For people living with HIV, viral rebound after starting and maintaining antiretroviral therapy (ART) is becoming far less common, according to a UK study published in The Lancet HIV.
Viral rebound, in general, is when HIV in the blood reaches persistent, detectable levels after a period of being undetectable. This can happen if HIV grows resistant to a person's drug regimen or because of poor adherence, which is why regular doctor visits and viral load tests are important. If viral rebound does occur, a switch to a different treatment regimen usually happens.
In this study, viral rebound was defined as having a viral load over 200 after being undetectable or stopping treatment for over a month. The study observed an overall viral rebound rate any time after starting successful therapy just below eight per year for every 100 individuals who are treated. Given the study's definition of viral rebound, this included viral load blips -- one-time detectable viral loads that quickly go back to undetectable, which is not considered dangerous or a sign or HIV progression or transmissibility -- so the true overall rebound rate is actually much lower.
Over the past 20 years, antiretroviral combinations have improved steadily. High proportions of people starting ART today reach and maintain an undetectable viral load. But the rate of viral rebound remained unknown until this UK analysis. British researchers conducted this study to (1) determine how often viral rebound happens after reaching an undetectable viral load on a first-line antiretroviral regimen, (2) determine factors that explain viral rebound and (3) predict long-term durability of an undetectable viral load.
UK CHIC is an ongoing study of adults in care for HIV at one of 21 centers across the UK. Researchers regularly collect health data on these people, including when they start a new antiretroviral combination and when they reach an undetectable viral load. This study focused on people who started their first antiretroviral combination between January 1998 and May 2013, were taking their combination nine months after they started and had a most-recent viral load below 50. The researchers defined a viral rebound as a single viral load above 200 or a period of stopping treatment for at least one month.
The analysis included 16,101 people who started ART and reached an undetectable viral load within nine months. The group had a median age of 37 years when they started ART, and 25% were women. Most study participants, 54%, were men who have sex with men (MSM), 26% were black African heterosexual men or women, 13% were nonblack heterosexual men or women and 2% were people who inject drugs.
During up to 15 years of follow-up, researchers counted 4,519 first viral rebounds for a rate of 7.8 per 100 person-years (meaning about eight of every 100 people had a rebound each year). While 69% of these rebounds reflected a single viral load above 200, 31% reflected at least a one-month treatment interruption. Among 2,999 people who had a viral load above 200 and a later viral load test, 46% had a later viral load below 50 without changing their antiretroviral regimen.
The viral rebound rate fell from 12.6 per 100 person-years in the first year of ART to just below six per 100 in the fifth year, to only 2.5 per 100 in years 10-15 combined, suggesting a steady decline in how often HIV rebounds the longer individuals are on treatment. The rebound rate fell 16% per year over the study period.
Statistical analysis identified two independent predictors of a lower rebound rate: older age and more recent year starting ART. Four factors independently predicted a higher rebound rate: being a black African man or woman (compared with MSM), having a higher viral load before ART and having a higher CD4 count before ART.
The researchers also estimated rebound rate per year for different subgroups, excluding temporary rebounds followed by another undetectable viral load. For a 35-year-old MSM who started ART in 2008 or later and reached a viral load below 50 within nine months of starting ART, estimated rebound rate per year was 5.8% in the first year of ART, 2.6% after four years, 1.1% after eight years and 1.0% from 11 years onward.
The investigators believe their findings "suggest that many people on ART will not have viral rebound over their lifetime." They propose that the falling rebound rate over time could mean that a person's behavior "changes over time and they become accustomed to taking antiretroviral drugs once the drugs are integrated into their everyday lifestyles." The lower rebound rate in more recent study years could reflect the lower side effect risk with new antiretrovirals and the greater convenience of taking today's once-daily single-pill combinations.