HIV disease progression in Australia in the time of combination antiretroviral therapies

OBJECTIVE: To examine the effect of recent developments in antiretroviral therapy on HIV disease progression and survival. DESIGN: Retrospective cohort study. PARTICIPANTS AND SETTING: Two cohorts of people with HIV were defined retrospectively from the records of a large immunology laboratory. The first cohort were subjects whose CD4+ T cell counts had dropped to 200 x 10(6)/L during 1990, and the second were subjects whose CD4+ T cell counts had dropped to 200 x 10(6)/L in 1994. MAIN OUTCOME MEASURES: HIV disease progression and survival was determined over a minimum three years of follow-up for each cohort (i.e., 1990-1993; 1994-1997). RESULTS: 346 subjects were included in the analysis (193 subjects from 1990 and 153 from 1994). The relative risk of progression to AIDS in the 1994 cohort compared with the 1990 cohort was 0.57 (95% confidence interval, 0.35-0.91; P = 0.018) and the relative risk of death was 0.20 (95% confidence interval, 0.08-0.49; P < 0.001). CONCLUSIONS: There were 43% fewer AIDS cases and 80% fewer deaths in the time following the increased availability of combination antiretroviral therapy in Australia.     

Presence of the variant mannose-binding lectin alleles associated with slower progression to AIDS. Amsterdam Cohort Study

OBJECTIVE: To examine the association between mannose-binding lectin (MBL) polymorphism and progression to AIDS and death in HIV-1 infection. DESIGN AND METHODS: In 131 HIV-1-infected homosexual seroconverters, survival analyses were performed to determine both the association between MBL genotype and time from HIV-1 seroconversion to AIDS and death, and time from AIDS to death. RESULTS: Of the 131 seroconverters, of whom 61 developed AIDS, 76 were typed as homozygous wild-type and 55 as carriers of variant alleles (52 heterozygous and three homozygous variant alleles). A Survival analyses suggested that HIV-1-infected men with the variant alleles progressed somewhat slower to AIDS [relative hazard (RH), 0.62; 95% confidence interval (CI), 0.36-1.10] and death (RH, 0.73; 95% CI, 0.42-1.25). Interestingly, CD4+ T-cell count determined at the moment of AIDS was found to be significantly lower among persons with the mutation (97 x 10(6)/l versus 204 x 10(6)/l; P=0.03). Furthermore, when AIDS-free times before the diagnosis of an opportunistic infection were compared with those preceding a diagnosis of Kaposi's sarcoma, Kaposi's sarcoma diagnosis was more postponed than that of an opportunistic infection (RH, 0.21; 95% CI, 0.05-0.95; versus RH, 0.67; 95% CI, 0.35-1.27). CONCLUSION: Indications for a weak pre-AIDS protective effect of variant MBL alleles were demonstrated.     

Combination antiretroviral therapy and recent declines in AIDS incidence and mortality

The reasons for recent declines in AIDS incidence and mortality may include advances in treatment, but these may be confounded by earlier declines in the incidence of human immunodeficiency virus (HIV) infection. To determine whether the declines in AIDS and mortality may, in part, stem from wider use of combination antiretroviral therapy, 622 HIV-positive men with well-characterized dates of seroconversion were followed. In this group, combination therapy came into widespread use in only 1996. In a Cox proportional hazards model, the 1996 calendar period was significantly associated with slower progression to AIDS (relative hazard [RH]=0. 19, 95% confidence interval [CI], 0.05-0.69, P=.01) and death (RH=0. 45, 95% CI, 0.21-0.95, P=.04). Declines in incidence of HIV infection, changes in HIV virulence, and end-point underreporting cannot fully explain the decline in AIDS and death in 1996. The introduction of combination antiretroviral therapy as the standard of care may already have had measurable effects.     

