An Evaluation to Determine the Strongest CD4 Count Covariates during HIV Disease Progression in Women in South Africa

INTRODUCTION: Past endeavours to deal with the obstacle of expensive Cluster of Difference 4 (CD4(+)) count diagnostics in resource-limited settings have left a long trail of suggested continuous CD4(+) count clinical covariates that turned out to be a potentially important integral part of the human immunodeficiency virus (HIV) treatment process during disease progression. However, an evaluation to determine the strongest candidates among these CD4(+) count covariates has not been well documented. METHODS: The Centre for the AIDS Programme of Research in South Africa (CAPRISA) initially enrolled HIV-negative (phase 1) patients into different study cohorts. The patients who seroconverted (237) during follow-up care were enrolled again into a post-HIV infection cohort where they were further followed up with weekly to fortnightly visits up to 3 months (phase 2: acute infection), monthly visits from 3–12 months (phase 3: early infection) and quarterly visits thereafter (phase 4: established infection) until antiretroviral therapy (ART) initiation (phase 5). The CD4(+) count and 46 covariates were repeatedly measured at each phase of the HIV disease progression. A multilevel partial least squares approach was applied as a variable reduction technique to determine the strongest CD4(+) count covariates. RESULTS: Only 18 of the 46 investigated clinical attributes were the strongest CD4(+) count covariates and the top 8 were positively and independently associated with the CD4(+) count. Besides the confirmatory lymphocytes, these were basophils, albumin, haematocrit, alkaline phosphatase (ALP), mean corpuscular volume (MCV), platelets, potassium and monocytes. Overall, electrolytes, proteins and red blood cells were the dominant categories for the strongest covariates. CONCLUSION: Only a few of the many previously suggested continuous CD4(+) count clinical covariates showed the potential to become an important integral part of the treatment process. Prolonging the pre-treatment period of the HIV disease progression by effectively incorporating and managing the covariates for long-term influence on the CD4(+) cell response has the potential to delay challenges associated with ART side effects. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40121-019-0235-4) contains supplementary material, which is available to authorized users.