Different degree of immune recovery using antiretroviral regimens with protease inhibitors or non-nucleosides

Background Protease inhibitors (PI) produce significant immune recovery in most HIV-infected persons, although toxicity and high pill burden often limit this benefit. Combinations including non-nucleoside reverse transcriptase inhibitors (NNRTI) result in similar virological success, but data on immune reconstitution are scarce. Methods Baseline plasma viraemia and CD4 cell counts were recorded from 100 patients who began two nucleoside analogue reverse transcriptase inhibitors plus either one PI or one NNRTI in a case-control study [indinavir (82%) and nevirapine (80%), respectively, were most frequently prescribed]. Only patients with baseline CD4 cell counts < 500 × 106 cells/l, good treatment adherence and plasma HIV RNA < 50 copies/ml sustained for 1 year were recruited. Results A rapid CD4 cell gain occurred within 12 weeks on therapy (average 41.8 × 106 cells/l per month), irrespective of treatment. In contrast, a trend towards a better CD4 cell gain was noticed between 12 and 48 weeks with a PI (mean CD4 cell increases per month: 15.2 × 106 cells/l using PI and 10.4 × 106 cells/l using NNRTI). During this period, the difference between therapy with a PI and a NNRTI reached statistical significance for subjects with baseline CD4 counts < 300 × 106 cells/l (17.1 × 106 and 6.4 × 106 cells/l, respectively;P < 0.05). Conclusion A rapid CD4 cell increase occurred shortly after beginning antiretroviral therapy using either PI or NNRTI. Late increases in CD4 cell counts, mostly owing to newly produced cells rather than redistribution, are more pronounced in therapy using a PI, especially in subjects with lower initial CD4 cell counts.