Cofactors of progression to acquired immunodeficiency syndrome in a cohort of male sexual contacts of men with human immunodeficiency virus disease

In a cohort of 249 male sexual contacts of men with acquired immunodeficiency syndrome (AIDS) or an AIDS-related condition in Toronto, Ontario, Canada, 143 cohort members were seropositive on enrollment and 16 seroconverted between initial recruitment in July 1984 to July 1985 and December 1988. Data on age, smoking and drinking status, recreational drug use, and history of sexually transmitted diseases and other diseases were obtained from interviews at induction and during follow-up on the cohort members every 3 months. Cox relative risk regression models, in which time was calculated from estimated date of human immunodeficiency virus (HIV) infection for seroprevalent cohort members and from 90 days prior to the first positive test for seroconverters, examined the potential effect of use of a variety of recreational drugs and the occurrence of selected infections on the risk of development of AIDS. Thirty-five cohort members developed AIDS while under study. No significant association with risk of progression to AIDS was noted for use of various recreational drugs (singly or in combination), history of specific infections, age at enrollment, or smoking and drinking status at enrollment. Only estimated duration of HIV infection appeared to be associated with increasing risk of development of AIDS.     

The probability of progression to AIDS in a cohort of male sexual contacts of men with HIV disease.

In a cohort of 249 male sexual contacts of men with AIDS or an AIDS-related condition (ARC), 143 cohort members were seropositive on enrollment and 16 seroconverted during follow-up. A logistic Weibull mixture model was used to estimate the probability of progression to AIDS after HIV infection when infection was assumed to occur during the period of sexual contact with the primary case. Forty cohort members developed AIDS while under study. It appears that at least 50% of men with HIV disease will progress to AIDS and that the best estimate of this probability lies anywhere in the interval 70% to 100%.     

Estimating the distribution of times from HIV seroconversion to AIDS using multiple imputation. Multicentre AIDS Cohort Study

Multiple imputation is a model based technique for handling missing data problems. In this application we use the technique to estimate the distribution of times from HIV seroconversion to AIDS diagnosis with data from a cohort study of 4954 homosexual men with 4 years of follow-up. In this example the missing data are the dates of diagnosis with AIDS. The imputation procedure is performed in two stages. In the first stage, we estimate the residual AIDS-free time distribution as a function of covariates measured on the study participants with data provided by the participants who were seropositive at study entry. Specifically, we assume the residual AIDS-free times follow a log-normal regression model that depends on the covariates measured at enrolment on the seropositive participants. In the second stage we impute the date of AIDS diagnosis for the participants who seroconverted during the course of the study and are AIDS-free with use of the log-normal distribution estimated in the first stage and the covariates from each seroconverter's latest visit. The estimated proportions developing AIDS within 4 and within 7 years of seroconversion are 15 and 36 per cent respectively, with associated 95 per cent confidence intervals of (10, 21) and (26, 47) per cent. We discuss the Bayesian foundations of the multiple imputation technique and the statistical and scientific assumptions.     

Modeling the HIV/AIDS epidemic via survivor functions

An original approach to simulation modeling of the HIV/AIDS epidemic is proposed. This approach uses survivor functions estimated from cohort studies conducted with seropositive and AIDS-diagnosed individuals. The model can be considered an alternative to the usual Markov models and accounts for time-dependent HIV progression to AIDS, and AIDS progression to death. By using various forms of survivor functions, it can also easily be extended to accommodate natural history events, as well as long-term survivors and cofactor effects, when appropriate data are available.     

