Laboratory markers as potential surrogates for clinical outcomes in AIDS trials.
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Biomedical subjects
Publications and source records attributed to A R Moss.
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In a closed population, the distribution of AIDS diagnoses over time is the convolution of the distributions of human immunodeficiency virus (HIV) infections and the incubation period. This has motivated estimates of the infection distribution, assuming known diagnosis and incubation distributions, but the usefulness of this method is limited by uncertainty about incubation. The large amount of information on the distribution of HIV infections in San Francisco's gay community suggests the opposite approach--estimating the incubation distribution, assuming known infection and diagnosis distributions. A non-parametric implementation of this strategy produced an estimate with a median at 9.8 years, increasing hazard rates, and less uncertainty than previous estimates.
We assessed risk factors for human immunodeficiency virus (HIV) infection in 633 heterosexual intravenous drug users. The HIV seroprevalence was 26% in blacks, 10% in Hispanics, and 6% in whites. Intravenous cocaine use significantly increased the risk of HIV infection, with a seroprevalence of 35% in daily cocaine users (odds ratio, 6.4; 95% confidence interval, 3.0 to 13.3). Black subjects were more likely to use cocaine regularly. Drug use in shooting galleries and sharing of drug injection equipment were also associated with HIV infection and were more common in cocaine users. By multivariate analysis, black race, daily cocaine injection by blacks and Hispanics, all other cocaine injection, heavy use prior to entry into methadone treatment by blacks, and use of drugs in shooting galleries were independent predictors of HIV infection. Methadone therapy was associated with substantial reductions in heroin use and some reduction in cocaine use, but 24% of cocaine users receiving methadone began or increased cocaine injection after entry into treatment.
A group of 10 leukocyte and lymphocyte subsets were measured by simultaneous dual immunofluorescence and flow cytometry in a group of homosexual men from the San Francisco General cohort. Absolute numbers and percentages of lymphocytes were determined in 30 individuals who progressed to AIDS and 29 who did not over a 44-month period at annual intervals. At entry into the study, all subjects were asymptomatic, HIV seropositive, and had multiple changes in lymphocyte subsets compared to HIV-negative controls. In progressors, large changes occurred from the first visit to the last visit before progression in both absolute numbers and percentages of CD4 cells. The percentage of HLA-DR-bearing CD8 cells also increased. We utilized a proportional hazards model to assign a predictive value for progression to AIDS to lymphocyte subsets in both univariate and multivariate tests. Increased DR-positive CD8 cells, decreased CD4 cells, and increased CD8-positive, Leu 7-positive cells independently predicted progression to AIDS at P less than 0.006 (relative hazard 5.8-4.0). In a multivariate model, the most useful tests were either increased numbers or percentages of DR-positive CD8 cells. These data suggest parsimonious approaches to following HIV-positive individuals and further support the possibility of autoreactive T cells in the pathogenesis of HIV-associated diseases.
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All HIV seronegative (HIV Ab-) and most HIV seropositive (HIV Ab+) individuals' lymphocytes failed to proliferate in primary cultures in response to purified HIV or to recombinant envelope and core antigens of HIV, even in the presence of recombinant interleukin 2 (rIL-2). Most HIV Ab- and HIV Ab+ individuals' lymphocytes, however, could proliferate or be induced by rIL-2 to proliferate in response to lysates of Escherichia coli or Saccharomyces cerevisiae. These findings indicate selective defects in lymphocyte proliferative responses to HIV antigens before the development of AIDS in which lymphocytes are unable to proliferate in response to any antigens. These defects in cell-mediated immune responses to HIV antigens are likely to play an important role in the pathobiology of HIV infections. Although intact HIV or glycosylated gp120 envelope protein of HIV are involved in these defects, a non-glycosylated recombinant form of the HIV gp120 envelope (ENV2-3) and p25 core proteins did not inhibit antigen- or mitogen-driven lymphocyte proliferation.
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The three year actuarial progression rate to the acquired immune deficiency syndrome (AIDS) in a cohort of men in San Francisco who were seropositive for the human immunodeficiency virus (HIV) was 22%. An additional 26 (19%) developed AIDS related conditions. Beta 2 Microglobulin concentration, packed cell volume, HIV p24 antigenaemia, and the proportion and number of T4 lymphocytes each independently predicted progression to AIDS. Beta 2 Microglobulin was the most powerful predictor. The 111 subjects tested who were normal by all predictors (40%) had a three year progression of 7%, and the 68 subjects who were abnormal by two or more predictors (24%) had a progression rate of 57%. Two thirds of all men who progressed to AIDS were in the last group. The median T4 lymphocyte count in subjects who did not progress to AIDS fell from 626 x 10(6) to 327 x 10(6)/l. HIV p24 antigenaemia developed in 7% of the subjects per year. The proportion who were abnormal by two or more predictive variables rose to 41%. At three years an estimated two thirds of the seropositive subjects showed clinical AIDS, an AIDS related condition, or laboratory results that were highly predictive of AIDS. It is concluded from the observed rates and the distribution of predictive variables at three years that half of the men who were seropositive for HIV will develop AIDS by six years after the start of the study, and three quarters will develop AIDS or an AIDS related condition.
