Search

Disturbances of vaginal flora are common among women of reproductive age. In areas of sub-Saharan Africa where the prevalence of HIV is high, the frequency of bacterial vaginosis (BV) is also high. In this study, we assessed the association of BV and other disturbances of vaginal flora with prevalent HIV infection in two cross-sectional studies among pregnant women in urban Malawi. The prevalence of HIV-1 was 23% in 1990 and 30% in 1993. Overall, 30% of the women had BV, 59% had mild or moderate disturbance of vaginal flora, and only 11% had normal vaginal flora. Increasing prevalence of HIV was significantly associated with increasing severity of disturbance of vaginal flora (p < .00001, chi2 trend test). This trend of increased prevalence persisted after controlling for concurrent sexually transmitted diseases (STDs), sexual activity, and socioeconomic factors. After multivariate adjustment for potential confounders, the odds ratio for the association of BV with prevalent HIV infection was 3.0 (95% confidence interval [CI], 2.4-3.8), that of moderate vaginal disturbance with HIV infection was 2.2 (95% CI, 1.7-2.8), and that of mild vaginal disturbance with HIV infection was 1.6 (95% CI, 1.3-2.1). Among women with BV, HIV infection was higher among younger women than older, implying more recent infection. Although these studies were cross-sectional, our data suggest that BV could be associated with increased susceptibility to HIV infection.

Background: Host genetic factors, such as HLA alleles, play an important role in mediating the course of HIV-1 disease progression through largely undefined mechanisms., Objectives: To examine the association of HLA markers with HIV-1 RNA plasma viral load and other factors associated with course of disease progression in HIV-1 infection., Design and Methods: A group of 139 HIV-1 seroconverters from the Multicenter AIDS Cohort Study had been typed for a variety of HLA markers. HIV-1 RNA plasma viral load was measured from frozen plasma specimens obtained approximately 9 months following seroconversion. CD4+ cell counts were available from the same study visit. Statistical analysis was performed using survival techniques and linear regression models to quantify the relative associations of an HLA score profile, HIV-1 RNA plasma viral load, CD4+ cell count and age with each other and with rate of progression to AIDS and death., Results: Cox proportional hazards models showed statistically significant differences in time to AIDS by HLA score profile category per unit increase [relative hazard (RH), 0.64; P < 0.0001], HIV-1 RNA plasma viral load per 10-fold increase (RH, 2.04; P = 0.0003), and CD4+ cell count per 100 cell (x 10(6)/l) increase (RH, 0.90; P = 0.02). Multivariate linear regression showed that viral load was 39% lower (P = 0.0001) for each unit increase in HLA score profile and 13% lower (P = 0.002) for each 100 cell (x 10(6)/l) increase in CD4+ cell count., Conclusion: The means by which the HLA score profile influences the time to AIDS is probably through immunologic responses that affect the rate of HIV-1 replication, as manifested by the HIV-1 RNA plasma viral load during the first 6-12 months following acute infection.

Background: Plasma HIV-1 RNA measurements are used for initiation of antiretroviral treatments. Whether the viral-load association with prognosis is similar in women and men is unknown., Methods: We studied 812 specimens from 650 injection-drug users (IDUs) participating in a continuous observational study of patients based in a community clinic. HIV-1 load was measured by branched-chain DNA on samples from 527 IDUs from the baseline visit, and by reverse-transcriptase PCR and quantitative microculture on samples from 285 IDUs at a follow-up visit 3 years later. FNDINGS: Women had lower median viral-load measurements than men by branched-chain DNA (3365 vs 8907 copies/mL; p=0.001), reverse-transcriptase PCR (45416 vs 93130 copies/mL; p=0.02), and quantitative microculture (5 vs 8 infectious units per million peripheral blood mononuclear cells; p=0.015). This association remained even after adjustment for CD4 cell count, race, and drug use within the previous 6 months. Time to AIDS was statistically similar for men and women in a univariate proportional-hazards model and in a model adjusting for CD4 cell count. Proportional-hazards models showed that women with the same viral load as men had a 1.6-fold higher risk of AIDS (95% CI 1.10-2.32); or, equivalently, that women with half the viral load of men had a similar time to AIDS as men., Interpretation: Although a biological mechanism remains unclear, these data suggest that current recommendations for HIV-1 viral-load thresholds to initiate antiretroviral therapy should be revised downwards for women.

Background: Cross-sectional studies suggest an association between bacterial vaginosis (BV) and HIV-1 infection. However, an assessment of a temporal effect was not possible., Objectives: To determine the association of BV and other disturbances of vaginal flora with HIV seroconversion among pregnant and postnatal women in Malawi, Africa., Design: Longitudinal follow-up of pregnant and postpartum women., Methods: Women attending their first antenatal care visit were screened for HIV after counselling and obtaining informed consent. HIV-seronegative women were enrolled and followed during pregnancy and after delivery. These women were again tested for HIV at delivery and at 6-monthly visits postnatally. Clinical examinations and collection of laboratory specimens (for BV and sexually transmitted diseases) were conducted at screening and at the postnatal 6-monthly visits. The diagnosis of BV was based on clinical criteria. Associations of BV and other risk factors with HIV seroconversion, were examined using contingency tables and multiple logistic regression analyses on antenatal data, and Kaplan-Meier proportional hazards analyses on postnatal data., Results: Among 1196 HIV-seronegative women who were followed antenatally for a median of 3.4 months, 27 women seroconverted by time of delivery. Postnatally, 97 seroconversions occurred among 1169 seronegative women who were followed for a median of 2.5 years. Bacterial vaginosis was significantly associated with antenatal HIV seroconversion (adjusted odds ratio = 3.7) and postnatal HIV seroconversion (adjusted rate ratio = 2.3). There was a significant trend of increased risk of HIV seroconversion with increasing severity of vaginal disturbance among both antenatal and postnatal women. The approximate attributable risk of BV alone was 23% for antenatal HIV seroconversions and 14% for postnatal seroconversions., Conclusions: This prospective study suggests that progressively greater disturbances of vaginal flora, increase HIV acquisition during pregnancy and postnatally. The screening and treating of women with BV could restore normal flora and reduce their susceptibility to HIV.

