The study, known as DUALITY, examined first-line therapy with dolutegravir and lamivudine, a two-drug combination that has become a recommended starting regimen for people living with HIV-1. Traditional antiretroviral therapy typically relies on three drugs from at least two classes, but dolutegravir, a potent integrase strand transfer inhibitor, has such a high genetic barrier to resistance that researchers have increasingly tested whether pairing it with the nucleoside reverse transcriptase inhibitor lamivudine could maintain full viral suppression while halving drug exposure. The approach has already proven effective at suppressing virus in the blood, but a critical question lingered: would two drugs maintain adequate concentrations in lymphoid tissue, where HIV establishes its most stubborn reservoirs?

Lymph nodes are not merely passive filters; they are the architectural hubs of the immune system, densely packed with CD4-positive T cells, the preferred targets of HIV. During untreated infection, these tissues become sites of explosive viral replication and profound structural damage. Even after years of suppressive therapy, when blood tests show no detectable virus, lymphoid tissues can harbor infected cells carrying transcriptionally silent proviral DNA. These reservoirs are the principal obstacle to any cure, and they have long raised concerns that reduced-drug regimens might leave pockets of residual replication unaddressed in tissue compartments where drug penetration could be weaker than in blood.

To address that concern, the DUALITY investigators randomized participants to initiate either the two-drug dolutegravir-lamivudine regimen or a standard dolutegravir-based triple therapy. The trial’s prespecified primary endpoint, the change in proviral HIV-1 DNA in peripheral blood CD4-positive T cells from baseline to week 48, was similar between the two groups, reinforcing earlier evidence that the simplified regimen performs comparably to conventional triple therapy in suppressing the measurable blood reservoir. But the blood is only part of the story, and the team designed a series of secondary analyses to look inside the tissues themselves.

Thirty-nine participants underwent surgical excision of an inguinal lymph node, either at the start of treatment or during the first year of therapy. These tissue samples became the foundation for a remarkably detailed multimodal imaging campaign. Using DNAscope and RNAscope, in situ hybridization techniques that can detect individual HIV-1 DNA and RNA molecules within intact tissue sections, the researchers visualized infected cells directly in their anatomical context. In parallel, they applied mass spectrometry imaging, a technology that maps the spatial distribution of small molecules across a tissue section pixel by pixel, to chart exactly where dolutegravir and lamivudine, along with other antiretrovirals, accumulated within the same lymph node specimens.

The results were striking on both fronts. First, HIV-1-infected cells declined rapidly after treatment initiation across both treatment groups, indicating that the two-drug regimen suppressed viral replication in lymphoid tissue just as effectively as triple therapy. Second, and perhaps more importantly for the field, the mass spectrometry imaging showed that antiretrovirals were widely detected within lymph node tissue regions containing HIV-positive cells or directly adjacent to them. In other words, the drugs were not merely present in the tissue in bulk; they were reaching the very neighborhoods where the virus persists, extending the picture of pharmacological coverage from the bloodstream into a key anatomical reservoir.

This spatial evidence matters because pharmacological sanctuary sites have been a persistent worry in HIV therapy design. Tissue penetration varies substantially among antiretroviral drugs, influenced by factors such as protein binding, molecular size, and active transport mechanisms at tissue barriers. If a two-drug regimen failed to achieve effective concentrations in lymphoid tissue, low-level residual replication could theoretically continue unnoticed, gradually replenishing the reservoir and eroding the durability of suppression. The DUALITY imaging data argue against that scenario for dolutegravir and lamivudine, showing co-localization of drug signal and viral signal within the same tissue microenvironments.

The technical achievement underlying these conclusions should not be understated. Detecting HIV-1 DNA and RNA by in situ hybridization in suppressed patients is analytically demanding, because infected cells are rare and the viral signal is faint. Mass spectrometry imaging of antiretrovirals in human tissue is similarly specialized, requiring careful method validation to distinguish true drug signal from background. By combining these modalities on the same lymph node sections, the research team, which spanned institutions including the University of North Carolina at Chapel Hill, Oregon Health and Science University, and the Germans Trias i Pujol research community in Badalona, Spain, could align viral geography with drug geography at a resolution that bulk tissue homogenization could never provide.

The trial was sponsored by Fundació Lluita contra les Infeccions and funded by ViiV Healthcare and the National Institutes of Health, with the academic investigator team retaining responsibility for study design, data analysis, and interpretation. As an open-label randomized study, it carries the usual caveats of unblinded design, and the number of lymph node excisions, while substantial for this kind of invasive tissue sampling, remains modest. The authors also note that the published version was shared early to accelerate access to the peer-reviewed findings. Nonetheless, the convergence of the primary blood-based endpoint and the tissue-level imaging results presents a coherent picture of two-drug therapy performing robustly across compartments.

For clinicians and patients, the findings add mechanistic reassurance to a regimen already validated by large outcome trials: dolutegravir plus lamivudine does not appear to leave the lymph nodes under-protected. For cure researchers, the study demonstrates a template for evaluating future interventions, whether simplified regimens, long-acting formulations, or reservoir-purging strategies, by directly measuring whether drugs and viral targets overlap in tissue. As the search for strategies that might eventually shrink or eliminate the HIV reservoir continues, knowing that first-line two-drug therapy reaches the cells it needs to reach is a meaningful step forward in ensuring that simplification does not come at the cost of silent viral persistence.

Subject of Research: Lymph node penetration of two-drug dolutegravir/lamivudine HIV-1 therapy and its effect on the viral reservoir

Article Title: First-line dolutegravir/lamivudine in HIV-1 infection: lymph node penetration and reservoir decline in a randomized open-label clinical trial

Article References: Rosen, E. P., Bondoc, S., Bailón, L., Blay, L., Caballero, A., García-Guerrero, M. C., Puertas, M. C., Moraes-Cardoso, I., Vazquez-Escobales, A., Blanco, J., Mothe, B., Kashuba, A. D., Estes, J. D., Martinez-Picado, J., Molto, J., On behalf of the DUALITY study group, Rosen, E. P., Bondoc, S., Bailón, L., … White, N. (2026). First-line dolutegravir/lamivudine in HIV-1 infection: lymph node penetration and reservoir decline in a randomized open-label clinical trial. Nature Communications. https://doi.org/10.1038/s41467-026-78190-9

Image Credits: AI Generated

DOI: 10.1038/s41467-026-78190-9

Keywords: HIV-1, dolutegravir, lamivudine, lymph nodes, viral reservoir, antiretroviral therapy, clinical trial, mass spectrometry imaging, DNAscope, RNAscope, proviral DNA, two-drug regimen

Dolutegravir belongs to a class of antiretroviral drugs known as integrase strand-transfer inhibitors, or INSTIs. These compounds block the integrase enzyme that HIV uses to insert its genetic material into the DNA of host cells, and they have become a cornerstone of modern antiretroviral therapy because of their potency, high genetic barrier to resistance and generally favorable tolerability. The widespread adoption of INSTI-based regimens has contributed significantly to the reduction in mortality associated with HIV infection, transforming the disease into a manageable chronic condition for millions of people. Dolutegravir in particular is recommended by major treatment guidelines as a first-line option and is a key component of the fixed-dose combination therapies used across both high-income and resource-limited settings.

