To investigate the effect of human immunodeficiency virus type 1 (HIV-I) infection on subsequent hepatitis B virus (HBY) infection, HIV antibody was sought in homosexual men who developedHBVinfection ...during a hepatitis B vaccine trial. Among 134 unvaccinated HIV-I-negative men, 7% became HBV carriers, 64% had viremia, and 42% had clinical illness. Among vaccinated HIV-1-negative men, HBY infection severity decreased with number of vaccine doses administered. When adjusted for prior hepatitis B vaccination status, persons with HIV-1 infection preceding HBV infection had a significantly higher risk of developing HBV carriage, viremia, prolonged ALT elevation, and clinical illness. Among HIV-1-infected men, the risk ofHBV carriage was increased in unvaccinated persons (21%) and those who failed to respond to vaccination (31%) and further increased in those who received vaccine doses at the time they developed new HBV infection (56%–80%), suggesting inactivated hepatitis B vaccine may temporarily impair the immune response to HBV infection in HIV-I-infected persons. HIV-1 infection was also associated with reduced alanine aminotransferase elevations during the first 36 months of follow-up of men who became HBV carriers.
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To determine the willingness of populations at high risk of HIV-1 infection to participate in HIV vaccine efficacy trials, determine factors influencing decision-making, and evaluate knowledge levels ...of vaccine trial concepts.
Cross-sectional study.
HIV-1-negative homosexual men, male and female injecting drug users and non-injecting women at heterosexual risk were recruited in eight cities in the United States (n=4892).
A substantial proportion of the study population (77%) would definitely (27%) or probably (50%) be willing to participate in a randomized vaccine efficacy trial. Increased willingness was associated with high-risk behaviors, lower education level, being uninsured or covered by public insurance, and not having been in a previous vaccine preparedness study. Altruism and a desire for protection from the vaccine were major motivators for participation. Major concerns included positive HIV-1 antibody test due to vaccine, safety of the vaccine, and possible problems with insurance or foreign travel. Baseline knowledge of vaccine trial concepts was low.
It is likely that high-risk volunteers will be willing to enroll in HIV vaccine efficacy trials. A variety of participant and community educational strategies are needed to address participant concerns, and to ensure understanding of key concepts prior to giving consent for participation.
Condom failure (slippage or breakage) has been shown to be associated with HIV seroconversion among men who have sex with men (MSM), but predictors of failure have been poorly elucidated. Of 2592 ...HIV-seronegative MSM participants in the HIV Network for Prevention Trials (HIVNET) multisite Vaccine Preparedness Study who reported condom use for anal sex in the 6 months before enrollment, condom failure was reported by 16.6%, with failure rates of 2.1/100 episodes of condom usage (2.5 failures/100 episodes for receptive anal sex and 1.9/100 episodes for insertive anal sex). In separate multivariate models evaluating predictors of condom failure reported by the insertive and receptive partners, more frequent condom use was associated with a decreased per-condom failure rate and amphetamine and heavy alcohol use with increased rates in both models. Being employed, having private medical insurance, and using lubricants for >80% of anal sex acts were significantly associated with decreased failure rates in the insertive model. Safer sex counseling should particularly target men of lower socioeconomic status, promote proper and consistent use of condoms with appropriate lubricants, and address the impact of drug use, especially amphetamines and alcohol, on condom failure.
Mutations of the recombinase-activating genes 1 and 2 (
and
) in humans are associated with a broad range of phenotypes. For patients with severe clinical presentation, hematopoietic stem cell ...transplantation (HSCT) represents the only curative treatment; however, high rates of graft failure and incomplete immune reconstitution have been observed, especially after unconditioned haploidentical transplantation. Studies in mice have shown that
natural killer (NK) cells have a mature phenotype, reduced fitness, and increased cytotoxicity. We aimed to analyze NK cell phenotype and function in patients with mutations in
and in non-homologous end joining (NHEJ) genes. Here, we provide evidence that NK cells from these patients have an immature phenotype, with significant expansion of CD56
CD16
CD57
cells, yet increased degranulation and high perforin content. Correlation was observed between
recombinase activity of the mutant proteins, NK cell abnormalities, and
clinical phenotype. Addition of serotherapy in the conditioning regimen, with the aim of depleting the autologous NK cell compartment, may be important to facilitate engraftment and immune reconstitution in patients with RAG and NHEJ defects treated by HSCT.
... fl u-like" symptoms after vaccination were more common in individuals with low pre-existing immunity to the vector,2 and were rare in individuals with pre-existing antibodies to adenovirus type ...5, making it unlikely that adenovirus type 5 seropositive individuals would be more likely to correctly guess whether they had received vaccine or placebo. ... we feel it is unlikely that knowledge of treatment assignment and diff erential risk between vaccine and placebo recipients explains the diff erences in the observed HIV-1 incidence in these subgroups.
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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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