The second AIDS-defining condition diagnosed chronologically is referred to in this report as the secondary AIDS diagnosis. In this study, we examined survival following a secondary AIDS diagnosis using demographic and clinical factors known within 1 year before secondary AIDS diagnosis. In a prospective cohort of 2412 HIV-seropositive homosexual men observed in the Multicenter AIDS Cohort Study (MACS), 609 presented with a secondary AIDS diagnosis between January 1, 1988 and March 31, 1995. To analyze the data, we used survival analysis methods including the Kaplan-Meier product-limit estimator and extended Cox models that allow for nonproportional hazards. The median survival time after a secondary diagnosis was 10.3 months. Rapidity of progression from an initial AIDS diagnosis to a secondary diagnosis was not associated with survival. Drug treatment did not show a beneficial effect because of confounding by indication (i.e., selection bias) and limited efficacy on advanced disease of treatments available prior to 1995. However, a beneficial effect was captured by the use of calendar periods as a proxy measure for the relative exposure to drug treatments. Later calendar year of secondary diagnosis, secondary Kaposi's sarcoma, and higher CD4+ cell count were found to be significantly (p < .05) associated with longer survival time. However, secondary AIDS diagnosis was a significant factor only in the short term. Using secondary Pneumocystis carinii pneumonia as the reference diagnosis, the relative hazard of death 3 months after the time of secondary Kaposi's sarcoma diagnosis was 0.56 (95% confidence interval [CI] = 0.36-0.89) whereas the relative hazard after concurrently diagnosed multiple secondary illnesses was 2.06 (95% CI = 1.26-3.38). After approximately 1 year from the secondary diagnosis, the type of diagnosis was no longer significantly associated with survival.

Imprecise usage of the terms "sensitivity" and "specificity" produces confusion in the diagnostic use sophisticated laboratory test results. "Analytical sensitivity" represents the smallest amount of substance in a sample that can accurately be measured by an assay. "Analytical specificity refers to the ability of an assay to measure one particular organism or substance, rather than others, in a sample. An assay's analytical sensitivity and analytical specificity are distinct from that assay's clinical diagnostic sensitivity and diagnostic specificity. Diagnostic "sensitivity" is the percentage of persons who have a given disorder who are identified by the assay as positive for the disorder. High analytical sensitivity does not guarantee acceptable diagnostic sensitivity. "Diagnostic sensitivity" is the percentage of persons who do not have a given condition who are identified by the assay as negative for the condition. False-positive reactions occur because of sample contamination and diminish the diagnostic specificity of the assay. The terms "sensitivity" and "specificity" should be used with the requisite adjectives because the "diagnostic" and the "analytical" meanings of these terms are very different.

To determine the clinical and virological correlates of neuropsychological test performance decline in HIV infection, we measured viral burden in blood in 272 HIV-seropositive men without dementia in the Baltimore arm of the Multicenter AIDS Cohort Study (MACS). These measures were then related to neuropsychological (NP) decline, defined as a decline relative to prior best performance of 2.0 standard deviations or more on one or more neuropsychological tests. A short battery of NP tests (Mini-Screen Battery) was administered to all 272 men. NP test performance decline was identified in 53/272 (19.5%) of participants on the Mini-Screen Battery. Follow-up NP data were available for 204 participants who had undergone the Mini-Screen. The frequency of sustained NP test performance decline was 7.8% for the Mini-Screen Battery. A lower CD4+ cell count was weakly associated with sustained NP test performance decline. After adjustment for CD4+ cell count, hemoglobin, body mass index, and presence of AIDS, none of the viral burden measures (p24 antigenemia, plasma viremia, quantitative culture) correlated with sustained NP test performance decline. We conclude that these measures of blood HIV viral burden are not markers for NP decline, but that a lower CD4+ cell count is.

Objectives: To examine rates of HIV-1 and sexually transmitted disease (STD) among pregnant and postpartum women in urban Malawi, Africa., Design: Serial cross-sectional surveys and a prospective study., Methods: Three major surveys were conducted in 1990, 1993 and 1994/1995. Consecutive first-visit antenatal women and women giving birth at the Queen Elizabeth Central Hospital were tested for HIV and STD after counseling and obtaining informed consent. Unlinked, anonymous HIV testing was also conducted on smaller samples of antenatal women in the same hospital to provide annual prevalence data. HIV-seronegative postpartum women from the 1990 and 1993 surveys were enrolled in a prospective study to determine HIV incidence., Results: HIV seroprevalence rose from 2.0% in 1985 to 32.8% in 1996, a 16-fold increase. The highest age-specific HIV prevalence was in the following age-groups: 20-24 years during 1990, 25-29 years during 1993, and 30-34 years during 1996. Among 1173 women followed for a median of 30.9 months, HIV incidence was 5.98 per 100 person-years in women aged < 20 years and declined steadily in older women. The prevalence of STD significantly declined among both HIV-positive and negative women. This decline in STD prevalence, however, was not accompanied by increased condom use over time., Conclusions: Among urban childbearing women in Malawi, incidence of HIV is highest among young women while, currently, prevalence is highest among older women. Recent declines in STD prevalence suggest that HIV prevention programs are having an impact either through improved STD diagnosis and treatment or reduced risk behaviors. Sequential cross-sectional STD prevalence measures may be useful in monitoring effectiveness of STD and HIV prevention activities.

Transbuccal administration of drugs provides an easy route of administration. To test the safety and efficacy of a novel testosterone (T) product, we performed a randomized, double blind, placebo-controlled study in a parallel design. Men with serum T levels below 250 ng/dL were administered either an active buccal tablet containing 10 mg T (n = 7) or a buccal placebo tablet (n = 6) containing 3 mg pseudoephedrine HCl for taste matching. Men were studied while taking a standard T enanthate dose, after 6 weeks of a wash-out period, and after 8 weeks of therapy. The men were matched for age (mean +/- SD, 41 +/- 16 vs. 47 +/- 16) and type of hypogonadism (three primary testicular failures in each group, with the remainder having a central etiology). Acute pharmacokinetic testing showed peak serum hormone levels at 30 min, with a mean serum T concentration of 2688 +/- 147 ng/dL (range, 1820-3770 ng/dL). Levels returned to baseline in 4-6 h, resulting in a total T area under the curve level of 3865 ng/hn.dL, less than that using other available forms of T administration. Similar pharmacokinetics were observed for the hormone's metabolites, bioavailable T, free T, and estradiol. After 8 weeks of treatment, the results of nocturnal penile tumescence studies evaluating rigidity and circumference were significantly different from those in the placebo group (P < 0.05) and comparable to those during T enanthate therapy. In conclusion, transbuccal T therapy was sufficient to maintain normal sexual function while minimizing the total time of exposure to elevated circulating serum T levels.

To evaluate the association between sexually transmitted diseases that commonly may cause genital ulceration and prevalent and incident HIV infections, we conducted three case control studies in a cohort of 21-year-old male military conscripts in northern Thailand. The men were evaluated at baseline in 1991 and semiannually until their discharge 2 years later. Serologic evidence of infection with herpes simplex virus type 2 (HSV-2), Haemophilus ducreyi, and HIV were more frequent at baseline in 83 men with a history of genital ulcer than in 97 men without such a history. Seropositivity to H. ducreyi (odds ratio [OR] = 3.46), HSV-2 (OR = 3.83), and syphilis (OR = 1.53) were more common in HIV-positive than HIV-negative men. Men (N = 45) who seroconverted to HIV while in the military were more often seropositive for H. ducreyi and HSV-2 before HIV seroconversion and also were more likely to seroconvert to HSV-2 and H. ducreyi during the same interval as their HIV seroconversion compared with men who remained HIV-negative. These data suggest that HSV-2 and H. ducreyi may be both markers for high-risk sexual behavior and risk factors for HIV infection among young men in Thailand.