Yet the drug’s safety profile in pregnancy has been scrutinized since 2018, when preliminary data from a Botswana surveillance study suggested an elevated incidence of neural tube defects among infants born to women who conceived while taking dolutegravir. The concern temporarily led the World Health Organization to advise caution in prescribing the drug to women of childbearing age, although subsequent and more extensive analyses substantially lowered the estimated risk, and the WHO eventually restored dolutegravir to its preferred first-line recommendations. Even so, the episode left open important questions about how the drug might affect other aspects of embryonic development, particularly in organ systems whose formation depends on precisely choreographed genetic programs during the earliest weeks of life.

The Brescia team, led by Sara Ferretti and Isabella Zanella together with clinical colleagues including Eugenia Quiros-Roldan and Francesco Castelli, turned to the zebrafish embryo to address those questions. Zebrafish have become a mainstay of developmental toxicology for good reason. Their embryos develop externally, are optically transparent, and form a functioning heart and circulatory system within the first days of life, which allows researchers to observe blood flow, heart rhythm and vessel formation directly under a microscope in a living vertebrate. Many of the molecular pathways governing cardiovascular development are conserved between fish and humans, making the model well suited for probing the mechanisms behind drug-induced developmental defects.

In the experiments, embryos were treated with dolutegravir at several concentrations. The drug produced clear signs of cardiovascular toxicity, including pericardial edema, an accumulation of fluid around the heart, and hemorrhage. At the one micromolar dosage, the researchers documented a deep impairment of cardiovascular function: the flow of blood through the vessels decreased, and the heartbeat slowed. These functional deficits were accompanied by morphological defects, with the atria and ventricles appearing shrunken, the normal looping of the developing heart altered, and the formation of new blood vessels disrupted. The combination of functional and structural abnormalities indicated that dolutegravir was not merely slowing development in a general way, but was specifically targeting the programs that build and operate the embryonic cardiovascular system.

To trace the molecular roots of these effects, the team analyzed the expression of genes that are crucial for cardiac myofibrillar organization, cardiomyocyte contractility and vascular morphogenesis and function. Dolutegravir exposure disturbed the regulation of several key players, including myh6, known in zebrafish as amhc, and myl7, known as cmlc2, both of which encode components of the contractile machinery of heart muscle cells. The drug also impaired vegfaa, a central driver of blood vessel growth, along with kdrl, the zebrafish counterpart of the vascular receptor vegfr2a, and flt1, the receptor vegfr1, which together mediate the signaling that guides endothelial cells as they assemble into vessels. In addition, the expression of hif1aa, a hypoxia-responsive factor involved in vascular adaptation, and of runx1 and gata1a, transcription factors essential for blood cell lineage development, was affected.

The pattern of gene disturbance offers a mechanistic explanation for what the researchers observed under the microscope. If the contractile genes of cardiomyocytes are downregulated, the heart muscle cannot organize its myofibrils properly and cannot beat with normal force or rhythm, which is consistent with the reduced heartbeat and diminished blood flow recorded in the treated embryos. If the vascular signaling axis centered on vegf and its receptors is disturbed, angiogenesis falters, and the embryonic vasculature fails to develop the network needed to perfuse the growing body. The involvement of runx1 and gata1a further suggests that the drug’s effects may extend into the hematopoietic system, since these transcription factors orchestrate the emergence of blood cells that the developing circulation depends on. The authors describe their findings as exploratory, but the coherence between the molecular data and the visible phenotypes strengthens the case that dolutegravir can perturb the genetic regulation of cardiovascular development.

The clinical implications of the work are cautious rather than alarmist. The concentration used in the zebrafish experiments, one micromolar, is a laboratory dosage chosen to probe mechanisms, and the study does not establish that pregnant people taking dolutegravir at therapeutic doses will experience the same embryonic effects. Pharmacokinetics, placental transfer, species differences and the timing of exposure all matter enormously in developmental toxicology, and the authors themselves frame their results as a prompt for further investigation rather than a verdict on the drug. Nonetheless, the study provides concrete mechanistic evidence that dolutegravir has an embryotoxic potential for the cardiovascular system in a vertebrate model, complementing the earlier literature that described cardiovascular defects alongside neural tube concerns in in vivo studies aimed primarily at neurodevelopment.

That evidence arrives at a moment when dolutegravir-based therapy is being scaled up globally, including in regions with high HIV prevalence among women of childbearing age. The drug remains a highly effective and generally well tolerated treatment, and the benefits of suppressing HIV in pregnancy, for both the parent and the infant, are well established. The task for researchers now is to refine the risk picture: to determine which embryonic windows are most sensitive, how the drug reaches embryonic tissues, and whether the cardiovascular gene programs identified in zebrafish are affected in mammalian models as well. The Brescia team’s work, funded by the University of Brescia, offers a clear starting point for that effort, having identified a specific set of genes, from the contractile markers myh6 and myl7 to the vascular regulators vegfaa, kdrl and flt1, whose disturbed regulation could mechanistically link dolutegravir exposure to embryonic cardiovascular impairment.

For a drug class that has reshaped HIV therapy worldwide, the study is a reminder that safety evaluation is never finished. Integrase inhibitors have delivered extraordinary clinical gains, and the reduction in HIV-associated mortality attributable to modern antiretroviral therapy is one of the great achievements of contemporary medicine. But the developing embryo is a system of exquisite sensitivity, in which transcription factors, growth factor signaling and contractile machinery must align within narrow developmental windows. The zebrafish experiments show that dolutegravir, at least under laboratory conditions, can disturb that alignment, producing pericardial edema, hemorrhage, slowed heartbeats and defective vessel formation in a living vertebrate. As the authors conclude, exposure of zebrafish embryos to one micromolar dolutegravir results in embryonic cardiovascular functional and morphological impairments that could be mechanistically linked to the disturbed regulation of key genes involved in cardiovascular development. Translating that insight into clinical guidance will require careful follow-up studies, but the study has already given investigators a molecular map of where to look next.

