Clinical, Biologic, and Behavioral Predictors of Early Immunologic and Virologic Response in HIV-Infected Patients Initiating Protease Inhibitors

Abstract

Predictors of virologic (plasma HIV RNA viral load [VL] < 500 copies/ml) and immunologic (rise in CD4+ cell count > 50 cells/mm3) response after 4 months of therapy (M4) were studied in 750 HIV-1-infected patients prospectively enrolled at the initiation of a protease inhibitor (PI)-containing regimen. A virologic response was observed in 80% of patients, and an immunologic response was observed in 64%. Sixty-two percent of patients self-reported full adherence to therapy at 1 month of therapy (M1) and M4. In multivariate analysis, a virologic response was more frequent in fully adherent patients (odds ratio [OR] = 2.0; p =.001). An immunologic response was associated with age < 36 years (OR =1.4; p =.03), baseline VL (OR = 1.5 per 1 log10 copies/ml higher; p <.01), decrease in VL at M1 (OR = 1.5 per 1 log10 copies/ml decrease; p <.01), baseline total lymphocyte count (OR = 1.7 per 50% lower; p <.001), and baseline CD4+ cell percentage > or = 20% (OR =1.9; p <.001) but not with adherence to therapy. Full adherence seems to be a major predictor of a virologic response to PI-containing triple therapy. An immunologic response may be possible despite incomplete adherence, at least early in therapy.

Virologic and immunologic response to highly active antiretroviral therapy

“…Similar proportions of reduction in HIV RNA by 6 months (from 60% to 100%, depending on the level of detection of the assay) have been reported by other studies of population and clinic cohorts [8][9][10][11]. In a report combining three European cohorts, 85% had less than 500 copies/mL by 8 months, confirming these earlier findings [12].…”

“…Other treatment determinants for the rapid suppression of plasma HIV RNA may include the medication components in the initial HAART regimen. In addition to the differential effect caused by specific treatment regimens, adherence to the prescribed therapy is a key determinant in immediate and maintaining suppressed virus [8,[17][18][19]. In one study of HAART initiators, low adherence was the only significant independent predictor of nonsuppression [19].…”

“…The effects of baseline HIV RNA plasma copy number on the response to HAART, as shown by some [8,10,11], may be the result of disease stage, an uncontrollable viremia comprised of resistant subtypes, or just be related to the design of the study (short follow-up periods). The observation made by Phillips et al [12] that individuals with greater than 100,000 copies/mL took longer to reach undetectable levels (< 500 copies/mL) but were just as likely to suppress to less than 500 copies/mL by the end of the 8-month follow-up as those individuals with less virus is logical.…”

Update on the virologic and immunologic response to highly active antiretroviral therapy

“…In MACS, 50.4% of HAART initiators overall had less than 400 HIV RNA copies/mL by 3 months after HAART initiation [6•]. Similar proportions of reduction in HIV RNA by 6 months (from 60% to 100%, depending on the level of detection of the assay) have been reported by other studies of population and clinic cohorts [8][9][10][11]. In a report combining three European cohorts, 85% had less than 500 copies/mL by 8 months, confirming these earlier findings [12].…”

“…Although HIV-RNA suppression has been shown to be the main driving force for the reconstitution of the immune system (ie, an increase in CD4 cell counts), there is not 100% concordance between the two markers [4,8,9,11,[36][37][38]. Several investigators have shown that CD4 cells may increase after HAART among patients who do not fully suppress virus and that an increase in CD4 cells is not uniformly observed among viral suppressors [9,11,37,39].…”