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Adding a second protease inhibitor to highly active antiretroviral therapy (HAART) may benefit some HIV patients, according to a study of 481 patients. About one-third of the patients achieved viral blood levels below 200 copies/mL., Context: Management of antiretroviral treatment failure in patients receiving protease inhibitor (PI)-containing regimens is a therapeutic challenge. Objective: To assess whether adding a second PI improves antiviral efficacy of a 4-drug combination in patients with virologic failure while taking a PI-containing regimen. Design: Multicenter, randomized, 4-arm trial, double-blind and placebo-controlled for second PI, conducted between October 1998 and April 2000, for which there was a 24-week primary analysis with extension to 48 weeks. Setting: Thirty-one participating AIDS (acquired immunodeficiency syndrome) Clinical Trials Units in the United States. Participants: A total of 481 human immunodeficiency virus (HIV)-infected persons with prior exposure to a maximum of 3 PIs and viral load above 1000 copies/mL. Intervention: Selectively randomized assignment (per prior PI exposure) to saquinavir (n = 116); indinavir (n=69); nelfinavir (n = 139); or placebo twice per day (n = 157); in combination with amprenavir, abacavir, efavirenz, and adefovir dipivoxil. Main Outcome Measures: Primary efficacy analysis involved the proportion with viral load below 200 copies/mL at 24 weeks. Other measures were changes in viral load and CD4 cell count from baseline, adverse events, and HIV drug susceptibility. Results: Of 481 patients, 148 (31%) had a viral load below 200 copies/mL at week 24. The proportions of patients with a viral load below 200 copies/mL in the saquinavir, indinavir, nelfinavir, and placebo arms were 34% (40/116), 36% (25/69), 34% (47/139), and 23% (36/157), respectively. The proportion in the combined dual-PI arms was higher than in the amprenavir-plus-placebo arm (35% [112/324] vs 23% [36/157], respectively; P=.002). Overall, a higher proportion of nonnucleoside reverse transcriptase inhibitor (NNRTI)-naive patients had a viral load below 200 copies/mL compared with NNRTI-experienced patients (43% [115/270) vs 16% [33/ 211], respectively; P Conclusions: In this study of antiretroviral-experienced patients with advanced immunodeficiency, viral load suppression to below 200 copies/mL was achieved in 31 % of patients with regimens containing 4 or 5 new drugs. Use of 2 PIs, being naive to N NRTIs, and baseline hypersusceptibility to efavirenz were associated with a favorable outcome.

HIV-infected patients who have severely compromised immune systems appear to be more likely than other HIV-infected patients to develop Pneumocystis carinii pneumonia (PCP) despite preventive drug therapy. PCP is a parasitic infection that may occur in people with damaged immune systems, particularly those with HIV infection. Researchers followed 476 HIV-infected homosexual men who took various drug regimens to prevent PCP between July 1989 and January 1993. Nineteen percent subsequently contracted PCP. Patients with helper T-cell counts below 50, which is indicative of severe immune system suppression, were nearly three times more likely to develop PCP than patients with helper T-cells counts between 100 and 200. Patients taking trimethoprim-sulfamethoxazole to prevent PCP and patients who smoked had approximately half the risk of developing PCP as the other patients. Those with fever were more than twice as likely to develop PCP as the other patients., Objective. - To identify clinical and epidemiological factors associated with failure of Pneumocystis carinii pneumonia (PCP) prophylaxis in those receiving primary and secondary prophylaxis. Design. - Longitudinal cohort study of participants infected with human immunodeficiency virus type 1 in the Multicenter AIDS Cohort Study who used PCP prophylaxis regimens after their T-helper lymphocyte counts had decreased to less than 0.200X[10.sup.9]/L (200/[mu]L). Main Outcome Measure. - Occurrence or recurrence of PCP. Results. - A total of 476 participants