Ten-year all-cause mortality proved similar -- at around 20% -- in HIV-positive people with a viral load measure of 400 to 999 copies/mL and in those with 1,000 to 4 million copies/mL six months after antiretroviral therapy (ART) began. Researchers believe this finding affirms the importance of rapid viral suppression after initiation of ART.
Although modern antiretroviral regimens have markedly improved viral load measures over the last decade, some people with HIV remain unable to reach or maintain an undetectable viral load on standard assays. Several studies suggest that a low but detectable viral load heightens the chances of clinical decline. However, the impact of low-level viremia on mortality remains unclear, and the existence of a "safe" low level has not been established.
To address these issues, U.S. Center for AIDS Research Network of Integrated Clinical Systems (CNICS) researchers aimed to see whether they could define a clinically meaningful threshold of detectable viral load below 1,000 copies/mL with a single viral load measure at six months after initiation of ART. CNICS is a multicenter cohort of HIV-positive people at least 18 years old who began primary HIV care in 1995 or later. The CNICS team prospectively records clinical data including viral load measure and antiretrovirals taken. This analysis included only people who started three or more antiretrovirals at a CNICS clinic between Jan. 1, 1998 and Dec. 31, 2013, and who survived the first six months of treatment. Everyone had a viral load measure approximately six months after starting ART.
The investigators confirmed death from any cause by checking the National Death Index and state death certificates, thereby including deaths of patients no longer being seen at a CNICS clinic. The researchers used a Cox proportional hazards model to estimate hazard ratios for 10-year mortality starting six months after initiation of ART.
The analysis focused on 7,944 CNICS patients with a median age of 40 years six months after they started ART. Most participants (83%) were men, 62% men who have sex with men, 45% white and 37% black. Participants initiated ART at a median start year of 2007 and at a median viral load measure of 74,827 copies/mL. Follow-up continued for a median of 6.2 years, during which time 862 people (11%) died. Six months after treatment began, 4,545 people (57%) had a viral load measure below 20 copies/mL, 2,184 (27%) had a viral load measure between 20 and 999 copies/mL, and 1,215 (15%) had a viral load measure above 999 copies/mL.
A six-month viral load measure above 999 copies/mL virtually doubled the risk of 10-year mortality (standardized hazard ratio [sHR] 1.96, 95% confidence interval [CI] 1.56 to 2.46). The analysis could not discern a precise viral load cutoff between 30 and 500 copies/mL that predicted substantially increased 10-year mortality, but higher sHR for death became discernible at 130 copies/mL (sHR 1.39, 95% CI 1.02 to 1.88).
Standardized risk of 10-year mortality was nearly the same in people with a six-month viral load measure below 20 copies/mL and in those with a six-month viral load measure between 20 and 400 copies/mL (13% and 14%). Among patients with 400 to 999 copies/mL after six months on ART, standardized risk of death was 20%, a result comparable with the risk in patients with a six-month viral load measure of 999 to 4 million copies/mL (23%).
The CNICS team believes their findings show "a clear pattern of increasing 10-year mortality risk with increasing viral load, based on one viral load measurement under 1,000 copies/mL after [six] months of therapy." They propose that a six-month viral load measure between 400 and 999 copies/mL suggests partial response to treatment and "may need to be treated similarly [to] viral loads that exceed 1,000 copies/mL."
Mark Mascolini writes about HIV infection.