antiretroviral therapy

Overview

Antiretroviral therapy (ART) is the standard treatment for human immunodeficiency virus infection: combinations of drugs that block distinct stages of the viral life cycle. Combination is not a matter of added potency but of necessity — HIV's reverse transcriptase is error-prone and its replication rate enormous, so any single agent selects a resistant variant within weeks, while simultaneous blockade at several steps requires more mutations than the virus can readily accumulate. The classes are nucleoside and nucleotide reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, and integrase strand transfer inhibitors, the last — exemplified by dolutegravir — now anchoring most regimens worldwide for their potency, tolerability and high barrier to resistance. Suppressing plasma HIV RNA below detection prevents progressive immunodeficiency, protects against opportunistic infection, and blocks sexual transmission entirely, the finding behind "undetectable equals untransmittable". The same drugs given to uninfected people at risk work as pre-exposure prophylaxis.

ART has turned a uniformly fatal disease into a chronic condition with near-normal life expectancy when suppression is maintained — the qualification that matters, since benefit depends on sustained adherence, and interruption brings both viral rebound and the risk of resistance. Long-acting injectable regimens given every one or two months address exactly that constraint.

What ART does not do is cure. Provirus integrates into the host genome of long-lived CD4+ T cells, including CD4+ effector memory T cells, within days of infection, and this reservoir is transcriptionally silent, invisible to immune surveillance and untouched by drugs that act only on replication — so rebound follows interruption within weeks. Chronic immune activation persists despite suppression, driven partly by residual antigen, microbial translocation and coinfection, raising inflammatory markers such as C-reactive protein (CRP) and dysregulating the Mechanistic target of rapamycin (mTOR) pathway, and linking treated HIV infection to accelerated aging, cardiometabolic disease and neurological injury. These residual pathologies, along with weight gain seen with integrase inhibitors, define the frontier of current research and motivate work toward functional cure and ART-free remission.

Recent Publications Summary

These recent publications treat antiretroviral therapy less as a pharmacological question than as a delivery and adherence problem, with most work situated in high-burden settings. A retrospective cohort across five provincial referral hospitals in Sierra Leone followed 1544 adults initiating ART between 2020 and 2024 and found substantial attrition: 550 patients (35.6%) were lost to follow-up, defined as ≥90 days without a documented clinical encounter or ART refill, against 55.2% retained in care, 4.1% transferred and 5.0% died, giving an LTFU incidence of 9.57 per 100 person-years (95% CI 8.78 to 10.37) over 5748.6 person-years of observation 42498473Jul. Countering that attrition, a randomised controlled trial in China evaluated 6-month multi-month dispensing as a differentiated service delivery model for clinically stable people living with HIV, assessing both retention and costs on the premise that fewer clinic visits reduce waiting time and travel burden 42339560Jun. Upstream of retention, programmatic data from eight African countries described how HIV self-testing has been folded into national testing strategies and how coverage, test positivity and linkage to ART have evolved 42051152Apr, while a population-level analysis of British Columbia's provincial drug treatment programme characterised ART utilisation trends from 2014 to 2024 and forecast near-term shifts in regimen distribution 42055616Apr.

A second cluster examines what erodes adherence at the individual and contextual level. A 2023 national NCDs/HIV survey in Zambia linked alcohol consumption and tobacco smoking to decreased ART adherence, framed against the 95-95-95 targets 42284276Jun. A cross-sectional study of pregnant women living with HIV in Uganda looked at stigma, food insecurity and limited social support not as separate exposures but as co-occurring factors that jointly shape nonadherence during pregnancy, when adherence also governs prevention of vertical transmission 42044489Apr. A multimodal qualitative protocol in Kenya, grounded in Social-Ecological and "Broken Windows" theory, is designed to examine how transportation barriers and perceived neighbourhood disorder influence ART adherence self-efficacy and HIV care engagement in a low- and middle-income setting 42082219May.

