CD4+ counts in seronegative homosexual men. The Multicenter AIDS Cohort Study.
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Biomedical subjects
Publications and source records attributed to S H Vermund.
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OBJECTIVES: The prevalence of Chlamydia trachomatis cervical infection in incarcerated adult women has not been reported. To develop a policy for testing and treatment, we determined the prevalence of and risk factors for chlamydial infection in women in a New York City jail. METHODS: Interviews and cervical cultures for C trachomatis were obtained from 101 consenting female inmates. RESULTS: Positive cultures for C trachomatis were found in 27% of the participants. Mucopurulent cervical discharge and education of 8 years or less were two independent risk factors for infection, but only 63% of the infected women had one or both of these factors. If pelvic tenderness were considered as a third factor, an additional 7% of the infected women would have been identified. CONCLUSIONS: The prevalence of chlamydial infection in this population was as high as that in populations for which presumptive treatment is recommended. Although the optimal policy for detection and treatment of chlamydial infection may vary depending on practical considerations, we suggest that women entering correctional facilities should be screened or offered presumptive therapy for C trachomatis infection.
The study was designed to test the hypothesis whether cervical dysplasias of the more severe grades are associated with elevated erythrocyte glutathione levels. Subjects were women who obtained Pap tests and were subsequently found (1) not to have any cervical lesions or (2) to have colposcopically visualized, biopsy-confirmed cervical abnormalities histopathologically diagnosed as mild, moderate, severe dysplasias, or carcinoma in situ (CIS). The erythrocyte levels of reduced glutathione (GSH), oxidized glutathione (GSSG), glutathione reductase (GR), glucose-6-phosphate dehydrogenase (G6PD), and 6-phosphogluconate dehydrogenase (6PGD) were analyzed from coded peripheral venous blood samples. GSH and GR concentrations increased with increasing severity of dysplasia. Exploratory data analysis and multiple pairwise comparisons suggested comparable levels of the glutathione-related variables between these histopathological pairs: (1) mild and moderate dysplasias or (2) severe dysplasia and CIS. We suggest that the changes in erythrocyte glutathione-related indices in conjunction with histopathological diagnosis may have the potential to distinguish between low- and high-grade cervical dysplastic lesions.
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BACKGROUND: Zidovudine has been shown to prolong survival in patients with the acquired immunodeficiency syndrome (AIDS) and, in persons with human immunodeficiency virus (HIV) infection but not AIDS, to delay the progression to AIDS. However, it is still uncertain whether treatment before the development of AIDS prolongs survival. METHODS: We analyzed data from a cohort of 2162 high-risk men who were already seropositive for HIV type 1 (HIV-1) and 406 men who seroconverted from October 1986 through April 1991. There were 306 deaths. The probabilities of death were compared among men at similar stages of disease who began zidovudine therapy before the diagnosis of AIDS and among those who did not. Relative risks of death were calculated for each of five initial disease states on the basis of CD4+ cell counts and clinical symptoms and signs appearing over follow-up periods of 6, 12, 18, and 24 months. Adjustments were also made for the use of prophylaxis against Pneumocystis carinii pneumonia (PCP). RESULTS: After we controlled for CD4+ cell count and symptoms, the use of zidovudine with or without PCP prophylaxis before the development of AIDS significantly reduced mortality in all follow-up periods. The relative risks of death were 0.43 (95 percent confidence interval, 0.23 to 0.78) at 6 months, 0.54 (95 percent confidence interval, 0.38 to 0.78) at 12 months, 0.59 (95 percent confidence interval, 0.44 to 0.79) at 18 months, and 0.67 (95 percent confidence interval, 0.52 to 0.86) at 24 months. After we adjusted for the effects of PCP prophylaxis, zidovudine alone significantly reduced mortality at 6, 12, and 18 months (relative risks, 0.45, 0.59, and 0.70, respectively), but not at 24 months (relative risk, 0.81). Among zidovudine users, those who also used PCP prophylaxis before the development of AIDS had significantly lower mortality at 18 and 24 months than those who did not (relative risks, 0.62 and 0.60, respectively). CONCLUSIONS: The results of this study support the hypothesis that in HIV-1 infection, early treatment with zidovudine and PCP prophylaxis improves survival in addition to slowing the progression to AIDS.