Objective: To determine the effect of sun exposure on HIV progression., Design: Cross-sectional survey nested within a longitudinal cohort study., Setting: The Multicenter AIDS Cohort Study., Participants: A total of 1155 white HIV-seronegative and 496 white HIV-seropositive homosexual men, of whom 142 seroconverted during the study., Main Outcome Measures: T-helper lymphocyte decline and AIDS., Results: No positive correlation was found between the development of AIDS or loss of T-helper lymphocytes and (i) phenotypic characteristics associated with enhanced ultraviolet radiation (UVR) sensitivity (hair or eye color, skin type), or (ii) reported UVR exposure (sun lamp/tanning bed use, frequency of beach vacations, sunscreen use), or (iii) composite score of UVR sensitivity and exposure history. The composite scores and individual measures of risk were not correlated with rate of T-helper lymphocyte decline (slope) based upon rank correlation (correlation coefficient, 0.04; P = 0.32). In fact, individuals purposefully seeking the sun had slower T-helper lymphocyte declines. Sensitivity to UVR was also not significantly associated with AIDS [odds ratio (OR), 1.11 per unit of higher composite score; 95% confidence interval (CI), 0.66-1.88; P = 0.63]. Among individuals who were HIV-infected at baseline, those who have been purposely seeking sun exposure were less likely to have AIDS (OR, 0.67; 95% CI, 0.39-1.11; P = 0.12)., Conclusions: These data suggest that phenotypic characteristics of high UVR sensitivity and exposure are not highly correlated with decline in T-helper lymphocyte count or with progression to AIDS.

Despite much investigation of zidovudine, little has been reported regarding its effect on the development of most individual AIDS-defining illnesses, including Kaposi's sarcoma (KS). We used observational data from the Multicenter AIDS Cohort Study (MACS) to estimate the effect of zidovudine use on the subsequent incidence of KS. To do this, we examined and adjusted for predictors of zidovudine use. CD4 lymphocyte counts, the development of HIV-related symptoms and AIDS, and changes in these factors were important predictors of zidovudine use. We used these associations to control for confounding by these and other factors with the G-estimation approach. We found no evidence that zidovudine use affected the time to KS in the MACS; the point estimate (95% confidence interval [CI]) for increase in time to KS was zero (-28%-68%). The relative risk was 1.0 (95% CI, 0.54-1.84). Randomized trials suggest that zidovudine may prevent KS. We discuss possible explanations for differences between results.

Background: We evaluated a newly developed enzyme-linked immunosorbent assay system for measuring helper T-lymphocyte count., Methods: Data from 111 human immunodeficiency virus-infected injection drug users in a cohort study were analyzed by flow cytometry and independent duplicate runs of the TRAx enzyme-linked immunosorbent assay., Results: The mean helper T-cell counts were 470, 480, and 506 per microliter by flow cytometry and TRAx runs 1 and 2, respectively. The correlation coefficients for TRAx runs 1 and 2 with the flow cytometry results as the dependent variable were .93 and .91, respectively. A cross-tabulation of the enzyme-linked immunosorbent assay helper T-lymphocyte counts with flow cytometry counts showed agreement of 71% and 76% when the flow count was between 201 and 500, and 88% and 90% when it was greater than 500 cells per microliter. In those samples with 200 or fewer helper T cells, agreement was 73% and 41% for each TRAx run., Conclusions: The TRAx enzyme-linked immunosorbent assay system is an acceptable method for measuring helper T-lymphocyte count, but should be recalibrated for better performance at helper T-cell counts below 200 per microliter.

Objectives: To assess the relationship between various injecting drug use patterns and the rate of CD4+ lymphocyte decline in HIV-1-infected injecting drug users in Baltimore, Maryland, USA., Methods: A cohort of 605 HIV-1-infected injecting drug users was recruited between 1988 and early 1989 in East Baltimore using extensive community outreach techniques. The participants were interviewed semi-annually to collect information on drug use practices. The outcome measure of interest was the rate of CD4+ lymphocyte decline between pairs of CD4+ lymphocyte counts. A mixed model was used to evaluate the relationship between the change in CD4+ lymphocyte count per month and previous CD4+ lymphocyte count and various drug use variables., Results: The 605 HIV-infected injecting drug users had a median initial CD4+ lymphocyte count of 513 cells x 10(6)/l. Using 3209 paired observations, the mean change in CD4+ lymphocyte count was -3.2 cells x 10(6)/l per month. The rate of decline was higher in those with a higher level of CD4+ lymphocytes (P < 0.01) and length of drug use (P < 0.01), but did not vary by injection frequency or injection intensity of specific drug types. Although animal studies have suggested that the pattern of drug administration (continuous versus intermittent) and episodes of withdrawal or overdose might impact the rate of CD4+ lymphocyte decline, this was not observed in the present study., Conclusion: Patterns of injecting drug use, based on self-report, were not associated with the rate of decline in CD4+ lymphocytes.

Imprecise usage of the terms "sensitivity" and "specificity" produces confusion in the diagnostic use of sophisticated laboratory test results. "Analytical sensitivity" represents the smallest amount of substance in a sample that can accurately be measured by an assay. "Analytical specificity" refers to the ability of an assay to measure on particular organism or substance, rather than others, in a sample. An assay's analytical sensitivity and analytical specificity are distinct from that assay's clinical diagnostic sensitivity and diagnostic specificity. "Diagnostic sensitivity" is the percentage of persons who have a given disorder who are identified by the assay as positive for the disorder. High analytical sensitivity does not guarantee acceptable diagnostic sensitivity. "Diagnostic specificity" is the percentage of persons who do not have a given condition who are identified by the assay as negative for the condition. False-positive reactions occur because of sample contamination and diminish the diagnostic specificity of the assay. The terms "sensitivity" and "specificity" should be used with the requisite adjectives because the "diagnostic" and the "analytical" meanings of these terms are very different.

Reduced CD4 T cell level and increased serum neopterin and beta 2-microglobulin levels, which reflect immunological activation and dysregulation, are three important markers of HIV disease. The aim in this study is to delineate more clearly the relation of activation to future CD4 values and disease progression. By analyzing a cohort of 198 seroconverters from the Multicenter AIDS Cohort Study with 9 years' follow-up, the dynamic changes and levels of these three markers and their interrelationships are explored. We observed that the levels of markers in the first year after seroconversion have a much stronger impact on the progression of the disease than the preseroconversion marker levels. The actual change during the year after seroconversion is not as important as the final level reached during that year. The early levels of markers after seroconversion appear to be good indicators of the subsequent course of disease as defined by CD4 level and slightly better than the quantitative changes following seroconversion or the changes in the period 1 to 2.5 years after seroconversion. To investigate the variation between subjects, the 198 seroconverters were stratified into three approximately equal-sized groups in 12 ways based on their pre- and postseroconversion levels and changes in the three markers. The group with the highest CD4 level within a year after seroconversion maintains the highest CD4 level 8 years after seroconversion. The group with the lowest level of neopterin or beta 2-microglobulin in this period has much higher future CD4 counts than the other two groups. The level of markers during the first year after seroconversion has a high predictive power for AIDS onset. Substantial differences in the hazards of AIDS are found between the groups with the highest and lowest CD4 count, neopterin, and beta 2-microglobulin following seroconversion. The three markers are generally correlated throughout the postseroconversion period but can provide distinct information. High current levels of neopterin or beta 2-microglobulin tend to be associated with low future CD4 count, while current levels of CD4 count have less association with future neopterin and beta 2-microglobulin levels.

