Dolutegravir belongs to a class of drugs called integrase strand transfer inhibitors. Rather than attacking reverse transcriptase, the enzyme that earlier generations of antiretrovirals targeted, it blocks HIV integrase, the viral enzyme that splices the virus’s DNA copy into the genome of the host cell. Because the drug binds tightly to the integrase active site and resists many common resistance mutations, it carries what virologists describe as a high genetic barrier: multiple mutations are typically required before the virus can replicate meaningfully in its presence. That property, combined with once-daily dosing and a favorable tolerability profile, is why the WHO endorsed dolutegravir-based regimens as preferred first-line therapy, and why Benin adopted the recommendation in 2019.

The new study was designed as a descriptive, cross-sectional assessment without a comparison group or a pre-dolutegravir reference cohort. The researchers, led by Edmond Tchiakpe of the University of Abomey-Calavi and Benin’s National Reference Laboratory of the Health Program Fighting Against AIDS, drew their participants from routine patients attending the laboratory program between January 1 and December 31, 2024. Viral load quantification was performed with the Abbott RealTime HIV-1 assay, a real-time polymerase chain reaction platform that counts copies of HIV-1 RNA in a milliliter of plasma. Following standard clinical definitions, a patient was classified as suppressed when the viral load was below 1,000 copies per milliliter, while any detected value at or above that threshold was treated as unsuppressed.

In total, 17,001 patients were included in the analysis. Women made up 70.3 percent of the cohort and men 29.7 percent, a distribution that mirrors the epidemiology of HIV in much of sub-Saharan Africa, where acquisition rates among women of reproductive age remain disproportionately high. Adults, who accounted for 92.1 percent of participants, were overwhelmingly treated with a backbone of tenofovir disoproxil fumarate or zidovudine combined with lamivudine and dolutegravir, written as TDF/AZT plus 3TC plus DTG. Children, 7.9 percent of the cohort, received a pediatric formulation built on abacavir or tenofovir with lamivudine and dolutegravir. Viral load and regimen data were extracted from facility registers, and the team applied univariate and multivariate logistic regression to test how regimen type, sex, and age related to virological outcomes.

The headline result is emphatic. Approximately ninety-one percent of all participants achieved viral load suppression below the 1,000-copy threshold. But that aggregate figure concealed a sharp divide between age groups: adults accounted for 92.8 percent of the suppressed patients while children represented only 7.2 percent, a difference the authors report as highly statistically significant, with a p-value below 0.0001. Among those who were suppressed, the researchers distinguished two states of residual viremia. Fully undetectable viral loads, meaning no measurable HIV-1 RNA, accounted for 68.5 percent of the suppressed group, while low-level replication viremia, detectable virus below the 1,000-copy threshold, made up the remaining 31.5 percent. That distinction matters clinically, because persistent low-level viremia can signal emerging adherence problems or the early stirrings of resistance, whereas complete suppression is the strongest guarantee of both individual health and blocked transmission.

Sex emerged as a second major axis of variation. The proportion of men with fully undetectable viral load was 24.6 percent, compared with 69.1 percent among women, a difference significant at p below 0.001. In the univariate analysis restricted to adults, men had roughly six percent lower odds of reaching an undetectable viral load than women, with an odds ratio of 0.94 and a p-value below 0.0001. Interestingly, when the analysis turned to the broader binary of suppression versus non-suppression, the sex difference largely dissolved: no statistically significant association between sex and viral load suppression was observed in the multivariable model, and male sex was associated with lower odds of undetectability with a modest adjusted odds ratio of 0.95. In children, the picture was one of parity, with boys at 3.1 percent and girls at 3.2 percent showing undetectable viremia, a difference that was not statistically significant.

The regimen comparison added a further layer. After adjusting for sex, and noting that age was entangled with regimen type and therefore excluded from the multivariable model, patients receiving the AZT or TDF backbone with lamivudine and dolutegravir had higher odds of achieving an undetectable viral load than those on the abacavir-based pediatric combination, with an adjusted odds ratio of 1.13 and a 95 percent confidence interval of 1.10 to 1.16. The same regimen was also associated with higher odds of suppression overall, at an adjusted odds ratio of 1.08 with a confidence interval of 1.06 to 1.10. The effect sizes are small, as is typical for registry-scale observational data, but the consistency across both outcome definitions suggests the difference is not merely statistical noise. It may also reflect the fact that the abacavir-containing regimen was concentrated in children, the group with the weakest suppression overall.

