The investigation was conducted as part of the Kenya Country Assessment under the People Living with HIV Stigma Index 2.0, a standardized, community-led surveillance instrument coordinated globally by networks of people living with HIV. Between February and March 2021, the study enrolled 2,125 participants drawn from both rural and urban settings across Kenya. Because the Stigma Index is administered by and for people living with HIV, it is designed to capture experiences of discrimination and self-stigma that participants might be reluctant to disclose in clinical settings, making it a uniquely sensitive tool for measuring the social environment surrounding treatment.

The research team, led by Yuanqi Mi of the Johns Hopkins Bloomberg School of Public Health together with colleagues at Kenyan community organizations including the International Community of Women Living with HIV, Women Fighting AIDS in Kenya, and the National Empowerment Network of People Living with HIV and AIDS, focused on three distinct forms of stigma. Internalized stigma refers to the adoption of negative beliefs about HIV by people living with the virus themselves, manifesting as shame, self-blame, or a decision to conceal one’s status. Healthcare-related enacted stigma, sometimes called experienced stigma, captures concrete discriminatory behaviors encountered in clinics, such as verbal abuse, denial of care, or breaches of confidentiality. Healthcare-related anticipated stigma measures the expectation that such discrimination will occur, whether or not it actually has. For each participant, the researchers calculated composite scores for each of the three stigma types by summing responses to stigma-specific survey items, and then categorized scores as low, moderate, or high.

The primary outcome was self-reported lifetime interruption of antiretroviral therapy, defined as ever having interrupted or stopped treatment. Of the 2,064 participants with complete data on this outcome, 456 individuals, or 22.1 percent, reported a lifetime interruption. This figure is striking in a country that has made enormous strides in expanding access to treatment, and it underscores the gap between the availability of medication and the consistent use of it. Interrupted therapy carries direct virological consequences: lapses in adherence allow viral replication to resume, driving viral load up, weakening immune recovery, increasing the risk of onward transmission, and creating conditions under which drug resistance can emerge.

To quantify the relationship between stigma and interruption, the researchers used Poisson regression with robust variance estimation, an approach well suited to common binary outcomes because it yields adjusted prevalence ratios that are directly interpretable as relative measures of risk. The models adjusted for potential confounders and compared each level of stigma against the low-stigma reference category. The results were consistent in direction across all three stigma domains. Moderate levels of internalized stigma were associated with a more than doubling of the prevalence of treatment interruption, with an adjusted prevalence ratio of 2.20, while high internalized stigma carried an adjusted prevalence ratio of 2.59, both statistically significant with confidence intervals comfortably excluding the null value.

The strongest signal, however, belonged to anticipated stigma in healthcare settings. Participants reporting anticipated healthcare-related stigma had an adjusted prevalence ratio of 4.09 for treatment interruption, meaning that, on average, the prevalence of interruption was roughly four times higher among those who expected discrimination from health workers compared with those who did not. Experienced healthcare-related stigma also doubled the prevalence of interruption, with an adjusted prevalence ratio of 2.16. The magnitude of the anticipated stigma estimate is the study’s most consequential finding, because it suggests that the fear of mistreatment, even before any actual mistreatment occurs, is enough to keep people away from the clinics and pharmacies where their medication is dispensed.

A central design question of the study was whether these relationships differed across the adult lifespan. Young people living with HIV face a disproportionate burden of new infections and consistently report high levels of stigma, which has led many programs to assume that stigma operates most powerfully on the young. The researchers therefore treated age as an effect measure modifier and stratified the analysis into three groups: adults aged 18 to 34, those aged 35 to 49, and those aged 50 and older. The stratified results showed that the associations between stigma and treatment interruption were generally consistent across age groups, with the single exception of moderate internalized stigma among participants above 50 years of age, where the pattern differed from the other strata.

Crucially, formal statistical interaction tests provided no evidence of effect measure modification by age for any of the three stigma measures. In epidemiological terms, this means the data do not support the idea that stigma drives treatment interruption only, or primarily, among younger adults. Older adults in the study were similarly vulnerable, and the authors conclude that stigma is significantly associated with HIV treatment outcomes across all age groups in Kenya. For program designers, this is an important corrective: interventions to reduce stigma cannot be confined to adolescent- and youth-friendly services but must address the clinical environments that people of all ages navigate.

The study’s authors argue that these findings reveal sustained challenges in achieving the consistent treatment uptake required for long-term viral suppression, a cornerstone of both individual health and population-level epidemic control under the UNAIDS treatment targets. They also point out that measurement of specific types of stigma remains limited in Kenya, which has constrained the ability of programs to target interventions precisely. The pattern of results, with anticipated stigma showing the strongest association, suggests that efforts should focus on the clinical encounter itself. The researchers highlight tailored approaches such as toolkits designed for healthcare providers to reduce healthcare-related stigmas, arguing that such tools may represent a critical component of optimizing HIV treatment programs in the country.

