We evaluated a multicenter cohort of 1219 subjects with hemophilia or related disorders prospectively, focusing on 319 subjects with documented dates of seroconversion to human immunodeficiency virus type 1 (HIV-1). The incidence rate of the acquired immunodeficiency syndrome (AIDS) after seroconversion was 2.67 per 100 person-years and was directly related to age (from 0.83 in persons 1 to 11 years old up to 5.66 in persons 35 to 70 years old; Ptrend = 0.00003). The annual incidence of AIDS ranged from zero during the first year after seroconversion to 7 percent during the eighth year, with eight-year cumulative rates (+/- SE) of 13.3 +/- 5.3 percent for ages 1 to 17, 26.8 +/- 6.4 percent for ages 18 to 34, and 43.7 +/- 16.4 percent for ages 35 to 70. Serial immunologic and virologic markers (total numbers of CD4 lymphocytes, presence of serum interferon or HIV-1 p24 antigen, and low or absent serum levels of anti-p24 or anti-gp120) predicted a high risk for the subsequent development of AIDS. Adults 35 to 70 years old had a higher incidence of low CD4 counts than younger subjects (P less than or equal to 0.005), whereas adolescents had a low rate of anti-p24 loss (P = 0.0007) and subjects 1 to 17 years old had a lower incidence of AIDS after loss of anti-p24 (P = 0.03). These findings not only demonstrate that the risk of AIDS is related directly to age but also suggest that older adults are disproportionately affected during the earlier phases of HIV disease, that adolescents may have a low replication rate of HIV, and that children and adolescents may tolerate severe immunodeficiency better because they have fewer other infections or because of some unmeasured, age-dependent cofactor or immune alteration in the later phase of HIV disease.
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"Estimating the progression from HIV infection to fullblown AIDS is of particular importance for patient counselling, for deciding if and when to administer treatment, for monitoring the success of therapy, and for health planning (Chiarotti, 1994). Estimates of progression to AIDS among haemophiliacs have recently been produced both in Italy and in other countries based on data from national or multinational cohort studies (Goedert et al., 1989; Darby, 1990). Chiarotti et al. (1992) has presented and discussed the effects of some parametric estimation procedures of seroconversion time on the analysis of progression to AIDS, using data for Italian haemophiliacs. "
[Show abstract][Hide abstract] ABSTRACT: The human immunodeficiency virus/ acquired immune deficiency syndrome (HIV/AIDS) epidemic represents the most serious public health problem in India. There is no denial of the enormity of the problem. The available surveillance data clearly indicates that HIV is prevalent in almost all parts of the country. Hence, knowledge of HIV incidence is important to formulate sensible strategies aimed at controlling the HIV/AIDS epidemic. The objective of this paper is to estimate the probability of dying in the stage of HIV (Grover and Das, 2005) in a year without passing to the state of AIDS (HIV mortality rate). Secondly, a double decrement life table approach (Biswas et al., 2006) has been followed for a cohort of hemophiliacs who were at risk of infection with the AIDS virus. This device consists essentially of two decrements: HIV positive hemophiliacs either depart from the AIDS-free group by eventually developing AIDS or by dying from other causes; those who eventually develop AIDS either remain alive with it until they die from it or die from other causes. The distribution of incubation period of AIDS is based on a two-stage parametric regression model (Brookmeyer and Goedert, 1989), proposed for the analysis of cohort of hemophiliacs.
"The study group consisted of total of 1455 patients of European ancestry from five longitudinal cohorts including the Multicenter AIDS Cohort Study (MACS) , the San Francisco City Clinic Study (SFCC) , Hemophilia Growth and Development Study (HGDS) , the Multicenter Hemophilia Cohort Study (MHCS), and the AIDS Linked to Intravenous Experiences (ALIVE) cohort (Table S1) . Informed written consent was obtained from all patients. "
[Show abstract][Hide abstract] ABSTRACT: The human mitochondrial genome includes only 13 coding genes while nuclear-encoded genes account for 99% of proteins responsible for mitochondrial morphology, redox regulation, and energetics. Mitochondrial pathogenesis occurs in HIV patients and genetically, mitochondrial DNA haplogroups with presumed functional differences have been associated with differential AIDS progression.
