Is moderate HIV viremia associated with a higher risk of clinical progression in HIV-infected people treated with highly active antiretroviral therapy: evidence from the Italian cohort of antiretroviral-naive patients study.

OBJECTIVE: To assess the risk of clinical progression (CP) according to the duration of time spent without complete viral load (VL) suppression compared with that associated with periods of stably suppressed viremia in HIV-infected people who started highly active antiretroviral therapy (HAART) when previously naïve to antiretrovirals. DESIGN: A cohort study of patients having started HAART after enrollment in the Italian Cohort of Antiretroviral-Naive Patients (ICoNA) and being followed for at least 6 months. METHODS: Person-years spent in different categories according to the VL level and the change in VL from the most recent value before the initiation of HAART were calculated. A multivariable Poisson regression model, including potential confounders, was constructed. RESULTS: A total of 3023 patients were studied. The overall rate of CP was 13.4 per 1000 person-years. Evidence for a higher risk of CP was observed for people with a current VL >10,000 copies/mL. For each year longer spent on HAART with a VL >100,000 copies/mL, a 5-fold increased risk was observed (relative risk [RR] = 5.34, 95% confidence interval [CI]: 2.83 to 1.08; P = 0.0001). An increased risk of CP in patients with current suppression <1.5 log10 copies/mL (RR = 2.34, 95% CI: 1.16 to 4.74; P = 0.02) and in those with no suppression or a VL higher than their set point (RR = 2.39, 95% CI: 1.17 to 4.89; P = 0.02) was observed compared with those with suppression of >3 log10 copies/mL, although it was not significant. Longer duration on HAART with a VL suppressed below set point seemed to confer protection against CP. CONCLUSIONS: Virologic failure to antiretroviral drugs is common. The risk of CP may remain low despite a low but detectable level of HIV viremia.

Variability in the interpretation of transmitted genotypic HIV-1 drug resistance and prediction of virological outcomes of the initial HAART by distinct systems.

High level HIV-1 drug resistance in recently infected treatment-naive individuals correlates with sub-optimal virological responses to highly active antiretroviral therapy (HAART). To determine whether genotypic HIV-1 drug resistance in chronic naive patients, as interpreted by various systems, could predict the virological outcomes of HAART, isolates from patients enrolled in a prospective observational cohort (ICoNA) prior to treatment start were genotyped. Genotypic susceptibility scores (GSS) assigned to the initial HAART regimens using the interpretations of pre-therapy resistance mutations by 13 systems were related to virological outcomes. Of 415 patients, 42 (10%) had at least one major resistance mutation. According to the different interpretations, 1.9-20.5% of patients had some level of resistance to at least one drug in the initial regimen. In multivariable analysis, GSS from two systems significantly predicted the time to virological success: Rega 5.5, for each unit increase in GSS adjusted relative hazard (RH) 1.86 [95% confidence intervals (95% CI): 1.15-3.02] and hivresistanceWeb v3, RH 1.87 (95% CI: 1.00-3.48). With three other systems, GSS showed a trend towards a significant prediction of success: Retrogram 1.6, RH 2.33 (95% CI: 0.98-5.53), Menéndez 2002, RH 2.36 (95% CI: 0.97-5.72) and Stanford hivdb, RH 2.06 (95% CI: 0.94-4.49). Genotypic resistance testing coupled with adequate interpretation in chronic naive patients can usefully identify those at risk of sub-optimal virological response to HAART. This work was presented in part at the First European Workshop on HIV Drug Resistance. Luxembourg, 4-6 March 2003 (Abstract 44); and at the 9th European Conference on CIinical AIDS Therapy. Warsaw, 25-28 October 2003 (Abstract F6/7).

Coinfection with hepatitis viruses and outcome of initial antiretroviral regimens in previously naive HIV-infected subjects.

BACKGROUND: The effect of chronic coinfection with hepatitis viruses on the response to therapy against human immunodeficiency virus 1 (HIV-1) remains debated. METHODS: In a prospective cohort study, the effect of hepatitis B virus (HBV) and hepatitis C virus (HCV) serostatus on the outcome of potent HIV-1 therapy was analyzed in HIV-1-infected patients previously naive to antiretroviral therapy. Changes from baseline CD4+ cell counts and HIV RNA levels over time were analyzed by linear regression models. Time to clinical progression and time to reach virologic and immunologic response were analyzed by multivariate Cox proportional hazards regression models. RESULTS: We studied 1320 patients, among whom 600 were HCV antibody-positive and 90 were HBV surface antigen-positive. During a median follow-up of 37 months (range, 1-48 months), clinical progression was observed in 99 patients (56 new acquired immunodeficiency syndrome-defining events and 43 deaths). In multivariate models, HCV-positive HBV-negative patients showed a shorter time to clinical progression (hazard ratio, 1.55; 95% confidence interval, 1.00-2.41). Patients who were HCV-positive also showed mean CD4+ recoveries over time that were at least 30 cells/ micro L fewer than those of seronegative patients. Hepatitis virus serostatus did not affect the virologic response to HIV-1 therapy. CONCLUSIONS: Clinical progression of HIV-1 disease after starting potent antiretroviral therapy is accelerated by concomitant infection with HCV. Compared with patients without coinfection, coinfected patients showed impaired CD4+ cell recovery, despite similar virologic response to HIV-1 therapy. These findings may have important implications for the treatment of HCV and for the timing of initiation of HIV-1 therapy in coinfected individuals.