The high error rate of the hepatitis B virus (HBV) polymerase leads to a genetically diverse quasispecies in individuals with chronic hepatitis B. Data regarding the propagation of these variants in individual hepatocytes may provide insight into viral replication and diversity of covalently closed circular DNA (cccDNA), which is the template for HBV replication.MethodsWe developed sequencing protocols to characterize HBV diversity between and within hepatocytes using RNA extracted from individually isolated hepatocytes. We sequenced HBV in >200 hepatocytes in 4 liver biopsies from people with HIV/HBV (HB1, HB2, HB3, HB6).ResultsWe found that 2 biopsies (HB1 and HB6) showed HBV diversity between hepatocytes that met an experimentally identified threshold. Specifically, in HB1, HBV sequences from 86 individual cells were from 2 different haplotypes of genotype D: 70.2% of cells with haplotype a, 5.8% with haplotype b, and 24% with both haplotypes in the same cell. Furthermore, within single hepatocytes, up to 3 different HBV sequences were present per cell, including some cells with both genotypes A and D. HB6, who received years of lamivudine monotherapy, had evidence of drug resistance mutations distributed among hepatocytes and demonstrated up to 3 different sequences, including wild-type and drug-resistant sequences, in the same hepatocyte. Modeling of infected hepatocytes did not reveal evidence of local HBV spread based on spatial proximity.ConclusionsTaken together, our findings demonstrate that individual hepatocytes may harbor multiple, transcriptionally active HBV cccDNA molecules, which likely arose from distinct infection events.

DTG/3TC achieves noninferior virologic suppression when compared with BIC/FTC/TAF in adults initiating first-line ART for HIV-1.

DTG/3TC achieves noninferior virologic suppression when compared with BIC/FTC/TAF in adults initiating first-line ART for HIV-1.

Despite demonstrated virological efficacy, real-world evidence on the long-term effectiveness of dolutegravir plus lamivudine (DTG/3TC) in people living with HIV (PLWH) remains limited; this study assessed effectiveness, examining immunological response, resistance and safety.MethodsCARAVEL was a French, prospective, noninterventional, single-arm, multicenter, 3-year cohort study in treatment-naive PLWH (TN-PLWH) and pretreated PLWH (PT-PLWH) receiving DTG/3TC for the first time.ResultsForty-nine centers enrolled 304 participants: 56 TN-PLWH and 248 PT-PLWH. Effectiveness was evaluable in 49 (87%) TN-PLWH and 234 (94%) PT-PLWH. Initial virological suppression was attained for 44 (89.8%) TN-PLWH after 6 months of initiating DTG/3TC, with a median time to virological suppression of 1.1 months (IQR 1.0 to 2.1), and no virological failure during the follow-up. After switching, 220 (94%) PT-PLWH maintained virological suppression. During the follow-up, 14 PT-PLWH did not maintain virological suppression: 5 due to intermittent viraemia, and 9 due to virological failure (VF). Among the 9 participants with VF, a genotypic resistance test was available for 3 participants of whom 1 developed 3TC resistance [M184V] in the context of nonadherence. DTG/3TC was discontinued in 63 participants, mainly at their request (N = 40, 64.5%), as well as tolerability and VF. The average change in body weight over the follow-up was +2.0 (±6.0) (P = .13) kg in TN-PLWH and −0.2 (±6.5) (P = .78) kg in PT-PLWH, among participants with available data (N = 156).ConclusionsThese real-world data demonstrated high virological success and good safety after up to 3 years on DTG/3TC in both TN-PLWH and PT-PLWH populations.

This randomized clinical trial compares the effects of a regimen with doravirine, lamivudine, and tenofovir disoproxil fumarate vs a regimen with dolutegravir, emtricitabine, and tenofovir alafenamide...