Certain human genital papillomaviruses (HPV) are strongly associated with cervical dysplasia and cancer. Evidence is accumulating that HPV infection and ano-genital cancers are more common in patients with the acquired immunodeficiency syndrome. The objective of our study was to evaluate the extent to which HPV infection and associated cervical disease constitute opportunistic complications of human immunodeficiency virus (HIV) infection in a population of sexually promiscuous, HIV-infected women in Kinshasa, Zaire. In 1989 we obtained Pap smears and cervicovaginal lavage specimens for HPV DNA testing from 47 HIV-seropositive and 48 HIV-seronegative prostitutes who were part of a cohort under observation since 1988. Thirty-eight percent of the HIV-seropositive and 8% of the seronegative women (odds ratio = 6.8; p = 0.001) had HPV DNA detected by either ViraType, a dot-blot assay which detects specific genital HPV types, or low-stringency Southern blot, which detects all HPV types. Eighty-two women (86%) had an interpretable Pap smear; 11 of 41 (27%) HIV-seropositive women and one of 41 (3%) seronegative women had cervical intra-epithelial neoplasia (CIN) (odds ratio = 14.7; p = 0.002). HIV seropositivity, HPV infection and CIN were highly associated. Eight (73%) of 11 seropositive women with CIN had HPV detected. Both HPV infection and cervical cancer may emerge as opportunistic complications of HIV infection in populations in which HIV, HPV and cervical cancer are common.
Acquired immunodeficiency syndrome (AIDS) and human immunodeficiency virus (HIV) are growing problems among U.S. adolescents. By examining recent data on AIDS surveillance and HIV seroprevalence, surveys on teenagers' knowledge, beliefs, and behaviors related to HIV/AIDS, key treatment issues, and barriers to prevention, this manuscript reviews the problem and proposes possible ways of combating it. African American youth have the highest rates of AIDS and white youth the lowest. However, the largest number of AIDS cases overall has been recorded in white males, reflecting relatively high case rates in boys with hemophilia and in young male homosexuals. Predominant HIV risk factors for adolescents are unprotected sex and/or sharing injection drug equipment with an infected partner. Relatively high rates of HIV infection in adolescent females may indicate their greater physiological vulnerability than adult females to sexually transmitted diseases (STDs). Data from HIV seroprevalence studies suggest a substantially increased heterosexual epidemic in the 1990s, especially in large east coast cities and southeastern rural areas where drug use and/or STDs are highly prevalent. More comprehensive prevention and treatment services are needed to prevent ongoing expansion of HIV infection and AIDS in the adolescent age group.
A pregnant woman experiences selective immunosuppression as a physiologic response to the presence of a genetically heterologous fetus. Case reports early in the acquired immunodeficiency syndrome (AIDS) epidemic suggested that adverse human immunodeficiency virus (HIV)-related clinical outcomes might be causally associated with pregnancy. A review of relevant published data indicates that: (1) Adverse clinical outcomes of pregnancy are common among HIV-infected pregnant women, but no studies to date have fully disentangled the many confounding factors. (2) HIV-related complications are common in pregnancy only among immunosuppressed (< 300 CD4+ cells/mm3) women. (3) The distinct effect of pregnancy on the expression of HIV infection cannot be evaluated in the absence of appropriately controlled observations. (4) Cofactors for perinatal transmission are poorly understood. (5) Research into the motives for reproductive decisions and behaviors is of critical importance for improving our health education and outreach efforts for high-risk women. (6) Adequate clinical treatment and prophylactic health care services must be made easily accessible and available to women at high risk of HIV disease. (7) Treatment with available antiviral and anti-Pneumocystis drugs is advisable for HIV-infected pregnant women with fewer than 300 to 350 CD4+ cells/mm3, though data to definitively guide therapeutic decision making are not available. (8) Large multicenter studies are needed to recruit patients and to retain them in sufficient numbers, allowing for better evaluation of the many variables determining clinical outcomes for HIV-infected mothers and their infants. The natural history of HIV in pregnant women must be studied to facilitate clinical decision making, and to design and implement interventions, including prevention (behavior change, vaccines) and treatment (chemotherapy, immunotherapy).
We performed a second examination for human papillomavirus (HPV) DNA on 51 sexually experienced 13- to 21-year-old (mean = 17.8 years) female patients seen at an urban teaching hospital. Cervicovaginal lavages were performed 6 to 36 months apart (median = 13.3 months) to collect cells for HPV DNA detection and typing by Southern blot hybridization. At the first and second visits, 39.2% (20/51) and 25.5% (13/51) of patients, respectively, were infected with HPV. Collectively, 56.9% (29/51) of patients had at least one positive HPV test result. Although 7.8% (4/51) were infected with HPV at both visits, only one patient had infection with the same HPV type. These findings suggest that although HPV infection is a common sexually transmitted disease, genotype-specific HPV infection detected by Southern blot at two visits was rare.