Why children fared so much worse than adults is a question the study raises but cannot fully answer with its descriptive design. Pediatric HIV care is notoriously difficult for reasons that have little to do with the drugs themselves. Weight-based dosing must be adjusted as children grow, pediatric formulations are less palatable and harder to stock in rural pharmacies, and young children depend entirely on caregivers to administer doses on schedule. Disclosure of HIV status to the child, a step associated with better adherence in adolescence, often happens late. The near-perfect parity between boys and girls in the pediatric cohort indicates that whatever drives the suppression gap, it operates at the level of age and care delivery rather than sex, which is itself a useful clue for program designers.

The sex gap among adults is equally consequential. Women were more likely to reach undetectable viremia, yet the study also found that the proportion of patients with viral loads above 1,000 copies per milliliter was higher in women than in men, meaning women occupied both tails of the distribution: more complete suppression, but also more overt failure. This bifurcation is consistent with patterns reported elsewhere in the region, where women engage with care earlier through antenatal screening but face interruption risks around pregnancy, postpartum periods, and partner disclosure. The authors’ finding that male sex independently predicted lower odds of undetectability, even after adjustment, suggests men’s engagement with viral monitoring itself may lag, since an undetectable result requires both adherence and regular laboratory follow-up.

For Benin’s national program, the practical message is twofold. First, the dolutegravir transition appears to be delivering on its promise at population scale, with suppression rates in adults approaching the levels seen in well-resourced settings and comfortably above the UNAIDS 95 percent suppression target’s trajectory. Second, the residual pockets of failure are now identifiable and concentrated: children on abacavir-based regimens and adults with low-level viremia rather than outright failure. Because the study was retrospective, cross-sectional, and lacked a pre-dolutegravir comparison group, it cannot definitively attribute the high suppression rates to dolutegravir alone, and the modest odds ratios around regimen and sex should be read as signals rather than proofs. Still, with seventeen thousand patients measured on a standardized platform, the dataset provides one of the most detailed snapshots to date of how integrase-inhibitor-based therapy performs in a West African national cohort, and it gives program managers a concrete map of where to direct adherence support, pediatric formulation improvements, and intensified viral load monitoring next.

Subject of Research: Real-world HIV-1 viral load suppression among patients on dolutegravir-based antiretroviral therapy in Benin

Article Title: High viral load suppression among HIV-1 infected patients receiving dolutegravir-based antiretroviral therapy in Benin, West Africa

Article References: Tchiakpe, E., Keke, R. K., Bachabi, M., & Yessoufou, A. (2026). High viral load suppression among HIV-1 infected patients receiving dolutegravir-based antiretroviral therapy in Benin, West Africa. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14561-3

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14561-3

Keywords: HIV-1, dolutegravir, antiretroviral therapy, viral load suppression, Benin, West Africa, integrase inhibitors, pediatric HIV, viremia, WHO guidelines, BMC Infectious Diseases, virological monitoring

The research team, led by Jingwei Tian and Yaokai Chen of Chongqing Public Health Medical Center together with collaborators at Zunyi Medical University and other Chinese institutions, followed 2,379 virologically suppressed people living with HIV for 144 weeks, nearly three years. All participants began the observation period on a classic first-line combination: tenofovir disoproxil fumarate plus lamivudine plus efavirenz, abbreviated TDF/3TC/EFV. This regimen served Chinese treatment programs for years, but it carries well-documented drawbacks, including kidney and bone toxicity from tenofovir disoproxil fumarate and central nervous system side effects from efavirenz. Some patients in the cohort continued on this older combination, while others switched to one of two modern alternatives: the single-tablet regimen bictegravir/emtricitabine/tenofovir alafenamide, known as BIC/FTC/TAF, or the two-drug combination dolutegravir plus lamivudine, known as DTG/3TC.

Because patients were not randomly assigned to their treatment paths, the investigators faced the fundamental challenge of any observational study: people who switch medications often differ systematically from those who do not. To address this, the team applied propensity score overlap weighting, a statistical technique that reweights the comparison groups so that baseline characteristics such as age, sex, body measurements, and laboratory values are balanced across them. This approach allows the analysis to approximate, though never perfectly replicate, the conditions of a randomized trial. The primary endpoint was the longitudinal change in body weight and body mass index from baseline to weeks 24, 48, 96, and 144. Secondary endpoints captured a broader metabolic picture, including changes in blood lipids, fasting blood glucose, the triglyceride-glucose index known as TyG, and serum uric acid.