A simple non-parametric approach is developed to simultaneously estimate net incidence and morbidity time from specific AIDS illnesses in populations at high risk for death from these illnesses and other causes. The disease-death process has four-stages that can be recast as two sandwiching three-state multiple decrement processes. Non-parametric estimation of net incidence and morbidity time with error bounds are achieved from these sandwiching models through modification of methods from Aalen and Greenwood, and bootstrapping. An application to immunosuppressed HIV-1 infected homosexual men reveals that cytomegalovirus disease, Kaposi's sarcoma and Pneumocystis pneumonia are likely to occur and cause significant morbidity time.

Objective: The authors sought to determine whether rates of depressive symptoms change from early- to late-stage HIV-1 infection and to determine the predictors of depressive symptoms as AIDS develops., Method: The data for this study were from 911 HIV-seropositive men-community volunteers from four U.S. cities-who entered the 10-year Multicenter AIDS Cohort Study without a diagnosis of AIDS and subsequently developed AIDS. The subjects underwent semiannual follow-ups during the study period. The outcome measures-overall depressive symptoms, nonsomatic depressive symptoms, syndromal depression, and severe depression-were assessed over the 5 years before and the 2 years after AIDS diagnosis from responses on the Center for Epidemiologic Studies Depression Scale (CES-D Scale)., Results: Depressive symptoms were stable over time from month 60 to month 18 before AIDS developed. However, beginning 12-18 months before AIDS diagnosis, there was a significant rise in all measures of depression, which reached a plateau within 6 months before AIDS developed. At this plateau, there was a 45% increase in mean CES-D Scale scores above baseline. An elevated CES-D Scale score in the earlier stages of infection, a self-report of AIDS-related symptoms (such as rash and lymphadenopathy), concurrent unemployment, cigarette smoking, and limited social supports were consistent predictors of higher rates of depression as AIDS developed., Conclusions: There is a dramatic, sustained rise in depressive symptoms as AIDS develops, beginning as early as 18 months before clinical AIDS is diagnosed. Prior depression, HIV-disease-related factors, and psychological stressors contribute to this rise. This robust phenomenon invites further characterization.

Objective: To determine whether racial differences exist in the rate of CD4 lymphocyte decline in HIV-1-infected homosexual men., Design: Prospective cohort study., Study Population: Non-Hispanic white (n = 321) and black (n = 102) HIV-1-seropositive homosexual and bisexual men were recruited from the Baltimore/Washington, DC metropolitan areas between 1984-1985 and 1987-1990, and evaluated semiannually., Main Measurements: Changes in CD4 lymphocyte count and CD4 percentage over time were analysed using linear regression methods for the 271 white and 69 black participants who had at least four semiannual CD4 lymphocyte measurements., Results: Rate of decline in CD4 lymphocyte count over 6 months was much slower among black than white seroprevalent men at all levels of baseline CD4 count (baseline 201-400 x 10(6)/l: + 0.24 versus -17.7 x 10(6)/l; 401-600 x 10(6)/l: -11.3 versus -23.9 x 10(6)/l; 601-800 x 10(6)/l: -15.1 versus -35.2 x 10(6)/l; > 800 x 10(6)/l: -4.3 versus -42.7 x 10(6)/l for black versus white, respectively), although this was only statistically significant for the lowest and highest strata of baseline CD4 count. These racial differences persisted after adjustment for recruitment period (1984-1985 or 1987-1990), follow-up duration, age and zidovudine therapy or Pneumocystis carinii pneumonia prophylaxis. Similar findings were observed among the 70 white and 11 black seroconverters. Black participants were also less likely than a subgroup of white participants matched on baseline CD4 lymphocyte count to be HIV-1 p24 antigen-positive. However, after acid dissociation of samples initially p24 antigen-negative, there were no significant differences in the prevalence of p24 antigenemia at enrollment or after 1 year of follow-up., Conclusions: This analysis suggests a more gradual decline in CD4 lymphocyte count among black than white Americans. The clinical significance of and reasons for this are unclear, but the lower prevalence of p24 antigenemia due to immune complexing among black Americans suggests that racial differences in the immune response to HIV may exist. Additional studies are needed to validate these findings in a larger cohort of non-whites, and to assess their relationship with other measures of cell-mediated immune function.

Background: High incidences of sexually transmitted diseases (STD) after posttest counseling have been documented in patients diagnosed with human immunodeficiency virus (HIV) in Baltimore STD clinics. In July 1991, the authors instituted an HIV early intervention program providing long-term medical care and social work services. This study compares the incidence of gonorrhea after post-HIV+ test counseling in patients diagnosed with HIV before and after the institution of the early intervention program., Methods: Medical records of a cohort composed of all patients newly diagnosed with HIV and those who underwent posttest counseling for HIV in 1991 to 1993 in two Baltimore STD clinics were reviewed. Patients were offered early intervention medical and social work services. Gonorrhea incidence in this cohort was compared to a historical cohort diagnosed and counseled for post-HIV+ testing in 1988 to 1989 who were not offered early intervention services., Results: The mean follow-up time was 418 days (range, 26 to 703 days). After post-HIV+ test counseling, gonorrhea developed in 39 of 468 (8.3%) men in the 1989 cohort and 13 of 400 (3.3%) men in the 1991 to 1993 cohort. Controlling for variable length of follow-up, the 1991 to 1993 cohort had a relative risk of 0.442 for the development of gonorrhea during the study period (95% confidence interval, 0.225 to 0.790; P = 0.006). Incident gonorrhea after post-HIV+ test counseling also was associated with a prevalent gonorrhea condition at the time of HIV diagnosis (RR = 3.02; 95% CI, 1.75 to 5.23; P = 0.0001) and failure to return for post-HIV+ test counseling as scheduled (RR = 2.27; 95% CI, 1.17-4.43; P = 0.013). After adjustment for gonorrhea at the time of HIV diagnosis and failure to return for scheduled posttest counseling, the difference in gonorrhea incidence between men in the two cohorts remained statistically significant (RR = 0.494; 95% CI, 0.260 to 0.941; P = 0.032). In comparison, overall gonorrhea rates in Baltimore changed little between 1988 and 1993. No significant difference was found in gonorrhea incidence in women, which may have been the result of active gonorrhea screening during the 1991 to 1993 period, which was not performed in 1988 to 1989., Conclusions: Providing clinical care to persons with HIV may facilitate the reduction of high-risk behaviors that lead to incident STDs and further HIV transmission.

