SummaryBackgroundThe length of time that people with HIV on antiretroviral therapy (ART) with viral load suppression will be able to continue before developing viral rebound is unknown. We aimed to investigate the rate of first viral rebound in people that have achieved initial suppression with ART, to determine factors associated with viral rebound, and to use these estimates to predict long-term durability of viral suppression.MethodsThe UK Collaborative HIV Cohort (UK CHIC) Study is an ongoing multicentre cohort study that brings together in a standardised format data on people with HIV attending clinics around the UK. We included participants who started ART with three or more drugs and who had achieved viral suppression (≤50 copies per mL) by 9 months after the start of ART (baseline). Viral rebound was defined as the first single viral load of more than 200 copies per mL or treatment interruption (for ≥1 month). We investigated factors associated with viral rebound with Poisson regression. These results were used to calculate the rate of viral rebound according to several key factors, including age, calendar year at start of ART, and time since baseline.ResultsOf the 16 101 people included, 4519 had a first viral rebound over 58 038 person-years (7·8 per 100 person-years, 95% CI 7·6–8·0). Of the 4519 viral rebounds, 3105 (69%) were defined by measurement of a single viral load of more than 200 copies per mL, and 1414 (31%) by a documented treatment interruption. The rate of first viral rebound declined substantially over time until 7 years from baseline. The other factors associated with viral rebound were current age at follow-up and calendar year at ART initiation (p<0·0001) and HIV risk group (p<0·0001); higher pre-ART CD4 count (p=0·0008) and pre-ART viral load (p=0·0003) were associated with viral rebound in the multivariate analysis only. For 1322 (29%) of the 3105 people with observed viral rebound, the next viral load value after rebound was 50 copies per mL or less with no regimen change. For HIV-positive men who have sex with men, our estimates suggest that the probability of first viral rebound reaches a plateau of 1·4% per year after 45 years of age, and 1·0% when accounting for the fact that 29% of viral rebounds are temporary elevations.InterpretationA substantial proportion of people on ART will not have viral rebound over their lifetime, which has implications for people with HIV and the planning of future drug development.FundingUK Medical Research Council.

Objectives:To compare rates of all-cause, liver-related, and AIDS-related mortality among individuals who are HIV-monoinfected with those coinfected with HIV and hepatitis B (HBV) and/or hepatitis C (HCV) viruses.Design:An ongoing observational cohort study collating routinely collected clinical data on HIV-positive individuals attending for care at HIV treatment centres throughout the United Kingdom.Methods:Individuals were included if they had been seen for care from 2004 onwards and had tested for HBV and HCV. Crude mortality rates (all cause, liver related, and AIDS related) were calculated among HIV-monoinfected individuals and those coinfected with HIV, HBV, and/or HCV. Poisson regression was used to adjust for confounding factors, identify independent predictors of mortality, and estimate the impact of hepatitis coinfection on mortality in this cohort.Results:Among 25 486 HIV-positive individuals, with a median follow-up 4.5 years, HBV coinfection was significantly associated with increased all-cause and liver-related mortality in multivariable analyses: adjusted rate ratios (ARR) [95% confidence intervals (95% CI)] were 1.60 (1.28–2.00) and 10.42 (5.78–18.80), respectively. HCV coinfection was significantly associated with increased all-cause (ARR 1.43, 95% CI 1.15–1.76) and liver-related mortality (ARR 6.20, 95% CI 3.31–11.60). Neither HBV nor HCV coinfection were associated with increased AIDS-related mortality: ARRs (95% CI) 1.07 (0.63–1.83) and 0.40 (0.20–0.81), respectively.Conclusion:The increased rate of all-cause and liver-related mortality among hepatitis-coinfected individuals in this HIV-positive cohort highlights the need for primary prevention and access to effective hepatitis treatment for HIV-positive individuals.

We discovered a highly virulent variant of subtype-B HIV-1 in the Netherlands. One hundred nine individuals with this variant had a 0.54 to 0.74 log 10 increase (i.e., a ~3.5-fold to 5.5-fold increase) in viral load compared with, and exhibited CD4 cell decline twice as fast as, 6604 individuals with other subtype-B strains. Without treatment, advanced HIV—CD4 cell counts below 350 cells per cubic millimeter, with long-term clinical consequences—is expected to be reached, on average, 9 months after diagnosis for individuals in their thirties with this variant. Age, sex, suspected mode of transmission, and place of birth for the aforementioned 109 individuals were typical for HIV-positive people in the Netherlands, which suggests that the increased virulence is attributable to the viral strain. Genetic sequence analysis suggests that this variant arose in the 1990s from de novo mutation, not recombination, with increased transmissibility and an unfamiliar molecular mechanism of virulence.

BackgroundDespite a decline in the number of new HIV infections in the UK overall, the number and proportion of new HIV diagnoses in people aged ≥50 years continues to increase. People aged ≥50 years are disproportionately affected by late diagnosis, which is associated with poorer health outcomes, increased treatment complexity and increased healthcare costs. Late HIV diagnosis also has significant public health implications in terms of onward HIV transmission. It is not fully understood what factors affect the decision of an older person to test for HIV. The aim of this study was to identify factors associated with testing for HIV in people aged ≥50 years who tested late for HIV.MethodsWe interviewed 20 people aged ≥50 years diagnosed late with HIV to identify factors associated with HIV testing. Interviews were audio recorded, transcribed verbatim and thematically analysed.ResultsSeven themes associated with HIV testing in people aged ≥50 years were identified: experience of early HIV/AIDS campaigns, HIV knowledge, presence of symptoms and symptom attribution, risk and risk perception, generational approaches to health and sexual health, stigma, and type of testing and testing venue.ConclusionSome factors associated with testing identified in this study were unique to older individuals. People aged ≥50 years often do not perceive themselves to be at risk of HIV. Further, stigma and a lack of knowledge of how to access HIV testing suggest a need for health promotion and suggest current sexual health services may need to adapt to better meet their needs.