Long-term perspective on the prevalent-cohort biases in studies of human immunodeficiency virus progression

Because considerable information about progression of human immunodeficiency virus (HIV) infection has been provided by studies of cohorts of individuals with prevalent HIV infection, this study was designed to investigate bias due to onset confounding (differential time-since-infection distributions) and differential length-biased sampling in epidemiologic analyses of data from such cohorts. Subjects were participants in the Italian Seroconverters Study, a seroincident cohort of more than 1,200 adults seen at ambulatory care clinics in Italy, with observed HIV seroconversion in 1980-1988. Acquired immunodeficiency syndrome (AIDS) diagnoses, based on the 1987 Centers for Disease Control case definition, and mortality were ascertained through Italian national registries through 1994. To estimate bias in prevalent cohorts, a series of pseudoseroprevalent (PSP) cohorts were drawn by sampling, from among the total seroincident cohort, prevalent AIDS-free subjects in each calendar year. The relative AIDS risk associated with a given covariate was calculated in each PSP cohort and compared with the relative AIDS risk for that covariate in the seroincident cohort. Relative risks were estimated by both the ratio of AIDS incidence densities and the relative AIDS hazards from proportional hazards regression. Differential length bias was not evident, as assessed in the following way: Among 338 individuals with seroconversion dates in 1983-1986, the relative risk of AIDS for subjects born before 1951 compared with those born more recently was 1.67 (95% confidence interval (CI) 1.30-2.14). Although differential length-biased sampling was expected to bias this relative risk toward 1.0, the observed relative risk for earlier birth ranged from 1.79 to 2.86 in 1987-1992 PSP cohorts. Onset bias was observed: Among 644 subjects with seroconversion in 1980-1988, the AIDS relative risk for 1980-1985 seroconverters compared with 1986-1988 seroconverters was 1.09 (95% CI 0.76-1.55). Onset bias was seen in 1988-1990 PSP cohorts (relative risks for early seroconversion = 1.47, 1.46, and 1.34, respectively); in 1991-1992, relative risks were close to the expected value of 1.09, and CIs on relative risks from all PSP cohorts after 1989 included 1.0. Confounding attributable to differential length-biased sampling in prevalent cohorts does not necessarily bias estimates of the impact of covariates on rate of progression to AIDS. Bias can arise when a covariate suspected of affecting AIDS risk is closely linked to date of acquisition of HIV infection. However, onset bias appears to wane as subjects' dates of infection become more remote.     

Cigarette smoking, bacterial pneumonia, and other clinical outcomes in HIV-1 infection. Terry Beirn Community Programs for Clinical Research on AIDS

Cigarette smoking has been associated with impaired immune defenses and an increased risk of certain infectious and neoplastic diseases in HIV-1 seronegative populations. We examined the relationship between cigarette smoking and clinical outcome in a prospective cohort of 3221 HIV-1-seropositive men and women enrolled in the Terry Beirn Community Programs for Clinical Research on AIDS. Differences in clinical outcomes between never, former, and current cigarette smokers were assessed using proportional hazards regression analysis. After adjustment for CD4+ cell count, prior disease progression, use of antiretroviral therapy, and other covariates, there was no difference between current smokers and never smokers in the overall risk of opportunistic diseases [relative hazard (RH) = 1.05; 95% confidence interval (CI) 0.90-1.23; p = 0.52] or death (RH = 1.00; 95% CI 0.86-1.18; p = 0.97). However, current smokers were more likely than never smokers to develop bacterial pneumonia (RH = 1.57; 95% CI 1.14-2.15; p = 0.006), oral candidiasis (RH = 1.37; 95% CI 1.16-1.62; p = 0.0002), and AIDS dementia complex (RH = 1.80; 95% CI 1.11-2.90; p = 0.02). In addition, current smokers were less likely to develop Kaposi's sarcoma (RH = 0.58; 95% CI 0.39-0.88; p = 0.01) and several other non-respiratory tract diseases. If confirmed by other studies, these findings have important clinical implications.     

The incubation period to AIDS in injecting drug users estimated from prevalent cohort data, accounting for death prior to an AIDS diagnosis