The headline finding was unambiguous: weight and body mass index increased in every group over the 144 weeks, but the gains were markedly larger among those who switched to INSTI-based regimens. Patients moving to BIC/FTC/TAF gained more weight than those moving to DTG/3TC at weeks 24, 48, and 144, with the bictegravir-based regimen showing the steepest trajectory. This pattern echoes signals from international trials and cohort studies that have linked INSTI initiation and switching to clinically meaningful weight gain, but the Chinese data are particularly valuable because most prior evidence came from North American, European, and African populations, where baseline body composition and dietary patterns differ considerably.

The lipid results revealed a more nuanced picture. Compared with patients who stayed on TDF/3TC/EFV, both switch groups experienced increases in total cholesterol and low-density lipoprotein cholesterol, the fraction commonly labeled bad cholesterol because of its association with atherosclerotic cardiovascular disease. However, high-density lipoprotein cholesterol, the protective fraction, declined only in the BIC/FTC/TAF group, while triglycerides remained stable among those taking DTG/3TC. The direction of these changes matters clinically: a rise in LDL-C paired with a fall in HDL-C, as seen with bictegravir-based switching, shifts the lipid profile in a direction generally considered atherogenic, whereas the dolutegravir two-drug regimen appeared metabolically gentler on this front.

Beyond weight and lipids, the study tracked two additional metabolic markers that are gaining attention in HIV care. Fasting blood glucose rose in both switch groups, and serum uric acid also climbed in both, with significantly larger uric acid increases among patients on BIC/FTC/TAF. Elevated uric acid is the biochemical hallmark of hyperuricemia, the precursor state for gout, and has emerged as a recurrent finding in INSTI pharmacovigilance. The triglyceride-glucose index, a simple surrogate for insulin resistance calculated from fasting triglycerides and glucose, provided a window into early metabolic dysfunction without requiring formal glucose tolerance testing.

When the researchers translated these continuous laboratory changes into clinical diagnoses using multivariable Cox proportional hazards models, the differences between the two switch strategies became striking. Patients who switched to BIC/FTC/TAF faced more than double the hazard of developing overweight or obesity compared with those continuing the older regimen, with an adjusted hazard ratio of 2.47 and a 95 percent confidence interval of 1.96 to 3.10. They also carried a modestly elevated risk of dyslipidemia, at an adjusted hazard ratio of 1.18, and a substantially increased risk of hyperuricemia, at 2.23. The DTG/3TC group also fared worse than those who stayed on TDF/3TC/EFV, with adjusted hazard ratios of 1.56 for overweight or obesity and 1.76 for hyperuricemia, but the magnitude of risk was consistently lower than for the bictegravir-based triple-drug regimen. Notably, neither switch strategy significantly changed the risk of developing type 2 diabetes over the follow-up period.

The mechanistic story behind these observations remains incomplete, but several hypotheses circulate in the field. Integrase inhibitors may influence adipocyte biology and appetite regulation, potentially through effects on melanocortin signaling pathways, while the reversal of efavirenz-related toxicity could unmask baseline metabolic differences. Tenofovir alafenamide, the prodrug used in the BIC/FTC/TAF regimen, achieves high intracellular concentrations with lower plasma tenofovir exposure, sparing kidneys and bones, but some studies suggest it contributes more to weight gain than the older disoproxil fumarate salt. The uric acid signal may reflect changes in renal tubular handling as patients transition away from tenofovir disoproxil fumarate, which has mild uricosuric properties that lower serum urate. Disentangling drug-specific effects from the metabolic recovery that follows viral suppression and from the removal of older drugs remains one of the central analytical challenges in this literature.

For clinicians, the study’s practical message is one of vigilance rather than alarm. The authors emphasize that switching from TDF/3TC/EFV to either INSTI regimen was associated with significant increases in body weight and selected lipid parameters, and that BIC/FTC/TAF displayed a more pronounced adverse metabolic profile than DTG/3TC. They argue that metabolic monitoring after any switch to INSTI-based therapy deserves routine incorporation into HIV care, with particular attention for patients moving to bictegravir-based regimens. This is especially relevant in China and other Asian settings, where populations may have different baseline metabolic risk profiles and where the threshold at which weight gain becomes clinically consequential may differ from Western populations.

