Background:  CD4 cell recovery in patients with continuous suppression of plasma HIV-1 viral load is highly variable. We investigated factors predictive for suboptimal CD4 increase in patients with sustained viral load suppression.

Methods:  All treatment-naive patients in the Swiss HIV Cohort Study starting combination ART (cART) with at least 2 subsequent viral load and CD4 measurements were included, and patients with 2 suppressed viral load (<50 copies/mL) at least 3 months apart and within 12 months after starting cART were identified. We studied CD4 cell count dynamics for these patients until viral rebound (viral load >400 copies/mL) or as long as 5 years subdivided into 3 periods of suppression:  year 1, years 2 to 3, and years 4 to 5. Multiple median regression with adjustment for multiple CD4 measurements within patient with a cluster bootstrap was used to study the dependence of the CD4 slopes on time-updated clinical covariates and drug classes.

Results:  Of 2860 patients starting cART, 1816 (63%) reached viral load suppression. Median CD4 count increases in suppressed patients were 87, 52, and 19 cells/μL and year in the 3 periods, ie, 1, 2 to 3, and 4 to 5 years. In the multivariate model, over the 5-year observation period median CD4 increase was significantly higher in females (p <0.001), patients with lower age (p = 0.002), higher viral load at start of cART (p <0.001), but lower in patients with CD4 cell count ≥650 cells/μL at start of the period (p = 0.014) and in those gaining more CD4 cells in the preceding period or from start of cART to first viral suppression for the year-1 period (p <0.001). Patients on non-nucleoside reverse transcriptase inhibitor (NNRTI) -based cART showed a lower CD4 increase compared to boosted protease inhibitor (PI) (p = 0.043) and there was a trend toward lower increases for patients on triple NRTI (p = 0.077). Other cART classes did not significantly differ. Patients with tenofovir as part of the regimen did significantly worse than patients on stavudine (p = 0.015); the median CD4 change per year was between –39 and  –44 cells/μL lower during the 3 periods and there was a trend toward lower CD4 changes for patients on zidovudine/lamivudine (p = 0.0504). The negative influence of tenofovir cannot be explained by concurrent administration of didanosine alone as a sensitivity analysis excluding these patients did not change the results.

Conclusions:  In patients with sustained viral load suppression age, gender, high viral load at start of cART, and CD4 cells <650/μL was associated with higher CD4 cell increase, whereas NNRTI-based cART and tenofovir were associated with lower CD4 cell increase.