Over the last 10 years the appreciation of the full breadth of the spectrum of human immunodeficiency virus (HIV) infection has gradually increased; it is now known that AIDS represents merely the end stage of this progressive infectious process. The surrogate marker that most closely correlates with the stage of HIV infection is the CD4+, or T helper, cell count. Because this count is relied on in making important therapeutic decisions, it is of paramount importance that clinicians be cognizant of and fully understand the multiple factors that can influence this parameter: the variability of the count from day to day and from morning to night, the influence of intercurrent viral infections, the influence of drugs. In this AIDS Commentary, Sten H. Vermund and his colleagues at the National Institutes of Health discuss these issues and put the CD4+ cell count into a lucid and practical clinical perspective.
A cross-sectional study was undertaken to determine the prevalence of Mycoplasma fermentans infection in patients with human immunodeficiency virus (HIV) infection using polymerase chain reaction methodology. Targeted M. fermentans DNA sequences could be amplified from the DNA extracted from the blood of 6 (11%) of 55 HIV-seropositive patients but from none of 26 HIV-seronegative subjects at low risk for HIV infection (P = .17). There was no correlation between M. fermentans infection and HIV clinical stage. There was a nonsignificant trend toward an association between M. fermentans infection and a history of syphilis. Infection with M. fermentans may occur more commonly in HIV-infected patients; however, a role as a copathogen or opportunistic infection was not established in this study.
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The authors studied the historical spread of human immunodeficiency virus type 1 (HIV-1) infection in homosexual/bisexual men and projected its future spread in these men using data from an AIDS-free cohort recruited during late 1984 in Baltimore, Maryland; Chicago, Illinois; Los Angeles, California; and Pittsburgh, Pennsylvania. Dates of preentry seroconversion in HIV-1 seroprevalent men were estimated using study entry values of hematologic variables influenced by HIV-1 infection. The authors used survival methods incorporating truncation to determine numbers/dates of seroconversion for men with a pre-1984 AIDS diagnosis who were selectively excluded by design from the 1984 AIDS-free cohort. Overall, the annual seroconversion hazard rose progressively from 0.4% in 1978 to 13.8% in 1983, dropped to 4.6% in 1985, and remained relatively stable at 1.1-2.2% from 1986 to 1990. By January 1990, almost 46% of men who were seronegative in 1978 had seroconverted. The authors estimated historical rates of spread by city, age, education, and ethnicity to examine the effects of these factors in the early and continuing stages of the HIV-1 epidemic. There were striking differences among cities with respect to pre-1985 seroconversion rates but not with respect to post-1985 seroconversion rates. Age, education, and ethnicity were all associated with 1978-1990 seroconversion rates. Future seroconversion among homosexual men was predicted assuming that the "stabilized" 1986-1990 hazards (stratified by age) observed here will be representative of future rates. Truncated Kaplan-Meier methods gave the probability of a seronegative 20-year-old man's remaining seronegative in subsequent years. Such a man has a 20.2% chance of seroconverting before reaching the age of 25 years (a 4.4% yearly hazard). The annual hazard drops to 2.5% between 25 and 30 years, to about 1.5% between 30 and 45 years, and to 1.0% between 45 and 55 years. The overall probability of seroconversion prior to age 55 years is about 50%, with seroconversion still continuing at and after age 55. Given that this cohort consists of volunteers receiving extensive anti-HIV-1 transmission education, the future seroconversion rates of the general homosexual population may be even higher than those observed here.
A case control design has been used to investigate risk factors associated with the development of cervical squamous intraepithelial lesions (SIL) in a population of urban women in which non-affluent minority groups were heavily represented. Eighty-five women with histologically confirmed SIL were compared to a control group of 70 cytologically normal women. HPV infection was determined using both Southern blot hybridization and polymerase chain reaction (PCR) amplification specific for HPV types 16, 18, and 33. When Southern blot was used to detect HPV, logistic regression analysis identified HPV infection (odds ratio (OR) = 17.9, 95% confidence interval (CI) = 6.2-51.6) and low educational achievement (OR = 3.4, 95% CI = 1.2-10.1) as major independent risk factors. When PCR was employed to detect HPV, the logistic regression model suggested that HPV infection (OR = 10.4, 95% CI = 3.6-30.4) and Hispanic ethnicity (OR = 5.0, 95% CI = 1.2-20.5) represented independent risk factors; low educational achievement and Black ethnicity were risk factors of borderline significance. PCR detection of simultaneous co-infection with more than one HPV type was associated with a very high risk of SIL (OR for one type = 7.2, 95% CI = 2.4-21.9; OR for greater than I type = 43.0, 95% CI = 6.9-266.6). Furthermore, increased viral load determined by either method carried an increased risk of disease. HPV infection with viral types previously reported to be related to neoplastic or dysplastic lesions carried the highest risk of SIL. The association of HPV detected by Southern blot and SIL in women less than 35 years old had an OR of 10.1, whereas in women greater than or equal to 35 the OR was 74.5 (p = 0.09 for homogeneity of ORs). We conclude that infection with HPV is the major risk factor for cervical SIL and suggest that targeted HPV screening of women over age 35 may represent an innovative strategy to detect women at high risk of cervical neoplasia.
