“A single viral load measurement collected six months after initiating ART [antiretroviral therapy] remains highly informative regarding the risk of death over 10 years,” write the authors.
The aim of ART is rapid and sustained suppression of viral load to below the limit of detection (between 50 to 20 copies/ml depending on testing assay). Treatment guidelines suggest that viral load should be undetectable six months after the initiation of treatment. Newer antiretroviral drug combinations, especially those containing an integrase inhibitor, suppress viral load more rapidly.
Ongoing low-level viral replication despite therapy is associated with the emergence of drug-resistant virus, causing treatment failure and an increase in the risk of HIV- and non-HIV-related illnesses. Small increases in viral load once complete suppression has been achieved, above the limit of detection on occasional tests, so-called viral load `blips`, do not predict treatment failure and are not problematic. This study looked at the failure of treatment to achieve viral suppression after six months.
Analysing viral load measurements taken six months after ART initiation, a team of US investigators sought to determine the level of low-level viraemia (up to 1000 copies/ml) which was associated with an increased risk of all-cause mortality over ten years.
Their study population consisted of approximately 8000 adults who initiated ART between 1998 and 2014. Study participants were followed until death or for up to ten years.
Median age at baseline was 40 years; 83% of participants were male; 62% were in the men who have sex with men risk group; 45% were white and 12% reported ever injecting drugs. The median pre-ART viral load was 75,000 copies/ml and the median year of ART initiation was 2007. Approximately a third of people had been diagnosed with AIDS before starting treatment.
The median period of follow-up was 6.2 years, during which time there were 863 deaths.
Over half (57%) of viral load measurements six months after starting therapy were below 20 copies/ml, with 15% measured at 1000 copies/ml or higher.
As expected, compared to a viral load below 20 copies/ml, a viral load above 999 copies/ml was strongly associated with an increased risk of all-cause mortality over ten years (HR = 1.96; 95% CI, 1.56-2.46). A slightly increased risk of mortality was discernible at a viral load as low as 130 copies/ml (HR = 1.39; 95% CI, 1.02-1.88).
“While we observed an increased hazard of death with low-level viral loads, discernible at 130 copies/ml,” write the authors, “this association was largely driven by the elevated mortality risk experienced by patients with viral load between 400 and 999 copies/ml.”
The average ten-year mortality risk for people with a viral load below 20 copies/ml was 13%, similar to the 14% risk observed in individuals with a viral load between 20 and 400 copies/ml. The ten-year mortality risk was 20% for people with a viral load between 400 and 999 copies/ml, comparable to the 23% risk for people with a viral load of 1000 copies/ml or higher.
“Low-level viral loads between 400 and 999 copies/ml shortly after starting ART appear to place patients at a significantly higher 10-year risk of death than patients with viral loads under 20 copies/ml, and occurrences of viral loads in this range may need to be treated similarly as viral load that exceed 1000 copies/ml,” conclude the authors. “Given the importance of rapidly achieving virologic suppression after initiating treatment, further investigation of the causes of unsuppressed viral loads between 400 and 999 copies/ml is warranted.”
The authors suggest that incomplete viral suppression six months after starting treatment may be a marker for several problems. Apart from lack of adherence to treatment or poor retention in care, incomplete viral suppression might be a consequence of undetected drug resistance, or of drug-drug interactions that lead to low levels of antiretroviral drugs. Planning in advance to prevent these problems from undermining treatment, and prompt investigation of any problems, are likely to improve the chances of viral suppression.