Background: If Kaposi's sarcoma-associated herpesvirus (KSHV) is the cause of Kaposi's sarcoma, serologic evidence of infection should be present in patients before the disease develops., Methods: Using an immunoblot assay for two latent nuclear antigens of KSHV, we tested serum samples from homosexual male patients with the acquired immunodeficiency syndrome (AIDS) with and without Kaposi's sarcoma (HIV-infected men with hemophilia), HIV-seronegative blood donors, and HIV-seronegative patients with high titers of antibodies against Epstein-Barr virus (EBV). Serial serum samples obtained from patients with Kaposi's sarcoma before the diagnosis of the disease were tested for evidence of seroconversion., Results: Of 40 patients with Kaposi's sarcoma, 32 (80 percent) were positive for antibodies against KSHV antigens by the immunoblot assay, as compared with only 7 of 40 homosexual men (18 percent) without Kaposi's sarcoma immediately before the onset of AIDS. Of 122 blood donors, 22 EBV-infected patients, and 20 HIV-infected men with hemophilia, none were seropositive. When studied by the immunoblot assay over a period of 13 to 103 months, 21 of the 40 patients with Kaposi's sarcoma (52 percent) seroconverted 6 to 75 months before the clinical appearance of Kaposi's sarcoma. The median duration of antibody seropositivity for KSHV-related latent nuclear antigens before the diagnosis of Kaposi's sarcoma was 33 months., Conclusions: In most patients with kaposi's sarcoma and AIDS, seroconversion to positivity for antibodies against KSHV-related nuclear antigens occurs before the clinical appearance of Kaposi's sarcoma. This supports the hypothesis that Kaposi's sarcoma results from infection with KSHV.

It is widely assumed that the time since human immunodeficiency virus (HIV) infection is an important indicator of HIV disease stage, yet for most infected individuals the date of infection is unknown. We consider whether marker values, such as CD4 lymphocyte number or percent and levels of serum beta2 microglobulin or serum neopterin, render time since infection unimportant for predicting the residual time to acquired immunodeficiency syndrome (AIDS) diagnosis. The Multicenter AIDS Cohort Study (MACS) contains a subsample of homosexual men whose date of HIV seroconversion is known within +/-6 months and who provide data for this analysis. From this subsample, we extract two overlapping data subsets. The first subset consists of 370 persons whose 3,723 study visits include complete data on the cellular markers CD4 lymphocyte number and percent for a period of 9 years. The second consists of 272 persons whose 1,593 visits include complete information on cellular markers and on the serological markers beta2-microglobulin and neopterin for a period of 5 1/2 years. We model the residual time to AIDS diagnosis with a regression model, in which cellular and serologic markers are the explanatory covariates (independent variables) and the residual time to AIDS is the responses variable (dependent variable). A robust estimate of the variance-covariance matrix corrects for the dependence of repeated measurements in the same individual. In the case of CD4 number and percent, the results indicate that time since infection is of none or at most little importance if the marker value is known, suggesting that time since infection can be adequately replaced by the combination of marker values. However, the serological markers alone do not eliminate the importance of the time since infection.

Objective: To estimate the incidence and prevalence of cytomegalovirus retinitis (CMV-R) in late-stage human immunodeficiency virus type 1 disease., Design: Cohort study., Setting: The Multicenter AIDS Cohort Study, an ongoing 10-year study of human immunodeficiency virus type 1-infected homosexual men with semiannual visits and CD4+ cell testing., Study Participants: Three hundred sixty-seven human immunodeficiency virus type 1-infected men from the Multicenter AIDS Cohort Study who were receiving zidovudine and Pneumocystis carinii prophylaxis and who had CD4+ cell counts fall below 0.10 x 10(9)/L (100/microL)., Main Outcome Measures: Kaplan-Meier-type estimates for various longitudinal quantifications of incidence and prevalence of CMV-R were obtained., Results: Among these 367 individuals, cytomegalovirus disease developed in 103, of whom 73 (71%) had ocular complications. At 4 years after the first CD4 cell count ( < 0.10 x 10(9)/L), the probability for these subjects to have (1) remained living without CMV-R was 11%, (2) died without experiencing CMV-R was 66%, (3) experienced CMV-R and be living was 6%, and (4) experienced CMV-R and died was 18%. During these 4 years, there was a 25% chance for the development of CMV-R and, on average, 0.211 person-years of CMV-R morbidity. Among those subjects in whom CMV-R developed, about 19% did have CMV-R before a CD4+ cell count of less than 0.05 x 10(9)/L ( < 50/microL) was observed, and 81% had CMV-R after the CD4+ cell count reached this threshold., Conclusion: These estimates may be relevant to current clinical practice and help in allocating resources and planning for treatment and prophylaxis against cytomegalovirus disease.

Background: Among patients who begin receiving zidovudine during intermediate-stage human immunodeficiency virus (HIV) infection, it is unclear whether changing to combination therapy (adding didanosine or zalcitabine) or sequential monotherapy (changing to didanosine or zalcitabine) significantly improves survival., Objective: To determine, among patients who began receiving zidovudine during intermediate-stage HIV infection, the differential effects of changing to combination therapy (zidovudine with didanosine or zalcitabine) or sequential monotherapy (with didanosine or zalcitabine) or continuing zidovudine monotherapy., Patients: 1077 HIV-seropositive men in the Multicenter AIDS (acquired immunodeficiency syndrome) Cohort Study who began receiving zidovudine before an AIDS-defining illness developed., Setting: University-affiliated clinics in Baltimore, Chicago, Los Angeles, and Pittsburgh., Design: Longitudinal cohort study, Treatment groups and important prognostic variables were modeled as time-dependent covariates in Cox proportional hazards models., Measurements: Progression to AIDS and death., Results: Compared with patients receiving continued zidovudine monotherapy, patients receiving combination therapy had a 45% improvement in survival (relative risk, 0.55 [95% Cl, 0.41 to 0.74; P < 0.001]) and patients who changed to sequential monotherapy had a 32% improvement in survival (relative risk, 0.68 [Cl, 0.52 to 0.89; P = 0.005]). In the landmark analyses, the median prolongation of survival associated with changing therapy was, at best, 3 to 6 months. Survival curves converged at 3.5 years for the 50 cells/mm3 disease-stage landmark, at 4.4 years for the 100 cells/mm3 landmark and at 4.9 years for the 150 cells/mm3 landmark. Mortality within these periods was 100%, regardless of treatment group or landmark., Conclusions: For patients who began receiving zidovudine during intermediate-stage disease, changing to either combination therapy or sequential monotherapy was associated with a statistically significant survival benefit compared with continuation of zidovudine monotherapy. The absolute increase in survival was modest, however, and long-term survival remained poor. Simultaneous time-dependent adjustment for changes in therapy and in important prognostic variables is necessary to derive relatively unbiased estimates of treatment effects in observational studies of HIV infection.