OBJECTIVE: To estimate the incubation-period distribution (time from seroconversion to AIDS) accounting for death before an AIDS diagnosis (DBAD) in a cohort of injecting drug users (IDU) in Amsterdam, The Netherlands and to compare these estimates with those previously obtained from a contemporaneous study of homosexual and bisexual men in Amsterdam carried out using the same facilities. DESIGN: Participants in a cohort study begun in Amsterdam at the end of 1985 have scheduled follow-up visits every 4 months. All participants of Dutch nationality and who had two or more follow-up visits before January 1996 from which CD4 measurements were available were included in this study. Data concerning AIDS diagnosis and death were verified through review of national and municipal registries. METHODS: Because time of seroconversion was unknown for study participants and because IDU are at substantial risk for DBAD, we used a Markov model with CD4-based stages that allows for DBAD. The parameters in this model were estimated using the method of maximum likelihood and confidence intervals were calculated using bootstrap methods. RESULTS: A total of 173 IDU (134 seroprevalent, 39 seroincident) made 1829 visits. Nearly 10% of the visits were non-consecutive. Forty-five IDU developed AIDS and 25 died without an AIDS diagnosis. We estimated that 24% [95% confidence interval (CI), 17-25%] of IDU die before an AIDS diagnosis. As a result, the median time from seroconversion to AIDS (10.5 years; 95% CI, 9.1-10.7 years) is considerably longer than the median time from seroconversion to death (8.3 years; 95% CI, 7.9-8.5 years). Conditional on survival to an AIDS diagnosis, the median time to AIDS is 8.2 years (95% CI, 7.7-8.7 years). The median survival time after a diagnosis of AIDS is estimated to be 1.0 years. CONCLUSION: The high occurrence of DBAD in IDU has a considerable influence on estimates of the incubation-period distribution. Progression from seroconversion to death was faster in the IDU cohort than in a cohort of homosexual men in Amsterdam (median, 8.3 years and 9.6 years, respectively). However, progression to AIDS conditional on survival to an AIDS diagnosis seems to be similar in both the IDU cohort and in the cohort of homosexual men (median, 8.2 years and 8.3 years, respectively).     

Changes in CD4+ cell count and the risk of opportunistic infection or death after highly active antiretroviral treatment. Groupe d'Epidémiologie Clinique du SIDA en Aquitaine

OBJECTIVE: To study the relationship between the CD4+ cell response after initiation of protease inhibitors and the occurrence of opportunistic infections and survival. DESIGN: Prospective observational cohort study. METHODS: HIV-1-seropositive subjects followed-up in HIV centres of Bordeaux University Hospital, Southwest France who were prescribed at least one available protease inhibitor between January and December 1996 were included in this analysis. A Cox model estimated the independent effect of baseline covariates and CD4+ cell response, considered as a time-dependent covariate, on the occurrence of new AIDS-defining opportunistic infection, new AIDS-defining events, new AIDS-defining opportunistic infection or death. RESULTS: A total of 556 HIV-positive patients were prescribed at least one protease inhibitor: 34% saquinavir, 52% indinavir, and 14% ritonavir. Median CD4+ cell count at baseline was 95 x 10(6)/l and mean plasma HIV RNA was 5.0 log10 copies/ml. After a median follow-up of 230 days, 65 patients experienced a new episode of opportunistic infection, 79 patients experienced at least one AIDS-defining event, and 24 had died. On average, the increase in CD4+ cell count was 42 x 10(6)/l (SD, 74) after a median of 49 days. In the multivariate analysis of opportunistic infection or death, each 50% higher CD4+ cell count at baseline was associated with a 23% reduction [95% confidence interval (CI), 14-30] of risk. Each 50% increase in CD4+ cell count during follow-up was associated with a 9% reduction (95% CI, 2-15) of risk, adjusted for the presence of AIDS prior to protease inhibitor therapy (hazard ratio, 3.76 versus absence of AIDS; P < 0.01) and haemoglobin level (hazard ratio, 0.48 if > 11 g/dl versus <11 g/dl; P < 0.01). CONCLUSION: Our results show, at least indirectly, how protease inhibitors might produce clinical stabilization. This result may be due to improved functionality of CD4+ cells in patients started on protease inhibitors.     

Apparent enhancement of perinatal transmission of human immunodeficiency virus type 1 by high maternal anti-gp160 antibody titer

The presence of antibodies able to enhance infection in vitro in sera from human immunodeficiency virus (HIV)-1-infected patients raises the possibility that antibodies exert a deleterious activity during natural infection. The anti-HIV-1 humoral response and plasma HIV-1 RNA were measured in a cohort of 98 infected mothers, included in the French Prospective Study on Pediatric HIV Infection, 49 of whom transmitted HIV to their children. Transmission from mother to child was associated with antibody responses to the envelope gp160 (P = .009 for serum dilution of 1/400) and to a highly conserved domain of the transmembrane glycoprotein (P = .055 for serum dilution of 1/400) and with plasma HIV-1 RNA levels (P < .0001). Multivariate logistic regression indicated that a high anti-gp160 response and a high plasma virus load are independent risk factors for perinatal transmission of HIV-1 (odds ratio, 3.4; 95% confidence interval, 1.1-9.9 for anti-gp160; odds ratio, 2.8; 95% confidence interval, 1.6-5.0 for virus load).     

