Cerebrospinal fluid virology in people with HIV.

OBJECTIVE: Our objectives were to investigate the recent frequency of cerebrospinal fluid (CSF) HIV RNA escape and other CSF viral nucleic acid detection in people with HIV with neurological symptoms and to assess associated clinical factors. METHOD: This was a retrospective cohort analysis of people with HIV who underwent CSF examination for clinical indications between 2017 and 2022. Individuals were identified from pathology records, and clinical data were recorded. CSF HIV RNA escape was defined as CSF HIV RNA concentrations greater than in plasma. CSF viral screen included herpes simplex virus types 1 (HSV-1) and 2 (HSV-2), varicella zoster virus (VZV), Epstein Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus 6 (HHV-6) and JC virus. When cases were detected in five or more people with HIV, associated clinical factors were assessed using linear regression modelling. RESULTS: CSF HIV RNA escape was observed in 19 of 114 individuals (17%) and was associated with the presence of HIV drug resistance mutations and non-integrase strand transfer inhibitor-based antiretroviral therapy (p < 0.05 for all) when compared to people with HIV without escape. Positive viral nucleic acid testing included EBV (n = 10), VZV (3), CMV (2), HHV-6 (2) and JC virus (4). Detectable CSF EBV was not considered related to neurological symptoms and was associated with concomitant CSF infections in eight of ten individuals and with CSF pleocytosis, previous AIDS, lower nadir and current CD4 T-cell count (p < 0.05 for all). CONCLUSION: In people with HIV with neurological symptoms, the frequency of CSF HIV RNA escape remains similar to that in historical reports. Detectable EBV viral nucleic acid in the CSF was observed frequently and, in the absence of clinical manifestations, may be a consequence of CSF pleocytosis.

Adults with Perinatally Acquired HIV; Emerging Clinical Outcomes and Data Gaps.

In resourced settings, adults living with perinatally acquired HIV are approaching the 5th decade of life. Their clinical and psychological outcomes highlight potential future issues for the much larger number of adolescents growing up with HIV in sub-Saharan Africa, and will inform the development of appropriate healthcare services. Lifelong exposure to HIV, and increasingly to antiretroviral therapy throughout growth and development, contrasts with adults acquiring HIV in later life. This review describes the clinical outcomes for adults living with perinatally acquired HIV including post transition mortality, morbidity and retention in care. Rates of viral suppression, drug resistance and immunological function are explored. Co-morbidities focus on metabolic, cardiovascular, respiratory and bone health with quality-of-life data including neurocognitive functioning and mental health. Sexual and reproductive health including vaccine-preventable disease and the prevention of onward transmission to partners and infants are considered. The data gaps and future research questions to optimise outcomes for this emerging adult cohort are highlighted.

Cardiovascular health in people with perinatally acquired HIV - where do we stand?

PURPOSE OF REVIEW: HIV-associated cardiac disease was well recognized in the preantiretroviral (ART) era among children with perinatally-acquired HIV infection (PHIV). While ART has dramatically improved survival, it has become increasingly apparent that individuals with PHIV continue to experience multisystem co-morbidities. We review the cardiac and vascular manifestations in people growing up with PHIV in the ART era. RECENT FINDINGS: ART has resulted in a drop in incidence of serious cardiac morbidity. However, there is a substantial body of evidence that demonstrates that cardiac and vascular structural and functional abnormalities, mostly subclinical, are common in people with PHIV taking ART. Studies have considerable heterogeneity with respect to types of cardiovascular assessments used. HIV-mediated chronic inflammation and potentially effects of ART contribute to these abnormalities. The long-term clinical significance of these abnormalities remains unknown as studies have mainly been cross-sectional, but it is likely that the burden of cardiovascular disease will grow as individuals with PHIV age and the prevalence of traditional risk factors increases. SUMMARY: Understanding the pathogenesis of cardiovascular disease in PHIV, is critical to inform screening and interventional strategies. Longitudinal studies are also needed to understand the natural history of cardiovascular abnormalities and incidence of clinical outcomes.

A randomised control trial of BIC/F/TAF vs DRV/c/F/TAF in context of HIV test-and-treat, BicTnT.