The study’s retrospective design imposes limits that the authors and the broader field acknowledge. Overlap weighting balances measured confounders but cannot account for unmeasured variables such as diet, physical activity, or the clinical reasons that prompted a switch in the first place. The 144-week horizon, while long by observational standards, may still underrepresent the cumulative metabolic burden of decades on therapy. Nevertheless, with 2,379 participants and nearly three years of longitudinal laboratory data, the analysis offers one of the clearest head-to-head real-world comparisons of these two widely used switch strategies in an Asian population. As INSTI regimens continue to displace older combinations globally, findings like these will shape how clinicians weigh the undeniable tolerability and convenience advantages of modern therapy against a metabolic cost that is now difficult to ignore.

Subject of Research: Long-term metabolic effects of switching from TDF/3TC/EFV to INSTI-based antiretroviral regimens in people living with HIV

Article Title: Long-term metabolic changes after switching from TDF/3TC/EFV to BIC/FTC/TAF or DTG/3TC in people living with HIV: a retrospective comparative cohort study in China

Article References: Tian, J., Zhou, Y., Qin, Y., Lu, Y., Wang, Q., Liu, P., Kong, F., Harypursat, V., & Chen, Y. (2026). Long-term metabolic changes after switching from TDF/3TC/EFV to BIC/FTC/TAF or DTG/3TC in people living with HIV: a retrospective comparative cohort study in China. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14425-w

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14425-w

Keywords: HIV, antiretroviral therapy, bictegravir, dolutegravir, tenofovir alafenamide, weight gain, dyslipidemia, hyperuricemia, integrase inhibitors, metabolic syndrome, cohort study, China

The investigation was designed as a cross-sectional study drawing participants from the provincial HIV-positive surveillance repository in Jiangxi, a province in southeastern China with a substantial population under long-term antiretroviral care. The researchers applied standardized sample submission criteria to assemble two distinct cohorts. The first comprised 104 treatment-naïve individuals whose baseline viral load had been measured before starting therapy or within 30 days of initiating antiretroviral treatment, allowing assessment of pretreatment drug resistance. The second comprised 307 treatment-experienced individuals who had received standardized antiretroviral therapy for at least six months and who met the definition of virological failure, operationalized as a viral load exceeding 400 copies per milliliter of plasma. By anchoring enrollment in the surveillance system rather than in convenience sampling from single clinics, the study sought to capture a province-wide snapshot of resistance rather than the picture at selected treatment centers alone.

Genotypic resistance testing focused on the pol gene, which encodes the viral enzymes reverse transcriptase and protease, and on the integrase gene, which encodes the enzyme that inserts viral DNA into the host genome. Resistance profiles were interpreted using the Stanford HIV Drug Resistance Database, a widely used algorithm that translates sequence mutations into predicted levels of susceptibility for individual antiretroviral drugs. This genotypic approach detects resistance-associated mutations in the viral genome, the molecular footprints left behind when imperfectly suppressed virus replicates under drug pressure. Because HIV-1 lacks proofreading capability in its reverse transcriptase and replicates prolifically, every untreated infection already carries a swarm of viral variants, and drug exposure selectively amplifies those variants fortunate enough to carry mutations that blunt drug binding or activity.

The headline numbers concern multidrug resistance. In the treatment-naïve group, representing the largely transmitted or pretreatment component of the resistance landscape, multidrug resistance stood at 10.58 percent. Among patients who had failed therapy, the figure reached 28.01 percent, a statistically significant increase reported at a p value below 0.001. This near tripling quantifies what the authors describe as a profound shift: once antiretroviral pressure is applied and virological control is lost, the virus does not merely accumulate resistance to one agent but frequently acquires mutations that compromise entire drug classes simultaneously. For clinicians, multidrug resistance is the form of resistance that matters most, because it constrains the options available for constructing an effective salvage regimen and foreshadows cumulative treatment failure at the population level.

Class-by-class analysis showed that mutations associated with non-nucleoside reverse transcriptase inhibitors predominated. The K103N and K103R mutations, classic signatures of resistance to nevirapine and efavirenz, were detected in 28.66 percent of the virological failure cohort, compared with 9.61 percent among treatment-naïve individuals. These substitutions alter the hydrophobic pocket to which non-nucleoside inhibitors bind, reducing drug affinity by orders of magnitude while leaving viral replicative capacity largely intact, which is precisely why they outcompete wild-type virus under non-nucleoside-based therapy. Alongside this, the M184V and M184I mutations were markedly enriched in the failure group at 25.73 percent. M184V/I confers resistance to lamivudine and emtricitabine, the nucleoside analogues that typically anchor first-line regimens, and its prevalence in failed therapy severely compromises the nucleoside reverse transcriptase inhibitor backbone on which those regimens depend.