Antiretroviral therapy (ART) that achieves virologic suppression using fewer antiretroviral agents is an optimized approach to HIV-1 treatment initiation. VOGUE is the first randomized, head-to-head study comparing the 2-drug regimen dolutegravir/lamivudine (DTG/3TC) with the 3-drug regimen bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) as initial ART, including among individuals with high viral loads (VLs) and/or low CD4+ cell counts.MethodThis phase 3b, randomized (1:1), open-label, noninferiority study compared DTG/3TC versus BIC/FTC/TAF as first-line ART in adults with HIV-1. Participants were enrolled without baseline VL or CD4+ cell count restrictions and initiated treatment before availability of resistance testing results. The primary endpoint was the proportion of participants with HIV-1 RNA <50 copies/mL at week 48 (Snapshot; −10% noninferiority margin).ResultsAmong 509 randomized participants (DTG/3TC, n = 254; BIC/FTC/TAF, n = 255), 47% had baseline VL ≥100 000 copies/mL and 16% had CD4+ cell count <200 cells/mm3. At week 48, DTG/3TC demonstrated noninferior efficacy to BIC/FTC/TAF, with HIV-1 RNA <50 copies/mL achieved in 89% and 92% of participants, respectively (adjusted difference, −3% [95% CI, −8%, 2%]). Median time to virologic suppression was rapid (4.1 weeks) in both groups. Confirmed virologic withdrawals were similar between groups (n = 7 each), with no treatment-emergent resistance identified. Safety outcomes were comparable.ConclusionsDolutegravir/Lamivudine demonstrated noninferior efficacy to BIC/FTC/TAF as initial ART, with no treatment-emergent resistance through week 48. These findings establish DTG/3TC as an effective and simplified initial ART regimen across a broad clinical spectrum.Clinical trial registration:  ClinicalTrials.gov identification number, NCT05979311; URL, https://clinicaltrials.gov/study/NCT05979311

This trial investigated whether a regimen with doravirine, lamivudine, and tenofovir disoproxil fumarate (DOR, 3TC, and TDF) would result in less weight gain compared with dolutegravir, emtricitabine, and tenofovir alafenamide (DTG, FTC, and TAF) while maintaining similar HIV viral suppression. Weight gain during initial HIV treatment can raise the risk of diabetes, high blood pressure, and heart disease. Integrase strand transfer inhibitor–based regimens, especially with DTG, are linked to larger weight increases, which disproportionately affect women and Black patients. Preventing treatment-associated weight gain may improve long-term health. Get Access

If you're a Black, 34-year-old South African woman living with HIV, antiretroviral (ARV) treatment options have likely been limited to tenofovir disoproxil fumarate (TDF), lamivudine (3TC) and the "gold standard," dolutegravir (DTG).

This randomized clinical trial compares the effects of a regimen with doravirine, lamivudine, and tenofovir disoproxil fumarate vs a regimen with dolutegravir, emtricitabine, and tenofovir alafenamide...

If you're a Black, 34-year-old South African woman living with HIV, antiretroviral (ARV) treatment options have likely been limited to tenofovir disoproxil fumarate (TDF), lamivudine (3TC) and the "gold standard," dolutegravir (DTG). Now, another once-daily, three-drug regimen has been found to be as effective as DTG in suppressing HIV viral load.

This randomized clinical trial compares the effects of a regimen with doravirine, lamivudine, and tenofovir disoproxil fumarate vs a regimen with dolutegravir, emtricitabine, and tenofovir alafenamide...

In the first randomized, head-to-head trial in adults initiating antiretroviral therapy, dolutegravir/lamivudine demonstrated non-inferior efficacy to bict

AbstractBackground. Long-acting cabotegravir+rilpivirine (CAB+RPV LA) and dolutegravir+lamivudine (DTG/3TC) are HIV-1 antiretroviral therapy regimens with