reported taking one or more of the following regimens: trimethoprim-sulfamethoxazole (TMP-SMX), dapsone, and/or aerosolized pentamidine - 367 as primary prophylaxis and 109 as secondary prophylaxis after a previous episode of PCP. A total of 92 (20%) developed PCP despite prophylaxis. The mean failure rates per person-year of follow-up were 16.0% for those receiving primary prophylaxis and 12.1% for those receiving secondary prophylaxis phylaxis (P=.19). Median times to death after initiation of primary or secondary prophylaxis were 2.0 and 1.2 years, respectively. The main predictor for failure of PCP prophylaxis was profound T-helper lymphocytopenia; 86% of failures occurred after T-helper cell counts decreased to less than 0.075 X [10.sup.9]/L and 76% occurred after counts decreased to less than 0.050 X [10.sup.9]/L. In multivariate time-dependent analysis, when compared with counts between 0.100 X [10.sup.9]/L and 0.200 X [10.sup.9]/L, the risk ratio for failure with counts less than 0.050 X 109/L was 2.90 (P

Importance: Human papillomavirus (HPV) infections cause anogenital cancers and warts. The 9-valent HPV vaccine provides protection against 7 high-risk types of HPV responsible for 90% of cervical cancers and 2 other HPV types accounting for 90% of genital warts. Objective: To determine whether HPV type-specific antibody responses would be noninferior among girls and boys aged 9 to 14 years after receiving 2 doses of the 9-valent HPV vaccine compared with adolescent girls and young women aged 16 to 26 years receiving 3 doses. Design, Setting, and Participants: Open-label, noninferiority, immunogenicity trial conducted at 52 ambulatory care sites in 15 countries. The study was initiated on December 16, 2013, with the last participant visit for this report on June 19, 2015. Five cohorts were enrolled: (1) girls aged 9 to 14 years to receive 2 doses 6 months apart (n = 301); (2) boys aged 9 to 14 years to receive 2 doses 6 months apart (n = 301); (3) girls and boys aged 9 to 14 years to receive 2 doses 12 months apart (n = 301); (4) girls aged 9 to 14 years to receive 3 doses over 6 months (n = 301); and (5) a control group of adolescent girls and young women aged 16 to 26 years to receive 3 doses over 6 months (n = 314). Interventions: Two doses of the 9-valent HPV vaccine administered 6 or 12 months apart or 3 doses administered over 6 months. Main Outcomes and Measures: The primary end point was prespecified as the antibody response against each HPV type assessed 1 month after the last dose using a competitive immunoassay. Each of the three 2-dose regimens was compared with the standard 3-dose schedule in adolescent girls and young women using a noninferiority margin of 0.67 for the ratio of the antibody geometric mean titers. Results: Of the 1518 participants (753 girls [mean age, 11.4 years]; 451 boys [mean age, 11.5 years]; and 314 adolescent girls and young women [mean age, 21.0 years]), 1474 completed the study and data from 1377 were analyzed. At 4 weeks after the last dose, HPV antibody responses in girls and boys given 2 doses were noninferior to HPV antibody responses in adolescent girls and young women given 3 doses (P < .001 for each HPV type). Compared with adolescent girls and young women who received 3 doses over 6 months, the 1-sided 97.5% CIs for the ratio of HPV antibody geometric mean titers at 1 month after the last dose across the 9 HPV subtypes ranged from 1.36 to ∞ to 2.50 to ∞ for girls who received 2 doses 6 months apart; from 1.37 to ∞ to 2.55 to ∞ for boys who received 2 doses 6 months apart; and from 1.61 to ∞ to 5.36 to ∞ for girls and boys who received 2 doses 12 months apart. Conclusions and Relevance: Among girls and boys aged 9 to 14 years receiving 2-dose regimens of a 9-valent HPV vaccine separated by 6 or 12 months, immunogenicity 4 weeks after the last dose was noninferior to a 3-dose regimen in a cohort of adolescent girls and young women. Further research is needed to assess persistence of antibody responses and effects on clinical outcomes. Trial Registration: clinicaltrials.gov Identifier: NCT01984697. [ABSTRACT FROM AUTHOR]