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Havlir D.V.,University of California at San Francisco | Kendall M.A.,Harvard University | Ive P.,University of Witwatersrand | Swindells S.,University of Nebraska at Omaha | And 24 more authors.
New England Journal of Medicine | Year: 2011

BACKGROUND: Antiretroviral therapy (ART) is indicated during tuberculosis treatment in patients infected with human immunodeficiency virus type 1 (HIV-1), but the timing for the initiation of ART when tuberculosis is diagnosed in patients with various levels of immune compromise is not known. METHODS: We conducted an open-label, randomized study comparing earlier ART (within 2 weeks after the initiation of treatment for tuberculosis) with later ART (between 8 and 12 weeks after the initiation of treatment for tuberculosis) in HIV-1 infected patients with CD4+ T-cell counts of less than 250 per cubic millimeter and suspected tuberculosis. The primary end point was the proportion of patients who survived and did not have a new (previously undiagnosed) acquired immunodeficiency syndrome (AIDS)-defining illness at 48 weeks. RESULTS: A total of 809 patients with a median baseline CD4+ T-cell count of 77 per cubic millimeter and an HIV-1 RNA level of 5.43 log10 copies per milliliter were enrolled. In the earlier-ART group, 12.9% of patients had a new AIDS-defining illness or died by 48 weeks, as compared with 16.1% in the later-ART group (95% confidence interval [CI], -1.8 to 8.1; P = 0.45). Among patients with screening CD4+ T-cell counts of less than 50 per cubic millimeter, 15.5% of patients in the earlier-ART group versus 26.6% in the later-ART group had a new AIDS-defining illness or died (95% CI, 1.5 to 20.5; P = 0.02). Tuberculosis-associated immune reconstitution inflammatory syndrome was more common with earlier ART than with later ART (11% vs. 5%, P = 0.002). The rate of viral suppression at 48 weeks was 74% and did not differ between the groups (P = 0.38). CONCLUSIONS: Overall, earlier ART did not reduce the rate of new AIDS-defining illness and death, as compared with later ART. In persons with CD4+ T-cell counts of less than 50 per cubic millimeter, earlier ART was associated with a lower rate of new AIDS-defining illnesses and death. (Funded by the National Institutes of Health and others; ACTG A5221 ClinicalTrials.gov number, NCT00108862.) Copyright © 2011 Massachusetts Medical Society. All rights reserved.


Nina Kim H.,Harborview Medical Center | Wang J.,Fred Hutchinson Cancer Research Center | Hughes J.,Fred Hutchinson Cancer Research Center | Sanchez J.,Asociacion Civil Impacta Salud y Educacion IMPACTA | And 10 more authors.
Journal of Infectious Diseases | Year: 2010

We evaluated whether acyclovir suppression during human immunodeficiency virus type 1 (HIV-1) acquisition reduces HIV-1 set point, increases CD4 cell counts, and selects reverse- transcriptase mutations among 76 HIV-1 seroconverters identified in a placebo-controlled trial of twice-daily acyclovir (400 mg) for the prevention of HIV acquisition in herpes simplex virus type 2 (HSV-2)-seropositive persons(HIV Prevention Trials Network study 039). We found no significant difference in plasma HIV-1 RNA levels (Pp.30) or CD4 cell counts (Pp.85) between the acyclovir and placebo recipients. V75I and other mutations in HIV-1 reverse transcriptase reported from in vitro acyclovir studies were not observed. In conclusion, acyclovir suppression during HIV-1 seroconversion and the subsequent 6 months does not affect HIV-1 set point. © 2010 by the Infectious Diseases Society of America.


Sullivan P.S.,Emory University | Carballo-Dieguez A.,Columbia University | Coates T.,University of California at Los Angeles | Goodreau S.M.,University of Washington | And 6 more authors.
The Lancet | Year: 2012

Men who have sex with men (MSM) have been substantially affected by HIV epidemics worldwide. Epidemics in MSM are re-emerging in many high-income countries and gaining greater recognition in many low-income and middle-income countries. Better HIV prevention strategies are urgently needed. Our review of HIV prevention strategies for MSM identified several important themes. At the beginning of the epidemic, stand-alone behavioural interventions mostly aimed to reduce unprotected anal intercourse, which, although somewhat efficacious, did not reduce HIV transmission. Biomedical prevention strategies reduce the incidence of HIV infection. Delivery of barrier and biomedical interventions with coordinated behavioural and structural strategies could optimise the effectiveness of prevention. Modelling suggests that, with sufficient coverage, available interventions are sufficient to avert at least a quarter of new HIV infections in MSM in diverse countries. Scale-up of HIV prevention programmes for MSM is difficult because of homophobia and bias, suboptimum access to HIV testing and care, and financial constraints.


Beyrer C.,Center for Public Health and Human Rights | Sullivan P.S.,Emory University | Sanchez J.,Asociacion Civil Impacta Salud y Educacion IMPACTA | Dowdy D.,Center for Public Health and Human Rights | And 7 more authors.
The Lancet | Year: 2012

Where surveillance has been done, it has shown that men (MSM) who have sex with men bear a disproportionate burden of HIV. Yet they continue to be excluded, sometimes systematically, from HIV services because of stigma, discrimination, and criminalisation. This situation must change if global control of the HIV epidemic is to be achieved. On both public health and human rights grounds, expansion of HIV prevention, treatment, and care to MSM is an urgent imperative. Effective combination prevention and treatment approaches are feasible, and culturally competent care can be developed, even in rights-challenged environments. Condom and lubricant access for MSM globally is highly cost effective. Antiretroviral-based prevention, and antiretroviral access for MSM globally, would also be cost effective, but would probably require substantial reductions in drug costs in high-income countries to be feasible. To address HIV in MSM will take continued research, political will, structural reform, community engagement, and strategic planning and programming, but it can and must be done.

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