Here we explore whether single nucleotide polymorphisms (SNPs) within 904 of the estimated 1,500 genes that specify nuclear-encoded mitochondrial proteins (NEMPs) influence AIDS progression among HIV-1 infected patients. We examined NEMPs for association with the rate of AIDS progression using genotypes generated by an Affymetrix 6.0 genotyping array of 1,455 European American patients from five US AIDS cohorts. Successfully genotyped SNPs gave 50% or better haplotype coverage for 679 of known NEMP genes. With a Bonferroni adjustment for the number of genes and tests examined, multiple SNPs within two NEMP genes showed significant association with AIDS progression: acyl-CoA synthetase medium-chain family member 4 (ACSM4) on chromosome 12 and peroxisomal D3,D2-enoyl-CoA isomerase (PECI) on chromosome 6.
Our previous studies on mitochondrial DNA showed that European haplogroups with presumed functional differences were associated with AIDS progression and HAART mediated adverse events. The modest influences of nuclear-encoded mitochondrial genes found in the current study add support to the idea that mitochondrial function plays a role in AIDS pathogenesis.
PLoS ONE 09/2010; 5(9):e12862. DOI:10.1371/journal.pone.0012862 · 3.23 Impact Factor
"Based on these in vitro findings, we next tested for ex vivo functional differences between dendritic cells from carriers of HLA-B*3503 (Px) or -B*3501 (PY). For this purpose , we conducted MLRs with dendritic cells isolated from the peripheral blood of HAART-naive HIV-1–infected carriers of HLA-B*3503 or -B*3501 recruited from a multicenter cohort of hemophiliac seroconverters (Goedert et al., 1989). HIV-1 viral loads (mean of 52,335 vs. 115,535 copies/ ml, P = 0.39) and CD4 cell counts (mean of 21 vs. 15%, P = 0.23) did not differ significantly between carriers of HLA- B*3501 (PY) and -B*3503 (Px), despite a longer duration of HIV-1 infection in the HLA-B*3501 (PY) group (mean of 13 vs. 10 yr). "
[Show abstract][Hide abstract] ABSTRACT: A subset of HLA-B*35 alleles, B*35-Px, are strongly associated with accelerated HIV-1 disease progression for reasons that are not understood. Interestingly, the alternative set of B*35 subtypes, B*35-PY, have no detectable impact on HIV-1 disease outcomes, even though they can present identical HIV-1 epitopes as B*35-Px molecules. Thus, the differential impact of these alleles on HIV-1 disease progression may be unrelated to interactions with HIV-1-specific CD8(+) T cells. Here, we show that the B*35-Px molecule B*3503 binds with greater affinity to immunoglobulin-like transcript 4 (ILT4), an inhibitory MHC class I receptor expressed on dendritic cells, than does the B*35-PY molecule B*3501, even though these two B*35 molecules differ by only one amino acid and present identical HIV-1 epitopes. The preferential recognition of B*3503 by ILT4 was associated with significantly stronger dendritic cell dysfunction in in vitro functional assays. Moreover, HIV-1-infected carriers of B*3503 had poor dendritic cell functional properties in ex vivo assessments when compared with carriers of the B*3501 allele. Differential interactions between HLA class I allele subtypes and immunoregulatory MHC class I receptors on dendritic cells thus provide a novel perspective for the understanding of MHC class I associations with HIV-1 disease progression and for the manipulation of host immunity against HIV-1.
Journal of Experimental Medicine 12/2009; 206(13):2959-66. DOI:10.1084/jem.20091386 · 12.52 Impact Factor