Although used widely, the effectiveness of zidovudine therapy and primary prophylaxis for Pneumocystis carinii pneumonia (PCP) in HIV-1-infected individuals, has not been assessed in a large cohort. We have done an observational study between October, 1986, and October, 1990, of a cohort of 2145 HIV-1-seropositive men and 371 who seroconverted during the study. A Markov chain transitional analysis was used to examine the effect of zidovudine and PCP prophylaxis on the probability of progression of HIV-1 infection to AIDS (after 6, 12, 18, and 24 months) after follow-up visits categorised into one of six disease states. The six starting states were based on CD4+ lymphocyte counts and the presence of HIV-related symptoms. Use of pre-AIDS zidovudine and PCP prophylaxis was associated with significant reductions in rates of progression to AIDS at 6, 12, 18, and 24 months for participants starting with less than 350 CD4+ lymphocytes/microliter. For those starting with 350 or more CD4+ lymphocytes/microliter, non-significant protective trends were seen during 12, 18, and 24 month intervals. In multivariate log-linear models virtually all the treatment effect was due to zidovudine. However, after adjusting for the effects of zidovudine, PCP prophylaxis reduced significantly the probability of progression to a first episode of PCP during 6, 12, 18, and 24 month intervals. This study suggests that early primary PCP prophylaxis is effective in preventing first episodes of PCP, and that the efficacy of zidovudine demonstrated in clinical trials can be translated to the population level.
Recruitment of disease-free subjects into cohort studies and measurement of their time from exposure/infection to disease selectively excludes individuals (the unseen sample) who had earlier exposure and who have shorter times to disease. The unseen and observed samples may differ in other characteristics in addition to incubation period and exposure/infection time. For data with known truncation times, we develop non-parametric maximum likelihood estimates of the size, exposure/infection dates and distribution of incubation time in the unseen sample. We provide procedures to estimate and compensate for the biasing effects due to exclusion of the unseen sample in descriptive and survival analysis. We give consistency properties of these estimates and assess variability using bootstrap methods. One can use imputation to derive the above estimates from data with unknown truncation times that have been estimated parametrically. Application is made to an AIDS cohort study of over 5000 homosexual men. Important estimates obtained from this application are the annual seroconversion rates from 1978 to 1983, not otherwise obtainable in this study population.
We investigated the relationship of human papillomavirus (by cervicovaginal lavage and Southern blot), human immunodeficiency virus, and squamous intraepithelial lesions in 96 high-risk women in the Bronx, New York. Antibodies for human immunodeficiency virus were detected in 51 (53%) women. Of the 33 women with symptomatic human immunodeficiency virus infection, 23 (70%) had human papillomavirus infection compared with 4 of 18 (22%) asymptomatic women who were human immunodeficiency virus seropositive and 10 of 45 (22%) uninfected women (p less than 0.0001). The rate of squamous intraepithelial lesions was 52% (14 of 27) for women with both viruses detected, 18% (6 of 34) for women with either virus detected, and 9% (3 of 35) for uninfected women. Among symptomatic human immunodeficiency virus-infected women, a strong association between human papillomavirus infection and squamous intraepithelial lesions was demonstrated (odds ratio, 12; 95% confidence interval, 1.3 to 108). Risk was highest for younger women from ethnic or racial minority groups. Advanced human immunodeficiency virus-related disease, with its associated immunosuppression, seems to exacerbate human papillomavirus-mediated cervical cytologic abnormalities. Public health measures are needed to provide Papanicolaou smear screening and appropriate clinical follow-up and treatment for women at high risk for human immunodeficiency virus infection.
Recent trends in reported primary genital syphilis and genital ulcer disease (GUD) were assessed in Burkina Faso using incidence data reported to the Ministry of Health. From 1978 to 1983 the yearly reports of genital syphilis and GUD rose by 42%. A single period moving average was calculated for each consecutive 13-week period from 1978 to 1983, documenting an average 7% rise per year. Severe limitations in the Ministry of Health of personnel and other resources for surveillance were noted and no improvements in surveillance methods were evident during this study. The rising trend suggests a growing problem of ulcerative sexually transmitted diseases, which may, in turn, facilitate infection with sexually acquired human immunodeficiency virus, coincident with the expansion of this epidemic in Africa. Syphilis complications are also almost certain to include adverse pregnancy outcome due to maternal syphilis. The rising trend in genital syphilis and GUD, and the probable increase in associated adverse sequellae, require that prevention and control of sexually transmitted diseases should be made a high priority.