Unlike patients in a randomized, clinical trial, patients in an observational study choose if and when to begin treatment. Patients who live longer have more opportunities to select treatment; those who die earlier may be untreated by default. These facts are the essence of an often overlooked bias, termed "survivor treatment selection bias," which can erroneously lead to the conclusion that an ineffective treatment prolongs survival. Unfortunately, misanalysis of survivor treatment selection bias has been prevalent in the recent literature on the acquired immunodeficiency syndrome. Approaches to mitigating this bias involve complex statistical models. At a minimum, initiation of therapy should be treated as a time-dependent covariate in a proportional hazards model. Investigators and readers should be on the alert for survivor treatment selection bias and should be cautious when interpreting the results of observational treatment studies.

A theoretical model was used to examine the influence of relationship factors, pregnancy intentions, contraceptive behavior and other psychosocial characteristics on stages of behavior change in condom use among heterosexual black women of reproductive age. Data from an inner-city street survey compared women who were not contemplating condom use, women who were attempting to use condoms or had used them consistently for short periods of time, and those who had achieved long-term consistent use. Women's relationship with their main partner appears to be an important factor in understanding their use of condoms both with main partners and with other partners. For condom use with the main partner, factors such as emotional closeness and partner support were significant predictors of the likelihood that women would be attempting to use condoms rather than not contemplating use. Cohabitation and the belief that condom use builds trust were significant predictors of long-term consistent condom use. Having a regular or main partner was strongly associated with intentions to use condoms with other partners. Women who wanted to become pregnant were much less likely to intend to use condoms with their main partner, and women using oral contraceptives were less likely to be long-term consistent condom users.

Objectives: Kaposi's sarcoma-associated herpesvirus (KSHV), a newly discovered human gammaherpesvirus, is found in the majority of KS lesions from patients with and without AIDS. Peripheral blood mononuclear cells (PBMC) were examined for KSHV DNA to determine whether viral infection precedes onset of this neoplasm., Design: Randomized and blinded case-control study of prospectively collected PBMC samples from ongoing cohort studies., Methods: Paired PBMC drawn before and after KS onset from 21 AIDS-KS patients were compared to paired PBMC from 23 high-risk HIV-infected homo-/bisexual patients who did not develop KS and to a single PBMC sample from 19 low-risk, HIV-infected hemophiliac patients. Extracted DNA samples were amplified by polymerase chain reaction (PCR) using two non-overlapping nested primer sets to control for potential PCR contamination., Results: In all comparisons, patients who went on to develop KS were significantly more likely to show evidence of KSHV infection prior to onset of KS than either control group. Of PBMC samples from AIDS-KS patients drawn prior to KS, 52% were positive for KSHV DNA whereas both high- and low-risk control groups had lower rates of PBMC infection (9-13%). KSHV infection can precede KS onset by up to 21 months among AIDS-KS patients., Conclusions: AIDS-KS patients are significantly more likely to show evidence of KSHV infection in PBMC prior to KS onset than control HIV-infected patients. Because identical PBMC samples from cases and controls were examined blindly, these results are not caused by a bias in tissue sampling. Homo-/bisexual and hemophiliac AIDS patients who do not develop KS appear to have a low prevalence of infection. These findings indicate that KSHV infection is specifically associated with the subsequent development of KS in AIDS patients.

Though the exact physiology and pathology of lipoprotein(a) [Lp(a)] remains unknown, it has been demonstrated that increased serum Lp(a) levels are correlated with an increased risk of atherosclerotic vascular disease. The effects of lipid-lowering drugs on Lp(a) levels is unclear because of inconsistencies between study designs. This study analyzes the effects of the commonly used lipid-lowering drugs pravastatin (PRAV), lovastatin (LOV), and cholestyramine (CHOL) on serum Lp(a) and other serum lipid levels in a parallel study design. Hyperlipidemic men (n = 32) were enrolled from three centers and treated for 48 weeks in a multicenter clinical trial using PRAV, LOV, CHOL, or a placebo (for the first 16 weeks only). Baseline serum low-density lipoproteins (LDL-C), high-density lipoproteins (HDL-C), and triglycerides were 199 +/- 38, 40 +/- 9, and 160 +/- 70 mg/dl, respectively. At the end of 48 weeks, serum plasma LDL-C declined in patients randomized to PRAV, LOV, and CHOL, respectively, by 31%, 29%, and 23% (all p < 0.001); HDL increased by 4%, 11%, and 11% (all p < 0.001); and TG changed by -16%, -28%, and +43% (all p < 0.001). Subjects in PRAV and LOV changed Lp(a) by 9% and 3%, respectively. Although there was an initial Lp(a) decline in the first 8 weeks of CHOL therapy (p < 0.05, ANOVA), this returned to baseline after 48 weeks. In this parallel study design PRAV, LOV, and CHOL are effective LDL-lowering medications with minimal effects on plasma Lp(a).

Objective: To identify clinical and epidemiological factors associated with failure of Pneumocystis carinii pneumonia (PCP) prophylaxis in those receiving primary and secondary prophylaxis., Design: Longitudinal cohort study of participants infected with human immunodeficiency virus type 1 in the Multicenter AIDS Cohort Study who used PCP prophylaxis regimens after their T-helper lymphocyte counts had decreased to less than 0.200 x 10(9)/L (200/microL)., Main Outcome Measure: Occurrence or recurrence of PCP., Results: A total of 476 participants reported taking one or more of the following regimens: trimethoprim-sulfamethoxazole (TMP-SMX), dapsone, and/or aerosolized pentamidine--367 as primary prophylaxis and 109 as secondary prophylaxis after a previous episode of PCP. A total of 92 (20%) developed PCP despite prophylaxis. The mean failure rates per person-year of follow-up were 16.0% for those receiving primary prophylaxis and 12.1% for those receiving secondary prophylaxis (P = .19). Median times to death after initiation of primary or secondary prophylaxis were 2.0 and 1.2 years, respectively. The main predictor for failure of PCP prophylaxis was profound T-helper lymphocytopenia; 86% of failures occurred after T-helper cell counts decreased to less than 0.075 x 10(9)/L and 76% occurred after counts decreased to less than 0.050 x 10(9)/L. In multivariate time-dependent analysis, when compared with counts between 0.100 x 10(9)/L and 0.200 x 10(9)/L, the risk ratio for failure with counts less than 0.050 x 10(9)/L was 2.90 (P < .001). Once T-helper cell counts were considered, fever was the only other health status indicator that predicted subsequent PCP (ie, a time-dependent risk ratio of 2.22; P = .01). Use of TMP-SMX as the prophylaxis regimen was protective but did not eliminate failure (ie, a time-dependent risk ratio of 0.55; P = .03)., Conclusions: These findings strongly support identifying improved methods of PCP prophylaxis once T-helper cell counts decrease to less than 0.075 x 10(9)/L or 0.100 x 10(9)/L. Given this severe degree of immunosuppression, an inherently more effective regimen against P carinii is required.