Like all observational, cross-sectional research, the study cannot establish temporality, since stigma and interruption were both measured at a single point in time and interruption was reported over a lifetime. Self-reported outcomes are also subject to recall and disclosure biases, although the community-led Stigma Index methodology is specifically intended to mitigate underreporting. Nevertheless, the size of the enrolled sample, its coverage of rural and urban settings across eight regions, and the consistency of associations across three distinct stigma constructs lend considerable weight to the conclusions. As Kenya and other high-burden countries pursue the final miles of epidemic control, this study makes clear that viral suppression is decided not only in laboratories and pharmacies but in the daily judgments of people weighing whether the clinic will treat them with dignity.

Subject of Research: The association between HIV-related stigma and antiretroviral therapy interruption among adults in Kenya

Article Title: Assessing the relationship between HIV-related stigma and antiretroviral therapy interruption among older and younger adults in Kenya

Article References: Mi, Y., Lyons, C., Turpin, G., Dunaway, K., Brion, S., Kibunja, P., Onyango, D., Otwoma, N., Oketch, B., Looze, P., Chiu, F., Anoubissi, J., Syarif, O., Baral, S., & Rao, A. (2026). Assessing the relationship between HIV-related stigma and antiretroviral therapy interruption among older and younger adults in Kenya. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14397-x

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14397-x

Keywords: HIV, antiretroviral therapy, stigma, Kenya, treatment interruption, internalized stigma, healthcare stigma, anticipated stigma, Stigma Index 2.0, viral suppression, epidemiology, BMC Infectious Diseases

The research, conducted in rhesus macaques infected with simian immunodeficiency virus, examined the consequence of administering an inhibitor of BCL-2 at the same time antiretroviral therapy was begun. BCL-2 is the founding member of a family of proteins that govern the intrinsic pathway of apoptosis, the programmed death machinery residing in the mitochondria of every nucleated cell. These proteins operate through a delicate balance: pro-survival members such as BCL-2, BCL-XL and MCL-1 sequester pro-apoptotic effectors like BAX and BAK, keeping the mitochondrial outer membrane intact. When the balance tips — through cellular stress, growth-factor withdrawal, or pharmacological inhibition — the effectors oligomerize, the membrane permeabilizes, and cytochrome c is released, committing the cell irreversibly to death. Lymphoid cells, and in particular long-lived memory T cells, depend heavily on BCL-2 for their extended lifespan, which is precisely why the latent reservoir exploits this pathway to survive the years of treatment that follow infection.

The rationale for the intervention rests on a conceptual reframing of the reservoir problem. Latency-reversing approaches attempt to shock the virus out of hiding and rely on the immune system or viral cytopathic effects to destroy the cells that harbor it. The BCL-2 strategy instead attacks the survival advantage of the infected cells themselves, arguing that if a latently infected cell can be nudged across the apoptotic threshold while the patient’s cells are protected from ongoing infection by ART, the intact reservoir should contract without the need for viral reactivation. This idea draws on clinical experience from oncology, where selective BCL-2 inhibitors such as venetoclax have transformed the treatment of chronic lymphocytic leukemia by triggering apoptosis in malignant lymphocytes that overexpress the protein. Repurposing that pharmacology for HIV cure research has long been proposed in model systems, but rigorous in vivo evidence that the approach works against the intact reservoir, in a setting that faithfully recapitulates human infection, had been lacking.

In the macaque study, animals infected with SIV received antiretroviral therapy accompanied by BCL-2 inhibition beginning at the time of treatment initiation, while control animals received ART alone. The investigators then tracked the composition of the reservoir over the course of suppression using quantitative methods capable of distinguishing intact proviruses from defective ones — an essential technical distinction, since measures that count all proviral DNA or rely solely on replication-competence assays can be dominated by defective genomes that pose no clinical threat. Single-genome sequencing approaches, in which viral genomes are amplified and analyzed individually, allow researchers to categorize each provirus as genetically intact or defective and to estimate the true size of the replication-competent reservoir. It is this intact-reservoir metric that predicts how long rebound would take after treatment interruption and that any realistic cure strategy must reduce.

The results demonstrated that the combined regimen reduced the frequency of intact SIV proviruses to a greater degree than ART alone. This finding carries significance well beyond the raw numbers. In the standard macaque model of ART suppression, the intact reservoir decays slowly and incompletely, mirroring the stubborn persistence observed in treated people living with HIV. An intervention applied at the start of therapy that accelerates this decay suggests that early intervention — the period in which the reservoir is being seeded and consolidated — represents a window of vulnerability that has been underexploited. Cells harboring latent virus during this period may be especially dependent on BCL-2-mediated survival, perhaps because they belong to recently activated, cytokine-dependent lineages that have not yet achieved the deep quiescence of long-term memory cells, or because the perturbation of the cellular environment by treatment initiation renders them more sensitive to apoptotic priming.

