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Background: The extent of short-term CD4(+) T-cell recovery in patients tolerating first-line highly active antiretroviral therapy (HAART) and attaining undetectable HIV RNA levels is inadequately defined., Methods: We retrospectively analysed patients in four Italian cohorts who started HAART between January 1996 and September 2006. All patients had known HCV coinfection status, did not modify the regimen for 6 months and had <50 HIV RNA copies/ml at the end of the sixth month., Results: The analysis involved 1,488 patients (1,096 males, 73.7%) with a median age of 43 years (interquartile range [IQR] 39-49); 435 (29.2%) were positive for HCV, 71 (4.8%) were positive for hepatitis B surface antigen (HBsAg) and 76 (5.1%) had experienced a previous AIDS-defining event. At baseline, patient CD4(+) T-cell counts were 226 cells/microl (IQR 99-332), CD4(+) T-cell percentages were 14.7% (IQR 8.7-21.2) and HIV RNA levels were 4.91 log(10) copies/ml (IQR 4.38-5.34). Overall, 24-week CD4(+) T-cell recovery was 144 cells/microl (IQR 70-240). At multivariable analysis, T-cell recovery was positively related to the use of a boosted protease inhibitor (P<0.0001) or thymidine analogues (P<0.0001), baseline HIV RNA levels (P<0.0001), the baseline percentage of CD4(+) T-cells (P<0.0001) and the absence of HCV coinfection (P=0.006). Age, gender, baseline CD4(+)/CD8(+) T-cell ratio and a history of AIDS-defining events had no independent effect on CD4(+) T-cell recovery., Conclusions: Among HIV-infected patients tolerating first-line HAART and with undetectable HIV RNA after 6 months, CD4(+) T-cell recovery is significantly greater in those without HCV coinfection, with a high baseline viral load, a high baseline percentage of CD4(+) T-cells and in those treated with a boosted protease inhibitor.

The prevalence of lipodystrophy in an HIV-infected population and the risk factors associated with body shape changes were analysed in this study. Five hundred and four subjects were included. Among these, 201 (39.9%) had features of lipodystrophy syndrome (cases); 303 (60.1%) constituted the control group. Compared with the control group, the lipodystrophy subjects were different in age (P = 0.01); duration of antiretroviral therapy (P < 0.001); length of exposure to nucleoside reverse transcriptase inhibitors (NRTIs) (P < 0.001) and to protease inhibitors (P < 0.001); nadir of CD4 cell count (P < 0.001); and value of plasma HIV-RNA before antiretroviral therapy (P = 0.008). In a multivariate analysis, length of therapy and a nadir CD4 cell count below 250 cell/microl were associated with an increased risk of lipodystrophy. Among patients with lipodystrophy, isolated fat loss was observed in 46 (23%); isolated fat accumulation in 40 (20%); mixed (loss and accumulation) syndrome in 50 (25%); and isolated metabolic changes in 65 (32%). Subjects with morphological alterations displayed a greater cumulative time of exposure to NRTIs and to protease inhibitors than patients with isolated metabolic alterations. Patients with lipoatrophy had had a greater exposure to stavudine.

Objective: To characterize the antiviral effect and tolerability of higher dose (HD, 600 mg two times daily) and lower dose (LD, 400 mg two times daily) combination regimens of ritonavir and saquinavir in British Columbia (BC), Canada., Design: Intent-to-treat analysis with suppression of plasma viral load to levels below 500 copies/ml as the main outcome measure., Patients: Adult human immunodeficiency virus (HIV)-positive individuals in the province of British Columbia prescribed ritonavir and saquinavir in combination between 1 September 1996 and 30 June 1997, with a minimum of two plasma viral loads, one at baseline and one after the initiation of therapy., Results: A total of 84 participants [27 HD (32%) and 57 LD (68%)] were prescribed ritonavir and saquinavir. There was no difference at baseline in the two groups with respect to age (P=0.466), CD4 cell count (P=0.373) and baseline plasma viral load (P=0.656). However, LD were more likely to have had prior protease experience than HD participants (65 versus 40%, P=0.037). The median follow-up time was 9 months. A total of 44 (52%) subjects demonstrated a decrease in plasma viral load to levels <500 copies/ml. After adjusting for length of follow-up, baseline CD4 cell count and prior AIDS diagnosis, HD participants were as likely to be suppressed to <500 copies/ml as LD individuals (P=0.760). HD participants did report more adverse effects (P=0.042) than LD subjects., Conclusion: Our results provide confirmatory evidence that lower doses of ritonavir and saquinavir in combination are better tolerated and as effective as the standard doses of these drugs. This response, however, is seriously compromised by prior exposure to protease inhibitors.