Subject of Research: Cardiovascular Development

Article Title: Insights into cardiovascular development of zebrafish embryo after exposure to dolutegravir

Article References: Ferretti, S., Zizioli, D., Manenti, M., Tiecco, G., Monti, E., Castelli, F., Quiros-Roldan, E., & Zanella, I. (2026). Insights into cardiovascular development of zebrafish embryo after exposure to dolutegravir. Scientific Reports. https://doi.org/10.1038/s41598-026-75116-9

Image Credits: AI Generated

DOI: 10.1038/s41598-026-75116-9

Keywords: Insights, cardiovascular, development, zebrafish, embryo, exposure, dolutegravir, scientific research

The research team, led by Xuelei Liang and corresponding author Fujie Zhang, enrolled 223 virologically suppressed men living with HIV who had low bone mineral density while taking TDF-based antiretroviral therapy. All participants were relatively young and free of chronic hepatitis B co-infection, a deliberate design choice that allowed the investigators to isolate the skeletal effects of treatment strategy from the confounding influence of hepatitis B, which itself mandates tenofovir use in most guidelines. The participants were allocated into four groups reflecting real-world clinical decisions: 48 men continued their existing TDF regimen, 37 remained on TDF but received a single intravenous infusion of 5 milligrams of zoledronic acid, a potent bisphosphonate, at the start of the study, 70 switched to a fixed-dose combination of bictegravir, emtricitabine, and tenofovir alafenamide, and 68 switched to a two-drug regimen of dolutegravir and lamivudine that eliminates tenofovir entirely.

The study’s primary endpoints were the absolute changes in bone mineral density from baseline to week 48 at three anatomically and clinically distinct sites: the femoral neck, the total hip, and the lumbar spine. These sites were measured with dual-energy X-ray absorptiometry, the standard technique for quantifying bone density, and the researchers used analysis of covariance with multivariable adjustment to compare outcomes between groups. Crucially, they bolstered their statistical confidence with 2,000 bootstrap resamples, generating bias-corrected and accelerated confidence intervals that are robust to the non-normal distributions common in clinical bone data. A total of 189 participants completed the full 48-week follow-up, and the team also ran sensitivity analyses using 20 imputed datasets under the intention-to-treat principle to guard against bias from missing data.

The findings were striking in their consistency. Men who simply continued TDF experienced persistent bone loss across all three measured sites over the 48 weeks, with median changes of approximately minus 0.01 grams per square centimeter at the femoral neck and total hip and minus 0.02 grams per square centimeter at the lumbar spine. While these absolute declines may appear modest, they represent a continued trajectory of skeletal demineralization in men who already had low bone density at baseline, a population in whom every fraction of a percentage point of bone mineral density carries meaningful implications for future fracture risk.

In contrast, all three intervention strategies produced significantly greater bone mineral density gains than continuing TDF, with the differences reaching statistical significance at every site. The magnitude of recovery was most clearly illustrated at the lumbar spine, where the adjusted mean differences relative to the TDF group were 0.09 grams per square centimeter for the TDF-plus-zoledronic-acid group, 0.07 grams per square centimeter for those switching to bictegravir, emtricitabine, and tenofovir alafenamide, and 0.11 grams per square centimeter for those switching to dolutegravir and lamivudine, all with confidence intervals excluding zero and p-values at or below 0.001. Perhaps the most clinically consequential finding was that no significant pairwise differences emerged among the three intervention regimens themselves, suggesting that switching drugs and adding an antiresorptive agent delivered broadly comparable skeletal benefits over one year.

Beneath these density measurements, the study tracked bone turnover markers, the biochemical fingerprints of skeletal remodeling. The researchers measured beta-C-terminal telopeptide of type 1 collagen, known as beta-CTX, a marker of bone resorption, and procollagen type 1 N-terminal propeptide, or P1NP, a marker of bone formation. Men who continued TDF showed significant increases in both markers from baseline, a pattern consistent with accelerated bone turnover, in which osteoclast-driven resorption outpaces osteoblast-driven formation and net bone is lost. This biochemical signature helps explain the density declines seen on dual-energy X-ray absorptiometry and aligns with the known mechanism of tenofovir disoproxil fumarate, whose active metabolite can impair mitochondrial function and differentiation of osteoblasts, the bone-forming cells, while also promoting osteoclast activity.

The zoledronic acid group displayed a distinctly different turnover profile. Co-administration of the bisphosphonate with TDF produced the greatest percentage reduction in P1NP compared with both switch groups, with both comparisons reaching p-values below 0.001, and also suppressed beta-CTX more strongly than the dolutegravir and lamivudine switch strategy. Zoledronic acid works by binding to hydroxyapatite crystals in bone and, once internalized by osteoclasts during resorption, disrupting their farnesyl pyrophosphate synthase pathway and triggering osteoclast apoptosis. The result is a deep and sustained braking of the entire remodeling cycle, which the marker data captured vividly. By contrast, the switch strategies allowed turnover markers to normalize more gradually as the offending tenofovir prodrug was withdrawn, permitting the remodeling system to rebalance without pharmacological suppression.

The multiple imputation sensitivity analyses yielded findings consistent with the primary per-protocol results, strengthening the internal validity of the study. The investigators also note that the work was supported by Capital’s Funds for Health Improvement and Research and by a program establishing longitudinal follow-up infrastructure for the hospital’s cohort of people living with HIV, and that the study was approved by the hospital’s ethics committee with all participants providing written informed consent. The research was conducted according to the Declaration of Helsinki, and the authors declare no competing interests.

The clinical implications are substantial. Tenofovir alafenamide achieves high intracellular concentrations of the active tenofovir diphosphate in lymphocytes while producing markedly lower plasma tenofovir exposure, which is thought to spare bone and kidneys, and the dolutegravir and lamivudine two-drug regimen goes further by removing tenofovir altogether. This study suggests that in men with low bone density on TDF, either approach can reverse the skeletal trajectory within a year, and that for patients who must remain on TDF for other reasons, a single dose of zoledronic acid offers an effective parallel strategy. The findings support individualized bone management, in which clinicians weigh hepatitis B status, renal function, fracture risk, drug cost, and patient preference when deciding whether to switch regimens or add bone-protective therapy.

