Nathan Ford

There are limited data on the impact of coronavirus disease 2019 (COVID-19) vaccines on mortality among people living with human immunodeficiency virus (HIV) (PLHIV) across different severe acute respiratory syndrome coronavirus 2 variants. We assessed the impact of the COVID-19 vaccine in reducing in-hospital mortality among PLHIV across various severe acute respiratory syndrome coronavirus 2 variant waves. We analyzed individual-level data from 159,150 patients hospitalized with COVID-19 across 43 countries. Flexible parametric survival models were used to estimate the association between COVID-19 vaccination and in-hospital mortality, accounting for HIV status. Among HIV-negative individuals, COVID-19 vaccination reduced the risk of in-hospital mortality by 38 to 42% across all variant waves compared to their unvaccinated counterparts. In PLHIV, the protective effect of vaccination was less pronounced. Vaccinated PLHIV exhibited higher mortality risks compared to unvaccinated HIV-negative individuals: 41% higher during the Omicron wave (adjusted hazard ratio [aHR] 1.41, 95% confidence interval [CI] 1.05–1.89) and no significant difference during the pre-Delta and Delta waves. However, vaccinated PLHIV consistently showed lower mortality risks than unvaccinated PLHIV, with mortality reductions of 60% (aHR 0.40, 95% CI 0.31–0.51) during the pre-Delta period, 50% during Delta (aHR 0.50, 95% CI 0.33–0.75), and 54% during Omicron (aHR 0.46, 95% CI 0.36–0.59). While COVID-19 vaccination significantly reduced inpatient mortality among PLHIV, mortality risks remained elevated compared to HIV-negative individuals, particularly during the Omicron variant wave. Overall, vaccination still offered substantial protection against death for PLHIV compared to unvaccinated PLHIV. These findings underscore the need for targeted vaccination strategies, including booster doses, to protect high-risk populations such as PLHIV, in alignment with World Health Organization recommendations.

Introduction: Despite increasingly widespread acceptance of the (undetectable = untransmittable) U = U concept, uncertainty remains about the implications of suppressed viral loads (detected but ≤1000 copies/ml, also often referred to as low‐level viraemia) for both sexual HIV transmission and individual patient outcomes. Discussion: There has been no documented evidence of a transmission event when the index partner had a viral load ≤ 1000 copies/ml) is negligible. The clinical implications, including drug resistance development, of persistent low‐level viraemia in people with HIV (PWH) taking dolutegravir‐containing antiretroviral therapy remains limited and relatively unknown; ongoing research and surveillance will be critical to monitor expanded scale‐up of optimized treatment. To support widespread access to treatment monitoring for all PWH, viral load testing should be expanded using any combination of available viral load technologies and sample types, as they can all support the primary objectives of understanding the viral load of PWH, for both prevention and treatment. Conclusions: PWH who have an undetectable or suppressed viral load should be celebrated and encouraged to maintain their treatment adherence and engagement in care, while ensuring that no remaining barriers exist for them to do so.

Despite increasingly widespread acceptance of the (undetectable = untransmittable) U = U concept, uncertainty remains about the implications of suppressed viral loads (detected but ≤1000 copies/ml, also often referred to as low-level viraemia) for both sexual HIV transmission and individual patient outcomes. There has been no documented evidence of a transmission event when the index partner had a viral load <200 copies/ml, suggesting zero risk of sexual transmission. Additionally, the risk of sexual transmission when the index partner is taking medication as prescribed and has a viral load that is detectable but suppressed (≤1000 copies/ml) is negligible. The clinical implications, including drug resistance development, of persistent low-level viraemia in people with HIV (PWH) taking dolutegravir-containing antiretroviral therapy remains limited and relatively unknown; ongoing research and surveillance will be critical to monitor expanded scale-up of optimized treatment. To support widespread access to treatment monitoring for all PWH, viral load testing should be expanded using any combination of available viral load technologies and sample types, as they can all support the primary objectives of understanding the viral load of PWH, for both prevention and treatment. PWH who have an undetectable or suppressed viral load should be celebrated and encouraged to maintain their treatment adherence and engagement in care, while ensuring that no remaining barriers exist for them to do so.

Introduction: People with advanced HIV disease face high risks of severe illness and death. CD4 testing enables timely diagnosis and appropriate care, yet access remains limited in many settings. This review investigated the diagnostic accuracy of the WHO clinical staging for identifying advanced HIV disease. Methods: We conducted a systematic review and meta‐analysis of studies published between 1 January 1998 and 1 May 2024 that assessed both WHO clinical staging and CD4 counts in people living with HIV aged 5 years and older (PROSPERO: CRD42024558372). We pooled sensitivity and specificity estimates of WHO Stage 3/4 for detecting advanced HIV disease (CD4 p < 0.001). In a population of 100,000 people living with HIV with 30% advanced HIV disease prevalence, WHO staging would miss 11,700 true advanced HIV disease cases and misclassify 19,600. Conclusions: WHO clinical staging alone shows low accuracy for detecting advanced HIV disease, risking both missed diagnoses and overtreatment. CD4 testing remains essential for accurately identifying and managing advanced HIV disease.