The difference between regimens met the trial's noninferiority threshold

The effect of archived lamivudine resistance mutations in the efficacy of dolutegravir plus lamivudine (DTG/3TC) remains unclear. We evaluated whether proviral-DNA M184V/I detection is associated with virological outcomes in the VOLVER-GESIDA 11820 study.MethodsThis open-label, single-arm, multicenter phase IIa trial (NCT04880785) enrolled virologically suppressed adults with documented or suspected historical lamivudine resistance if the M184V/I mutation was not detected in baseline proviral DNA population sequencing. Participants switched to DTG/3TC and were followed through week 96. Proviral-DNA M184V/I was assessed retrospectively by next-generation sequencing (NGS) of peripheral blood mononuclear cells at baseline and week 96.ResultsOf 121 participants, 94% had documented historical M184V/I. Proviral-DNA NGS detected M184V/I at ≥5% frequency in 37 (30.6%; 32 M184V, 5 M184I) at baseline and/or week 96: 12 only at baseline, 13 only at week 96, and 12 at both timepoints. Two virological failures occurred within the first 48 weeks; none were observed thereafter. No treatment-emergent resistance was detected. In the ITT-e population (Snapshot analysis), HIV-1 RNA <50 copies/mL at week 96 was maintained in 85.7% (72/84) with no detection of M184V/I, 66.7% (8/12) with detection only at baseline, and 100% with detection only at week 96 (13/13) or both time points (12/12). Among those with M184V/I at both time points, the proportion of proviral sequences carrying the mutation increased from 30% to 45% (P = .0037)ConclusionsProviral-DNA M184V/I detection was not associated with virological outcomes in participants receiving DTG/3TC supporting its limited clinical value in this specific setting.

LoveYourself, a non-government organization (NGO), said the arrival of the first batch of life-saving HIV medicines would help ensure uninterrupted treatment for thousands of Filipinos living with HIV (PLHIV), while urging the government to strengthen the country’s procurement and distribution system for HIV commodities. According to the Department of Health (DOH), the initial batch of 455,188 bottles of Lamivudine+Tenofovir+Dolutegravir (LTD) has been cleared for rollout next week following quality inspection. The shipment is the first tranche of the 1.2 million HIV commodities procured by the DOH and scheduled to arrive through September, helping ensure a continuous supply of treatment despite global shipping disruptions linked to the Middle East crisis. LoveYourself said it hopes the arrival of the medicines marks the beginning of a more reliable procurement and distribution system for HIV commodities nationwide. “Umaasa kami na ito na ang simula ng mas matatag na procurement at distribution system para sa HIV commodities sa buong bansa (We hope this marks the beginning of a stronger procurement and distribution system for HIV commodities across the country),” the NGO said in a statement. Also, the group urged the government to continue strengthening the country’s HIV supply chain, particularly by prioritizing treatment hubs serving the largest number of patients. “Sana ay patuloy nating mapabuti ang supply chain at mabigyang prayoridad ang mga hubs na may pinakamalaking bilang ng mga kliyenteng nangangailangan ng serbisyo. Sa LoveYourself pa lamang, halos 15,000 na ang aming mga kliyenteng kasalukuyang nasa treatment (We hope we can continue to strengthen the supply chain and prioritize treatment hubs that serve the largest number of clients in need of services. At LoveYourself alone, nearly 15,000 of our clients are currently on treatment,” it said. Beyond treatment, LoveYourself also called for increased investments in HIV prevention, including wider access to pre-exposure prophylaxis (PrEP), HIV testing, HIV self-testing, and other evidence-based preventive services. Grateful to Office of the President, DOH LoveYourself thanked the Office of the President for acting on its appeals regarding the shortage of HIV commodities in the country. “Nais muna naming magpasalamat sa Office of the President sa pakikinig at pag-aksyon sa mga liham at apelang aming ipinadala hinggil sa kakulangan ng HIV commodities sa bansa (We would first like to thank the Office of the President for listening to and acting on the letters and appeals we sent regarding the shortage of HIV commodities in the country),” it said. Likewise, the organization expressed its appreciation to newly appointed Health Secretary Jose “Brix” Pujalte Jr. for acting swiftly on the issue. “Maraming salamat din kay DOH Secretary Dr. Brix Pujalte sa mabilis na pag-aksyon sa usaping ito. Nakakaengganyo makita na sa mga unang araw pa lamang ng kanyang panunungkulan ay may agarang pagtugon sa pangangailangan ng ating HIV community (We also thank DOH Secretary Dr. Brix Pujalte for his swift action on this matter. It is encouraging to see that, in the very first days of his tenure, there has already been an immediate response to the needs of our HIV community),”it added. As such, the organization expressed optimism about working with the new DOH leadership to further strengthen the country’s HIV response. “Excited kaming makatrabaho ang bagong kalihim ng kalusugan. Marami pa tayong kailangang gawin, pero marami rin tayong pwedeng makamit kung sama-sama tayong kikilos (We are excited to work with the new Health Secretary. There is still much work to be done, but there is also much we can achieve if we work together).” Earlier, the DOH reported that the Philippines logged 4,277 new HIV cases from October to December 2025. As of December 2025, the country had recorded a total of 163,454 reported HIV infections since January 1984.