Early prognostic indicators in primary perinatal human immunodeficiency virus type 1 infection: importance of viral RNA and the timing of transmission on long-term outcome

The time of perinatal human immunodeficiency virus type 1 (HIV-1) transmission and the pattern of early plasma viremia as predictors of disease progression were evaluated in infected infants followed from birth. Cox proportional hazards modeling demonstrated that a 1-log higher HIV-1 RNA copy number at birth was associated with a 40% increase in the relative hazard (RH) of developing CDC class A or B symptoms (P = .004), a 60% increase in developing AIDS (P = .01), and an 80% increase in the of risk death (P = .023) over the follow-up period of up to 8 years. The peak HIV-1 RNA copy number for infants during primary viremia was also predictive of progression to AIDS (RH, 9.9; 95% confidence interval [95% CI], 1.8-54.1; P = .008) and death (RH, 6.9; 95% CI, 1.1-43.8; P = .04). The results indicate that high levels of HIV-1 RNA at birth and during primary viremia are associated with early onset of symptoms and rapid disease progression to AIDS and death in perinatally infected children.     

Herpes zoster, immunological deterioration and disease progression in HIV-1 infection

OBJECTIVE: To study the incidence of herpes zoster, the relationship between herpes zoster and immunological markers, and the prognostic value of herpes zoster for progression of HIV disease. DESIGN AND METHODS: A total of 966 homosexual participants in The Amsterdam Cohort Study were studied. Herpes zoster was defined by its characteristic clinical presentation. Incidence was calculated using Poisson regression, cumulative incidence by the Kaplan-Meier product-limit method and the prognostic value was evaluated using Cox proportional hazards model. RESULTS: The incidence of first episodes of herpes zoster was 3.31 per 1000 person-years (PY) in HIV-seronegatives and 51.51 per 1000 PY in HIV-1-seropositive individuals. Recurrences only occurred in HIV-1-positive patients (25.6%). Cumulative incidences of first episodes increased linearly with the duration of follow-up. In HIV-1-seropositives the incidence was 31.2 per 1000 PY at CD4+ cells > or = 500 x 10(6)/l, 47.2 per 1000 PY [relative risk (RR), 1.51; 95% confidence interval (CI), 0.78-2.94] at CD4+ cells 200-499 x 10(6)/l and 97.5 per 1000 PY (RR, 3.13; 95% CI, 1.54-6.32) at CD4+ cells < 200 x 10(6)/l. Besides CD4+ cell counts, CD3 monoclonal antibodies and phytohaemagglutinin-induced T-cell reactivity were independent predictors for herpes zoster. The hazard ratio for AIDS after herpes zoster was 1.6 (95% CI, 1.1-2.4) and for death 1.7 (95% CI, 1.1-2.5), but these were not independent from CD4+ cell counts. CONCLUSION: In HIV-1 infection the incidence of herpes zoster increases with the decrease of CD4+ cell counts and T-cell reactivity, but herpes zoster is not an independent predictor for disease progression.     

Bilateral thrombosis of the internal carotid arteries after a closed trauma. Advantages of magnetic resonance imaging and review of the literature

OBJECTIVE: Hospital and physician experience have been linked to improved outcomes for persons with HIV. Because many HIV-infected patients receive care in clinics, we studied clinic HIV experience and survival for women with AIDS. DESIGN: Retrospective cohort study of women with AIDS whose dominant sources of care were clinics. Clinic HIV experience was estimated as the cumulative number of Medicaid enrollees with advanced HIV who used a particular clinic as their dominant provider up to the year of the patient's AIDS diagnosis: low experience (< 20 patients), medium (20-99 patients), high (> or = 100 patients). Proportional hazards models examined relationships between experience and survival. SETTING: A total of 117 New York State clinics. PATIENTS: A total of 887 New York State Medicaid-enrolled women diagnosed with AIDS in 1989-1992. MAIN OUTCOME MEASURE: Survival after AIDS diagnosis. RESULTS: In later study years (1991-1992), patients in high experience clinics had an approximately 50% reduction in the relative hazard of death (0.53; 95% confidence interval, 0.35-0.82) compared with patients in low experience clinics. Adjusting for demographic and clinical variables, 71% of patients in high experience clinics were alive 21 months after diagnosis compared with 53% in low experience clinics. Experience and survival were not significantly associated in the early study years (1989-1990). CONCLUSIONS: In more recent years, women with AIDS receiving care in high experience clinics survived longer after AIDS diagnosis than those in low experience clinics, providing further evidence of a relationship between provider HIV experience and outcomes.     

