Abstract
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.
Highlights
We did several sensitivity analyses in which we considered alternative definitions of first viral rebound with the following modifications: not counting treatment interruption as a rebound; censoring follow-up at the date of treatment interruption instead of defining it as viral rebound; including loss to follow-up as a component of the viral rebound endpoint; defining viral rebound as the first of two consecutive viral load measurements of more than 200 copies per mL, including treatment interruption; and without censoring follow-up when a gap in viral load measurements of more than 12 months occurred
Black African heterosexual men Black African heterosexual women Men who have sex with men Non-black heterosexual men and women Injectable drug users Unknown Women pregnant at start of antiretroviral therapy (ART) Starting regimen type Non-nucleoside reverse transcriptase inhibitor based Ritonavir-boosted protease inhibitor based Unboosted protease inhibitor Nucleoside or nucleotide-only Calendar year of start of ART 1998–99 2000–01 2002–03 2004–05 2006–07 2008–09 2010–11 2012–13 Pre-ART viral load* 51–500 501–5000 5001–20 000 20 001–100 000 100 001–500 000 >500 000 Pre-ART HIV viral load* Pre-ART CD4 count† Time from baseline‡ to end of follow-up
In agreement with other studies, we found that older age[15,16] and later calendar year[13,20] at start of ART were associated with a reduced risk of viral rebound
Summary
The goal of antiretroviral therapy (ART) for people infected with HIV is to achieve and maintain continuous maximal virological suppression to allow immune recon stitution, minimise the risk of resistance emergence,[1,2,3,4] prevent HIV-related morbidity and mortality, and to prevent transmission.[1,2,3,4,5,6,7,8,9] Most people starting treatment achieve virological suppression within around 3–6 months.[10,11,12] Rates of viral rebound have decreased over the years and the risk of rebound decreases with increasing duration of viral suppression.[13,14,15,16,17] current regimens seem to be durably effective, the extent to which people living with HIV will be able to sustain sufficient adherence to maintain viral suppression on ART in the long term is unknown. No study that we could identify has investigated the factors associated with the rate of viral rebound and used such findings to project rates of viral rebound over a lifetime or calculated the implied probability of requiring only one ART regimen in a lifetime. With the number of people on ART worldw ide approaching 20 million, this information is of public health significance worldwide
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