Gender differences in progression to AIDS and death from HIV seroconversion in a cohort of injecting drug users from 1986 to 2001

BACKGROUND: Although the consensus is that gender does not influence HIV progression, its relevance may depend on the setting. AIM: To study gender differences in HIV progression to AIDS and death from 1986 to 2001 in a cohort of injecting drug user (IDU) seroconverters in Spain. METHODS: Risk of AIDS and death in persons infected for the same length of time were compared through Kaplan-Meier, allowing for late entry, and Cox regression adjusting for gender, age, and calendar period (before 1992, 1992-1995, 1996-1998, 1999-2001) fitted as time dependent covariates. RESULTS: Of 929 IDU, 24.7% were women. Median seroconversion year was 1993.3 for men and women. 44% of women and 34% of men received antiretroviral therapy. Risk of AIDS was lower in women in univariate (hazard ratio (HR) 0.72; 95%CI:0.51 to 1.01) and multivariate analyses (HR 0.73 95%CI:0.52 to 1.03). A 46% reduction in risk of AIDS for period 1999-2001 compared with 1992-1995 was seen in both men and women (HR: 0.56 (95%CI:0.36 to 0.87). As for mortality, women's risk of death was lower univariately (HR 0.67 95%CI:0.45 to 0.99) although compared with 1992-95, men experienced a 34% reduction in mortality during 1999-2001 (HR 0.66 95%CI:0.40 to 1.01), which was not statistically significant in women. CONCLUSIONS: HIV progression was lower in female IDU before and after 1997 and their uptake of antiretroviral therapy was higher than male IDU. The inability to detect a reduction in mortality for women during 1999-2001 is probably attributable to lack of power. Differences in severity of addiction, drug using patterns, and competing causes of death may explain these findings.     

Effect of highly active antiretroviral therapy on time to acquired immunodeficiency syndrome or death using marginal structural models

To estimate the net (i.e., overall) effect of highly active antiretroviral therapy (HAART) on time to acquired immunodeficiency syndrome (AIDS) or death, the authors used inverse probability-of-treatment weighted estimation of a marginal structural model, which can appropriately adjust for time-varying confounders affected by prior treatment or exposure. Human immunodeficiency virus (HIV)-positive men and women (n = 1,498) were followed in two ongoing cohort studies between 1995 and 2002. Sixty-one percent (n = 918) of the participants initiated HAART during 6,763 person-years of follow-up, and 382 developed AIDS or died. Strong confounding by indication for HAART was apparent; the unadjusted hazard ratio for AIDS or death was 0.98. The hazard ratio from a standard time-dependent Cox model that included time-varying CD4 cell count, HIV RNA level, and other time-varying and fixed covariates as regressors was 0.81 (95% confidence interval: 0.61, 1.07). In contrast, the hazard ratio from a marginal structural survival model was 0.54 (robust 95% confidence interval: 0.38, 0.78), suggesting a clinically meaningful net benefit of HAART. Standard Cox analysis failed to detect a clear net benefit, because it does not appropriately adjust for time-dependent covariates, such as HIV RNA level and CD4 cell count, that are simultaneously confounders and intermediate variables.     

Secular trends in the survival of HIV-infected homosexual men in Amsterdam and Vancouver estimated from a death-included CD4-staged Markov model

BACKGROUND: The purpose of this study was to investigate secular trends in waiting times in CD4-based stages of human immunodeficiency virus (HIV) disease progression in two cohorts of homosexual men, one in Vancouver and one in Amsterdam. All HIV-positive men with two or more CD4 counts in their AIDS-free period between 1 January 1985 and 1 January 1997 were included in this study. Data regarding clinical AIDS diagnoses (using the 1987 Centers for Disease Control and Prevention [CDC] AIDS case definition) and death were collected through active follow-up, review of hospital records, and municipal/national registries. The Vancouver Lymphadenopathy-AIDS Study (VLAS), was started in November 1982 and had enrollment until December 1984. Both HIV-negative and HIV-positive men were followed at intervals of 3-6 months until 1986 and annually thereafter. The Amsterdam cohort study on HIV and AIDS (ACS) started in December 1984, has ongoing enrollment and follow-up of both HIV-negative and HIV-positive homosexual men. The HIV-positive men were followed at intervals of 3 months. METHODS: The CD4-based stage of an individual at each visit was determined using smoothed data. For each cohort and in each calendar time period, a CD4-based Markov model with death as the absorbing stage was fitted to the data. 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 509 homosexual men participating in the VLAS were included in this study, providing 5356 visits. Some 292 men developed AIDS before 1 January 1997 and 239 died before this date. In all, 232 of the 239 deaths were AIDS related. Thirty-seven per cent of all visits were related to treatment. A total of 543 homosexual men participating in the ACS were included in this study, providing 10 043 visits; 277 men developed AIDS before 1 January 1997 and 250 died before this date. The date of AIDS diagnosis was known for 225 of the 250 deaths. Twenty per cent of all visits were related to treatment. We found that in both cohort studies the stage-specific waiting times were longer in the low CD4-based stages (stages 4, 5 and 6: i.e. CD4 count <500 cells per mm(3)) after March 1990 compared to waiting times before March 1990. The increase in mean waiting time in these stages with low CD4 count was 21%, 33% and 53%, respectively in the ACS and 20%, 2% and 29% in the VLAS. Because waiting times alone are not exclusive for progression in a reversible model we also calculated the stage-specific median incubation periods till death. Men spent considerably longer in these CD4-based stages after March 1990 compared to before March 1990. CONCLUSIONS: Data from these population-based cohort studies showed that HIV disease progression in the calendar period where treatment was administered was slower for individuals in stages with low CD4 counts. We found no evidence for shortening of the incubation period that may have appeared from increasing virulence of the HIV in the population.     