Cystic prostatic disease associated with adrenocortical lesions in the ferret (Mustela putorius furo)

CONTEXT: In British Columbia, human immunodeficiency virus (HIV)-infected persons eligible for antiretroviral therapy may receive it free but the extent to which HIV-infected injection drug users access it is unknown. OBJECTIVE: To identify patient and physician characteristics associated with antiretroviral therapy utilization in HIV-infected injection drug users. DESIGN: Prospective cohort study with record linkage between survey data and data from a provincial HIV/AIDS (acquired immunodeficiency syndrome) drug treatment program. SETTING: British Columbia, where antiretroviral therapies are offered free to all persons with HIV infection with CD4 cell counts less than 0.50 x 10(9)/L (500/microL) and/or HIV-1 RNA levels higher than 5000 copies/mL. SUBJECTS: A total of 177 HIV-infected injection drug users eligible for antiretroviral therapy, recruited through the prospective cohort study since May 1996. MAIN OUTCOME MEASURES: Patient use of antiretroviral drugs through the provincial drug treatment program and physician experience treating HIV infection. RESULTS: After a median of 11 months after first eligibility, only 71 (40%) of 177 patients had received any antiretroviral drugs, primarily double combinations (47/71 [66%]). Both patient and physician characteristics were associated with use of antiretroviral drugs. After adjusting for CD4 cell count and HIV-1 RNA level at eligibility, odds of not receiving antiretrovirals were increased more than 2-fold for females (odds ratio [OR], 2.53; 95% confidence interval [CI], 1.08-5.93) and 3-fold for those not currently enrolled in drug or alcohol treatment programs (OR, 3.49; 95% CI, 1.45-8.40). Younger drug users were less likely to receive therapy (OR, 0.47/10-y increase; 95% CI, 0.28-0.80). Those with physicians having the least experience treating persons with HIV infection were more than 5 times less likely to receive therapy (OR, 5.55; 95% CI, 2.49-12.37). CONCLUSIONS: Despite free antiretroviral therapy, many HIV-infected injection drug users are not receiving it. Public health efforts should target younger and female drug users, and physicians with less experience treating HIV infection.     

The associations between cervicovaginal HIV shedding, sexually transmitted diseases and immunosuppression in female sex workers in Abidjan, C?te d'Ivoire

OBJECTIVE: To measure the frequency and associated factors of cervicovaginal HIV shedding and to determine the impact of sexually transmitted disease (STD) treatment on HIV shedding. DESIGN: Cross-sectional study with 1-week follow-up. SETTING: Confidential clinic for female sex workers in Abidjan, C?te d'Ivoire. PARTICIPANTS: A total of 1201 female sex workers. INTERVENTIONS: STD treatment based on clinical signs. MAIN OUTCOME MEASURES: HIV serostatus; cervicovaginal HIV shedding at enrollment and at 1-week follow-up; STD status at enrollment and at 1-week follow-up. RESULTS: Cervicovaginal shedding of HIV-1 in HIV-1-seropositive women was more frequent (96 out of 404, 24%) than shedding of HIV-2 in HIV-2-seropositive women [one out of 21, 5%; odds ratio (OR), 6.2; 95% confidence interval (CI), 1.0-261]. Among 609 HIV-1-seropositive or dually seroreactive women, HIV-1 shedding was significantly more frequent in immunosuppressed women [adjusted OR (AOR), 6.3; 95% CI, 3.4-11.9; and AOR, 2.9; 95% CI, 1.6-5.0 for CD4 < 14% and CD4 14-28%, respectively, versus CD4 > 28%], and in women with Neisseria gonorrhoeae (AOR, 1.9; 95% CI, 1.2-3.0), those with Chlamydia trachomatis (AOR, 2.5; 95% CI, 1.1-5.8), and with a cervical or vaginal ulcer (AOR, 3.9; 95% CI, 2.1-7.4). HIV-1 shedding decreased from 42 to 21% (P < 0.005) in women whose STD were cured. CONCLUSIONS: These data help to explain the difference in transmissibility between HIV-1 and HIV-2 and the increased infectiousness of HIV in the presence of immunosuppression and STD. In addition, they lend biological plausibility to arguments for making STD control an integral part of HIV prevention strategies in Africa.     