WHO merilis pembaruan panduan dosis ARV pediatrik 2026, menyelaraskan dosis dolutegravir dan abacavir/lamivudine pada neonatus, menghapus zidovudine sebagai profilaksis pascanatal, serta memperjelas penyesuaian dosis untuk ko-infeksi TB dan bayi prematur. Bagi Indonesia, pembaruan ini menegaskan urgensi menyelaraskan protokol nasional dengan standar dosis terbaru demi keselamatan bayi dan anak dengan HIV.

ABSTRACTThe newly approved oral anti-HIV doravirine (DOR)-based regimen in China in treatment-naïve people living with HIV (PLWH) remains inadequately characterized in China, particularly regarding antiviral efficacy and lipid profile changes. This study aimed to assess 48-week antiviral effectiveness and lipid changes associated with a DOR-based regimen in treatment-naïve PLWH compared with other regimens. A real-world retrospective study was conducted involving treatment-naïve PLWH who initiated DOR/TDF/3TC, EFV/TDF/3TC, DTG/TDF/3TC, or BIC/TAF/FTC. At week 48, 96.22% of participants receiving DOR/TDF/3TC achieved viral suppression, accompanied by significant increases in CD4+ T-cell counts. No treatment-related adverse events were reported in the DOR group. There were no statistically significant differences in virologic suppression or CD4+ T-cell increases among the four regimens (all P > 0.05). Regarding lipid parameters, DOR/TDF/3TC was associated with significant reductions in total cholesterol (TC) and triglycerides (TG) at weeks 36 and 48 (all P < 0.05), whereas BIC/TAF/FTC showed significant increases at all four post-treatment timepoints in TG, TC, and low-density lipoprotein cholesterol (LDL-C) (all P < 0.05). Between-group comparisons showed lower levels with DOR group versus BIC group in TG, TC, and LDL-C at week 48 (P < 0.05). DOR showed lower levels in TC than EFV across the four time points (all P < 0.05). DOR/TDF/3TC demonstrated antiviral effectiveness comparable to DTG/TDF/3TC and BIC/TAF/FTC, with a favorable tolerability profile at week 48. Additionally, DOR/TDF/3TC was associated with more favorable lipid changes.

ABSTRACTIntermittent preventive treatment during pregnancy (IPTp) for malaria prevention with sulfadoxine-pyrimethamine is contraindicated in pregnant women living with HIV receiving cotrimoxazole prophylaxis. A recent clinical trial showed that dihydroartemisinin-piperaquine (DHA-PPQ) for IPTp is a safe and effective option for malaria prevention in this population. The present study evaluated the impact of monthly IPTp with DHA-PPQ on antiretroviral (ARV) drug concentrations in 105 participants recruited in the aforementioned trial in Mozambique and Gabon between January and November 2021. ARV serum concentrations from maternal venous and cord blood collected at the first antenatal care visit and at the end of pregnancy were measured by ultra-high-performance liquid chromatography-tandem mass spectrometry. At the end of pregnancy, median concentrations of dolutegravir were 835.1 ng/mL (248.1–1,687.6) in maternal and 1,204.2 ng/mL (456.4–1,883.3) in cord blood. For lamivudine (3TC), median concentrations were 108.3 ng/mL (28.8–246.1) in maternal and 186.5 ng/mL (81.9–427.6) in cord blood. No significant differences in ARV concentrations were found between the antimalarial treatment arm and the placebo arm. Furthermore, in multivariate exploratory analysis, no independent associations were found between ARV concentrations and participant characteristics. Our study found similar ARV concentrations in both treatment groups, suggesting that DHA-PPQ for monthly IPTp does not affect ARV concentrations in maternal and cord blood in women living with HIV.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT03671109.