at enrollment, 8 (36.4%) also had Histoplasma antigenuria. Among patients who died during the 48-week follow-up period, the prevalence of Histoplasma antigenuria was 35.7% (22–52), compared with 22.3% (17.3 %–28.2%) among survivors. The survivors had a higher body mass index, CD4+ T-cell count, hemoglobin level, and platelet count than the patients who died.

Conclusion: The prevalence of Histoplasma antigenuria was comparable to that of tuberculosis, and histoplasmosis was potentially responsible for preventable deaths. Prospective studies are needed to confirm these findings and promote screening strategies in sub-Saharan Africa.

Background: Multidose HPV vaccination is effective, yet this vaccine is underutilized worldwide. Recent data suggest that a single dose of the vaccine may provide protection, but it is unclear whether a single dose offers protection comparable to that of two doses.

Methods: A trial evaluating the non-inferiority of a single dose of HPV vaccine compared with two doses. Girls aged 12 to 16 years were randomized in a 1:1:1:1 ratio to receive one or two doses of a bivalent HPV vaccine or one or two doses of a nonavalent HPV vaccine. The primary outcome measure was a new infection with HPV types 16 or 18 occurring between the 12th and 60th months and persisting for at least 6 months. The predefined non-inferiority margin was 1.25 infections per 100 participants. We also assessed the vaccine’s efficacy by comparing HPV16 or HPV18 infection among trial participants with that of girls and women enrolled in a nonrandomized survey.

Results: A total of 20,330 participants were randomized, and 3,005 unvaccinated participants were included in the study. The non-inferiority analysis showed that one dose of the vaccine was non-inferior to two doses in preventing infection with HPV16 or HPV18. The difference in infection rates between 1 and 2 doses of the bivalent vaccine was −0.13 infections per 100 participants (95% CI −0.45 to 0.15; p < 0.001 for non-inferiority), and the difference between 1 and 2 doses of the nonavalent vaccine was 0.21 infections per 100 participants (95% CI, −0.09 to 0.51; p < 0.001 for non-inferiority). Vaccine efficacy was at least 97% in each of the four trial groups. No safety concerns were identified.

Conclusion: A single dose of a bivalent or nonavalent HPV vaccine provided protection against infection with HPV16 or HPV18 and was not inferior to two doses.

Identifying therapeutic strategies that can induce sustained control of HIV infection without antiretroviral therapy is a major priority. Combined immunotherapy — including HIV vaccination, immune stimulation/reactivation of latent infection, and passive transfer of broadly neutralizing antibodies (bNAbs) — has shown promise in non-human primate models, but few studies have translated these approaches to humans. We conducted a single-arm proof-of-concept study in 10 HIV-positive individuals on ARV therapy, combining the following three approaches: (1) therapeutic vaccination with DNA targeting the conserved HIV/Gag element plus IL-12 priming and MVA boosting, followed by (2) administration of two bNAbs (10-1074, VRC07-523LS) and a Toll-like receptor 9 agonist (lefitolimod) during viral suppression on ARV therapy, followed by (3) a further administration of bNAb at the time of ARV treatment discontinuation (NCT04357821). Seven of the ten participants achieved post- intervention viral control after discontinuing ARV therapy, regardless of residual plasma levels of bNAbs. A significant expansion of early-activated CD8+ T cells in response to viral rebound correlated with a lower median viral load after the peak of post-ARV-discontinuation viremia. These data suggest that combination immunotherapies may prove effective in inducing sustained HIV control by reducing viral rebound and enhancing CD8+ T-cell responses, and that these approaches should continue to be optimized.

Background: Superior protection against confirmed influenza has been demonstrated for the high-dose inactivated influenza vaccine compared with the standard dose in adults aged 65 years and older. However, data on the relative efficacy of the high-dose vaccine against severe forms of influenza, including hospitalizations, are limited.

