Immunological efficacy of a prime-boost pneumococcal vaccination in HIV-infected adults.

OBJECTIVE: To evaluate whether a strategy combining a prime with a 7-valent conjugate pneumococcal vaccine (PCV) followed by a boost with the 23-valent polysaccharide vaccine (PPV) would improve immunogenicity against Streptococcus pneumoniae polysaccharides in HIV-infected patients. DESIGN: Randomized controlled phase II trial. METHODS: Two-hundred and twelve patients with CD4 cell counts of 200-500 cells/mul and HIV RNA< 4 log10 copies/ml, regardless of antiretroviral treatment, were randomized to receive either PCV at week 0 and PPV at week 4 (n = 106) or PPV alone at week 4 (n = 106). The proportion of responders to 0, 1-2, 3-4, 5-7 serotypes shared by the two vaccines was evaluated at week 8 and compared using a proportional odds model allowing for adjustment for CD4 cell count, HIV RNA and antiretroviral treatment. RESULTS: At week 8, the profile of response was better in the prime-boost group compared to the PPV group, as determined by the frequency of patients who reached both a twofold increase of serotype-specific IgG levels and IgG level >/= 1 mug/ml [proportional odds ratio (OR), 2.09; 95% confidence interval (CI), 1.25-3.51; P = 0.005]. No differences in responders were found 4 weeks after PCV or PPV alone, suggesting that PCV primed for response to PPV. Early differences between groups remained significant at week 24 (proportional OR, 2.14; 95% CI, 1.30-3.54; P = 0.003). CONCLUSIONS: In a setting of practical care, a PCV prime-PPV boost strategy enhances the frequency, breadth and magnitude of antibody responses against SPP in HIV-infected adults.

Salvage therapy with ritonavir-boosted amprenavir/fosamprenavir: virological and immunological response in two years follow-up.

OBJECTIVE: To evaluate the efficacy of salvage regimens containing ritonavir-boosted amprenavir (APV/r) or fosamprenavir (FPV/r) in heavily pretreated protease inhibitor (PI)-experienced HIV-1 patients. METHOD: Evaluation of APV/r- or FPV/r-containing antiretroviral regimens in PI-experienced HIV-1 patients with 2 or more antiretroviral failures. Follow-up continued to 96 weeks with prospective collection of data. RESULTS: 54 episodes (48 on APV/r and 6 on FPV/r) were considered in 45 patients who had received a median of 5 prior antiretroviral regimens (range, 2-13) including a median of 3 PIs (range, 2-4). Median time of treatment at analysis was 72 weeks (range, 12-210). At baseline, plasma viral load (pVL) and CD4 cell count was 67,000 copies/mL and 167 cell/mm(3), respectively. At week 96, the median pVL was < 50 copies/mL and CD4 cell count was 519 cells/mm(3). Proportion of patients with pVL below detection was 62% at week 48 and 61% at week 96. Fifteen patients stopped treatment because of virologic failure; one presented a full resistance profile to APV/r, based on the ANRS 2003 resistance algorithm. Median trough APV plasma concentration 4 weeks after treatment initiation was 1406 ng/mL (range, 452-4321); dose adaptation was required in only 7 patients. CONCLUSION: This study provides long-term follow-up of APV/r and FPV/r in the setting of salvage therapy, showing a high and sustained rate of virologic and immunologic response.