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Biomedical subjects

W Winkelstein

Publications and source records attributed to W Winkelstein.

At least 37 records · Page 2Linked to original sources

Lack of detection of human immunodeficiency virus in persistently seronegative homosexual men with high or medium risks for infection.

Some studies have suggested that seronegative homosexual men who have practiced high-risk sexual behavior can carry the human immunodeficiency virus (HIV) in a silent state, detectable only by polymerase chain reaction (PCR) or selective viral culture. To assess this concept, blood specimens were studied from 59 homosexual men with recognized risk behaviors: unprotected anal receptive intercourse at least once and many lifetime sex partners. After extensive virologic studies and PCR analysis, only one virus-positive, antibody-negative individual was identified. These findings indicate that HIV virus-positive, seronegative individuals are rare.

Adult

CD8+ T lymphocytes and progression to AIDS in HIV-infected men: some observations.

The relationship between CD8+ lymphocyte counts and progression to AIDS was studied in 340 HIV-1-seropositive men participating in a population-based prospective study. Overall, the relative hazard for developing AIDS during 60 months of observation was slightly elevated (1.08, P = 0.003), indicating an 8% increase in risk of progression for every 100 CD8+ cell count increment. When the data were analyzed in relation to date of diagnosis, the relative hazard was depressed (0.90, P less than 0.001) for the period 6 months prior to diagnosis, but was close to 1.0 for the period 6-36 months prior to diagnosis. These findings suggest a complex relationship between CD8+ cell counts and progression to AIDS, with the possibility that various subsets of the CD8+ compartment play different roles.

Acquired Immunodeficiency Syndrome

The natural history of HIV-1 infection: staging classifications of disease.

We evaluated and compared four staging classification systems for HIV infection in a population-based cohort: (1) a staging based on prodromal clinical criteria; (2) the Walter Reed Staging Classification (WRSC); (3) the immunologic staging system (ISS), and (4) a simple staging based on oral disease and CD4+ T-cell depletion. The staging systems were applied to 386 HIV-infected men in the San Francisco Men's Health Study cohort who did not have AIDS at the baseline examination. After 48-56 months of follow-up the cumulative incidence of AIDS and the cumulative mortality by stage was determined for each staging. Unlike the other systems, the WRSC could not classify a substantial proportion of HIV-infected men (51.9%). The WRSC and ISS include one or more stages which did not appear to be associated with a prognosis substantially different from that of adjacent stages. The simplified staging system based on CD4+ T-cell depletion and oral disease may be the most effective of the systems studied. A more complete understanding of the pathophysiology during the evolution of HIV infection will be required to define a more detailed staging of this disease.

Acquired Immunodeficiency Syndrome

The prevalence of oral lesions in HIV-infected homosexual and bisexual men: three San Francisco epidemiological cohorts.

To establish the prevalence of HIV-related oral lesions, we performed oral examinations of members of three San Francisco epidemiological cohorts of homosexual and bisexual men over a 3-year period. Hairy leukoplakia, pseudomembranous and erythematous candidiasis, angular cheilitis, Kaposi's sarcoma, and oral ulcers were more common in HIV-infected subjects than in HIV-negative subjects. Among HIV-infected individuals, hairy leukoplakia was the most common lesion [20.4%, 95% confidence interval (CI) 17.5-23.3%] and pseudomembranous candidiasis was the next most common (5.8%, 95% CI 4.1-7.5%). Hairy leukoplakia, pseudomembranous candidiasis, angular cheilitis and Kaposi's sarcoma were significantly more common in patients with lower CD4 lymphocyte counts (P less than 0.05). The prevalence of erythematous candidiasis and Kaposi's sarcoma increased during the 3-year period. Careful oral examinations may identify infected patients and provide suggestive information concerning their immune status.

Acquired Immunodeficiency Syndrome

Population-based estimates of zidovudine and aerosol pentamidine use in San Francisco: 1987-1989.