Against this troubling backdrop, two drug classes remained notably durable. Susceptibility to protease inhibitors and to integrase strand transfer inhibitors exceeded 93 percent in the study population, indicating that these components of combination therapy retained activity in the overwhelming majority of patients even after treatment failure. This durability reflects both the genetic barrier and the usage patterns of these drugs in the region: protease inhibitors require multiple sequential mutations to lose potency, and integrase inhibitors, particularly the second-generation agents dolutegravir and bictegravir, impose a high fitness cost on resistant variants. The findings therefore support a clinical pivot toward robust salvage regimens built around integrase strand transfer inhibitors, which the authors advocate urgently, especially as Jiangxi and comparable high-burden settings transition toward dolutegravir-based first-line therapy as the new standard of care.

Yet the integrase picture was not entirely reassuring. The study detected the polymorphic accessory mutations L74I or L74M in 2.93 percent of the virological failure cohort. Accessory mutations of this kind do not usually cause outright resistance to first-generation integrase inhibitors such as raltegravir or elvitegravir on their own, but they can contribute to reduced susceptibility and may serve as stepping stones toward higher-level resistance when combined with other substitutions. Their presence at baseline, before patients have accumulated extensive integrase inhibitor exposure, underscores a gap in current surveillance practice: because integrase inhibitors have only recently been scaled up in many Chinese treatment programs, baseline integrase gene sequences have not been routinely collected. The authors argue that establishing integrase surveillance now, before widespread dolutegravir and bictegravir exposure reshapes the viral population, is essential for detecting emerging resistance pathways early.

The distinction between pretreatment drug resistance and acquired drug resistance frames the public health interpretation of these findings. Pretreatment resistance, at roughly one in ten treatment-naïve individuals, reflects resistance transmitted from person to person or acquired during prior, sometimes undocumented, drug exposure. Acquired resistance, by contrast, is generated de novo within patients whose replication is incompletely suppressed, often through adherence gaps, pharmacokinetic variability, or inadequate regimens. The Jiangxi data show that the second process is the dominant engine of the province’s multidrug resistance burden, nearly tripling its prevalence. Each case of virological failure left unmanaged does not merely harm the individual patient; it can seed transmitted resistance into the wider epidemic, so intensified molecular surveillance and prompt regimen switching upon failure are the twin strategies the findings support.

Operationally, the study argues for concrete changes in the region’s treatment architecture. Regular viral load monitoring must be strengthened so that failure, defined here as a viral load above 400 copies per milliliter, is detected and acted upon before extensive resistance accumulates. Resistance genotyping should be deployed at the point of confirmed failure rather than reserved for exceptional cases, and the tested gene panel should expand to include integrase as second-generation integrase inhibitors become first-line. Salvage regimens should be anchored in drugs retaining high susceptibility, with the >93 percent susceptibility to protease and integrase inhibitors in this cohort suggesting these classes are the most reliable foundations. As China consolidates dolutegravir-based therapy nationally, the Jiangxi experience offers a quantitative baseline: a population carrying 10.58 percent pretreatment multidrug resistance that, under prior regimens, climbed to 28.01 percent after treatment exposure. Sustaining the durability that integrase inhibitors currently provide will depend on surveillance that moves as fast as the virus does.

Subject of Research: Acquired multi-class HIV-1 drug resistance emerging after antiretroviral therapy exposure in Jiangxi Province, China

Article Title: Treatment exposure drives a profound shift toward complex multi-class HIV-1 drug resistance

Article References: Mao, Z. Q., Mao, J., Zheng, H., Hu, Y., Tang, X. M., & Zhang, Q. L. (2026). Treatment exposure drives a profound shift toward complex multi-class HIV-1 drug resistance. Virology Journal. https://doi.org/10.1186/s12985-026-03308-w

Image Credits: AI Generated

DOI: 10.1186/s12985-026-03308-w

Keywords: HIV-1, drug resistance, antiretroviral therapy, virological failure, multidrug resistance, NNRTI, NRTI, integrase inhibitors, protease inhibitors, pretreatment drug resistance, acquired drug resistance, genotypic resistance testing