Important caveats temper the enthusiasm. The cohort consisted exclusively of relatively young men without chronic hepatitis B co-infection, so the results cannot be directly extrapolated to women, older patients, or those co-infected with hepatitis B, for whom tenofovir remains essential. As a prospective observational cohort rather than a randomized trial, the study cannot fully exclude residual confounding, although the multivariable adjustment and bootstrap-based inference mitigate this concern. The 48-week horizon captures early recovery but not long-term fracture outcomes, and the comparable efficacy of the three strategies means the choice among them will likely hinge on factors beyond bone, including tolerability, drug interactions, and access. Even so, the study delivers a clear and encouraging message: bone lost to tenofovir disoproxil fumarate is not necessarily lost forever, and clinicians now have evidence-backed pathways, whether through regimen switching or targeted bisphosphonate therapy, to help their patients rebuild it.

Subject of Research: Bone mineral density recovery in men with HIV after switching from TDF-based antiretroviral therapy

Article Title: Bone health trajectories following regimen optimization in male people living with HIV receiving TDF: a prospective, observational, cohort study

Article References: Liang, X., Yang, D., Zhang, H., Zhao, H., Wang, Y., Yu, F., Guo, M., Yang, X., Yan, C., & Zhang, F. (2026). Bone health trajectories following regimen optimization in male people living with HIV receiving TDF: a prospective, observational, cohort study. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14623-6

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14623-6

Keywords: HIV, bone mineral density, tenofovir disoproxil fumarate, tenofovir alafenamide, zoledronic acid, bone turnover markers, antiretroviral therapy, osteoporosis, dolutegravir, bisphosphonates, cohort study, BMC Infectious Diseases

Combination antiretroviral therapy has transformed HIV from a fatal infection into a manageable chronic condition for roughly 41 million people worldwide, most of them in sub-Saharan Africa, where Nigeria carries one of the heaviest burdens with about two million infected individuals. The World Health Organization recommends TLD as the standard first-line regimen: two nucleotide or nucleoside reverse transcriptase inhibitors that block viral replication, paired with dolutegravir, an integrase strand transfer inhibitor that prevents viral DNA from inserting into the host genome. Although the therapy suppresses the virus, restores immune function, and reduces opportunistic infections, clinicians have increasingly observed that women living with HIV may experience earlier decline in ovarian function, more menstrual abnormalities, and earlier menopause than HIV-negative women. Whether these disturbances stem from the virus itself or from the drugs has remained an open question.

To probe that question, researchers at the University of Lagos and the Medical University of Vienna turned to a two-pronged design. In the experimental arm, fifteen adult female Wistar rats with established estrous cycles were randomized into three groups of five. One group received distilled water as a control, a second received TLD-based therapy at 22 milligrams per kilogram of body weight—a weight-based conversion of the standard 650-milligram fixed-dose combination pill—and a third received dolutegravir alone at 2.5 milligrams per kilogram. All drugs were given orally once daily for 28 consecutive days, a duration consistent with the OECD test guideline 407 for repeated-dose toxicity, and the doses were deliberately chosen to mimic minimal therapeutic exposure rather than overdose conditions.

The results were striking even at these low doses. Daily microscopic examination of vaginal smears revealed that both treated groups spent significantly longer in the diestrus phase of the estrous cycle—the resting phase between ovulations—and significantly fewer days in metestrus, a pattern indicative of impaired ovulatory function. The number of ovulated ova recovered from the fallopian tubes fell sharply in both treated groups compared with controls, with p-values of 0.0002 for the combination therapy group and 0.0003 for the dolutegravir-only group. Under the microscope, ovarian sections from treated animals showed atretic follicles, distorted antral follicles, degenerate nuclei, vascular congestion, and sparsely distributed theca and granulosa cells, all hallmarks of follicular degeneration and disordered folliculogenesis.

Biochemical assays of ovarian tissue pointed to oxidative stress as a central mechanism. The combination-treated animals showed significantly elevated malondialdehyde, a lipid peroxidation product that marks oxidative damage to cell membranes, alongside significantly depleted glutathione and reduced catalase activity, two of the tissue’s principal antioxidant defenses. The authors propose that the nucleoside reverse transcriptase inhibitors contribute substantially to this oxidative burden by inhibiting mitochondrial DNA polymerase-gamma, which depletes mitochondrial DNA, impairs oxidative phosphorylation, drains cellular ATP, and generates excess reactive oxygen species. Granulosa cells are exceptionally dependent on mitochondrial energy production for follicular maturation and steroidogenesis, making them particularly vulnerable to this kind of metabolic injury. Dolutegravir, for its part, has been shown in cellular models to alter mitochondrial membrane potential and increase reactive oxygen species, and recent work has also linked it to endoplasmic reticulum stress at the blood-brain barrier, suggesting that disturbances of intracellular protein and metabolic homeostasis may amplify the oxidative cascade.

The endocrine data reinforced the picture of a disrupted hypothalamic-pituitary-ovarian axis. Serum follicle-stimulating hormone and luteinizing hormone—the pituitary signals that drive follicle development and ovulation—were significantly reduced in both treated groups, with the combination regimen producing the stronger suppression. The authors suggest a plausible inflammatory route for this suppression: mitochondrial stress and excess reactive oxygen species activate the NF-kappa-B pathway and the NLRP3 inflammasome, promoting pro-inflammatory cytokines such as tumor necrosis factor-alpha and interleukin-6. Patients on long-term antiretroviral therapy have been shown to carry persistent elevations of these cytokines, which are known to suppress hypothalamic gonadotropin-releasing hormone pulsatility and reduce pituitary responsiveness, ultimately lowering downstream LH and FSH secretion. The greater suppression seen with the full combination suggests that tenofovir and lamivudine add to the burden imposed by dolutegravir alone, consistent with a model in which reproductive toxicity arises from cumulative mitochondrial and oxidative stress across multiple drugs rather than from any single agent.

The clinical arm of the study, though small, lent human relevance to these mechanisms. Twenty women living with HIV, all aged 40 or younger and all taking TLD-based therapy for at least twelve months, were recruited from the AIDS Prevention Initiative of Nigeria clinic at Lagos University Teaching Hospital. Serum anti-Müllerian hormone, produced by granulosa cells of growing follicles and widely regarded as the most reliable biomarker of functional ovarian reserve, was measured with a sandwich ELISA. Ten of the twenty participants—50 percent—had AMH values below 1.0 nanogram per milliliter, falling into the low or very low categories, and eleven—55 percent—fell below the 1.5 nanogram per milliliter threshold that the study classified as the floor of the normal range. Notably, menstrual patterns were largely preserved: 90 percent of participants had normal flow duration, and menstrual interval and dysmenorrhea showed no significant changes, suggesting that overt menstrual disruption may lag well behind underlying follicular depletion.