From the San Francisco Men's Health Study (SFMHS) and the San Francisco General Hospital Cohort we derived partially population-based estimates of zidovudine (ZDV) use in San Francisco from 1987 to 1989. Data from the SFMHS alone were used to make estimates of aerosol pentamidine (AP) use in 1989. From 1987 to 1989, zidovudine use increased from 36 to 68% in participants with AIDS. In participants with symptomatic HIV infection without AIDS and in those with less than 200 CD4 cells, ZDV use increased initially but then leveled off (from 6 to 25% and 24 to 55%, respectively). Zidovudine use with more than 500 CD4 cells increased from 0.5 to 4%. In 1989 AP use with less than 200 CD4 cells was 42% and with AIDS was 44%. Whereas 50% of participants with AIDS and less than 200 CD4 were using both ZDV and AP, only 14% of those without AIDS but with less than 200 CD4 cells were using both. Surprisingly few members of these cohorts are using therapies proven effective in reducing the morbidity and mortality of HIV infection.

Acquired Immunodeficiency Syndrome

An evaluation of the polymerase chain reaction in HIV-1 seronegative men.

The apparent detection of human immunodeficiency virus (HIV-1) DNA by the polymerase chain reaction (PCR) in seronegative individuals has been the subject of great concern. In this study, 324 seronegative participants in the San Francisco Men's Health Study were evaluated for evidence of infection using a PCR testing algorithm with multiple amplifications targeting different regions of the HIV-1 genome. While most PCR reactions were negative, 8.6% of the specimens showed weak reactivity with one or more primer sets. However, all were negative with at least one primer set and no definitively positive specimens were identified. This study addressed the possibility that some of these PCR reactions might represent latent infection or abortive exposure, leaving residual integrated DNA, rather than false-positive reactions. The frequency of such reactions was determined in homosexual men who have been at risk for HIV-1 infection and in exclusively heterosexual men who have little or no past exposure. The results demonstrate an identical frequency and distribution of equivocal PCR reactions in both populations. Assuming that there is minimal HIV-1 infection among seronegative heterosexual men in San Francisco, we conclude that PCR testing does not provide evidence for a reservoir of occult HIV-1 infection in seronegative homosexual men.

Adult

Changes in sexual practices over 5 years of follow-up among heterosexual men in San Francisco.

This report describes changes in sexual behavior of 209 heterosexual men enrolled in a prospective study since 1984. Data were analyzed separately for men who married during the 60 months of follow-up. Study subjects reported fewer total sexual partners and an increase in condom use in the more recent time periods compared to the first period. The proportion of never married men reporting two or more partners in the previous 6 months decreased from 53.2 to 40.7%. All of these men were human immunodeficiency virus seronegative on entry and only one documented seroconversion occurred during the follow-up.

Adult

National AIDS incidence trends and the extent of zidovudine therapy in selected demographic and transmission groups.

After mid-1987 fewer than the expected number of cases of AIDS were reported in the United States in some demographic and transmission groups but not in others. Gay men (regardless of intravenous drug use), adults with hemophilia, and transfusion recipients exhibited fewer cases than expected based on previously reliable models. These favorable trends could not be explained by assuming earlier cessation of human immunodeficiency virus (HIV) infection. Favorable AIDS incidence trends were not found in heterosexual intravenous drug users or in persons infected through heterosexual contact. White gay men from New York City, Los Angeles, and San Francisco experienced markedly favorable trends, whereas little changes was observed for nonwhite gay men from nonurban areas. AIDS incidence trends were quantitatively consistent with the fraction of AIDS-free persons with severe immunodeficiency who received zidovudine in three cohorts. Gay men in San Francisco used zidovudine more frequently than did adults with hemophilia, while little was used by intravenous drug users in New York City. Data describing the initial national distribution of zidovudine (March 31-September 18, 1987) indicated relatively high use by patients with severe immunodeficiency in those groups, such as urban white gay men, that subsequently experienced fewer cases of AIDS than expected. Available data suggest that zidovudine, perhaps in combination with other therapies, has been one factor contributing to favorable AIDS incidence trends in some groups. Broader application of therapy might further retard the incidence of AIDS, especially in intravenous drug users, persons infected through heterosexual contact, minorities, women, and persons diagnosed outside major metropolitan areas.

