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Open Access Research article

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

Alexandra Calmy119*, Eric Balestre23, Fabrice Bonnet234, Andrew Boulle5, Eduardo Sprinz6, Robin Wood7, Eric Delaporte8, Eugène Messou9, James McIntyre10, Kamal Marhoum El Filali11, Mauro Schechter12, N Kumarasamy13, David Bangsberg14, Patrick McPhail15, Stefaan Van Der Borght16, Carlos Zala17, Matthias Egger18, Rodolphe Thiébaut23, François Dabis23 and for the ART-LINC of IeDEA Collaboration (Asia, South America, East, Southern and West Africa)

Author affiliations

1 HIV Unit, Geneva University Hospital, Geneva, Switzerland

2 Univ. Bordeaux, ISPED, Centre Inserm U897- Epidemiologie-Biostatistique, F-33000, Bordeaux, France

3 INSERM, ISPED, Centre Inserm U897- Epidemiologie-Biostatistique, F-33000, Bordeaux, France

4 Service de Médecine Interne et Maladies Infectieuses, Centre Hospitalier Universitaire (CHU), Bordeaux, France

5 School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa

6 South Brazil HIV Cohort, Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil

7 Gugulethu ART Programme, Gugulethu, South Africa

8 Institut de Recherche et de Développement (IRD), Montpellier, France

9 Centre de Prise en Charge, de Recherche et de Formation sur le VIH/SIDA (CePReF), Abidjan, Côte d’Ivoire

10 Perinatal HIV Research Unit, Operational Research on ART (OPERA), Soweto, South Africa

11 Service des Maladies Infectieuses, Hôpital Ibn Rochd, Casablanca, Maroc

12 Rio HIV Cohort, Rio de Janeiro, Brazil

13 YRG Centre for AIDS Research and Education, Chennai, India

14 Immune Suppression Syndrome Clinic (ISS), Mbarara, Uganda

15 Helen Joseph Hospital Themba Lethu Clinic, Johannesburg, South Africa

16 Heineken International Health Affairs, Amsterdam, Netherlands

17 Prospective Evaluation in the Use and Monitoring of Antiretrovirals in Argentina (PUMA), Buenos Aires, Argentina

18 Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland

19 4 rue Gabrielle Perret Gentil, Geneva University Hospital, 1211, Geneva 4, Switzerland

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Citation and License

BMC Infectious Diseases 2012, 12:147  doi:10.1186/1471-2334-12-147

Published: 28 June 2012

Abstract

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.

Keywords:
HIV-1; CD4 count; CD4 slope; HIV-RNA threshold; Resource limited settings