HIV-positive patients who do not experience both an increase in their CD4 cell count and a fall in their viral load to undetectable levels soon after starting antiretroviral therapy are more likely to develop an AIDS-defining illness or die than patients who have increases in their CD4 cell count and an undetectable viral load, according to a US study published in the April 15th edition of the Journal of Acquired Immune Deficiency Syndromes.
Antiretroviral therapy can mean a longer and healthier life for HIV-positive individuals. The aim of anti-HIV treatment is to suppress viral load to undetectable levels (the lower limit of detection is 50 copies/ml in the tests used in most clinics), and this allows an increase in CD4 cell count. It is possible to predict the long-term benefits of antiretroviral therapy by looking at viral load and CD4 cell count three to nine months after anti-HIV therapy has been started.
About 20% - 40% of patients starting antiretroviral therapy have what is called a “discordant response.” This means that their viral load falls to undetectable levels, but their CD4 cell count does not increase, or, their CD4 cell count increases but their viral load fails to become undetectable.
Investigators in the US wanted to see if patients who had a discordant response to treatment had an increased risk of experiencing HIV disease progression or death. They also wanted to see if any particular groups of patients had an increased risk of experiencing a discordant treatment response.
Doctors at the University of Alabama therefore looked at the medical records of 404 patients starting antiretroviral therapy for the first time since 1995. The majority of these patients (51%) were non-white, 76% were men, 51% became infected with HIV through sex with another man, and the mean age was 38 years.
When anti-HIV treatment was initiated, mean CD4 cell count was 213 cells/mm3 and mean viral load was 250,000 copies/ml.
Approximately six months after starting anti-HIV treatment, 71% of patients had experienced both a fall in their viral load to undetectable levels and an increase in their CD4 cell count. In all, 5% of patients had neither an undetectable viral load nor an increase in their CD4 cell count. A significant proportion of patients had a discordant response, with 9% achieving an undetectable viral load but no increase in their CD4 cell count and 16% an increase in their CD4 cell count without an undetectable viral load.
During a median of 38 months of follow-up, 35 (9%) patients developed a new AIDS-defining opportunistic infection and 25 (6%) died.
Unsurprisingly, statistical analysis showed that patients who had both a fall in their viral load to undetectable levels and an increase in their CD4 cell count had the lowest risk of disease progression, and that patients with neither of these outcomes had the highest risk of a new opportunistic infection or death.
Further analysis showed that compared to patients with both an immunological and virological response to treatment, patients with a discordant response to treatment were 2.24 times more likely to experience disease progression (95% CI: 1.3 – 4.), and patients with neither an undetectable viral load nor an increase in their CD4 cell count were 4.83 times more likely to develop a new opportunistic infection or die (95% CI: 2.1 – 11.1).
Non-white race was the only patient characteristic with a significant association with either no response to treatment (odds ratio = 6.5; 95% CI: 1.7 – 24.7) or a discordant response to treatment (failure to suppress viral load, but increase in CD4 cell count, OR = 2.83; 95% CI: 1.5 – 5.5).
The investigators call for further research to identify why non-whites are less likely to have an early response to antiretroviral therapy.
Tan R et al. Clinical outcome of HIV-infected antiretroviral-naïve patients with discordant immunologic and virologic responses to highly active antiretroviral therapy. J Acquir Immune Defic Syndr 47: 553 – 558, 2008.