Effectiveness of potent antiretroviral therapy on time to AIDS and death in men with known HIV infection duration. Multicenter AIDS Cohort Study Investigators

CONTEXT: Time to development of acquired immunodeficiency syndrome (AIDS) and time to death have been extended with the increased use of combination therapy and protease inhibitors. Cohort studies following up persons with human immunodeficiency virus (HIV) infection in periods characterized by different therapies offer the opportunity to estimate therapy effectiveness at the population level. OBJECTIVE: To assess the effectiveness of self-reported, long-term potent antiretroviral therapy in a cohort of 536 men whose duration of HIV infection was known (seroconverters). DESIGN: Cohort study. The cohort was compared for time to development of AIDS and time to death in 1984 to 1990, 1990 to 1993, 1993 to July 1995, and July 1995 to July 1997 when the major treatments were no therapy, monotherapy, combined therapy, and potent antiretroviral therapy, respectively. Survival analysis methods with time zero set as the date of seroconversion and incorporating staggered entries into each period were used. Mean CD4 cell change, stratified by infection duration, was determined for each period using a random effects model. SETTING: The Multicenter AIDS Cohort Study (MACS) in 4 urban areas (Baltimore, Md; Chicago, III; Los Angeles, Calif; and Pittsburgh, Pa). PARTICIPANTS: A total of 5622 men who were 18 years or older were enrolled into MACS. Of the 5622, there were 2191 HIV-positive individuals at enrollment. Of the 3431 men who were HIV-negative, 536 were observed to seroconvert and were followed up for up to 13 years. The group of 536 who seroconverted constituted the study population. MAIN OUTCOME MEASURES: Time from seroconversion to development of AIDS and to death and change in CD4 cell count. RESULTS: A total of 231 seroconverters developed AIDS, and 200 men died. Using 1990 to 1993 as the reference period, the relative hazard of AIDS was 1.04 (95% confidence interval [CI], 0.73-1.48) during 1993 to July 1995 and 0.35 (95% CI, 0.20-0.61) during July 1995 to July 1997. Relative hazards of death were 0.87 (95% CI, 0.58-1.31) and 0.62 (95% CI, 0.38-1.01 ) for the same periods. The relative time (the factor by which times are contracted or expanded) to development of AIDS was 0.97 (95% CI, 0.86-1.09) for 1993 to July 1995 and 1.63 (95% CI, 1.40-1.89) for July 1995 to July 1997. Relative survival time for 1993 to July 1995 was 1.01 (95% CI, 0.91-1.12) and for July 1995 to July 1997 was 1.21 (95% CI, 1.07-1.36) relative to 1990 to 1993. The rate of CD4 cell count decline in July 1995 to July 1997 was significantly lower (P<.05) compared with the previous 2 periods. CONCLUSIONS: In the calendar period when potent antiretroviral therapy was introduced, the time to development of AIDS and time to death were extended, and rate of CD4 cell count decline was arrested.     

The prognostic value of the QT interval and QT interval dispersion in all-cause and cardiac mortality and morbidity in a population of Danish citizens

AIMS: To evaluate the prognostic value of the QT interval and QT interval dispersion in total and in cardiovascular mortality, as well as in cardiac morbidity, in a general population. METHODS AND RESULTS: The QT interval was measured in all leads from a standard 12-lead ECG in a random sample of 1658 women and 1797 men aged 30-60 years. QT interval dispersion was calculated from the maximal difference between QT intervals in any two leads. All cause mortality over 13 years, and cardiovascular mortality as well as cardiac morbidity over 11 years, were the main outcome parameters. Subjects with a prolonged QT interval (430 ms or more) or prolonged QT interval dispersion (80 ms or more) were at higher risk of cardiovascular death and cardiac morbidity than subjects whose QT interval was less than 360 ms, or whose QT interval dispersion was less than 30 ms. Cardiovascular death relative risk ratios, adjusted for age, gender, myocardial infarct, angina pectoris, diabetes mellitus, arterial hypertension, smoking habits, serum cholesterol level, and heart rate were 2.9 for the QT interval (95% confidence interval 1.1-7.8) and 4.4 for QT interval dispersion (95% confidence interval 1.0-19-1). Fatal and non-fatal cardiac morbidity relative risk ratios were similar, at 2.7 (95% confidence interval 1.4-5.5) for the QT interval and 2.2 (95% confidence interval 1.1-4.0) for QT interval dispersion. CONCLUSION: Prolongation of the QT interval and QT interval dispersion independently affected the prognosis of cardiovascular mortality and cardiac fatal and non-fatal morbidity in a general population over 11 years.     

