Most people on ART will not experience viral rebound

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British investigators have determined that a substantial proportion of people with HIV who are taking antiretroviral therapy (ART) will not experience viral rebound during their lifetime.

Using data from the UK CHIC (UK Collaborative HIV Cohort) study, an ongoing multi-centre cohort study, researchers from London set out to investigate the rate of viral rebound in individuals who have achieved initial suppression via the use of ART. The results review factors associated with viral rebound and aim to predict the long-term durability of viral suppression.

The analyses, which were based on data from the 2014 UK CHIC study update, include information about 16,101 HIV-positive individuals aged 16 years and older who received treatment at one of 21 UK-based clinical centres. The included patients all initiated ART between Jan. 1, 1998, and May 31, 2013; had at least nine months of follow-up since the start of ART; and were on ART nine months after initiation, with a most recent viral load of 50 copies/mL or lower. A total of 4,519 of the people included had a viral rebound, defined either as a single viral load of more than 200 copies/mL or a documented treatment interruption, which included no ART for a period of at least one month.

The investigators found that rates of viral rebound in the study population were generally low and declined substantially over a period of seven years, where it then plateaus. In MSM older than 45 years, the estimated plateau rate is 1.4% per year. This percentage drops further when combined with the fact that in 29% of the population, viral rebound was temporary, with their next viral load value after rebound being 50 copies/mL or less with no regimen change.

“Our work suggests that a substantial proportion of people on therapy for HIV will be able to be sufficiently adherent to their medications to keep their virus suppressed for their entire lifetime,” said Dr Andrew Phillips, a professor of epidemiology at University College London, and one of the study’s authors.

Phillips and his colleagues noted that these data are promising for patients with HIV and the individuals who treat them, and support continued adherence to testing and treatment. “Our findings support the strategy of encouraging HIV testing in people who may have acquired HIV, and therapy initiation in those found to have the virus, for personal and public health benefit,” Phillips said.

Summary
Background: The 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.
Methods: The 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.
Results: Of 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.
Interpretation: A 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.

Authors
Jemma O’Connor, Colette Smith, Fiona C Lampe, Margaret A Johnson, David R Chadwick, Mark Nelson, David Dunn, Alan Winston, Frank A Post, Caroline Sabin, Andrew N Phillips

IDSE report
The Lancet HIV abstract


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