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Background:  Interactions between host and pathogen determine the natural history of infectious diseases. Characteristics of HIV may impact rates of CD4 lymphocyte decline over time and influence the potential for CD4 regeneration with antiretroviral therapy (ARV).

Methods:  Patients who initiated highly active antiretroviral therapy (HAART) and achieved long-term viral suppression (HIV RNA < 400 copies/mL) after 12 months were identified from clinical databases at Duke University Medical Center, the University of North Carolina, and the University of Texas-Southwestern. The study population consisted of 109 ARV-naïve patients initiating antiretroviral therapy: 71 males, 37 females (gender not recorded for one patient); 66 African Americans, 28 whites, 12 Hispanics, and 3 other. The mean age was 40 years (range 19 to 69). Pretreatment baseline (BL)-stored serum samples collected 0 to 3 months prior to HAART initiation were analyzed for the presence of phenotypic resistance and HIV replication capacity (RC) using a single-cycle pseudo-typed virus construct (ViroLogic modified PhenoSense assay). Multiple linear regression (SAS v8.2) was used to examine relationships between demographics, viral replication, and CD4 counts. HAART regimens used were non-nucleoside reverse tramnsciptase (RT) inhibitor, 56%; protease inhibitor , 37%; and triple nucleoside RT inhibitor, 7%. The median BL CD4 count was 186 cells/mm³ (range 3 to 1066), and the median BL VL was 75,729 copies RNA/mL (range 400 to >750,000)

Results:  All patients achieved suppression of HIV RNA to below 400 copies RNA/mL after 12 months of therapy. BL RC and viral load were independently associated with a lower BL CD4 count. In a model adjusting for both variables, for every increase of 1log₁₀ in HIV RNA viral load, BL CD4 tended to be 97 cells/mm³ lower (p  = 0.001), and for every increase of 1 unit (percentage) in the RC, BL CD4 count tended to be 1.13 cells/mm³ lower

(p = 0.021).

Conclusions:  These data suggest that more advanced HIV is associated with both the quantity of viral replication and the fitness of the virus, as measured by the RC assay. RC appears to measure an intrinsic viral characteristic influencing HIV-1 disease progression independently of the magnitude of viral load.

Keywords: Replication Capacity; CD4 count; Progression