Weight loss and body mass index as predictors of HIV disease progression to AIDS in adults. Aquitaine cohort, France, 1985-1997.

OBJECTIVE: To assess the performance of weight related nutritional markers (reported involuntary weight loss greater than 10%, measured weight loss and body mass index-BMI-) in predicting HIV disease progression. DESIGN: Multirisk cohort of HIV-1 infected patients. METHOD: The three nutritional variables were studied in Cox proportional hazard models as time dependant variables. RESULTS: The sample included 2376 subjects (median follow up: 43.1 months), of those 675 experienced an AIDS defining event. After adjustment for well known prognostic factors, the reported weight loss greater than 10% tripled the risk of progression to clinical AIDS (Hazard ratio [HR] 3.0. 95% confidence interval [CI] 2.5-3.7). For measured weight loss under 5%. between 5% and 10% and greater than 10% of baseline weight compared with no weight loss, hazard ratios were respectively 1.8 (CI 1.5-2.2), 2.6 (CI 2.1-3.2) and 5.1 (CI 4.1-6.4). The relative risks of AIDS were 1.7 (CI 1.3-2.2) for BMI between 17 kg/m2 and 18.5 kg/m2, 2.6 (CI 1.7-4.0) for BMI between 16 kg/m2 and 17 kg/m2 and 4.7 (CI 3.0-7.4) for BMI under 16 kg/m2. COMMENTS: Even a limited weight loss measured at a given time during follow up increases the risk of HIV progression; moreover, a simple cross-sectionnal measure of BMI has a good predictive value for subsequent development of clinical disease.     

Retention of women enrolled in a prospective study of human immunodeficiency virus infection: impact of race, unstable housing, and use of human immunodeficiency virus therapy.

Even though women and people of color represent an increasing proportion of US acquired immunodeficiency syndrome (AIDS) cases, few research studies include adequate representation of these populations. Here the authors describe recruitment and retention of a diverse group of human immunodeficiency virus (HIV)-infected and at risk HIV-uninfected women in a prospective study operating in six sites across the United States. Methods used to minimize loss to follow-up in this cohort are also described. For the first 10 study visits that occurred during a 5-year period between 1994 and 1999, the retention rate of participants was approximately 82%. In adjusted Cox analysis, factors associated with retention among all women were older age, African-American race, stable housing, HIV-infected serostatus, past experience in studies of HIV/AIDS, and site of enrollment. In an adjusted Cox analysis of HIV-infected women, African-American race, past experience in studies of HIV/AIDS, site of enrollment, and reported use of combination or highly active antiretroviral HIV therapy at the last visit were significantly associated with retention. In adjusted Cox analysis of HIV-uninfected study participants, only the site of enrollment was significantly associated with study retention. These results show that women with and at risk for HIV infection, especially African-American women, can be successfully recruited and retained in prospective studies.     

