Highly active antiretroviral therapy and the management of HIV-1 infection: Can short-term changes in the plasma HIV-1 RNA levels predict long-term responses to therapy?
Individuals who are unable to achieve an undetectable plasma HIV-1 RNA level (viral load) after the initiation of highly active antiretroviral therapy (HAART) may be at an increased risk of accelerated virological rebound. The purpose of this study was to determine how the six month viral nadir in response to HAART is related to the future probability of virological rebound A non-concurrent cohort study of all HIV-infected, protease inhibitor and non-nucleoside reverse transcriptase inhibitor naive individuals initiating HAART at the HIV Outpatient Program clinic in New Orleans, LA between January 1997 and December 2000 was conducted. Patients were followed for six months in order to allow sufficient time to achieve their virological nadir. At six months, patients were classified as complete responders (undetectable viral load), incomplete responders (>400 copies/mL and ≥0.5 log10 decrease in the viral load) or non-responders (<0.5log10 decrease in the viral load). All patients were then followed to virological rebound (≥0.5 log10 increase in the viral load) or study end. Multivariate logistic and Cox proportional hazards regression were used to examine predictors of achieving an undetectable plasma HIV-1 RNA level six months after the initiation of HAART and experiencing treatment failure after the viral nadir had been achieved Of the 1755 participants included in the analyses, 76% were male, 64% non-white, 39% had a baseline CD4 cell count ≤200 cell/mm3, 58% had a baseline viral load ≤10,000 copies/mL, and 29% had prior medication experience. In multivariate analyses, individuals with the greatest degree of immune suppression were at the greatest risk of virological rebound. The prognostic significance of an intermediate response to HAART was most apparent for individuals who began HAART with a baseline plasma HIV-1 RNA level greater than 30,000 copies/mL. These individuals were 2.22 (95% C.I. 1.25, 3.93) times more likely to virological rebound than individuals who began HAART with a baseline viral load <10,000 copies/mL. Patients with incomplete responses to HAART at six months remained at a significantly greater risk of virological rebound. Intensification strategies may be warranted in this population