Methods: A pragmatic, open-label, randomized, active-controlled trial to evaluate the relative efficacy of the high-dose inactivated influenza vaccine, compared with the standard dose, against severe forms of influenza in adults aged 65 to 79 years living at home. The trial was conducted over two influenza seasons (2023–2024 and 2024–2025) using data from the Galician Regional Health Registry, in Spain. During each flu season, participants were randomized in a 1:1 ratio to receive either the high-dose vaccine or the standard-dose vaccine. The primary outcome measure was a composite endpoint of hospitalization for influenza or pneumonia, starting 14 days after vaccination through May 31 of the following year.

Results: 103,169 unique participants were randomized; 31,307 participants were included in both seasons and counted for each. During the 2023–2024 and 2024–2025 seasons, 59,490 and 74,986 participants were randomized, respectively. The mean age was 72.3 ± 4.3 years, and 53.6% were men. A primary endpoint event occurred in 174 of the 67,093 participants (absolute risk: 0.26%) in the high-dose group and in 227 of the 66,789 participants (absolute risk: 0.34%) in the standard-dose group (relative vaccine efficacy: 23.7%; 95% CI: 6.6 to 37.7). Hospitalization for influenza occurred in 0.09% of participants in the high-dose group and in 0.14% of participants in the standard-dose group (relative vaccine efficacy: 31.8%; 5.0 to 51.3). The incidence of serious adverse events appeared to be similar in both groups.

Conclusions: Among community-dwelling adults aged 65 to 79 years, there appear to be fewer hospitalizations for influenza or pneumonia with the high- dose influenza vaccine than with the standard-dose vaccine.

Background: The high-dose inactivated influenza vaccine provides greater protection against influenza than the standard-dose vaccine. Data from individual randomized trials on the efficacy of the high-dose vaccine against severe disease are limited.

Methods: In this pragmatic, open-label, randomized, controlled trial conducted in Denmark during the 2022–2023, 2023–2024, and 2024–2025, we randomly assigned adults aged 65 years and older to two groups: one receiving the high-dose inactivated influenza vaccine, the other receiving the standard dose. Data collection relied on national administrative health registries. The primary outcome measure was hospitalization for influenza or pneumonia occurring between 14 days after vaccination and May 31 of the following year.

Results: Among the 332,438 randomized participants, 166,218 received the high-dose vaccine and 166,220 received the standard-dose vaccine. The mean age was 73.7 ± 5.8 years, and 48.6% were women. A primary outcome event occurred in 1,138 participants (0.68%) in the high-dose group and in 1,210 (0.73%) in the standard-dose group (relative vaccine efficacy: 5.9%; 95.2% CI: −2.1 to 13.4; p = 0.14). Hospitalization for influenza occurred in 0.06% of participants in the high-dose group and in 0.11% of those in the standard-dose group (relative vaccine efficacy: 43.6%; 27.5 to 56.3); hospitalization for pneumonia occurred in 0.63% of participants in both groups (relative efficacy: 0.5%; −8.6 to 8.8); hospitalization for cardiorespiratory disease occurred in 2.25% of participants in the high-dose group and in 2.38 % of those in the standard-dose group (relative efficacy: 5.7%; 1.4 to 9.9). All-cause hospitalization: 9.38% and 9.58% (relative efficacy: 2.1%; –0.1 to 4.3) and all-cause mortality: 0.67% and 0.66% (relative efficacy: –2.5%; –11.6 to 5.9). The incidence of serious adverse events was similar in both groups.

Conclusion: In this trial, a high-dose inactivated influenza vaccine did not result in a significantly lower incidence of hospitalizations for influenza or pneumonia than a standard dose among older adults.

Background: Although cefazolin is widely used in the treatment of SASM bacteremia, its efficacy has not yet been studied in a clinical trial. This study aimed to compare the efficacy and safety of cefazolin with those of cloxacillin in patients with SASM bacteremia.

