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AbstractIt is not fully elucidated whether patients who receive antiretroviral therapy (ART) can maintain continued CD4 count increases. Previous studies suggested a plateau 2–4 years after treatment initiation. We aimed to characterize the evolution of CD4 counts in HIV-infected individuals receiving long-term suppressive ART, by performing a retrospective study of patients who maintained viral suppression (HIV RNA <400 copies/ml) for ≥5 years. We used linear regression models to determine for each individual whether the CD4 count continued to increase or plateau. Furthermore, we estimated whether the slope of the CD4 count for each individual became zero, which we defined as the CD4 set-point. We assessed factors associated with continued CD4 count rise, reaching a CD4 set-point and time to the CD4 set-point. Fifty-nine patients were included. The median baseline CD4 count was 238 (IQR, 120–360) cells/μl and the median duration on ART was 7.6 (IQR, 5.9–9.3) years. On ART, CD4 count continued to increase in 37 subjects (63%). Significant predictors of continued CD4 count increase included a lower baseline log10HIV RNA (OR, 0.35; 95% CI, 0.14–0.89; p= 0.026) and a shorter duration on ART (OR, 0.65; 95% CI, 0.47–0.91; p= 0.021). Twenty-four (41%) subjects reached a set-point after a median 4.3 (IQR 1.8–6.4) years on ART. A lower baseline CD4 percentage was associated with both a longer time to reach the CD4 set-point and a lower CD4 count at the CD4 set-point. These findings suggest that CD4 count may continue to increase in some patients after several years of ART. Our results point to an advantage to commencing ART at higher CD4+T cell strata. These data should be considered when estimating the optimal time to initiate ART. [ABSTRACT FROM AUTHOR]

AbstractDarunavir is the most recently licensed protease inhibitor currently used in treatment-experienced HIV-infected individuals. Our objective was to determine darunavir concentrations in cerebrospinal fluid (CSF) and plasma in subjects receiving antiretroviral treatment regimens containing ritonavir-boosted darunavir. Darunavir concentrations were determined by liquid chromatography tandem mass spectrometry in 14 paired CSF and plasma samples from eight HIV-1-infected individuals. The lower limit of quantification was 5.0 ng/ml. All of the 14 CSF samples had detectable darunavir concentrations with a median darunavir concentration of 34.2 ng/ml (range 15.9–212.0 ng/ml). The median (range) plasma darunavir concentration was 3930 (1800–12900) ng/ml. All CSF samples had detectable darunavir concentrations. Most of them exceeded or were in the same range as levels needed to inhibit replication of wild type virus, making it probable that darunavir, at least to some extent, contributes to the suppression of HIV replication in the central nervous system. [ABSTRACT FROM AUTHOR]