Determinants of progression to AIDS or death after HIV diagnosis, United States, 1996 to 2001

PURPOSE: The aim of the study is to determine factors associated with disease progression after human immunodeficiency virus (HIV) infection diagnosis. METHODS: We applied generalized linear models with Poisson errors to obtain adjusted relative excess risk for death for persons diagnosed with acquired immunodeficiency syndrome (AIDS) or HIV infection (with or without concurrent AIDS) during 1996 to 2001. We examined differences in time between HIV diagnosis and AIDS by using standardized Kaplan-Meier survival methods. RESULTS: Relative excess risk for death within 3 years after AIDS diagnosis was significantly greater for non-Hispanic blacks (1.15; 95% confidence interval [CI], 1.12-1.18), American Indians (1.33; 95% CI, 1.16-1.52), and Hispanics (1.16; 95% CI, 1.13-1.20) compared with whites. Risk for death also was greater among injection drug users (men, 1.50; 95% CI, 1.46-1.54; women, 1.57; 95% CI, 1.51-1.62) compared with men who have sex with men and among those diagnosed at older ages compared with younger persons. Similar disparities between groups in risk for death were observed from HIV diagnosis. Risk for progression from HIV to AIDS was greater for nonwhites, men, and older persons compared with whites, women, and younger persons, respectively. CONCLUSIONS: Interventions should target those at excess risk for death or morbidity to ensure access to quality care and adherence to treatment to slow disease progression.     

Risk factors for progression of human immunodeficiency virus (HIV) infection among seroconverted and seropositive homosexual men

For identification of risk factors for progression of human immunodeficiency virus (HIV) infection, 746 homosexual men participating in a cohort study in Amsterdam, The Netherlands, were studied since October 1984. A total of 234 of these men were HIV antibody-positive at baseline, and 52 seroconverted during follow-up. These 286 individuals were categorized as high- and low-risk for progression to the acquired immunodeficiency syndrome (AIDS) on the basis of the presence or absence of HIV antigenemia, antibody to HIV core antigen, or a number of T helper lymphocytes less than 0.5 x 10(9)/liter during three or more subsequential blood samples. Ninety-six (41%) of the seropositives and 32 (62%) of those who seroconverted remained low-risk throughout the study period. Bivariate analyses revealed that educational level and a history of herpes zoster were associated with a low- and high-risk status, respectively. In multivariate analyses, a history of herpes zoster and a history of sexual intercourse with a person who had AIDS were associated with a more rapid disease progression. While herpes zoster is considered to be a marker of progressive immunodeficiency, a history of having sexual intercourse with a person who had AIDS points to the more virulent properties of HIV in these persons. Because both seropositives and seroconverters who had sexual intercourse with a person with AIDS had a more rapid disease progression, it seems plausible that being infected by a person with AIDS is a risk factor for a relative short incubation period.     

Predictors of the risk of development of acquired immunodeficiency syndrome within 24 months among gay men seropositive for human immunodeficiency virus type 1: a report from the Multicenter AIDS Cohort Study.

The natural history of infection with human immunodeficiency virus type 1 (HIV-1) is characterized by a relentless decline in CD4-positive lymphocytes and the ultimate development of acquired immunodeficiency syndrome (AIDS). However, variables other than the CD4-positive lymphocyte level contribute to the measurement of risk for AIDS and can be used as predictors of AIDS onset. This study was undertaken to identify factors that, independently of the CD4-positive lymphocyte level, would predict the risk of AIDS over 24 months in a cohort of HIV-1 seropositive homosexual men receiving no antiretroviral therapy. Demographic, clinical, and laboratory data from 1,325 white, HIV-1 seropositive participants in the Multicenter AIDS Cohort Study who have been studied for 4 years were analyzed with univariate and multivariate methods. To control for stage of infection, the baseline percentage of CD4-positive lymphocytes (a known marker of disease progression), and the decline of CD4-positive cells during the first 6 months of observation were used as continuous variables. The variables that were independently associated with an increased risk of developing AIDS were: low baseline CD4 percentage, decline in the CD4 percentage during the first 6 months of follow-up, the presence of serum immunoglobulin A at baseline, decrease in hemoglobin during the first 6 months of follow-up, incident fatigue, and the interaction of decline in the CD4 percentage and incident thrush. While low CD4 percentage and other variables have been previously described as prognostic markers, decline in the CD4 percentage and the interaction of that decline and incident thrush have not previously been described as being of prognostic importance. These variables and the analytic method for estimating prognosis may prove useful for selecting and evaluating antiretroviral therapy, instituting prophylactic measures against certain opportunistic infections, and recruitment into clinical trials. Because study participants received no antiretroviral prophylaxis during the period under analysis, the method could be used to estimate the prognosis for those receiving investigational treatment were they to remain untreated, effectively making any participant in a clinical trial his own untreated control.     