Mortality from tuberculosis in Spain from 1970 to 1993: changes in epidemiological trends during the acquired immune-deficiency syndrome epidemic

SETTING: Spain has the highest rates in Europe of the acquired immune-deficiency syndrome (AIDS), and probably a high rate of dual human immunodeficiency virus (HIV)/tuberculosis infection. OBJECTIVE: To determine the trends of tuberculosis mortality in Spain from 1970 to 1993, and to draw conclusions about the effects of the AIDS epidemic on these trends. DESIGN: Official population figures and data on deaths from tuberculosis were used to calculate specific tuberculosis mortality rates by age and sex (per 100000 population). Causes of death from tuberculosis were grouped according to the International Classification of Diseases. RESULTS: The crude death rate decreased from 10.28 to 1.84, with an annual mean decrease of 8.1% (95% confidence interval 7.5% to 8.7%). No changes in mortality from tuberculosis of the central nervous system (CNS) have been recorded since 1982, and none in mortality from other tuberculosis and in the age group 20-49 years since 1986. Mortality was higher among males and in the older age groups. The peak observed in the 1970s, due to the excess of deaths from CNS tuberculosis in children under the age of 5 years, has disappeared. CONCLUSION: Between 1970 and 1993, tuberculosis mortality in Spain decreased, although an excess of deaths occurred in young adults and from extra-pulmonary tuberculosis, coinciding with the AIDS epidemic.     

Mortality associated with HIV-1 infection over five years in a rural Ugandan population: cohort study

OBJECTIVE: To assess the impact of HIV-1 infection on mortality over five years in a rural Ugandan population. DESIGN: Longitudinal cohort study followed up annually by a house to house census and medical survey. SETTING: Rural population in south west Uganda. SUBJECTS: About 10,000 people from 15 villages who were enrolled in 1989-90 or later. MAIN OUTCOME MEASURES: Number of deaths from all causes, death rates, mortality fraction attributable to HIV-1 infection. RESULTS: Of 9777 people resident in the study area in 1989-90, 8833 (90%) had an unambiguous result on testing for HIV-1 antibody; throughout the period of follow up adult seroprevalence was about 8%. During 35,083 person years of follow up, 459 deaths occurred, 273 in seronegative subjects and 186 in seropositive subjects, corresponding to standardised death rates of 8.1 and 129.3 per 1000 person years. Standardised death rates for adults were 10.4 (95% confidence interval 9.0 to 11.8) and 114.0 (93.2 to 134.8) per 1000 person years respectively. The mortality fraction attributable to HIV-1 infection was 41% for adults and was in excess of 70% for men aged 25-44 and women aged 20-44 years. Median survival from time of enrollment was less than three years in subjects aged 55 years or more who were infected with HIV-1. Life expectancy from birth in the total population resident at any time was estimated to be 42.5 years (41.4 years in men; 43.5 years in women), which compares with 58.3 years (56.5 years in men; 60.5 years in women) in people known to be seronegative. CONCLUSIONS: These data confirm that in a rural African population HIV-1 infection is associated with high death rates and a substantial reduction in life expectancy.     

Myocardial ischemia alters immunoregulatory cell traffic and function in the rat independent of exogenous catecholamine administration

OBJECTIVES: To investigate the occurrence of AIDS dementia complex (ADC) in Italy and its incidence over time, examining possible correlations between this condition and some demographic and immunological variables. DESIGN: Inception cohort. Data collected from the case notification forms of the Italian National AIDS Registry. SUBJECTS: 16813 consecutive AIDS cases reported to the National AIDS Registry from August 1, 1987 through October 31, 1993 were included. STATISTICAL METHODS: All data refer to the time of AIDS diagnosis as reported on the case notification forms. Main analyses of the monthly proportion of ADC cases were by multiple logistic regression. RESULTS: 1364 subjects (8.1%) were reported with a diagnosis of ADC as the first AIDS defining disease, either as the only manifestation or associated with other AIDS defining conditions. At the time of AIDS diagnosis, the observed ADC/AIDS proportion was significantly higher among intravenous drug users (IVDU), 9.1%, compared to heterosexuals, 6.3%, and homo-bisexual men, 5.2%. Simple logistic regression analysis showed a significant (p < 0.0001) quadratic trend in the monthly ADC/AIDS proportion, peaking in March 1990 and decreasing thereafter. Multiple logistic regression, adjusting for month of diagnosis, showed that IVDUs have consistently the highest risk and homo-bisexual men the lowest, although differences tended to decrease with increasing age. Older age, in fact, was highly associated with an increased risk, especially within the homo-bisexual and heterosexual transmission categories. CD4 + cells counts proved to have no significant effect on the risk of progressing to AIDS with ADC rather than with any other AIDS indicative disease. CONCLUSIONS: ADC is a relatively frequent manifestation at diagnosis of AIDS among Italian patients, and particularly in IVDUs. Differences in its occurrence were found according to time of diagnosis, transmission category and age.     