This analysis investigated variability of survival time in a cohort of 553 human immunodeficiency virus type 1 (HIV-1)-infected homosexual or bisexual men with < 50 CD4+ cells/microL. Median survival after the first CD4+ cell count < 50/microL was 1.34 years; 25% survived > or = 2 years. Multivariate analysis showed longer survival with concurrent acyclovir and zidovudine use, hemoglobin > or = 12 g/dL, and full-time employment (P < .0001). Other significant covariates associated with longer survival included African-American race, no prior AIDS illness, weight loss < 4.5 kg, and zidovudine use (with or without concurrent acyclovir) after CD4+ cells fell to < 50/microL. An easily derived score identified Multicenter AIDS Cohort Study subjects likely to survive > 2 years after CD4+ cell count was < 50/microL. Survival once CD4+ cell count fell below 50/microL may be longer for persons with a good performance status and specific clinical markers. Health care providers should consider these variables in decision-making strategies and design of clinical trials.

Objective: Quantify and study cofactors of long-term survival without AIDS in HIV-1-infected individuals with CD4+ cell counts < 200 x 10(6)/l., Design: Comparison of 579 participants who could be longitudinally evaluated for at least 3 years after the earliest date of first reaching a CD4+ cell count < 200 x 10(6)/l or an AIDS-defining illness (1987 Centers for Disease Control and Prevention definition)., Setting: Ongoing 9-year cohort study with data collected at 6-month intervals., Patients: HIV-1-infected homosexual men., Measurements and Main Results: Of the men, 20% did not develop an AIDS illness within 3 years following a confirmed CD4+ cell count < 200 x 10(6)/l; 29 and 28% were diagnosed with a first clinical AIDS illness from 1-3 and < 1 years, respectively, beyond their first CD4+ cell count < 200 x 10(6)/l; 23% were diagnosed with a clinical AIDS illness prior to their first CD4+ cell count < 200 x 10(6)/l. Slower decline of CD4+ cell count (P < 0.001) and presence of higher body-mass index during the period prior to the first CD4+ cell count < 200 x 10(6)/l (P < 0.001) predicted longer time to an AIDS illness once this threshold was reached. Most men had rapid loss of CD4+ cells, total T cells, and hemoglobin during the period after CD4+ cells declined below 200 x 10(6)/l. However, those remaining free of AIDS illnesses the longest arrested their decline in CD4+ cell counts and hemoglobin levels and increased total T cells during this period. Although antiretroviral therapy and Pneumocystis carinii prophylaxis extend AIDS-free survival, 45% of the group who were AIDS-free > or = 3 years after CD4+ cells fell below 200 x 10(6)/l had not used these treatments., Conclusions: Significant numbers of individuals remain free of illnesses and AIDS symptoms > or = 3 years after CD4+ cell counts drop below 200 x 10(6)/l. This occurs even in the absence of treatment. The associations seen here suggest that host and viral factors play important roles. Thus, further studies are needed to determine the biological basis of long-term survival without AIDS illnesses in HIV-1-immunosuppressed patients.

Two lines of attack have been used against HIV-1 disease: (1) antiretroviral therapy (notably zidovudine) directed against the HIV-1 virus; and (2) chemoprophylaxis against end-stage diseases of HIV-1 infection, most notably against Pneumocystis carinii pneumonia. Many studies and clinical trials have found that zidovudine and P. carinii prophylaxis each significantly reduce short term morbidity and mortality from HIV-1 disease. However, these drugs have costs, adverse effects and (particularly with zidovudine) cumulative toxicity that suggest that their long term benefits may not necessarily be as great as their short term prospects. Due to the pressing needs of the HIV-1 epidemic, social considerations and proven short term benefits, long term clinical trials of zidovudine and P. carinii prophylaxis employing untreated control groups are impossible. Thus, the long term benefits of these anti-AIDS therapies must be estimated from observational studies comparing those who choose to use those therapies and those who do not. Strong epidemiological biases and common statistical misanalyses of observational data occur, leading to seemingly contradictory results. On the basis of the aggregate of short term clinical data and long term observational studies, zidovudine therapy taken either before or after AIDS delays the date of death by 12 months. If zidovudine therapy is initiated before AIDS, it may delay the date of diagnosis of AIDS by 12 months. However, issues of cost effectiveness, detrimental effects and optimal time to begin zidovudine therapy remain unresolved. Limited observational study data suggest that P. carinii prophylaxis initiated before the onset of clinical AIDS will delay both the date of diagnosis of AIDS and the date of death by 9 months in North American men. The net benefits from P. carinii prophylaxis will be less in those who begin this treatment after a diagnosis of AIDS. Benefits from P. carinii prophylaxis will also probably be less in regions outside of North America, in particular underdeveloped countries, where P. carinii pneumonia is less common as an end-stage HIV-1-related illness.

Men from the Multicenter AIDS Cohort Study were classified as "susceptible" and "resistant" to HIV infection. Resistant men were still HIV antibody negative in 1993 and were estimated to have had > 45 different anal intercourse partners (median, 92; range, 46-504) in the 2.5 years before visit 2 (1985). Susceptible men were seroconverters who were estimated to have had < 13 different anal partners (median, 4; range, 0-12). Leukocyte groups were compared between the two groups of men. Values were excluded for 12 months before the first antibody-positive visit in the susceptible men. White blood cells, polymorphonuclear neutrophils, total lymphocyte count, CD8+ percentage and number, and CD3+ and CD4+ number were higher in the resistant men. Logistic regression analyses were used to develop 50 bivariate models. Higher levels of neutrophils and CD8+ cells were included in four of the six best-fitting bivariate models, suggesting that each is associated with resistance to HIV-1 infection. These results support the hypothesis that CD8+ cells may modulate the outcome of HIV-1 exposure.

Incidence rates of AIDS illnesses are described among patients with < or = 100 CD4 cells/mm3 grouped by use of antiretrovirals and chemoprophylaxis. Data were obtained from 2646 homosexual men infected with human immunodeficiency virus type 1. Participants were in the Multicenter AIDS Cohort Study during 1985-1993. The incidence rates per 100 person-years for Pneumocystis carinii pneumonia were 47.4 without treatment, 21.5 with antiretrovirals alone, and 12.8 with antiretrovirals combined with chemoprophylaxis. For Kaposi's sarcoma these rates were 23.2, 11.3, and 15.1, respectively. The incidence of some opportunistic infections, including Mycobacterium avium complex, nonretinitis cytomegalovirus disease, and cytomegalovirus retinitis, increased among persons receiving P. carinii pneumonia prophylaxis, because of reduction of this pneumonia and extension of life span. The incidence pattern of AIDS-defining illnesses in patients receiving treatment points to the changing AIDS epidemic and the need for new therapies. The data are particularly relevant to the development and planning of clinical trials and to health care providers.

