Three generic nevirapine-based antiretroviral treatments in Chinese HIV/AIDS patients: multicentric observation cohort

Abstract

Background: The purpose of this study was to evaluate the efficacy and safety of three nevirapine-based antiretroviral treatments for adult antiretroviral-naïve Chinese patients with HIV-1 infection.

Methodology: This was a prospective, multicenter study. 198 antiretroviral-naïve HIV-1 positive subjects with CD4 lymphocyte counts between 100/ul and 350/ul and plasma HIV-1 RNA levels more than 500 copies/ml were randomized to start three NVP-based antiretroviral treatments: group A, NVP+AZT+ddI; group B, NVP+3TC+d4T; group C, NVP+AZT+3TC. Viral responses, immunologic responses, adverse events and drug resistance were monitored at baseline and the end of week 4, 12, 24, 36, 52. Viralogical response and immunological response were also compared in different strata of baseline CD4 T lymphocyte counts and plasma HIV-1 RNA concentrations. At baseline, the plasma HIV-1 RNA was 4.44+/-0.68, 4.52+/-0.71 and 4.41+/-0.63 lg copies/ml in group A, B and C respectively (p = 0.628). At the end of the study, the plasma viral load reached 2.54+/-1.11, 1.89+/-0.46 and 1.92+/-0.58 lg copies/ml in group A, B and C respectively (p<0.001). At week 52, suppression of plasma HIV-1 RNA to less than 50 copies/ml was achieved in more patients in group B and C than in group A (68.2%, 69% vs. 39.7%; p<0.001). In planned subgroup analyses, the decrease of viral response rate was seen in group A when CD4 cell count >200/ul (subgroup H). But in subgroup L, viral response rate of three groups has no significant statistic difference. There were no statistically significant differences among three groups in immunological response within any of the CD4 or pVL strata. 3 out of 193 patients with available genotype at baseline showed primary drug resistant. Of 26 patients with virologic failure, 17 patients showed secondary drug resistant, 16 subjects in group A and 1 subject in group B. Logistic regression analysis indicated that presence of hepatotoxicity was associated with HCV-Ab positive (OR = 2.096, 95%CI: 1.106-3.973, P = 0.023) and higher CD4 baseline (CD4 count >250/ul) (OR = 2.096, 95%CI: 1.07-4.107, P = 0.031).

Conclusion: Our findings strongly support the use of 3TC+d4T and 3TC+AZT as the nucleoside analogue combination in NVP-based antiretroviral therapy. The regimen of AZT+ddI+NVP produced poor virological response especially in the stratum of CD4 count more than 200/ul. More patients showed secondary drug resistant in this arm too. Patients with HCV-Ab+ and CD4 count >250/ul appear to have significantly high risk of hepatoxicity.

Trial registration: ClinicalTrials.gov NCT00618176.

Figure 1. Disposition of patients (AZT, zidovudine; ddI, didanosine; NVP, nevirapine; 3TC, lamivudine; d4T, stavudine)

Figure 2. The plasma VL of three treatment groups.

According to an analysis based on the intention-to-treat analysis (a) and actual treat analysis (b).P value is calculated by comparing the plasma VL of three groups.

Figure 3. Percentage of patients with plasma VL of <50 copies/ml and <400 copies/ul at week 52.

According to an analysis based on the intention-to-treat analysis (a, c) and actual tren\atment analysis (b, d). P values are calculated by pair wise comparing the viral response rate of two groups at week 52.

Figure 4. The increase of mean CD4+T cell count in three therapy group during HAART.

According to an analysis based on the intention-to-treat analysis (a) and actual treat analysis (b). P value is calculated by comparing the CD4+ T cell count of three groups.