Determination of the beginning of follow-up in longitudinal studies applied to HIV infections

BACKGROUND: In cohort or longitudinal studies, subjects are recruited some time after the beginning of the problem, as in HIV infection. The aim of this paper is to show several imputation techniques of the beginning of follow up and evaluate its use in the framework of a study of HIV progression. METHODS: Three subcohorts of HIV+ subjects recruited in Valencia and Castellón CIPS up to 1996 are available. Seroconversion date was estimated for 244 Seroincidents, 887 seroprevalents with CD4 measurements and 337 without CD4 measurements. For seroincidents midpoint between last HIV- and first HIV+ visits was considered. For prevalent with CD4 serocon version date was imputed from 5 random samples of a progression model of infection to a CD4 level. For prevalent without CD4 seroconversion date was imputed from 5 random samples of HIV incidence density obtained from the other subcohorts. The imputation was repeated 500 times, assigning the seroconversion date as the median of imputations and obtaining confidence limits from 5 and 95 percentiles. Imputation validity was tested comparing time to AIDS and death for each one of the 3 groups. RESULTS: 443 and 405 deaths were observed among the 1468 subjects. Median of seroconversion was January 1993 for incidents, January 1991 for prevalents with CD4 and November 1988 for prevalents without CD4. The latest group showed a worse survival and AIDS free time compared to the other two cohorts. CONCLUSIONS: The imputation tools used showed their usefulness to reduce the survival bias in observational studies. Their generalization depends on the viability of incident cohorts, the availability of a progression marker or a origin on time.     

HIV感染者不同时期艾滋病知识及高危性行为变化的调查

目的 了解HIV感染者接受HIV检测阳性告知后不同时期艾滋病知识和高危性行为改变情况,为进一步做好HIV感染者的行为干预提供依据. 方法 采用方便抽样法,对云南、广西两地四县(区)于2006年1月初至2008年6月底期间通过网络直报上报到"艾滋病综合防治数据信息管理系统",并且血清HIV抗体确认实验阳性或替代策略Ⅱ阳性且完成首次随访的HIV感染者进行调查,在2008年7月至2009年1月进行问卷调查,调查内容为一般情况、艾滋病相关知识和高危性行为等. 结果 2006年1月至2008年6月期间共889名HIV感染者接受了HIV阳性检测结果告知,其中以2008年1月至6月接受告知的HIV感染者比例最高(32.2%).单因素logistic回归分析结果显示,知晓HIV检测阳性结果后1.5～2.0年组和0.5～1.0年组艾滋病知识知晓率之间的差异有统计学意义(X~2=5.86,P＜0.05),两组过去6个月性行为发生频次之间的差异亦有统计学意义(X~2=8.93,P＜0.01),且HIV感染者在知晓阳性结果后使用安全套的比例,会随着时间的延长而降低(X~2=11.92,P＜0.01). 结论 HIV感染者在接受HIV检测阳性结果告知后,不同时期内艾滋病相关知识和危险性行为均有相应的变化.完善HIV检测咨询和阳性结果告知后的服务,在HIV感染者接受HIV检测阳性结果告知后2年进行1次随访,加强艾滋病方面的预防干预可降低高危性行为,防止HIV二代传播.     

