Transient HIV infections have been invoked to account for the cellular immune responses detected in highly virus-exposed individuals who have remained HIV-seronegative. We tested for very low levels ...of HIV RNA in 524 seronegative plasma samples from 311 highly exposed women and men from three longitudinal HIV cohorts.
Two thousand and seventy-three transcription-mediated amplification (TMA) HIV RNA tests were performed for an average of 3.95 TMA assays per plasma sample. Quadruplicate TMA assays, analyzing a total of 2 ml of plasma, provided an estimated sensitivity of 3.5 HIV RNA copies/ml.
Four samples from individuals who did not seroconvert within the following 6 months were positive for HIV RNA. For one sample, human polymorphism DNA analysis indicated a sample mix-up. Borderline HIV RNA detection signals were detected for the other three positive samples but further replicate TMA testing yielded no positive results. Nested PCR assays (n = 254) for HIV proviral DNA in peripheral blood mononuclear cells (PBMCs) from these three individuals were negative.
Transient viremia was not reproducibly detected in highly HIV-exposed seronegative men and women. If transient infections do occur, plasma HIV RNA levels may remain below the detection limits of the sensitive assay used here, be of very short duration, or viral replication may be restricted to mucosal surfaces or their draining lymphoid tissues.
From a prospective cohort study, 24 asymptomatic men were identified who had been antibody positive for human immunodeficiency virus (HIV) for at least 5 years (median = 9.1) with CD4⁺ lymphocyte ...counts ≥400 cells/mm³. Of these "nonprogressors," 23 (96%) had evidence of HIV infection by either HIV culture or the polymerase chain reaction (PCR) for HIV DNA, although only 1 (4%) had a positive assay for HIV RNA (by PCR) and no one was positive for p24 antigen. Compared with 24 antibody-negative men and 14 men with AIDS, nonprogressors had higher CD8⁺ counts and lower natural killer cell activity. Nonprogressors had higher β₂-microglobulin levels than did seronegative controls, suggesting some degree of immune system activation. Compared with men with AIDS, nonprogressors seemed to have a stronger antibody response to six different HIV-related proteins but did not differ significantly in neutralizing antibody or antibodydependent cellular cytotoxic activity.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
The human immunodeficiency virus (HIV) type 1 reverse transcriptase (RT) is an important target for therapeutic intervention and for HIV-l-specific cytotoxic T lymphocytes (CTL). An HLAA2-restricted ...CTL epitope containing the sequence YMDD, which is highly conserved among human and animal retroviruses and essential for function of the RNA-dependent DNA polymerase, is identified. The drug resistance mutation at RT amino acid 184 (MI84V), associated with (−)-2′-deoxy-3′-thiacytidine (lamivudine), (−)-2′-deoxy-5-ftuoro-3′-thiacytidine (FTC), and dideoxyinosine resistance, is located within this epitope and abolishes recognition by an established CTL response. This study demonstrates that the CTL response may target functionally relevant regions of the RT protein and suggests drug therapy may select for viral variants with altered susceptibility to established cellular immune responses.
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According to a number of previous reports, control of HIV replication in humans appears to be linked to the presence of anti-HIV-1 Gag-specific CD8 responses. During the chronic phase of HIV-1 ...infection, up to 75% of the HIV-infected individuals who express the histocompatibility leukocyte Ag (HLA)-A*0201 recognize the Gag p17 SLYNTVATL (aa residues 77-85) epitope (SL9). However, the role of the anti-SL9 CD8 CTL in controlling HIV-1 infection remains controversial. In this study we determined whether the pattern of SL9 immunodominance in uninfected, HLA-A*0201 HIV vaccine recipients is similar to that seen in chronically HIV-infected subjects. The presence of anti-SL9 responses was determined using a panel of highly sensitive cellular immunoassays, including peptide:MHC tetramer binding, IFN-gamma ELISPOT, and cytokine flow cytometry. Thirteen HLA-A*0201 vaccinees with documented anti-Gag CD8 CTL reactivities were tested, and none had a detectable anti-SL9 response. These findings strongly suggest that the pattern of SL9 epitope immunodominance previously reported among chronically infected, HLA-A*0201-positive patients is not recapitulated in noninfected recipients of Gag-containing canarypox-based candidate vaccines and may be influenced by the relative immunogenicity of these constructs.
Among 178 HIV-infected men from the San Francisco City Clinic Cohort (SFCCC), we examined the association between health insurance and use of outpatient services and treatment. For men with private ...insurance, we also assessed the frequency of avoiding the use of health insurance. Men without private insurance reported fewer outpatient visits than men with fee-for-service or managed-care plans. Use of zidovudine for eligible men was similar for those with fee-for-service plans (74%), managed-care plans (77%), or no insurance (61%). Use of Pneumocytstis carinii pneumonia prophylaxis was similar for those with fee-for-service (93%) and managed-care plans (83%) but lower for those with no insurance (63%). Of 149 men with private insurance, 31 (21%) reported that they had avoided using their health insurance for medical expenses in the previous year. In multivariate analysis, the independent predictors of avoiding the use of insurance were working for a small company and living outside the San Francisco Bay Area. Having private insurance resulted in higher use of outpatient services, but the type of private insurance did not appear to affect the use of service or treatment. Fears of loss of coverage and confidentiality may negate some benefits of health insurance for HIV-infected persons.
Patient satisfaction is a valuable indicator of the quality of medical care. We assessed the impact of type of health insurance on satisfaction with seven aspects of medical care among 593 ...HIV-infected men without AIDS, drawn from three sites in San Francisco, California and Denver, Colorado. After adjustment for site of medical care, patient age, race, income, education, and CD4 lymphocyte count, there were few differences in satisfaction between men with fee-for-service and those with managed care insurance. Men with fee-for-service insurance were significantly more satisfied with their interpersonal relations with their clinicians (p = 0.01) but less satisfied with their finances (p = 0.0001) than persons with managed care. Uninsured men were significantly less satisfied with several aspects of care than insured persons. There were no significant differences in satisfaction between men with managed care and those with public insurance. HIV-infected persons who have a choice of insurance should carefully weigh their options, recognizing the implicit trade-offs between types of insurance. Those who choose fee-for-service insurance can expect to be more satisfied with interpersonal relations with their medical providers but less satisfied with financial aspects of their plans. Efforts to address the low satisfaction of uninsured persons are needed.
Control of HIV-1 viremia and progression to AIDS has been associated with specific HLA genes. The tumor necrosis factor ( TNF) and the non-classical major histocompatibility (MHC) class I ...chain-related A ( MICA) genes are located in the genomic segment between the HLA class I and II genes and variants of both genes have been identified. We thus analyzed TNF promoter and MICA variants in a well-characterized group of HIV-1 infected individuals with different abilities to control HIV-1 viremia. In our cohort, the -1030/-862-linked TNF promoter single-nucleotide polymorphisms (SNPs), but not MICA variants, are significantly associated with lack of control of HIV-1 viremia ( P=0.03). This association is independent of those HLA-B35 alleles associated with HIV-1 disease progression with which the -862 TNF SNP has previously been independently associated. Thus, non-randomly associated genes near the TNF locus are likely involved in control of HIV-1 viremia.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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