Methods: A randomized, open-label, non-inferiority clinical trial conducted at 21 centers in France, involving adults (≥ 18 years) with SASM bacteremia who had no intravascular implants and no suspicion of CNS infection. Participants were randomized (1:1) to receive either cefazolin (25–50 mg/kg every 8 hours) or cloxacillin (25–50 mg/kg every 4–6 hours) for the first 7 days of treatment, with stratification based on the presence or absence of a catheter (central or peripheral) and the study site. Subsequent treatment was left to the investigator’s discretion (total duration ≥ 14 days). The primary endpoint was a composite endpoint comprising sterile blood cultures on Day 3 (Day 5 in cases of endocarditis) without recurrence of bacteremia, survival, and clinical success on Day 90, and was assessed in the intention-to-treat population. A non-inferiority margin of 12% was selected.

Results: Among the 315 participants enrolled (cefazolin [n = 158] and cloxacillin [n = 157]), 12 were excluded from the analysis in the cefazolin group and 11 in the cloxacillin group (final population of 146 participants in each group). The mean age was 62.7 years; 74% were men. The median Pitt score was 0. The primary endpoint was met in 75% of participants in the cefazolin group, compared with 74% in the cloxacillin group (difference: -1%; 95% CI: -11 to 9%; p = 0.012). At the end of treatment, 15% of participants in the cefazolin group and 27% in the cloxacillin group experienced a serious adverse event (p = 0.010). Acute kidney injury occurred more frequently among participants in the cloxacillin group (15 [12%] out of 128) than in the cefazolin group (1 [1%] out of 134; p = 0.0002).

Interpretation: Cefazolin is an alternative to cloxacillin for the treatment of SASM bacteremia, offering non-inferior clinical efficacy and potentially improved tolerability.

Background: This study aimed to determine whether resistance detected in HIV-1 DNA could evolve in virologically controlled individuals with a long history of treatment and multidrug resistance.

Methods: Twenty-three virologically controlled individuals with multidrug resistance from the PRESTIGIO registry, for whom two longitudinal samples were available during virologic suppression at two different time points (T0 and T1), were analyzed. HIV-1 DNA levels were quantified by digital droplet PCR, and resistance was assessed by next-generation sequencing (NGS) with a 5% threshold. The mutational burden was also assessed.

Results: At T0, participants had been virologically suppressed for a median duration of 3 years (IQR: 3–5 years) thanks to catch-up therapy, consisting primarily of DTG (95.7%) and/or DRV/b (69.6%). The median HIV-1 DNA level was 2,588 copies/10 CD4+ cells at T0 and remained stable at T1 (2,322 copies/10 CD4+; p = 0.831). Twenty participants (87.0%) had resistance to at least three classes of ARVs in their HIV-1 DNA at T0, and 18 (78.2%) at T1 (p = 0.607). Among participants receiving NNRTI-free therapy (52.2%), the number of major NNRTI resistance mutations decreased significantly over time (T0: 2 [1–3]; T1: 0 [0–1]; p = 0.027). No significant changes over time were observed in the number of resistance mutations to protease inhibitors (PIs), nucleoside reverse transcriptase inhibitors (NRTIs), and non-nucleoside reverse transcriptase inhibitors (NNRTIs). Certain mutations, such as M184V, decreased over time, particularly among individuals receiving rescue therapy without 3TC/FTC or who had a baseline (T0) mutational burden of less than 1,000 copies/10⁶ CD4+.

Conclusions: Over a one-year period, HIV-1 DNA mutations remained largely unchanged in people living with HIV who were multiresistant, with the exception of a significant decrease in M184V and a reduction in NNRTI resistance in the absence of NNRTI pressure.

Background: Influenza vaccination is widely recommended to prevent deaths and severe illness among vulnerable individuals, particularly those with heart failure. However, evidence from randomized trials supporting this practice is limited, and vaccination rates remain low in many regions of the world. Our objective was to determine whether influenza vaccination could improve patient outcomes following an episode of acute heart failure requiring hospitalization in China.