Acquired Immunodeficiency Syndrome

Projections of AIDS morbidity and mortality in San Francisco.

To develop a model for predicting acquired immunodeficiency syndrome (AIDS) morbidity in San Francisco, Calif, through June 1993, we combined annual human immunodeficiency virus seroconversion rates for homosexual and bisexual men and for heterosexual intravenous drug users with estimates of the cumulative proportion of the population with AIDS by duration of human immunodeficiency virus infection and with estimates of the size of the at-risk populations. We projected AIDS mortality by applying Kaplan-Meier estimates of survival time following diagnosis to the projected number of cases. The median incubation period for AIDS among homosexual and bisexual men infected with the human immunodeficiency virus was estimated to be 11.0 years (mean, 11.8 years; 95% confidence interval, 10.6 to 13.0 years). The model projects 12,349 to 17,022 cumulative cases of AIDS in San Francisco through June 1993, with 9,966 to 12,767 cumulative deaths.

Acquired Immunodeficiency Syndrome

Use of beta 2-microglobulin level and CD4 lymphocyte count to predict development of acquired immunodeficiency syndrome in persons with human immunodeficiency virus infection.

Serum beta 2-microglobulin (beta 2M) levels were measured by radioimmunoassay in 962 unmarried men recruited by probability sampling from areas in San Francisco, Calif, most severely affected by the epidemic of acquired immunodeficiency syndrome (AIDS). From July 1984 to December 1987, 65 incident AIDS cases occurred in 388 homosexual/bisexual men infected by the human immunodeficiency virus (HIV) at the time of recruitment. The mean level of beta 2M in uninfected individuals at entry was 170 nmol/L. In HIV-seropositive patients who had not developed AIDS, the mean beta 2M level was 254 nmol/L, and in those who had developed AIDS, the beta 2M level was 347 nmol/L. After 36 months of follow-up, 34% of individuals with beta 2M levels greater than 322 nmol/L at entry developed AIDS, 21% of individuals with levels between 246 and 322 nmol/L developed AIDS, while only 7.3% of those with levels below 246 nmol/L developed AIDS. The beta 2M level predicted the development of AIDS independently of the CD4 lymphocyte count in HIV-seropositive individuals. Thus, 65.5% of HIV-seropositive individuals with beta 2M levels above 322 nmol/L and CD4 lymphocyte counts of below 500/microL developed AIDS in 3 years. This represents an 18.4-fold increased relative hazard at 3 years over individuals with beta 2M and CD4 cell counts within the reference range for uninfected individuals. A nomogram is provided that allows the easy calculation of the probability of an HIV-infected person developing AIDS in 36 months depending on prevalent levels of CD4 lymphocytes and serum beta 2M.

Acquired Immunodeficiency Syndrome

HIV infection, cigarette smoking and CD4+ T-lymphocyte counts: preliminary results from the San Francisco Men's Health Study.

The effect of cigarette smoking on CD4+ T lymphocytes was investigated in the San Francisco Men's Health Study cohort. The cohort was established by probability sampling in 1984 to study infection with HIV. Smoking showed an association with increased CD4+ cell counts in all men but the effect was attenuated in HIV-seropositive men (85 cells/microliter difference in median counts, non-smokers compared with smokers) compared with HIV-seronegative men (230 cells/microliter difference in median counts). The positive dose response between packs smoked per day and CD4+ counts observed in uninfected men was substantially reduced in infected men (slope 87 versus 27 cells/microliter). Analysis of data from HIV seroconverters suggest that smokers' counts fall faster than non-smokers' following infection, and that response to smoking becomes less pronounced soon after infection. This report demonstrates that those who monitor CD4+ cell counts in HIV-infected individuals for clinical and/or research purposes should also consider smoking status.

Adult