BACKGROUND: Head-to-head data for bictegravir/emtricitabine/tenofovir alafenamide (BIC/F/TAF; B) and darunavir/cobicistat/emtricitabine/tenofovir alafenamide (DRV/c/F/TAF; D) are lacking in the context of rapid antiretroviral therapy (ART) initiation. This study, BIC-T&T, evaluates the efficacy and tolerability of B vs D in a UK test-and-treat setting. SETTING: BIC-T&T was a randomised, open-label, multi-centre, study in which participants initiated ART within 14 days after confirmed HIV-1 diagnosis before baseline laboratory. METHODS: The primary endpoint is the virological response (HIV RNA < 50copies/mL) at week 12 by time-weighted average change in log10 HIV RNA recorded in viral load assays from treatment initiation to week 12, using two-sample Wilcoxon rank-sum test. RESULTS: 36 participants were randomised: 94% were male, 53% white; mean (SD) age was 35 years (11.8). Baseline mean (±SD) log10 HIV-RNA was 4.79 (± 0.87) log10 copies/mL and CD4 505 (±253) cells/mm3. The mean (±SD) time from confirmed HIV diagnosis to ART initiation was 7.9 (± 3.7) days. The time-weighted mean decrease in log10 HIV RNA from treatment initiation to week 12 was significantly greater in B in comparison to D (3.1 vs. 2.6 log10 copies/mL, p < 0.001). Both regimens demonstrated good tolerability with infrequent laboratory abnormalities and no grade 3 or 4 adverse events. CONCLUSION: In this first head-to-head study in the context of ART initiation, HIV RNA decline from baseline to week 12 was significantly more rapid for BIC/F/TAF compared with DRV/c/F/TAF.

Mitigation strategies to safely conduct HIV treatment research in the context of COVID-19.

INTRODUCTION: The International AIDS Society convened a multidisciplinary committee of experts in December 2020 to provide guidance and key considerations for the safe and ethical management of clinical trials involving people living with HIV (PLWH) during the SARS-CoV-2 pandemic. This consultation did not discuss guidance for the design of prevention studies for people at risk of HIV acquisition, nor for the programmatic delivery of antiretroviral therapy (ART). DISCUSSION: There is strong ambition to continue with HIV research from both PLWH and the research community despite the ongoing SARS-CoV-2 pandemic. How to do this safely and justly remains a critical debate. The SARS-CoV-2 pandemic continues to be highly dynamic. It is expected that with the emergence of effective SARS-CoV-2 prevention and treatment strategies, the risk to PLWH in clinical trials will decline over time. However, with the emergence of more contagious and potentially pathogenic SARS-CoV-2 variants, the effectiveness of current prevention and treatment strategies may be compromised. Uncertainty exists about how equally SARS-CoV-2 prevention and treatment strategies will be available globally, particularly for marginalized populations, many of whom are at high risk of reduced access to ART and/or HIV disease progression. All of these factors must be taken into account when deciding on the feasibility and safety of developing and implementing HIV research. CONCLUSIONS: It can be assumed for the foreseeable future that SARS-CoV-2 will persist and continue to pose challenges to conducting clinical research in PLWH. Guidelines regarding how best to implement HIV treatment studies will evolve accordingly. The risks and benefits of performing an HIV clinical trial must be carefully evaluated in the local context on an ongoing basis. With this document, we hope to provide a broad guidance that should remain viable and relevant even as the nature of the pandemic continues to develop.

Predicting drug-induced liver injury from anti-tuberculous medications by early monitoring of liver tests.

OBJECTIVE: Tuberculosis Drug Induced Liver Injury (TB-DILI) is a common and potentially severe complication associated with anti-tuberculous treatment (ATT). Optimal liver test monitoring for standard TB medication has not been established. We describe the predictive value of pre-treatment liver tests (LTs) and at 2-weeks after initiation of ATT for the detection of TB-DILI. METHODS: Patients initiating ATT were monitored with routine LTs pre-treatment and after 2-weeks. Logistic regression models were constructed to retrospectively identify pre-treatment variables associated with 'late' TB-DILI (>2 weeks after treatment initiation) and whether pre-treatment and 2-week alanine aminotransferase (ALT) levels could predict late TB-DILI. RESULTS: 1247 patients with active tuberculosis managed at 5 sites across north west London between January 2015 and December 2018 were monitored with routine LTs. 103 cases (8.3%) of ATT-associated DILI were diagnosed. 60 cases (58.3%) of TB-DILI occurred later than 2-weeks. The risk of late TB-DILI was 2.2-fold greater for every 30 U/L increment in ALT pre-treatment (OR 2.16, 95% CI 1.38-3.29 p<0.001) and 2.1-fold greater for every 30 U/L increment in ALT gradient at 2-weeks (OR 2.06, 95% CI 1.52-2.76 p<0.001). CONCLUSION: Routine 2-week LTs capture early TB-DILI and may be valuable in predicting late TB-DILI in patients on ATT.