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Nurses are increasingly striving to be recognized as independent professionals and often use the nursing process as evidence that they have their own area of expert knowledge. The nursing process is, in theory at least, an effective framework on which to base nursing care. However, there are a number of studies which indicate that nursing care is influenced to a significant degree by the attitudes of nursing staff. If nursing is to attain the status of an independent profession it must identify, and if possible, rectify the factors that influence nursing attitudes.
We interviewed, and tested for HIV antibody, 117 homosexual men who had been regular sexual partners of men who developed acquired immunodeficiency syndrome (AIDS); 85 tested seropositive. Receptive anal intercourse with the index AIDS case and number of different sexual partners with whom subjects were anally receptive were both risk factors. Controlling for the number of partners with whom subjects were anally receptive, we found that the odds ratio of receptive anal intercourse with the case was infinite (95% confidence intervals, 3.3-infinity) if sexual contact continued up to or beyond the time of diagnosis, while the odds ratio was 1.0 (95% CI 0.3-3.2) if contact ceased before the case's AIDS diagnosis. Risk was not associated with the duration or frequency of contact. Our data suggest that the potential for sexual transmission from an HIV-infected person may be greater close to or after the onset of disease.
Serum and leukocytes from a cohort of homosexual males were analyzed to determine the interrelationships of antibodies to human immunodeficiency virus (HIV), serum HIV antigen levels, and phenotypical differences in lymphocyte subpopulations of HIV antibody-positive (HIV Ab+) and HIV antibody-negative (HIV Ab-) homosexual males. Significant reductions were observed in the percentages of B lymphocytes, CD4+ and CD4+ kappa lambda- T lymphocytes and the CD4+/CD8+ ratios of HIV Ab+ homosexual males in comparison to HIV Ab- homosexual males. Significant increases were observed in the percentages of CD8+, CD8+ CD11b-, CD8+ kappa lambda-, CD8+ DR+, CD8+Leu7+, and Leu7+ lymphocytes of HIV Ab+ study subjects. Statistical analysis revealed that among the immunological variables tested, decreases in the CD4+/CD8+ ratio and in the percentage of CD4+ kappa lambda- lymphocytes showed the strongest associations with HIV-sero-positivity in asymptomatic homosexual males. Only 44 (16.5%) of 267 HIV Ab+ homosexual males had detectable levels of HIV antigen (HIV Ag) in their serum. The percentages of CD4+ or CD4+ kappa lambda- lymphocytes and the CD4+/CD8+ ratios of HIV Ab+ males differed significantly between HIV Ag-positive (HIV Ag+) and--negative (HIV Ag-) homosexual males. These variables, however, did not correlate well with HIV Ag levels,indicating that no clear associations can be drawn between levels of HIV antigen and lymphocyte subset abnormalities of HIV-infected individuals.
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This prospective cohort study was designed to evaluate the risk of occupational transmission of human immunodeficiency virus (HIV), hepatitis B virus (HBV), and cytomegalovirus (CMV) to health care workers with intensive exposure to HIV-infected patients. Seventy-five percent of the 270 subjects had been exposed to patients with AIDS and AIDS-related conditions (ARC) for at least one year before enrollment, 18% worked in specialized AIDS units, and 35% sustained a total of 342 accidental parenteral exposures to HIV-infected body fluids. At the time of enrollment, none had antibody to HIV, and none of the 175 subjects retested 10 months later had acquired antibody. No evidence of increased risk of acquiring CMV or HBV was obtained. These results indicate that health care workers are at minimal risk for HIV, CMV, and HBV transmission from occupational exposure to patients with AIDS or ARC, even when intensively exposed for prolonged periods of time.
The authors compared cases of acquired immunodeficiency syndrome (AIDS) diagnosed in San Francisco, California, during 1983-1984 with human immuno-deficiency virus (HIV) antibody-negative neighborhood and clinic controls, looking for risk factors for clinical AIDS. They also compared antibody-positive with antibody-negative neighborhood and clinic controls for risk factors for HIV infection. Odds ratios were 52.0 for AIDs and 7.8 for seropositivity for more than 100 sexual partners versus 0-5 partners when antibody-negative neighborhood controls were compared with cases and with antibody-positive neighborhood controls, respectively. Odds ratios were only 2.9 and 3.4 when antibody-negative clinic controls were compared with cases and with antibody-positive clinic controls, respectively. Odds ratios of 4.6-7.3 for rectal receptivity with most or all partners versus none or one partner were statistically significant, independent of the number of partners. Douching before sex was independently associated with odds ratios of 2.2-2.8. There was no evidence for oral-genital, oral-anal, or other sexual transmission of AIDS. In multivariate analysis, independent odds ratios of 2.4-6.0 for prior syphilis and 10.8-27.9 for prior giardiasis were statistically significant or marginally significant in all comparisons. There was a moderate association with nitrite use. No other drugs were consistently associated with clinical AIDS or HIV seropositivity. Odds ratios associated with AIDS and seropositivity were closely comparable except for number of partners.