Methods are developed to estimate and test for the impact of intervention use on a population's survival function (time to AIDS). Each participant's history is divided into J + 1 components: omega 0 occurring before the intervention is available and omega 1 to omega J occurring later, as the intervention becomes successively more available. Distribution free truncated Kaplan-Meier models based on time since exposure fit separately to the risk sets/outcomes in omega 0 to omega J directly show the changing patterns of survival. Multivariate proportional hazards models can be used to adjust for covariates. Application of these methods indicates that availability of proven anti-AIDS interventions may have delayed time to AIDS by 8 months in an educated HIV-1 infected homosexual cohort with good access to medical care.

Studies show that around 10-40% HIV-positive women will give birth to children who are also infected. However, the risk factors for transmission from mother to child are not well understood and the effects of maternal nutritional status are unknown. We conducted a study of vitamin A status in pregnant women as a risk factor for mother-to-child transmission of HIV in Malawi. Serum vitamin A, height, weight, CD4 T-cell counts, and duration of breastfeeding were measured in 338 HIV-positive mothers whose infant's HIV serostatus was known. Mother-to-child transmission of HIV was 21.9% among mothers whose infants survived to 12 months of age. Mean vitamin A concentration in 74 mothers who transmitted HIV to their infants was lower than that in 264 mothers who did not transmit HIV to their infants (0.86 [0.03] vs 1.07 [0.02], p < 0.0001). We divided HIV positive mothers to 4 groups, those with vitamin A concentrations of less than 0.70, between 0.70 and 1.05, between 1.05 and 1.40, and greater than or equal to 1.40 mumol/L. The mother-to-child transmission rates for each group were 32.4%, 26.2%, 16.0%, and 7.2%, respectively (p < 0.0001). Maternal CD4 cell counts, CD4%, and CD4/CD8 ratio were also associated with increased mother-to-child transmission of HIV. Maternal age, body-mass index, and breastfeeding practices were not significantly associated with higher mother-to-child transmission. Our study suggests that maternal vitamin A deficiency contributes to mother-to-child transmission of HIV.

Nonidentified response (NR), an important form of nonindependent censoring, is modelled in a proportional hazards setting. Methods to test for existence of and identify NR censored observations are developed. Incorporation of NR censoring information into appropriate algorithms can improve parameter and underlying baseline hazard estimation. Application to estimating time until death from AIDS is made.

The objective of this study was to determine if clinical signs, symptoms, laboratory variables, and use of therapeutic or prophylactic agents have prognostic associations with survival after diagnosis of clinical AIDS. A total of 2,168 homosexual men, seropositive for human immunodeficiency virus type 1 (HIV-1) participated in a longitudinal cohort study of the greater metropolitan areas of Baltimore, Maryland, Washington, D.C., Chicago, Illinois, Pittsburgh, Pennsylvania, and Los Angeles, California, U.S.A.--the Multicenter AIDS Cohort Study (MACS). Variables within 6 months prior to AIDS diagnosis included age, CD4+ lymphocyte counts, hemoglobin, and self-reported thrush, fever, anti-retroviral therapy (ART) beginning prior to AIDS onset, and ART beginning after AIDS (as a time-dependent covariate) were analyzed as mutually exclusive categories, as was prophylaxis for Pneumocystis carinii pneumonia (PCP). Univariate and multivariate survival models of time from AIDS to death were fit. In univariate analysis, younger age, higher counts of CD4+ lymphocytes, hemoglobin, and absence of thrush or fever prior to AIDS onset were associated with longer survival after AIDS. Those who began ART within 3 months after AIDS onset had longer median survival (1.75 years), from 3 months after AIDS, when compared with those who began ART prior to AIDS (1.18 years). This comparison is not influenced by the bias that those who survive longer have a greater likelihood to subsequently receive ART. Prophylaxis for PCP beginning after AIDS onset was also associated with longer post-AIDS survival when compared with beginning prophylaxis prior to AIDS or never using prophylaxis.(ABSTRACT TRUNCATED AT 250 WORDS)

The objective of this study was to determine whether beta 2-microglobulin, neopterin, nutritional status, clinical status, immunosuppression, and hematologic status are predictors of human immunodeficiency virus (HIV)-related wasting and wasting syndrome. In addition, we aimed to determine which factors are early predictors and which are late predictors of wasting. For this cohort study of HIV-1-seropositive men seen semiannually from 1984 to 1991, a nested case-control design was used to analyze the predictive value of independent variables collected at baseline (first study visit for the seropositive cohort, first seropositive visit for seroconverters), 12 to 18 months prior, 6 to 12 months prior, and less than 6 months prior to the time at which case patients and control subjects were identified. Data on beta 2-microglobulin, neopterin, educational status, and diet were only available at baseline. A total of 41 case patients and 161 control subjects (n = 202) were identified. These were homosexual/bisexual men who were either HIV-seropositive on entering the study (n = 177) or who seroconverted during the study period (n = 25). Case patients were defined as men who had lost more than 10% of their baseline weight or who had a clinical diagnosis of wasting syndrome using the 1987 Centers for Disease Control definition. Control subjects had less than 5% weight loss from baseline or no weight loss at all. Four control subjects were matched to each case patient (where possible) by age and duration of follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Background: Among patients infected with human immunodeficiency virus type 1 (HIV-1), early and widespread use of prophylactic regimens against Pneumocystis carinii is changing the pattern of illnesses related to the acquired immunodeficiency syndrome (AIDS)., Methods: We conducted a subcohort analysis of 844 men with AIDS (87 percent of whom have since died) from a prospectively followed cohort of 2592 HIV-1-infected homosexual men., Results: A total of 138 men received prophylaxis before the diagnosis of AIDS, but 39 (28 percent) nevertheless had P. carinii pneumonia at some time. Only four illnesses occurred more frequently in men who received P. carinii prophylaxis before the onset of AIDS: Mycobacterium avium complex disease, which developed in 33.4 percent, as compared with 17.3 percent of the 706 men who did not receive early prophylaxis; wasting syndrome (18.4 percent vs. 6.4 percent); cytomegalovirus disease (44.9 percent vs. 24.8 percent); and esophageal candidiasis (21.3 percent vs. 12.8 percent). Collectively, these four diseases accounted for the initial AIDS-related illness in 42.7 percent of those who received prophylaxis before the onset of AIDS, as compared with 10.7 percent of those who did not. During the three six-month periods before the diagnosis of AIDS (0 to 6, > 6 to 12, and > 12 to 18 months), the geometric mean CD4+ cell counts were 48, 87, and 147 per cubic millimeter, respectively, in men who received prophylaxis against P. carinii, as compared with 118, 211, and 279 per cubic millimeter in those who did not., Conclusions: M. avium complex disease, esophageal candidiasis, wasting syndrome, and cytomegalovirus disease are more common in HIV-infected patients who have received prophylaxis against P. carinii than in those who have not. Prophylaxis may delay the first AIDS illness for 6 to 12 months.