The dissociation between preserved menstruation and reduced ovarian reserve carries implications that extend beyond fertility. Low AMH in this population may serve as a systemic marker of accelerated biological aging: prior work has shown that women living with HIV exhibit shorter leukocyte telomere length, a hallmark of cellular senescence that correlates with prematurely low AMH. Epidemiological studies have also linked low AMH in reproductive age to a two-fold increased risk of metabolic dysfunction-associated steatotic liver disease, while women with that liver condition transition to menopause earlier. Depletion of the follicle pool also erodes estrogen’s cardioprotective effects, raising the possibility of elevated cardiovascular risk, although estradiol was not directly assayed in this study. The authors caution that these broader outcomes were not measured here and remain hypotheses for future research.

The study has clear limitations that temper its conclusions. The 28-day animal exposure cannot replicate the chronic, often lifelong treatment that women living with HIV receive, and it remains unknown whether the observed ovarian effects are reversible or progressive over years. The clinical cohort of twenty participants, without a control group, introduces variability in AMH measurements and limits statistical power, and the design cannot disentangle the effects of HIV infection itself from those of the drug regimen. The authors did not adjust for nutritional status, socioeconomic factors, or viral suppression levels, all of which could influence reproductive hormones. They recommend future studies comparing HIV-negative women, HIV-positive women on alternative regimens, and HIV-positive women on TLD, adequately powered for age, duration of infection, and disease severity.

Importantly, the researchers stop short of recommending any change to clinical practice. The exploratory nature of the AMH findings is insufficient to justify routine AMH screening or modification of standard TLD-based therapy, which remains a highly effective and well-tolerated regimen that has saved millions of lives. What the study does argue for is attention: reproductive health and future fertility should remain part of clinical counseling for women of reproductive age on long-term antiretroviral therapy, with individualized assessment where clinically appropriate. As the population of women receiving lifelong TLD continues to grow, longitudinal and adequately controlled studies will be essential to determine whether the subtle ovarian changes documented here translate into meaningful fertility and health consequences over decades of treatment.

Subject of Research: Effects of TLD-based antiretroviral therapy on ovarian function and reserve

Article Title: TLD-Based Antiretroviral Therapy Compromises Ovarian Function and Reserve: Evidence from Experimental and Clinical Studies

Article References: Ugwu, M., Bakare, A. A., Nafiu, T., Dosumu, O. O., & Akang, E. N. (2026). TLD-Based Antiretroviral Therapy Compromises Ovarian Function and Reserve: Evidence from Experimental and Clinical Studies. Reproductive Sciences. https://doi.org/10.1007/s43032-026-02229-x

Image Credits: AI Generated

DOI: 10.1007/s43032-026-02229-x

Keywords: HIV, antiretroviral therapy, dolutegravir, tenofovir, lamivudine, ovarian reserve, anti-Müllerian hormone, oxidative stress, fertility, reproductive health, mitochondrial toxicity, women's health

Dolutegravir was embraced worldwide for good reasons. The drug belongs to the integrase strand transfer inhibitor class, blocking the HIV enzyme that inserts viral DNA into the host genome. It offers a high genetic barrier to resistance, meaning the virus struggles to evolve escape mutations, and it is generally well tolerated, potent at low doses, and affordable in generic form. These properties made it the cornerstone of first-line therapy recommended by international guidelines and adopted enthusiastically across sub-Saharan Africa, where the majority of the world’s HIV infections are concentrated. However, as experience with the drug has accumulated, clinicians and researchers have reported a cluster of metabolic side effects, including abdominal obesity, hypertension, impaired glucose regulation, and abnormal lipid levels. These conditions do not occur in isolation; they tend to cluster together in the same patients, multiplying the long-term risk of cardiovascular disease and type 2 diabetes, the two conditions most likely to erode the survival gains that antiretroviral therapy has delivered.

The Zimbabwean study was designed as an exploratory, hypothesis-generating investigation to quantify this burden in a setting where such data had been scarce. Between 20 January and 13 February 2025, the researchers recruited 171 adults receiving first-line dolutegravir-based treatment at Parirenyatwa Group of Hospitals, one of Zimbabwe’s largest referral centres. Each participant completed a structured questionnaire covering demographics, lifestyle habits, and clinical history, and underwent anthropometric assessment including body mass index calculation. Blood pressure was measured with the participant at rest, and blood samples were drawn for laboratory analysis of glycated haemoglobin, fasting glucose, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. This combination of self-reported, physical, and biochemical measures allowed the team to build a reasonably complete metabolic picture of each patient in a single visit, a pragmatic approach suited to resource-constrained clinical settings.

The demographic profile of the cohort reflects the face of the HIV epidemic in Zimbabwe. Two-thirds of the participants, 67.8 percent, were female, and the median age was 42.1 years, with an interquartile range spanning 32.4 to 50.2 years. Most participants had at least a secondary education. Lifestyle risk factors were unevenly distributed: only nine participants were smokers, 23 percent reported alcohol use, and a substantial 62.2 percent reported engaging in no regular exercise. The physical measurements were already telling before any blood was analysed. More than half of the cohort, 57.9 percent, was overweight or obese, and 39.8 percent had elevated blood pressure meeting the threshold for hypertension. These figures suggest that the metabolic consequences of long-term HIV treatment in this population are not confined to laboratory values but are visible in body composition and vascular health.

The lipid results were the most dramatic finding. Dyslipidaemia, defined as one or more abnormal lipid values, affected 74.3 percent of participants. Breaking the pattern down, non-ideal high-density lipoprotein cholesterol, the so-called good cholesterol that protects arteries, was the most common abnormality at 50.5 percent, followed by raised low-density lipoprotein cholesterol at 33.3 percent, raised triglycerides at 16 percent, and hypercholesterolaemia, or elevated total cholesterol, at 10.3 percent. Low HDL cholesterol is a particularly insidious abnormality because it often produces no symptoms, yet it is strongly linked to atherosclerotic cardiovascular disease. The predominance of low HDL alongside elevated LDL mirrors the classic atherogenic lipid profile seen in metabolic syndrome and suggests that many patients on dolutegravir-based therapy are accumulating cardiovascular risk silently, years before any clinical event such as a heart attack or stroke might occur.

