Mean CD4 cell count changes in patients failing a first-line antiretroviral therapy in resource-limited settings

Calmy, Alexandra; Balestre, Eric; Bonnet, Fabrice; Boulle, Andrew; Sprinz, Eduardo; Wood, Robin; Delaporte, Eric; Messou, Eugène; McIntyre, James; El Filali, Kamal Marhoum; Schechter, Mauro; Kumarasamy, N; Bangsberg, David; McPhail, Patrick; Van Der Borght, Stefaan; Zala, Carlos; Egger, Matthias; Thiébaut, Rodolphe; Dabis, François and T-LINC of IeDEA Collaboration (Asia South America East Southe, (2012). Mean CD4 cell count changes in patients failing a first-line antiretroviral therapy in resource-limited settings. BMC infectious diseases, 12, p. 147. London: BioMed Central 10.1186/1471-2334-12-147

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Background

Changes in CD4 cell counts are poorly documented in individuals with low or moderate-level viremia while on antiretroviral treatment (ART) in resource-limited settings. We assessed the impact of on-going HIV-RNA replication on CD4 cell count slopes in patients treated with a first-line combination ART.
Method

Naïve patients on a first-line ART regimen with at least two measures of HIV-RNA available after ART initiation were included in the study. The relationships between mean CD4 cell count change and HIV-RNA at 6 and 12 months after ART initiation (M6 and M12) were assessed by linear mixed models adjusted for gender, age, clinical stage and year of starting ART.
Results

3,338 patients were included (14 cohorts, 64% female) and the group had the following characteristics: a median follow-up time of 1.6 years, a median age of 34 years, and a median CD4 cell count at ART initiation of 107 cells/μL. All patients with suppressed HIV-RNA at M12 had a continuous increase in CD4 cell count up to 18 months after treatment initiation. By contrast, any degree of HIV-RNA replication both at M6 and M12 was associated with a flat or a decreasing CD4 cell count slope. Multivariable analysis using HIV-RNA thresholds of 10,000 and 5,000 copies confirmed the significant effect of HIV-RNA on CD4 cell counts both at M6 and M12.
Conclusion

In routinely monitored patients on an NNRTI-based first-line ART, on-going low-level HIV-RNA replication was associated with a poor immune outcome in patients who had detectable levels of the virus after one year of ART.

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