Introduction: Rwanda has initiated recency testing alongside existing HIV testing services of provider-initiated testing, partner notification services (PNSs), and of prevention of mother-to-child HIV transmission. We aimed to determine characteristics of the newly diagnosed population using a nationwide cohort. Methods: We included all newly diagnosed patients with HIV aged 15 and above who consented to recency testing and assessed patient- and health center–related predictors of recent HIV infection using multivariable logistic regression models. Results: We obtained data from 485 of 565 health facilities in Rwanda that introduced PNS and recency testing alongside preexisting testing services. From October 2018 to February 2024, 8940 individuals consented to HIV recency testing. Among them, 537 (6.0%) were recently infected. The odds of detecting a recent HIV infection increased by 1% for each month of experience in PNS. Patient-related factors associated with recent infections included female sex, younger age (15–24 years), residing in southern or northern provinces compared with the western province, and self-reported sex with a known HIV-infected person or unprotected sex outside of a relationship in the last 12 months. Conclusions: Only 6% of newly diagnosed HIV infections were characterized as recent. Public health interventions targeting younger females may assist in reducing new infections in this group.

Background: Individuals hospitalized with HIV-related complications face high post-discharge mortality and morbidity, particularly in resource-limited settings. This systematic review evaluated the impact of interventions to reduce post-hospital mortality, lower readmissions, and improve linkage to care. Methods: We searched the PubMed, Embase, and Cochrane databases up to 1 October 2024 for studies reporting outcomes of post-discharge interventions. Two independent reviewers performed study selection, extracted data, and assessed risk of bias. We pooled data using random effects meta-analysis. Results: We included 4 randomized controlled trials (conducted in Spain, South Africa, Tanzania, and the United States) and 6 observational studies (Canada, Thailand, Zambia, and the United States). Interventions included pre-discharge counseling, medication review, referral to care, and goal setting, as well as post-discharge follow-up via home visits, telephone calls, and support from social workers or community health workers. Pooled data from randomized controlled trials showed no difference between post-discharge interventions and usual care in mortality, but the estimate was imprecise (relative risk [RR], 0.98; 95% CI, .59–1.63). However, interventions may reduce readmissions (RR, 0.82; 95% CI, .52–1.30) and may slightly improve linkage/retention in care (RR, 1.10; 95% CI, .95–1.27). Observational studies reported similar results, with no mortality effect but potential reductions in readmissions (RR, 0.77; 95% CI, .48–1.25) and improved linkage/retention (RR, 1.42; 95% CI, 1.11–1.81). Interventions were largely feasible, acceptable, and low cost. Conclusions: Interventions that include pre-discharge care planning and post-discharge follow-up, such as telephone contact and home visits, may improve linkage to care and reduce readmissions. However, interventions were not associated with reduced post-discharge mortality.

Introduction: Recent studies have indicated a high enduring burden of advanced HIV disease, but estimates across regions and settings are lacking. The aim of this study was to estimate the prevalence of advanced HIV disease since 2015 among those people with CD4 measured in healthcare settings, disaggregated by age group, level of healthcare and region. Methods: We searched MedLine via Pubmed and Hinari for studies that reported the proportion of individuals with advanced HIV disease (defined as CD4 cell count 3 ) in healthcare settings since 2015; this search was complemented by conference abstracts and data from the International epidemiology Databases to Evaluate AIDS Consortium (IeDEA). We estimated pooled prevalence of advanced HIV disease using random‐effects models and performed subgroup and sensitivity analyses to explore heterogeneity. Results: We obtained data from 117 cohorts, representing 1,814,362 individuals from 52 countries across all six World Health Organization regions. The majority of studies ( n = 83) were conducted among adults and recorded CD4 cell count among treatment naïve individuals at antiretroviral therapy start ( n = 86). Studies included data reported up to 2023. The proportion of individuals with advanced HIV disease was higher in inpatient settings (44.3%, 95% CI 39.1−49.6%) compared to outpatient settings (33.5%, 95% CI 31.5−35.4%). Prevalence was similar across age groups, time since HIV diagnosis and treatment status, and highest in West and Central Africa, South‐East Asia and the Eastern Mediterranean region. Discussion: This review finds that at least a third of people presenting to healthcare settings have advanced HIV disease, with no evidence that this has changed in recent years. Screening for advanced HIV remains important to be able to direct appropriate preventive, diagnostic and therapeutic interventions to prevent progression to severe illness and death. Conclusions: This review summarizes recent evidence of the continued high proportion of individuals who (re)present to care with advanced HIV disease. These findings underscore the urgent need to reinforce programme capacity to diagnose, prevent and treat advanced HIV disease as an essential pillar of the global AIDS response.