Glucose metabolism told a parallel story. While overt hyperglycaemia affected 13.4 percent of participants, insulin resistance was far more widespread at 56.1 percent. This gap matters clinically. Insulin resistance represents a state in which the body’s tissues respond poorly to insulin, forcing the pancreas to compensate by producing more of the hormone. This compensation can maintain normal blood sugar for years, but it is metabolically costly and often precedes frank diabetes by a decade or more. A screening strategy that measures only glucose would miss the majority of patients already on the diabetic pathway. The authors’ finding that more than half of a relatively young cohort showed insulin resistance raises the prospect of a future wave of type 2 diabetes among people living with HIV in Zimbabwe unless preventive interventions are introduced early.

To identify which factors independently predicted these metabolic abnormalities, the researchers performed multivariate analysis, a statistical technique that adjusts for the influence of multiple variables simultaneously. Two correlates emerged with statistical significance. Increasing age was independently associated with hyperglycaemia, with an adjusted odds ratio of 1.08 per year of age, a 95 percent confidence interval of 1.03 to 1.13, and a p-value of 0.002. This means that each additional year of life raised the odds of elevated blood sugar by roughly 8 percent after accounting for other factors. Meanwhile, elevated blood pressure was independently associated with dyslipidaemia, with an adjusted odds ratio of 2.64, a 95 percent confidence interval of 1.03 to 6.78, and a p-value of 0.043. Patients with high blood pressure were more than two and a half times as likely to have abnormal blood fats as those with normal readings. The co-occurrence of hypertension and dyslipidaemia is a hallmark of cardiometabolic syndrome and compounds vascular risk multiplicatively rather than additively.

The study’s cross-sectional design imposes important limits on interpretation. Because all measurements were taken at a single point in time, the analysis cannot establish whether dolutegravir itself caused the metabolic abnormalities, whether they predated treatment, or whether they stem from other contributors such as diet, physical inactivity, prior exposure to older antiretroviral drugs known to disrupt lipid metabolism, or background genetic and environmental factors in the Zimbabwean population. The authors explicitly frame the work as exploratory and hypothesis-generating rather than definitive. The modest sample size of 171, recruited from a single hospital, also means the confidence intervals around some estimates are wide, as seen with the blood pressure and dyslipidaemia association. Nevertheless, the consistency of the findings with reports from other countries where dolutegravir has been rolled out strengthens the case that metabolic monitoring deserves a central place in HIV care programmes throughout the region.

The clinical implications are nonetheless clear and actionable. As people living with HIV age on long-term dolutegravir-based therapy, the population is transitioning from a disease dominated by immune suppression to one where chronic, non-communicable conditions threaten the longevity that treatment has made possible. The authors conclude that routine, integrated screening of body mass index, blood pressure, glucose, and lipid profiles is essential to mitigate cardiometabolic risk and sustain the success of dolutegravir-based ART in Zimbabwe. Such screening is technically simple and inexpensive compared with the cost of treating advanced diabetes or cardiovascular disease, but it requires deliberate integration into HIV clinics, which have historically focused almost exclusively on viral suppression and CD4 counts. The Zimbabwean findings add to a growing body of evidence that the next frontier of HIV medicine lies not in controlling the virus, which modern therapy does remarkably well, but in managing the metabolic and cardiovascular consequences of decades of life with treated infection.

For the global HIV response, the study is a timely reminder that the success of a drug regimen must be measured not only in viral load suppression but in the long-term health of the people taking it. Dolutegravir has transformed treatment outcomes across Africa, and nothing in these findings argues for abandoning it. Instead, they argue for a broader model of care in which the HIV clinic doubles as a gateway for detecting and managing hypertension, diabetes risk, and dyslipidaemia. With 12.9 percent of Zimbabwean adults living with HIV and the vast majority now on dolutegravir-based regimens, the country has both an urgent need and a real opportunity to pioneer integrated cardiometabolic care within its antiretroviral programme. The alternative, allowing a silent epidemic of insulin resistance and abnormal blood fats to progress unchecked among a young and increasingly healthy HIV population, would squander much of the progress that antiretroviral therapy has achieved over the past two decades.

Subject of Research: Metabolic complications of dolutegravir-based antiretroviral therapy in Zimbabwean adults living with HIV

Article Title: Burden and determinants of hyperglycaemia and dyslipidaemia in Zimbabwean adults living with HIV on dolutegravir-based first-line antiretroviral therapy: A cross-sectional study

Article References: Chirimo, R., Zhou, D. T., Mudzviti, T., Ruredzo, I. M., Manasa, J., Maponga, C. C., Reginald Gomo, Z. A., Gomo, E., & Morse, G. D. (2026). Burden and determinants of hyperglycaemia and dyslipidaemia in Zimbabwean adults living with HIV on dolutegravir-based first-line antiretroviral therapy: A cross-sectional study. PLOS One, 21(10), e0359196. https://doi.org/10.1371/journal.pone.0359196

Image Credits: AI Generated

DOI: 10.1371/journal.pone.0359196

Keywords: HIV, dolutegravir, dyslipidaemia, hyperglycaemia, insulin resistance, Zimbabwe, antiretroviral therapy, cardiovascular risk, hypertension, PLOS One, metabolic syndrome, cross-sectional study

The research team, led by Ahd Ouladlahsen of the Faculté de Médecine et de Pharmacie at Hassan II University and the infectious diseases service of CHU Ibn Rochd, enrolled 396 consecutive adults newly diagnosed with HIV between January 1 and December 31, 2023. Unlike retrospective chart reviews, this was a prospective cohort: demographic, clinical, laboratory, and treatment outcome data were systematically collected as patients moved through care. The investigators then used multivariable logistic and Cox regression models to identify independent predictors of three key outcomes: advanced HIV disease at presentation, virological failure at six months, and all-cause mortality. The study was approved by the Ethics Committee of the Faculty of Medicine in Rabat and conducted in accordance with the Declaration of Helsinki, with informed consent obtained from all participants.

The demographic profile of the cohort reflects a mixture of social vulnerability and mobility. The median age was 34 years, with a range spanning 18 to 74, and men made up 55 percent of newly diagnosed patients. Most participants were single, 60.1 percent, and nearly half, 46.1 percent, were unemployed. Perhaps the most striking socioeconomic figure is that 83.6 percent of patients had no health insurance, a factor that shapes both access to testing and the ability to remain in care. Nearly one in five patients, 19.9 percent, were of Sub-Saharan African origin, underscoring the role of migration corridors in the regional epidemiology of HIV and the need for screening strategies that reach migrant populations effectively.

