PREDICTIVE FACTORS INFLUENCING PEAK VIRAL LOAD DROP IN RESPONSE TO NUCLEOSIDE REVERSE-TRANSCRIPTASE INHIBITOR-5 IN ANTIRETROVIRAL-NAIVE HIV-1-INFECTED PATIENTS

Therapy with two nucleoside reverse transcriptase inhibitors (NRTI), t he backbone of triple combinations, is still widely used in early stag es of HIV-1 disease. However, factors influencing virologic response n eed to be further analyzed, to test the hypothesis that the reduction of plasma RNA viremia with NRTI may be greater in patients with higher baseline viral load (BVL) and to analyze the predictive factors of vi ral load drop below detection (200 HIV RNA copies/ml of plasma). Selec ted for the study were 169 HIV-l-infected antiretroviral therapy-naive patients with CD4(+) T-lymphocyte counts ranging from 6 to 1040/mu l coming from three randomized studies comparing the efficacy of monothe rapy (zidovudine [ZDV], 250 mg every 12 hours; N = 40) versus two-drug therapy consisting of ZDV (250 mg every 12 hours) with dideoxycytidin e (ddC, 0.75 mg every 8 hours) or didanosine (ddI, 200 mg every 12 hou rs; N = 129). Viral load was measured at 1, 3, and 6 months by polymer ase chain reaction (PCR). A linear regression model was used to analyz e the relation between BVL and the peak reduction of plasma RNA viremi a. The variables included in a logistic regression model to determine the likelihood of VLs dropping below detection levels were age, gender , risk group for HIV-I infection, baseline CD4(+) lymphocyte count, BV L, clinical status (AIDS versus non-AIDS), HIV-1 phenotype (syncytium- inducing [SI] versus non-syncytium-inducing [NSI]) and type of treatme nt (monotherapy versus double therapy). The peak reduction of VL was r elated to baseline level following a linear model in both monotherapy and double-therapy regimens. In the subgroup of patients treated with two NRTIs, the regression line that fitted best with the data was log, , (peak reduction) = 1.8-0.36 log(10) (BVL) (F = 23.5; p < .0001). Thi s indicates that for every increase of 1 log(10) of BVL, the peak redu ction would be of 0.64 log(10) greater. Forty-nine (29%) of the 169 pa tients dropped to <200 copies/ml. The likelihood of dropping below det ection level was significantly greater in those receiving double thera py versus monotherapy (odds ratio [OR] = 16.1; 95% confidence interval [CI], 2-128), in those with baseline CD4(+) lymphocyte count >350/mu l (OR = 2.28; 95% CI, 1.1-4.9) and in those with BVL <10,000 HIV-I RNA copies/ml (OR = 2.25; 95% CI, 1.1-6.1). None of the 13 patients with an SI phenotype at baseline dropped below detection levels. The reduct ion of VL in response to two NRTIs was greater in those patients with a higher level of BVL. In conclusion, peak reduction below detection i n response to NRTI can be predicted and is associated with double ther apy, with a baseline CD4+ cell count >350/mu l and with a BVL <10,000 RNA copies/ml.