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Implications of Poor CD4 Recovery During HIV Suppressive ART in Sub-Saharan Africa
Marieke E. de Pundert1, Tamara Sonia Boender1, Raph L. Hamers1, Kim Sigaloff1, Cissy M. Kityo2, Alani S. Akanmu3, Maureen Wellington4, Tobias F. Rinke de WIt1, Pascale Ondoa1
1 Amsterdam Institute for Global Health and Development, Brasschaat, Belgium. 2 Joint Clinical Research Centre Kampala, Kampala, Uganda. 3 Lagos University Teaching Hospital, Lagos, Nigeria. 4 Newlands Clinic, Harare, Zimbabwe.
Background: Achieving undetectable plasma viral load (VL) on antiretroviral therapy (ART) is not always accompanied by the recovery of CD4 count. This study evaluates determinants, clinical outcomes and time trends of poor CD4 recovery in patients receiving suppressive ART in the Pan-African Studies to Evaluate Resistance Monitoring (PASER-M) cohort.
Methods: In 2585 patients with pre-ART CD4<200 cells/µL VL<50 RNA c/mL, poor CD4 recovery was defined as CD4<200 or gain <100 cells/µL at month 12, and CD4<350 or gain <100 cells/µL at month 24. Determinants were assessed using logistic regression. Clinical outcome beyond 12 months was assessed using logistic regression and Kaplan-Meier analysis. Positive predictive value (PPV) was used to determine the (change in) predictive capacity of CD4 count to identify virological failure using WHO-recommended immunological criteria, at month 12, 24 and 36.
Results: At month 12, risk factors were older age ≥40 (OR=2.38, 95%CI1.45-3.90), nevirapine (OR=1.52, 95% CI1.05-2.22), and lower pre-ART CD4 count per 50 cells/µL stage (OR=0.65, 95%CI 0.59-0.72). At month 24, these factors were male sex (OR=1.61, 95%CI1.12-2.31), AIDS at ART initiation (OR=0.46, CI 95%0.25-0.84), and poor CD4 recovery at month 12 (OR=9.45, CI95% 6.33-14.10). Determinants of persistent poor CD4 recovery, at both month 12 and 24, were older age (OR=3.90, CI95%1.45-10.49), lower pre-ART CD4 count (OR=0.74, CI95%0.63-0.87) and AIDS at ART initiation (OR=0.36, CI95%0.15-0.89). Poor CD4 recovery at month 12 was associated with a significantly higher risk of HIV-related mortality between month 12 and 24 (OR=3.78, CI95%1.26-11.41). Proportions of poor CD4 recovery remained stable during the follow-up period (between 12.8 and 19.8%), with persistently low predictive capacity of WHO-defined immunological criteria on virological failure throughout the observation period (PPV= 16%, 34% and 37% at month 12, 24 and 36).
Conclusions: Early ART initiation prevents the occurrence of adverse clinical outcomes in the face of undetectable VL. Proportions of poor CD4 recovery do not decrease over time, suggesting that risk factors for poor CD4 recovery that were not present at baseline may emerge in the course of the treatment. Routine VL monitoring is warranted to reliably identify virological failure during early and long-term response to ART. CD4 count might carry important information on clinical outcome during suppressive ART.