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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
PubMed1993

Differences in time from HIV seroconversion to CD4+ lymphocyte end-points and AIDS in cohorts of homosexual men.

OBJECTIVE: To evaluate the decline in CD4+ counts in relation to the incidence of AIDS in different cohorts of homosexual men and to quantify possible consequences of laboratory variation in CD4+ measurement. METHODS: Our study includes 403 men with well documented dates of HIV seroconversion originating from five cohort studies among homosexual men. Differences in time from HIV seroconversion to the first CD4+ count dropping < 500 or 200 x 10(6)/l and to AIDS were evaluated using Kaplan-Meier survival analyses. RESULTS: We found considerable differences between cohorts in CD4+ depletion, but not in the incidence of AIDS (1987 definition). CONCLUSIONS: Variation in CD4+ depletion appears to be mainly the result of laboratory differences. Policy recommendations on a basis of CD4+ counts probably requires a calibration of measurement. The 1993 AIDS case definition leads to a site-specific shortening of the incubation time, which complicates the study of the natural history of HIV infection and of trends in the AIDS epidemic.

Acquired Immunodeficiency Syndrome↗
PubMed1993

The characterization of non-progressors: long-term HIV-1 infection with stable CD4+ T-cell levels.

OBJECTIVE: To identify and characterize individuals with long-term HIV-1 infection who have experienced little or no progressive CD4+ T-cell loss during follow-up. PATIENTS AND METHODS: The rate of CD4+ T-cell loss (CD4 slope) was determined for each of the 290 participants in the San Francisco Men's Health Study who were seropositive at study entry in 1984. The study population was stratified, by CD4 slope, into 10 groups of 29 individuals and each group was characterized using a variety of cross-sectional and longitudinal laboratory measurements. RESULTS: Approximately 10% of the HIV-1-infected men experienced no net CD4+ T-cell loss during 78 months of follow-up. Compared with all other seropositive subjects, these 'non-progressors' were the extreme cases in a relatively continuous distribution of CD4 slopes, rather than a discrete subpopulation. Although they had no net cell loss, their mean CD4+ cell count was approximately 400 x 10(6)/l lower and their mean CD8+ cell count approximately 250 x 10(6)/l higher than seronegative subjects, suggesting early changes followed by stabilization. The CD4 slope was associated with the levels of beta 2-microglobulin, neopterin, p24 antibody, erythrocyte sedimentation rate, viral burden, and the proportion of HIV-1 isolates with tropism for the MT-2 T-cell line. Multivariate cluster analysis of these laboratory markers did not distinguish the non-progressors as a distinct subgroup. CONCLUSIONS: These findings support both a biphasic natural history and the suggestion that the broad range in HIV disease progression rates may be the result of several independent factors interacting in a variety of combinations. Recent changes in laboratory markers, known to predict both CD4+ cell loss and AIDS, suggest that non-progressors are undergoing slow HIV disease progression.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Population-based estimates of antiretroviral therapy and anti-Pneumocystis prophylaxis in San Francisco: 1991.

Using data from the San Francisco Men's Health Study and the San Francisco General Hospital Cohort, we derived partially population-based estimates of human immunodeficiency virus (HIV) antiretroviral therapy and Pneumocystis carinii prophylaxis use in HIV-infected men in 1991. Zidovudine, didanosine, and dideoxycytidine were the antiretroviral therapies and aerosolized pentamidine, trimethoprim-sulfamethoxazole, and dapsone were the Pneumocystis prophylaxis evaluated. Among 81 men (29 of whom had AIDS) with < or = 200 CD4 cells, 76 (94%) had ever used and 56 (69%) were currently using an antiretroviral drug; 73 (90%) had ever used and 61 (75%) were currently using Pneumocystis prophylaxis. Among 127 men with 201-499 CD4 cells, 95 (75%) had ever used and 81 (64%) were currently using antiretroviral therapy; 49 (39%) had ever used and 36 (28%) were currently using Pneumocystis prophylaxis. Among 122 men with > or = 500 CD4 cells, 29 (24%) were currently receiving antiretroviral therapy. Forty-three men had discontinued antiretroviral therapy, 29 (67%) because of side effects. Thirty-seven men with < or = 500 CD4 cells had never used antiretroviral drugs: 48% because of feeling well and 28% because of possible side effects. Compared with 1987-1989, there were substantial increases in both antiretroviral therapy and anti-Pneumocystis prophylaxis use.

AIDS-Related Opportunistic Infections↗
PubMed1993

Use of T lymphocyte subset analysis in the case definition for AIDS.

Infection with HIV-1 and < 200 CD4+ lymphocytes/mm3 has been proposed as an AIDS-defining condition. We have evaluated the effects of using this and other T-cell subset measurements, in the diagnosis of AIDS in two cohorts of homosexual/bisexual men in San Francisco. Among 762 HIV-1 infected men, 200 CD4+ lymphocytes/mm3 corresponded to 13 percent CD4+ lymphocytes and a CD4+/CD8+ ratio of 0.23. If these AIDS-defining criteria had been implemented in mid-1991, the number of living AIDS cases would have increased by 106 (212%), 133 (266%), and 136 (272%), respectively. When these criteria were first met, either before or in the absence of a clinical AIDS diagnosis, about half of the subjects were asymptomatic and the median clinically AIDS-free interval was approximately 2 years. Using two consecutive tests or pair-wise combinations of criteria reduced the number of cases identified by testing error or transient biological variation, but the number of living AIDS cases would still be increased more than twofold. Finally, any AIDS case definition using a specific T-cell subset value will be compromised by the inherent variability in these measurements and the substantial overlap in the results for those with and without clinical manifestations of HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Factors associated with human immunodeficiency virus seroconversion in homosexual men in three San Francisco cohort studies, 1984-1989.

A total of 83 HIV seroconversions occurred between 1984 and 1989 in three San Francisco cohorts of homosexual and bisexual men. A nested case-control analysis was performed to assess the risk of seroconversion associated with sexual practices. Strong associations were found with total number of intercourse partners and receptive anal intercourse. Weaker, but significant associations were found with receptive oral intercourse. Individuals reporting condom use with some partners were more likely to become infected than those reporting no condom use. Some of this difference was due to increased numbers of sexual partners among those reporting some condom use, but the association remained significant in multivariate analyses. This observation indicates there is some unmeasured risk associated with those using condoms, such as more HIV seropositive partners.

Cohort Studies↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