Timing is a theme that recurs throughout the reservoir literature, and the placement of BCL-2 inhibition at therapy initiation rather than during established suppression is one of the study’s most consequential design choices. A large body of observational work in humans has shown that the size of the reservoir is strongly determined by how quickly ART is started after infection; treatment during acute infection produces a smaller reservoir that, in rare cases, permits sustained remission after analytic treatment interruption, as famously demonstrated in the Mississippi child and a cohort of post-treatment controllers. The macaque data now suggest that pharmacological manipulation of cell-survival pathways can augment that early-treatment advantage. By pairing BCL-2 inhibition with the first days of ART, the intervention may eliminate infected cells at a stage when the reservoir is most dynamic and most chemically vulnerable, before proviruses disperse into the heterogeneous, long-lived populations that make later cure attempts so difficult.

The mechanistic logic of the approach also deserves attention. Unlike broadly neutralizing antibodies or therapeutic vaccines, which act on the viral side of the host-pathogen interface, BCL-2 inhibitors modulate host biology, raising the specter of on-target toxicity: excessive apoptosis of bystander lymphocytes, immunosuppression, or hematologic complications. The anti-apoptotic family is redundant, with different members protecting different cell lineages, and selective inhibition of BCL-2 alone is generally tolerated in leukemia patients, where the drug’s therapeutic window has been mapped in detail. Nevertheless, translating a cancer dosing schedule to an infectious-disease indication in otherwise healthy carriers requires careful attention to CD4+ and CD8+ T cell counts, neutrophil dynamics, and the possibility of transient cytokine release from dying cells. The macaque model, with its close immunological correspondence to humans and its validated SIV challenge system, provides the appropriate preclinical platform for establishing that window, and the observed reduction of the intact reservoir without catastrophic loss of immune competence represents an encouraging early signal.

Broader implications extend to the architecture of cure strategies as a whole. The field has converged on the view that no single intervention will eradicate the reservoir; combination regimens — pairing a reservoir-reduction modality with an immune effector such as broadly neutralizing antibodies, and a means of protecting uninfected cells such as long-acting antiretrovirals — are widely considered necessary. A BCL-2-directed agent could plausibly occupy the reduction slot in such combinations, working synergistically with latency-reversal approaches by first shrinking the intact pool and then rendering residual infected cells more susceptible to immune clearance. The study also reinforces a growing appreciation that the intracellular death machinery is a legitimate pharmacological target in virology, opening a search for other host-survival dependencies — metabolic, epigenetic, or signaling-based — that latently infected cells might share and that could be exploited with existing drugs.

Substantial questions remain before any human application. The durability of the reduction, its reproducibility across animals with different reservoir sizes and infection timelines, the effect of delaying inhibition until after prolonged suppression, and the interaction with viral rebound dynamics all require further investigation. Human reservoir biology differs from the macaque model in heterogeneity and scale, and the intact reservoir in chronically infected adults is orders of magnitude larger than in early-treated cases, which may limit what a survival-pathway intervention can achieve late in disease. Yet the study’s core contribution is conceptual as much as empirical: it shows in a rigorous animal model that the intact reservoir — not merely the total proviral burden — can be attacked by targeting the host determinants of cellular longevity, and that treatment initiation offers a pharmacologically exploitable moment to do so. As cure research matures beyond proof-of-concept latency reversal, strategies of this kind may help define a realistic path toward functional remission, in which residual virus is so scarce and so fragile that antiretroviral therapy can be safely suspended for extended periods.

Subject of Research: BCL-2 inhibition combined with antiretroviral therapy to reduce the intact simian immunodeficiency virus reservoir in macaques

Article Title: BCL-2 inhibition at antiretroviral therapy initiation reduces the intact SIV reservoir in macaques

Article References: Wiche Salinas, T. R., Harper, J., Deleage, C., Nguyen, K., Auger, J., Flores, H. R., Kaushik, S. R., Wilkes, A. C., Stammen, R. L., Wood, J. S., Easley, K. A., Nelson, S., Tharp, G. K., Bosinger, S. E., Cottrell, M. L., Kose, E., Immonen, T. T., Lifson, J. D., Laird, G. M., … Paiardini, M. (2026). BCL-2 inhibition at antiretroviral therapy initiation reduces the intact SIV reservoir in macaques. Nature Microbiology. https://doi.org/10.1038/s41564-026-02464-7

Image Credits: AI Generated

DOI: 10.1038/s41564-026-02464-7

Keywords: HIV cure, SIV, viral reservoir, BCL-2, apoptosis, antiretroviral therapy, latency, CD4+ T cells, macaques, provirus, treatment interruption, Nature Microbiology