Long‐term therapy with nevirapine and tropism

Abstract

Objective

A more potent effect on the residual viraemia was ascribed to nevirapine (NVP) with respect to other antiretroviral drugs; moreover a selection of X4 strains was described in patients (pts) with undetectable viraemia; our aim was to study viro‐immunological parameters and tropism for co‐receptor in pts on a long term successful therapy with NVP.

Methods

14 pts on HAART from 130 months (GL, median value, range 118–156 months) without occurrence of blips, as assessable with the available methods at that time, were retrospectively selected from a single center cohort (Bolzano). Tropism for V3 was determined by population sequencing on blood, and using geno2pheno algorithm; cellular HIV DNA load was analysed by in‐house Real‐Time. A further eighteen months (mo) follow up was then observed. Data were compared with those obtained from a control group of 50 naïve pts (GS), evaluated after a 36‐mo successful therapy (median, range 12–84) with various drug combinations, with median baseline (BL) CD4 of 50/μl, comparable value with the GL cohort.

Results

In 7 pts a R5‐tropic (GLR5, FPR median 84.8%) and in 7 an X4‐tropic strain (GLX4, FPR median 1.1%) was demonstrated. BL data of GLR5 were 46 y old, CD4 54/l, HIV‐RNA 104,000 cps/ml; HAART from 142 mo, with NVP from 125 (one after 70 mo on NVP switched to protease from 57); at follow up CD4 were 679/l, HIV‐DNA 60 cps/106 PBMCs (range<5–252). GLX4 were 46 y, at BL 38 CD4/l, HIV‐RNA 250,000 cps/ml; in HAART from 121 mo, with NVP from 97; at follow up CD4 902/l, HIV‐DNA 60 cps/106 PBMCs (range<5–225). Six out of seven pts of the two groups were on treatment with abacavir+lamivudine (ABC+3TC) and one with tenofovir+emtricitabine. In the subsequent 18 mo four blips were observed (21–71 cps/ml); the backbone was changed to raltegravir in two GLR5 and one GLX4 for convenience. In the 50 GS pts at follow up an X4 strain was found in 50% of 14 efavirenz‐treated, in 16% of 6 NVP, and 63% of 30 protease.

Discussion

In a group of very long‐term treated pts with NVP plus two NRTI (ABC+3TC in 12 out of 14), a tropism for CXCR4 was demonstrated in 50%, without significant differences in the CD4 gain and in the HIV‐DNA load archived in the peripheral blood. With respect to pts on various therapies from a median of 36 mo, the type of archived virus does not seem to have a role on the outcome of a very long therapy, 130 mo, with NVP+ABC+3TC; this therapy does not seem able to select a special tropism in pts.