Digital and pharmacist-led interventions address the same adherence gap through different routes. The Living in the Face of Trauma intervention was adapted into an iOS- and Android-native app for violence-affected people living with HIV, combining daily diary-triggered coping skill recommendations, self-guided psychoeducational sessions and a customisable geofencing function, with ART adherence positioned as a downstream endpoint of better in-the-moment stress management; the study reported on acceptability, feasibility and user experience 42360924Jun. In parallel, the Lu Dedoo Project used a human-centered design framework to adapt the MASI adherence app — originally built for South Africa — for adolescents and young adults living with HIV in Benue State, Nigeria, ahead of pilot testing 42213746May. On the inpatient side, a multicenter retrospective chart review across six community hospitals evaluated pharmacist-led antiretroviral stewardship against ART-related medication errors, defined as incomplete regimens, inappropriate or absent opportunistic infection prophylaxis, incorrect renal dose adjustments, or unaddressed drug–drug interactions — extending a model previously studied mainly in tertiary and quaternary centres 41689280Feb.

Biological and modelling work focuses on early treatment and the reservoir. A randomised controlled trial protocol at a tertiary infectious disease hospital in Beijing will test pegylated interferon-α combined with ART in acute HIV infection, on the rationale that the reservoir is established early and that the antiviral and immunomodulatory properties of Peg-IFN-α may enhance reservoir clearance and immune reconstitution 42392622Jul. A separate study measured neurofilament light chain, glial fibrillary acidic protein and soluble TREM2 in cerebrospinal fluid collected before ART during acute infection and at post-ART visits up to five years, assessing both the degree of neuroaxonal injury in neuroasymptomatic acute HIV infection and the neuroprotective effect of immediately initiated therapy 41254882Nov. Complementing these, a within-host HIV dynamics model incorporated a Beddington-DeAngelis incidence term, logistic CD4+ T-cell growth, and a cure rate representing ART efficacy or intrinsic immune clearance alongside explicit cytotoxic T-lymphocyte and antibody responses; the authors derived the basic reproduction number as a sharp threshold, established existence and uniqueness of disease-free and endemic equilibria, and proved global asymptotic stability of the endemic equilibrium via a Lyapunov function 42191796May.

What Changes, What Holds

1. Retention is now as central to ART impact as pharmacology -- NEW DIRECTION -- The Sierra Leone cohort and the service-delivery studies move ART understanding beyond drug choice alone: in high-burden settings, the limiting factor is often whether people can stay engaged long enough for suppression to matter. That does not alter the baseline efficacy story, but it does show that real-world ART success is constrained by loss to follow-up, visit burden, and program design, with retention and differentiated delivery becoming core determinants of outcome 42498473Jul42339560Jun.

2. Adherence is shaped by social and behavioral context more than by regimen alone -- NEW DIRECTION -- The Zambia, Uganda, and Kenya studies extend ART from a biomedical intervention to one whose effectiveness is strongly mediated by alcohol use, smoking, stigma, food insecurity, social support, transport, and neighborhood conditions. The baseline already notes chronic HIV morbidity despite suppression; these findings add that suppression itself is often undermined by contextual barriers that are not solved by better drugs, especially in pregnancy where adherence also affects vertical transmission 42284276Jun42044489Apr.

3. Digital and pharmacist-led tools are becoming part of ART delivery, not just adherence aids -- METHOD -- The app adaptations and stewardship review do not revise what ART does, but they change how it is operationalized: adherence support is being embedded in mobile, geofenced, and user-centered platforms, while inpatient ART safety is being managed through pharmacist-led review of prescribing errors. These are implementation advances rather than new biological claims, and they sharpen the baseline’s emphasis on ART as a long-term management system that depends on reliable delivery 42360924Jun41689280Feb.

4. Very early treatment may be needed to influence reservoir formation and neuroinjury -- NEW DIRECTION -- The acute-infection protocol and cerebrospinal-fluid biomarker study push against any implicit assumption that starting ART after diagnosis is equally sufficient for all downstream outcomes. The baseline says ART suppresses replication but does not cure because reservoirs persist; these papers suggest that the timing of initiation may determine how much reservoir seeding and neuroaxonal injury can be prevented, making early treatment a distinct therapeutic objective rather than only a faster route to suppression 42392622Jul41254882Nov.

Overview update candidates: retention and differentiated service delivery as major determinants of ART success; contextual and behavioral drivers of nonadherence; the importance of very early ART for reservoir and neuroprotection.