Methods: A pragmatic, multiregional, parallel-group, cluster-randomized (hospitals), controlled, superiority trial conducted over three winter seasons in China. Participating hospitals were located in 12 provinces and were able to provide a free point-of-care influenza vaccination service for a sufficient number of patients prior to discharge, if they were assigned to the intervention group. This service was not offered in hospitals assigned to the usual-care group (control group), but patients were informed of the availability of fee-based influenza vaccination at local community health centers, in accordance with standard care practices. Hospitals were randomized (1:1) each year, stratified by province and up to three times (i.e., a new randomization for each season), to include eligible adult patients (aged 18 years and older) with moderate-to-severe heart failure (NYHA Class III or IV) and no contraindications to influenza vaccination. Patient recruitment took place over three consecutive winter seasons, from October through March of the following year, between 2021 and 2024. All patients received standard of care and were followed up at 1, 3, 6, and 12 months after hospital discharge by trained research staff, according to a standardized protocol. The primary outcome measure was a composite of all-cause mortality or any rehospitalization over 12 months, excluding events occurring within 30 days of hospital discharge at all sites and during the summer season only for sites in northern China. The effect of the intervention was assessed at the individual level in the modified ITT population (all randomized patients for whom information was available up to the last follow-up date, excluding censored events) using a two-level hierarchical logistic regression model that included the study period (year) as a fixed effect, and the hospital and length of hospital stay as random effects, with censored events excluded.

Results: A total of 7,771 participants were enrolled at 164 hospitals each winter between December 3, 2021, and February 14, 2024: 3,570 in the flu vaccination group and 4,201 in the control group (usual care). The primary outcome occurred in 1,378 (41.2%) of the 3,342 patients in the vaccination group and in 1,843 (47.0%) of the 3,919 patients in the control group (odds ratio: 0.83 [95% CI: 0.72–0.97]; p = 0.019). This result was confirmed by sensitivity analysis. The proportion of participants who experienced a serious adverse event was significantly lower in the vaccination group (52.5%) than in the control group (59.0%; OR 0.82 [0.70–0.96]; p = 0.013).

Conclusion: Influenza vaccination during hospitalization for acute heart failure may improve survival and reduce the likelihood of rehospitalization over the following 12 months. Incorporating influenza vaccination into hospital care could be a widely applicable strategy for a high-risk and underserved patient population, which would be relevant in resource-limited settings but also, potentially, in settings with greater resources.

Background: We investigated the efficacy of DTG/3TC as maintenance therapy in people living with HIV who had a history of resistance to 3TC.

Methods: A multicenter, open-label, single-arm clinical trial enrolling people living with HIV who had virologic suppression, prior resistance to 3TC (confirmed by genotypic testing or suspected based on clinical history), no integrase resistance, and a CD4 count > 200/mm³. ARV therapy was switched to DTG/3TC if the M184V/I mutation was not detected during initial proviral DNA sequencing. Next-generation sequencing (NGS) of proviral DNA was performed retrospectively on samples collected on Day 0. The primary endpoint was the proportion of participants with a viral load ≥ 50 copies/mL at 48 weeks in the exposed ITT population (snasphot algorithm).

Results: 121 participants were enrolled, of whom 114 had a prior genotype carrying the M184V/I mutation. The median duration of virologic suppression was 9 years. In 24 participants (19.8%), the M184V/I mutation was detected by next-generation sequencing (NGS) of proviral DNA at enrollment (threshold > 5%). At 48 weeks, 4 participants had a viral load ≥ 50 copies/mL (3.3%, 95% CI: 0.9%–8.2%, FDA-Snapshot ITT-e analysis): 1 confirmed treatment discontinuation for virologic reasons, 1 precautionary treatment discontinuation for virologic reasons, and 2 treatment discontinuations for other reasons, with a final viral load ≥ 50 copies/mL. None of these 4 participants had the M184V/I mutation in the proviral DNA analyzed by NGS at enrollment, and no emerging integrase resistance was observed. 90.1% of participants (109/121) had a viral load < 50 copies/mL (95% CI: 83.3% – 94.8%), and data were missing for 6.6% of them (8/121) at 48 weeks.

Conclusions: After excluding 3TC resistance mutations in proviral DNA via population sequencing, the DTG/3TC combination effectively maintained virologic suppression in people living with HIV who had a CD4 count > 200/mm³ and a history of 3TC resistance. It should be noted that no treatment- emergent resistance was observed.