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Association of Y chromosome haplogroup I with HIV progression, and HAART outcome.

ABSTRACT: The host genetic basis of differential outcomes in HIV infection, progression, viral load set point and highly active retroviral therapy (HAART) responses was examined for the common Y haplogroups in European Americans and African Americans. Accelerated progression to acquired immune deficiency syndrome (AIDS) and related death in European Americans among Y chromosome haplogroup I (Y-I) subjects was discovered. Additionally, Y-I haplogroup subjects on HAART took a longer time to HIV-1 viral suppression and were more likely to fail HAART. Both the accelerated progression and longer time to viral suppression results observed in haplogroup Y-I were significant after false-discovery-rate corrections. A higher frequency of AIDS-defining illnesses was also observed in haplogroup Y-I. These effects were independent of the previously identified autosomal AIDS restriction genes. When the Y-I haplogroup subjects were further subdivided into six I subhaplogroups, no one subhaplogroup accounted for the effects on HIV progression, viral load or HAART response. Adjustment of the analyses for population stratification found significant and concordant haplogroup Y-I results. The Y chromosome haplogroup analyses of HIV infection and progression in African Americans were not significant. Our results suggest that one or more loci on the Y chromosome found on haplogroup Y-I have an effect on AIDS progression and treatment responses in European Americans.

SUBMITTER: Sezgin E

PROVIDER: S-EPMC2885350 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature

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Association of Y chromosome haplogroup I with HIV progression, and HAART outcome.

Sezgin Efe E Lind Joanne M JM Shrestha Sadeep S Hendrickson Sher S Goedert James J JJ Donfield Sharyne S Kirk Gregory D GD Phair John P JP Troyer Jennifer L JL O'Brien Stephen J SJ Smith Michael W MW

Human genetics 20090124 3

The host genetic basis of differential outcomes in HIV infection, progression, viral load set point and highly active retroviral therapy (HAART) responses was examined for the common Y haplogroups in European Americans and African Americans. Accelerated progression to acquired immune deficiency syndrome (AIDS) and related death in European Americans among Y chromosome haplogroup I (Y-I) subjects was discovered. Additionally, Y-I haplogroup subjects on HAART took a longer time to HIV-1 viral supp ...[more]

PMID: 19169712

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Project description:BackgroundOver 850 million people worldwide and 200 million adults in Sub-Saharan Africa suffer from malnutrition. Countries most affected by HIV are also stricken by elevated rates of food insecurity and malnutrition. HIV infection and insufficient nutritional intake are part of a vicious cycle that contributes to immunodeficiency and negative health outcomes. However, the effect of the overlap between HIV infection and undernutrition on the immune response following antiretroviral initiation remains unclear. A possible explanation could be the lack of consensus concerning the definition and assessment of nutritional status. Our objectives are to investigate the existence of an association between undernutrition and immune response at antiretroviral treatment initiation and the following year in low- and middle-income countries where malnutrition is most prevalent.Methods/designOur systematic review will identify studies originating from low- and middle-income countries (LMICs) published from 1996 onwards, through searches in MEDLINE (PubMed interface), EMBASE (OVID interface), Cochrane Central (OVID interface) and grey literature. No language restrictions will be applied. We will seek out studies of any design investigating the association between the nutritional status (for example, undernourished versus well nourished) and the immune response, either in terms of CD4 count or immune failure, in seropositive patients initiating antiretroviral therapy or in their first year of treatment. Two reviewers will independently screen articles, extract data and assess scientific quality using standardized forms and published quality assessment tools tailored for each study design. Where feasible, pooled measures of association will be obtained through meta-analyses. Results will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement. This protocol has been registered in the PROSPERO database (registration number: CRD42014005961).ConclusionUndernutrition and weight loss are prevalent amongst highly active antiretroviral therapy (HAART)-treated patients in LMICs and contribute to excess early mortality. A possible intermediate pathway could be poor immune reconstitution secondary to deficient nutritional status. In the face of limited access to second line treatments, raising HIV resistance and cut backs to HIV programs, it is crucial to identify the factors associated with suboptimal response and therapeutic failure in order to better customize the care strategies employed in LMICs.

Dataset Information

Association of Y chromosome haplogroup I with HIV progression, and HAART outcome.

Publications

Association of Y chromosome haplogroup I with HIV progression, and HAART outcome.

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