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O15.1 Sub-Optimal CD4 T-Cell Recovery in HIV-1 Subtype C Patients on Antiretroviral Therapy: A Search For Predictive Biomarkers and Baseline Characteristics
  1. G Retshabile1,2,
  2. E R Kisanga2,
  3. S Gaseitsiwe1,
  4. S M Moyo1,
  5. H Bussmann1,
  6. J Makhema1,
  7. M Essex3,
  8. R Marlink3,
  9. R Musonda1
  1. 1Botswana-Harvard AIDS Institute Partnership, Gaborone, Botswana
  2. 2Kilimanjaro Christian Medical University College, Moshi, Tanzania
  3. 3Dept of Immunology and Infectious Diseases, Harvard School of Public Health AIDS Institute, Boston, MA, United States

Abstract

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.

  • HAART responses
  • HIV
  • Immune activation

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