Demographic and behavioral predictors of knowledge and HIV seropositivity: Results of a survey conducted in three anonymous and free counselling and testing centers

This paper deals with subjects seeking counselling and testing for human immunodeficiency virus (HIV); it analyses which sociodemographic and behavioral characteristics are related to beliefs concerning HIV infection and to HIV seropositivity. A one month survey among individuals who attended HIV testing in three anonymous and free centers (CIDAGs) was carried out in Paris city, on March 1994. 2059 subjects completed a self-administered questionnaire. Data collected included demographic information, sexual and IVDU behavior, and HIV seropositivity. Subjects also had to evaluate their own risk of getting the acquired immunodeficiency syndrome (AIDS) and the perceived risk of getting AIDS in specific situations such as unprotected anal/vaginal intercourse with a casual partner, with multiple partners, with a seropositive partner, current dental treatment, French kiss etc. . . . Multiple linear and logistic regressions have been used to model the dependent variables. Subjects correctly evaluated the risk level of HIV transmission associated with different situations, and women, young men and those engaged in homo/bisexual behavior were in general more conscious of the increased danger resulting from high risk sexual practices. Among males, homo/bisexuals, drug users and the less educated considered themselves to be more at risk. The most important factors related to HIV seropositivity were sexual orientation, intravenous drug use (IVDU), and the perceived risk of getting aids. Despite a good awareness of HIV contamination and an accurate perception of their own risk, many subjects continued to engage in high risk AIDS activities. Better targeted interventions need to be developed to promote and maintain behavior changes.     

A simple G‐computation algorithm to quantify the causal effect of a secondary illness on the progression of a chronic disease

Progression of a chronic disease can lead to the development of secondary illnesses. An example is the development of active tuberculosis (TB) in HIV‐infected individuals. HIV disease progression, as indicated by declining CD4 + T‐cell count (CD4), increases both the risk of TB and the risk of AIDS‐related mortality. This means that CD4 is a time‐dependent confounder for the effect of TB on AIDS‐related mortality. Part of the effect of TB on AIDS‐related mortality may be indirect by causing a drop in CD4. Estimating the total causal effect of TB on AIDS‐related mortality using standard statistical techniques, conditioning on CD4 to adjust for confounding, then gives an underestimate of the true effect. Marginal structural models (MSMs) can be used to obtain an unbiased estimate. We describe an easily implemented algorithm that uses G‐computation to fit an MSM, as an alternative to inverse probability weighting (IPW). Our algorithm is simplified by utilizing individual baseline parameters that describe CD4 development. Simulation confirms that the algorithm can produce an unbiased estimate of the effect of a secondary illness, when a marker for primary disease progression is both a confounder and intermediary for the effect of the secondary illness. We used the algorithm to estimate the total causal effect of TB on AIDS‐related mortality in HIV‐infected individuals, and found a hazard ratio of 3.5 (95 per cent confidence interval 1.2–9.1). Copyright © 2009 John Wiley & Sons, Ltd.     

Association between exercise and HIV disease progression in a cohort of homosexual men

PURPOSE: To study the relationship between exercise and human immunodeficiency virus (HIV) disease progression. METHODS: 415 individuals (156 HIV positive, 259 HIV negative), from a cohort study of 851 homosexual men from New York City, 1985-1991. By 1991, 68 of the 156 persons developed Acquired Immune Deficiency Syndrome (AIDS) and 49 died with AIDS. Exercise was defined as self-report of exercising 3-4 times/week or daily at entry; less was considered nonexercise. CD4 lymphocyte decline was constructed for each subject by modeling log CD4 count against time in days. The association between exercise and progression to AIDS and death with AIDS, adjusting for baseline CD4 count, was determined using Cox model. Linear regression was used to model CD4 decline with exercise for HIV positive and HIV negative groups separately, adjusting for initial CD4 count. RESULTS: Having exercised was associated with slower progression to AIDS at 1 year (HR = 0.68, 90% confidence interval (CI): 0.4-1.17); hazard ratios (HR) at 2, 3, and 4 years were 0.96, 1.18, and 1.36, respectively. Having exercised was also associated with slower progression to death with AIDS at 1 year (HR = 0.37, 90% CI: 0.14-0.94) with hazard ratios at 2, 3, and 4 years of 0.68, 0.98, and 1.27, respectively, suggesting a protective effect close to the time exercise was assessed, but an increased risk after 2 years. Exercising 3-4 times/week had a more protective effect than daily exercise. Exercisers in the HIV positive group showed an increase in CD4 count during a year by a factor of 1.07. CONCLUSION: Moderate physical activity may slow HIV disease progression.     

