Background Despite receipt of combination antiretroviral therapy (cART) and subsequent viral suppression some 15–30% of treated HIV infected patients fail to achieve optimal CD4 T-cell reconstitution. Sub-optimal CD4 recovery has been associated with unfavourable outcomes for patients on cART. We assessed markers of immune activation, microbial translocation and patient baseline characteristics for associations with sub-optimal CD4 T-cell recovery post cART initiation.

Methods This was a retrospective case control analysis of CD4 T-cell recovery from a completed (2002–2007) clinical trial, the Adult Antiretroviral Treatment and Drug Resistance (“Tshepo”) Trial, in Gaborone, Botswana. Cases (sub-optimal CD4 response) were defined as CD4 ≤ 200 cells/µl at 12 months post ART initiation, with virologic suppression achieved within 6 months. Microbial translocation (sCD14) and immune activation (interferon-gamma) markers were quantified using Enzyme Linked Immuno-Sorbent Assays on a subset of 30 cases and 30 controls gender matched baseline and 12 month plasma samples. Univariate and logistic regression analysis were used to assess predictors of sub-optimal CD4 T-cell recovery.

Results Fifty-one cases (21%) from 249 virologically suppressed patients had sub-optimal CD4 recovery. The median age was 33.39 years and 69.9% were female. Baseline CD4 count < 100cells, haemoglobin and aspartate transaminase were associated with sub-optimal CD4 recovery (adjusted OR (aOR) = 3.03 95% CI [1.65, 5.57], p < 0.001; aOR = 0.81 [0.67, 0.99], p = 0.038 and aOR = 1.03 [1.00, 1.05], respectively). sCD14 levels were significantly different between cases and controls, p = 0.0011, at 12 months. Baseline Tuberculosis infection, body-mass-index, interferon-gamma, alanine transaminase and age were not associated with poor CD4 T-cell response.

Conclusion Low baseline CD4 T-cell count, haemoglobin, aspartate transaminase and sCD14 levels are predictive of suboptimal CD4 T-cell recovery in this cohort of HIV-1 subtype C infected patients. These markers are potentially useful in identifying patients who need frequent clinical monitoring to minimise unfavourable outcomes associated with poor CD4 T-cell recovery.