Transmission patterns in the cohort were dominated by heterosexual contact, which accounted for 72.0 percent of new diagnoses. That figure matters for public health planning because it signals that HIV in this setting is not confined to networks traditionally classified as key populations; it is embedded in the general adult population. At the same time, the way patients entered care is perhaps the most consequential finding of the entire study: symptoms prompted the diagnosis in 58.9 percent of cases. In other words, the majority of people were not identified through proactive, voluntary testing but because something was already clinically wrong, which almost by definition implies that the virus had been replicating, and the immune system deteriorating, for a considerable period before anyone looked for it.

The immunological data confirm just how far disease had progressed by the time of diagnosis. The median baseline CD4 count was 186 cells per cubic millimeter, well below the 200-cell threshold that defines one of the classic boundaries of severe immunosuppression, and 60.6 percent of patients presented with CD4 counts below that mark. Under the Centers for Disease Control and Prevention staging system, 41.4 percent of patients were already at stage C, the stage corresponding to AIDS-defining illness. Tuberculosis was the leading opportunistic infection, affecting 35.1 percent of the cohort. This convergence of low CD4 counts, advanced clinical staging, and rampant tuberculosis coinfection paints a portrait of an epidemic in which the virus is being discovered only after it has done most of its damage, a pattern that global health authorities have repeatedly identified as one of the chief obstacles to ending AIDS as a public health threat.

Treatment outcomes at six months tell a more nuanced story. On the positive side, 75.0 percent of patients achieved viral suppression within half a year of starting therapy, a respectable figure for a cohort in which most patients began treatment profoundly immunocompromised. The backbone of modern first-line therapy in the region is dolutegravir-based antiretroviral therapy, and the suppression rate suggests that when patients reach care and start the recommended regimens, the drugs largely do their job. However, 10.0 percent of patients experienced virological failure at six months, and overall mortality in the cohort reached 8.3 percent. An early death rate approaching one in twelve among newly diagnosed patients is a direct consequence of late presentation: people who arrive with CD4 counts below 200 cells per cubic millimeter and active tuberculosis face a fundamentally different prognosis than those identified early.

The regression analyses sharpen these associations into a hierarchy of risk. For mortality, four independent predictors emerged: a CD4 count below 200 cells per cubic millimeter carried an adjusted hazard ratio of 3.67, by far the strongest signal in the model; age of 40 years or older carried an adjusted hazard ratio of 1.62; active tuberculosis carried an adjusted hazard ratio of 2.56; and higher baseline viral load carried an adjusted hazard ratio of 1.18. Each of these factors is, in principle, addressable. CD4 nadir and viral load at diagnosis are proxies for how long infection went undetected; tuberculosis coinfection can be prevented or caught earlier through integrated TB/HIV screening; and age is a reminder that testing strategies must not neglect middle-aged and older adults who are rarely the focus of HIV awareness campaigns.

Advanced HIV disease at presentation was itself predicted by a distinct cluster of characteristics: age of 40 or older, Sub-Saharan African origin, unemployment, divorced or widowed status, and tuberculosis. Read together, these predictors describe patients who sit at the intersection of biological and social risk. Unemployment and lack of insurance limit both the incentive and the means to seek voluntary testing, while marital status may affect disclosure, support, and health-seeking behavior. For migrants, language barriers, documentation concerns, and discontinuous access to health systems can delay entry into care for years. The finding that virological failure at six months was independently predicted by advanced HIV disease at baseline, with an adjusted odds ratio of 1.85, higher baseline viral load, with an adjusted odds ratio of 1.92 per log10 increase, and receipt of non-TDF/3TC/DTG regimens, with an adjusted odds ratio of 1.89, adds a therapeutic dimension: patients who start treatment with very high viral burdens and non-standard regimens are the ones most likely to fail, reinforcing the case for prompt diagnosis and rapid initiation of preferred first-line therapy.

The authors are careful about the limits of their work. This was a single-center study at a tertiary referral hospital in Casablanca, which means the cohort may overrepresent complicated cases referred from elsewhere while underrepresenting people diagnosed and managed entirely in primary care. Some analyses were restricted to subsets of patients: the advanced disease model included 236 patients with available CD4 data, and the virological failure model included 280 patients with six-month viral load measurements. The investigators themselves call for multi-center validation with extended follow-up, noting that six months captures early treatment outcomes but not the longer arc of retention, adherence, and survival.

Even with those caveats, the policy implications are difficult to ignore. The study argues for expanded community-based screening so that diagnoses are driven by testing rather than by symptoms, integrated TB/HIV services capable of detecting coinfection at or before the moment of HIV diagnosis, socioeconomic support for unemployed and uninsured patients whose life circumstances compete with clinic attendance, and enhanced, culturally competent screening for migrant populations. Dolutegravir-based therapy has already proven capable of suppressing the virus in three-quarters of newly diagnosed patients within six months; the remaining losses, the deaths, the failures, the late presentations, are largely problems of timing and access rather than of pharmacology. In that sense, the Casablanca cohort is less a story about the virus than about the systems that fail to intercept it, and a reminder that in 2023, in a Moroccan tertiary care center, the median person diagnosed with HIV had a CD4 count of 186 cells per cubic millimeter, a number that should be an anachronism but is not.

Subject of Research: Epidemiological and clinical profile of newly diagnosed HIV patients in Morocco

Article Title: Epidemiological and clinical profile of newly diagnosed HIV patients at a moroccan tertiary care center in 2023

Article References: Ouladlahsen, A., Lkhider, M., Haddaji, A., Bensghir, R., Badi, H., Sodqi, M., Ihbibane, F., Marih, L., Ezzikouri, S., & El Filali, K. M. (2026). Epidemiological and clinical profile of newly diagnosed HIV patients at a moroccan tertiary care center in 2023. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14422-z

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14422-z

Keywords: HIV, late diagnosis, Morocco, tuberculosis, antiretroviral therapy, dolutegravir, CD4 count, virological suppression, opportunistic infections, Sub-Saharan migrants, public health, Casablanca

The research, led by Allan Wandera of the Department of Biochemistry at Lira University and colleagues from institutions including Soroti University, was published in BMC Endocrine Disorders. It enrolled 54 HIV-positive adults with type 2 diabetes, all of whom had been receiving both antiretroviral therapy and glucose-lowering medication for at least six months at the hospital’s Chronic Care Clinic. The study was funded by the Lira University Research and Innovations Fund, financed by the Government of Uganda for the 2023/2024 cycle, and approved by the Lira University Research Ethics Committee under approval number LUREC-2025-400, with administrative clearance from the hospital itself. Every participant provided written informed consent, and the work was conducted in line with the Declaration of Helsinki.