Evidence for a sexually transmitted cofactor for AIDS-related Kaposi's sarcoma in a cohort of homosexual men.

We examined factors associated with the subsequent development of AIDS-related Kaposi's sarcoma in a cohort of 353 homosexual men infected with human immunodeficiency virus (HIV). Cumulative incidence curves for the development of Kaposi's sarcoma and opportunistic infection were stratified over a wide range of variables at enrollment, including those related to demographics, sexual behavior, illicit drug use, and medical history. We found no strong associations between any of these variables and the development of opportunistic infection, but two were related to Kaposi's sarcoma: use of nitrite inhalants (relative risk, 2.3; 95% confidence interval, 1.0-5.0) and high numbers of sexual contacts during the period 1978-1982 in the AIDS epidemic centers of San Francisco, Los Angeles, and/or New York (relative risk, 3.5; 95% confidence interval, 1.6-7.6). The latter variables remained independently associated with risk of Kaposi's sarcoma even after multivariate adjustment for a number of classical HIV risk factors. These results are consistent with the hypothesis that Kaposi's sarcoma is caused by a sexually transmitted cofactor that has remained more prevalent in the original epidemic centers. The effect of nitrites could be due to an independent biological mechanism or to enhancement of transmission of the cofactor.     

Survival of AIDS patients in Norway

The survival function of the 100 first AIDS patients in Norway is presented and analyzed with respect to four factors obtained at the time of diagnosis; a) year of diagnosis b) initial AIDS related disease c) knowledge of HIV seropositivity prior to onset of AIDS and d) age at time of diagnosis. The median survival was 9.3 months. Among the known seropositive AIDS patients there were almost twice as many with Pneumocystis carinii pneumonia as initial AIDS related disease, as among the not known seropositives (relative risk 1.8). With Cox regression analysis we found that known seropositivity and age are factors that appear to influence survival, whereas year of diagnosis and initial AIDS related disease apparently do not. The mechanism whereby prior knowledge of HIV seropositivity leads to apparent increase in survival may be due to better follow-up and thereby an earlier date of diagnosis.     

Gender differences in HIV progression to AIDS and death in industrialized countries: slower disease progression following HIV seroconversion in women

To evaluate sex differences in human immunodeficiency virus (HIV) disease progression before (pre-1997) and after (1997-2006) introduction of highly active antiretroviral therapy, the authors used data from a collaboration of 23 HIV seroconverter cohort studies from Europe, Australia, and Canada restricted to the 6,923 seroconverters infected through injecting drug use and sex between men and women. Within a competing risk framework, they used Cox proportional hazards models allowing for late entry to evaluate sex differences in time from HIV seroconversion to death, to acquired immunodeficiency syndrome (AIDS), and to each first AIDS-defining disease and death without AIDS. While no significant sex differences were found before 1997, from 1997 onward, women had a lower risk of AIDS (adjusted cumulative relative risk (aCRR) = 0.76, 95% confidence interval (CI): 0.63, 0.90) and death (adjusted hazard ratio = 0.68, 95% CI: 0.56, 0.82) than men did. Compared with men, women also had lower risks of AIDS dementia complex (aCRR = 0.23, 95% CI: 0.07, 0.74), tuberculosis (aCRR = 0.60, 95% CI: 0.39, 0.92), Kaposi's sarcoma (aCRR = 0.27, 95% CI: 0.07, 0.99), lymphomas (aCRR = 0.47, 95% CI: 0.23, 0.96), and death without AIDS (aCRR = 0.74, 95% CI: 0.56, 0.98). Sex differences in HIV disease progression have become larger and statistically significant in the era of highly active antiretroviral therapy, supporting a stronger impact of health interventions among women.