Effects of malaria infection in human immunodeficiency virus type 1-infected Ugandan children

BACKGROUND: Malaria causes severe morbidity and mortality in many areas of Africa where HIV-1 infection is also prevalent. Immunosuppression is associated with both diseases but most reports do not find significant interactions between them. METHODS: A collaborative study of HIV-1 infection in Ugandan women and their infants was established between the Ministry of Health, Makerere University, Kampala, and Case Western Reserve University in 1988. Four hundred fifty-eight infants, including 77 HIV-1-infected, 232 seroreverter and 125 control children born to HIV-1-negative mothers and 24 of indeterminate status were followed closely from birth for 4 years. Data on these infants were reviewed with respect to episodes of general illness and infections, suspected and confirmed episodes of malaria, onset and frequency of malaria, use of chloroquine and occurrence of selected illnesses after episodes of febrile illnesses. Thick and thin blood smears for malaria were obtained from children with fever. RESULTS: There was no association between occurrence of febrile illnesses and childrens' HIV-1 category. The relative rates of occurrence were 1.0 (95% confidence interval (CI), 0.8 to 1.2) and 1.1 (95% CI 0.9 to 1.4) for the HIV seroreverter and control children compared with the HIV-infected children. Although there was no association (P = 0.83) between HIV-1 status and a smear being taken during a febrile episode, there was an increase in smears positive for malaria parasitemia among seroreverter (risk ratio, 1.5; 95% CI 1.1 to 1.9) and control infants (risk ratio, 1.6; 95% CI 1.2 to 2.2) compared with HIV-1-infected infants. The level of parasitemia was similar in each group. A greater proportion of malaria episodes among the HIV-infected group than among the control groups resulted in hospitalizations (P = 0.001) and blood transfusions (P = 0.02). There was a positive association between time to clinical AIDS and absence of malaria (adjusted for follow-up age) in infected children (P = 0.02). Use of chloroquine was similarly high in each HIV-1 category (80%). CONCLUSIONS: In this group of HIV-infected children there was no significant increase in malarial episodes as compared with their HIV-negative controls. The results suggest a possibility that malaria may offer some protection against HIV-1 progression or that chloroquine used to treat malaria may have a direct effect against the HIV-1 virus.     

Impact of human immunodeficiency virus infection on mortality among young men and women in Spain

BACKGROUND: This paper describes the impact of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) mortality among young adults in Spain with specific reference to other causes of death. METHODS: Based on death registration data for the period 1980-1993, HIV/AIDS was compared against all other causes of death by gender, using specific rates in the 25-44 age group and standardized rates for potential years of life lost (PYLL). RESULTS: In 1993, HIV/AIDS was the leading cause of death among men aged 25-44 years (21.8% of all deaths) and the second leading cause of death among women (14.9%), exceeded only by cancer. Since 1982, the trend in the overall standardized mortality rate for men in the 25-44 age group has been reversed, showing a progressive increase. Similarly, since 1984 there has been a halt in the decline in female mortality. For both sexes, maintenance of these trends in mortality was largely ascribable to the effect of HIV/AIDS deaths which registered a marked rise, a rise far sharper than that witnessed for variations in all other causes studied. In 1993, the adjusted PYLL rate for HIV/AIDS for ages 1-70 rose to 615 per 100,000 population in men and 156 in women. These values accounted for 9.2% and 5.8% of PYLL for all causes, thereby ranking HIV/AIDS behind motor vehicle accidents as the second leading cause of premature death in men, and behind motor vehicle accidents and breast cancer as the third leading cause in women. For both sexes, the rise in the PYLL rate for HIV/AIDS from 1992 to 1993 proved far greater than that for all other causes of death. CONCLUSION: In Spain, HIV/AIDS has become the leading cause of death among young adults and is counteracting improvements in mortality due to other causes. It should therefore be regarded as a priority public health problem.