The clinical backdrop is important for understanding why the study exists. Dolutegravir-based regimens are now recommended widely because they are potent, durable, and have a high genetic barrier to resistance. Yet at Lira Regional Referral Hospital, diabetic patients are frequently switched away from dolutegravir onto alternative combinations, most commonly tenofovir disoproxil fumarate, lamivudine, and efavirenz, known as TDF/3TC/EFV, or onto protease inhibitor-based or abacavir-based therapies. The metabolic consequences of these non-dolutegravir regimens in patients who also have diabetes had not been systematically documented, leaving clinicians without evidence to guide treatment choices for a growing and vulnerable subgroup.

To fill that gap, the researchers combined a review of medical records with fresh laboratory investigations. Blood samples were drawn to measure glycated hemoglobin, or HbA1c, the standard long-term marker of blood glucose control, along with liver function tests, kidney function tests, lipid profiles, and CD4 cell counts. Viral load data were retrieved from patient records. Participants were then sorted into six groups according to the specific combination of antiretroviral therapy and diabetes medication they were receiving, and the investigators applied descriptive statistics and one-way analysis of variance to compare outcomes across the groups.

The virological picture was reassuring. Every participant had a documented suppressed viral load, and CD4 counts were above 350 cells per cubic millimeter in all cases, with a mean of 518.5 plus or minus 56.8 cells per cubic millimeter. In other words, whatever regimen the patients were taking, their HIV infection was well controlled. The cohort itself skewed female and middle-aged to older: 70.4 percent of participants were women, and the average age was 54.8 plus or minus 9.5 years. These demographics reflect the broader epidemiological shift in sub-Saharan Africa, where an aging population of people living with HIV is increasingly confronting non-communicable diseases.

Glycemic control, however, told a more complicated story. HbA1c values varied significantly across the six treatment groups, and the statistical analysis confirmed that this variation was unlikely to be due to chance, with an F statistic of 3.794 and a p value of 0.006. The lowest average HbA1c, 7.81 percent, was recorded in the largest group, 23 patients taking TDF/3TC/EFV combined with metformin alone. The next lowest was a small group of four patients on abacavir, lamivudine, and efavirenz without insulin or protease inhibitors, at 8.50 percent, followed by five patients on protease inhibitor-based therapy without insulin at 8.94 percent. Patients on TDF/3TC/EFV with both metformin and glibenclamide averaged 9.43 percent, those on TDF/3TC/EFV with insulin averaged 9.47 percent, and the highest figure, 11.08 percent, appeared in a group of four patients on other highly active antiretroviral combinations with insulin. Post-hoc testing pinpointed one statistically significant pairwise difference: the metformin-only group had an HbA1c 3.27 percentage points lower than the other-HAART-plus-insulin group, with a p value of 0.014.

The authors are careful about how these numbers should be interpreted. They note that the findings align with clinical practice, in which more severe diabetes cases are typically escalated to insulin or to additional oral agents. A patient whose diabetes is aggressive enough to require insulin is, almost by definition, harder to control than one who can be managed with metformin alone, so the observed differences in HbA1c likely reflect underlying disease severity as much as any direct pharmacological effect of the antiretroviral regimens themselves. This is a crucial caveat for a cross-sectional design, which captures a single moment in time and cannot establish whether a particular drug combination caused better or worse glucose control. The researchers explicitly describe their results as baseline descriptive data and call for prospective studies to examine the practice of switching diabetic patients away from dolutegravir.

Beyond glucose, the study examined a panel of metabolic and organ-function markers that are often overlooked in resource-limited settings. Alkaline phosphatase was elevated above 120 units per liter across all six groups, with the highest levels seen in the groups whose treatment included insulin. Gamma-glutamyl transferase elevations in the 40 to 60 units per liter range were observed in the metformin-only group and in the TDF/3TC/EFV-plus-insulin group. Importantly, the transaminases alanine aminotransferase and aspartate aminotransferase, the classic markers of hepatocellular injury, remained within normal ranges across all groups, with mean values of 21.7 plus or minus 12.5 and 20.5 plus or minus 5.8 units per liter respectively. Elevated total cholesterol and triglycerides appeared only in the group taking TDF/3TC/EFV with insulin, a pattern that echoes the known lipid effects of both insulin therapy and some antiretroviral agents.

Kidney function, a persistent concern for patients on tenofovir disoproxil fumarate, appeared well preserved. The estimated glomerular filtration rate, calculated using the contemporary CKD-EPI 2021 formula, averaged 97.5 plus or minus 14.8 milliliters per minute per 1.73 square meters of body surface area, a value consistent with normal renal clearance. That finding is clinically meaningful because TDF has long been associated with proximal tubular injury in some patients, and the combination of HIV, diabetes, and tenofovir could theoretically compound renal risk. In this cohort, at least over the observation window, the kidneys held their ground.

What emerges from Lira is less a verdict on any single drug than a portrait of a treatment landscape in transition. As dolutegravir becomes the default first-line option across the region, clinicians are increasingly making individualized decisions to move patients with diabetes onto older regimens, often without robust evidence about the metabolic trade-offs involved. This study provides the first quantitative baseline for such decisions in a Ugandan regional hospital, showing that HIV control remains excellent across all non-dolutegravir regimens, that glycemic outcomes differ substantially by treatment combination in ways that likely track disease severity, and that liver and kidney function are broadly preserved even as alkaline phosphatase elevations raise questions worth pursuing. The researchers, who declare no competing interests, argue that the next step must be longitudinal work that follows patients before and after a switch away from dolutegravir, so that cause and effect can finally be separated from correlation. For the growing number of people navigating both HIV and diabetes in northern Uganda and beyond, that evidence cannot come soon enough.

Subject of Research: Glycemic control and metabolic parameters in HIV-positive patients with type 2 diabetes on non-dolutegravir antiretroviral regimens in Uganda

Article Title: Glycemic control and metabolic parameters among HIV-positive diabetic patients on non-dolutegravir-based antiretroviral regimens at lira regional referral hospital, uganda: a cross-sectional study

Article References: Wandera, A., Nakaziba, R., Okello, N., Wandera, S. K., Otim, T. C., & Olwa, F. (2026). Glycemic control and metabolic parameters among HIV-positive diabetic patients on non-dolutegravir-based antiretroviral regimens at lira regional referral hospital, uganda: a cross-sectional study. BMC Endocrine Disorders. https://doi.org/10.1186/s12902-026-02597-0

Image Credits: AI Generated

DOI: 10.1186/s12902-026-02597-0

Keywords: HIV, type 2 diabetes, antiretroviral therapy, dolutegravir, glycemic control, HbA1c, metformin, efavirenz, Uganda, metabolic parameters, liver function, renal function

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