Baseline cardiovascular risk in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial.

OBJECTIVES: The Strategic Timing of AntiRetroviral Treatment (START) trial has recruited antiretroviral-naïve individuals with high CD4 cell counts from all regions of the world. We describe the distribution of cardiovascular disease (CVD) risk factors, overall and by geographical region, at study baseline. METHODS: The distribution of CVD risk factors was assessed and compared by geographical region among START participants who had a baseline electrocardiogram (n = 4019; North America, 11%; Europe/Australia/Israel, 36%; South America, 26%; Asia, 4%; Africa, 23%; median age 36 years; 26% female). RESULTS: About 58.3% (n = 2344) of the participants had at least one CVD risk factor and 18.9% (n = 761) had two or more. The most common CVD risk factors were current smoking (32%), hypertension (19.3%) and obesity (16.5%). There were significant differences in the prevalence of CVD risk factors among geographical regions. The prevalence of at least one risk factor across regions was as follows: North America, 70.0%; Europe/Australia/Israel, 65.1%; South America, 49.4%; Asia, 37.0%; Africa, 55.8% (P-value < 0.001). Significant regional differences were also observed when risk factors were used as part of the Framingham and Data Collection on Adverse events of Anti-HIV Drugs (D:A:D) risk scores or used to define a favourable risk profile. CONCLUSIONS: CVD risk factors are common among START participants, and their distribution varies by geographical region. Better understanding of how and why CVD risk factors develop in people with HIV infection and their geographical distributions could shed light on appropriate strategies for CVD prevention and may inform the interpretation of the results of START, as CVD is expected to be a major fraction of the primary endpoints observed.

The design and conduct of clinical trials to limit missing data.

This article summarizes recommendations on the design and conduct of clinical trials of a National Research Council study on missing data in clinical trials. Key findings of the study are that (a) substantial missing data is a serious problem that undermines the scientific credibility of causal conclusions from clinical trials; (b) the assumption that analysis methods can compensate for substantial missing data is not justified; hence (c) clinical trial design, including the choice of key causal estimands, the target population, and the length of the study, should include limiting missing data as one of its goals; (d) missing-data procedures should be discussed explicitly in the clinical trial protocol; (e) clinical trial conduct should take steps to limit the extent of missing data; (f) there is no universal method for handling missing data in the analysis of clinical trials - methods should be justified on the plausibility of the underlying scientific assumptions; and (g) when alternative assumptions are plausible, sensitivity analysis should be conducted to assess robustness of findings to these alternatives. This article focuses on the panel's recommendations on the design and conduct of clinical trials to limit missing data. A companion paper addresses the panel's findings on analysis methods.

Interleukin-2 therapy in patients with HIV infection.

BACKGROUND: Used in combination with antiretroviral therapy, subcutaneous recombinant interleukin-2 raises CD4+ cell counts more than does antiretroviral therapy alone. The clinical implication of these increases is not known. METHODS: We conducted two trials: the Subcutaneous Recombinant, Human Interleukin-2 in HIV-Infected Patients with Low CD4+ Counts under Active Antiretroviral Therapy (SILCAAT) study and the Evaluation of Subcutaneous Proleukin in a Randomized International Trial (ESPRIT). In each, patients infected with the human immunodeficiency virus (HIV) who had CD4+ cell counts of either 50 to 299 per cubic millimeter (SILCAAT) or 300 or more per cubic millimeter (ESPRIT) were randomly assigned to receive interleukin-2 plus antiretroviral therapy or antiretroviral therapy alone. The interleukin-2 regimen consisted of cycles of 5 consecutive days each, administered at 8-week intervals. The SILCAAT study involved six cycles and a dose of 4.5 million IU of interleukin-2 twice daily; ESPRIT involved three cycles and a dose of 7.5 million IU twice daily. Additional cycles were recommended to maintain the CD4+ cell count above predefined target levels. The primary end point of both studies was opportunistic disease or death from any cause. RESULTS: In the SILCAAT study, 1695 patients (849 receiving interleukin-2 plus antiretroviral therapy and 846 receiving antiretroviral therapy alone) who had a median CD4+ cell count of 202 cells per cubic millimeter were enrolled; in ESPRIT, 4111 patients (2071 receiving interleukin-2 plus antiretroviral therapy and 2040 receiving antiretroviral therapy alone) who had a median CD4+ cell count of 457 cells per cubic millimeter were enrolled. Over a median follow-up period of 7 to 8 years, the CD4+ cell count was higher in the interleukin-2 group than in the group receiving antiretroviral therapy alone--by 53 and 159 cells per cubic millimeter, on average, in the SILCAAT study and ESPRIT, respectively. Hazard ratios for opportunistic disease or death from any cause with interleukin-2 plus antiretroviral therapy (vs. antiretroviral therapy alone) were 0.91 (95% confidence interval [CI], 0.70 to 1.18; P=0.47) in the SILCAAT study and 0.94 (95% CI, 0.75 to 1.16; P=0.55) in ESPRIT. The hazard ratios for death from any cause and for grade 4 clinical events were 1.06 (P=0.73) and 1.10 (P=0.35), respectively, in the SILCAAT study and 0.90 (P=0.42) and 1.23 (P=0.003), respectively, in ESPRIT. CONCLUSIONS: Despite a substantial and sustained increase in the CD4+ cell count, as compared with antiretroviral therapy alone, interleukin-2 plus antiretroviral therapy yielded no clinical benefit in either study. (ClinicalTrials.gov numbers, NCT00004978 [ESPRIT] and NCT00013611 [SILCAAT study].)

Risk for opportunistic disease and death after reinitiating continuous antiretroviral therapy in patients with HIV previously receiving episodic therapy: a randomized trial.

BACKGROUND: Episodic use of antiretroviral therapy guided by CD4+ cell counts is inferior to continuous antiretroviral therapy. OBJECTIVE: To determine whether reinitiating continuous antiretroviral therapy in patients who received episodic treatment reduces excess risk for opportunistic disease or death. DESIGN: Randomized, controlled trial. SETTING: Sites in 33 countries. PATIENTS: 5472 HIV-infected individuals with CD4(+) cell counts greater than 0.350 x 10(9) cells/L enrolled from January 2002 to January 2006. INTERVENTION: Episodic or continuous antiretroviral therapy initially, followed by continuous therapy in participants previously assigned to episodic treatment. MEASUREMENTS: Opportunistic disease or death was the primary outcome. RESULTS: Eighteen months after the recommendation to reinitiate continuous therapy, mean CD4+ cell counts were 0.152 x 10(9) cells/L (95% CI, 0.136 to 0.167 x 10(9) cells/L) less in participants previously assigned to episodic treatment (P < 0.001). The proportion of follow-up time spent with CD4+ cell counts of 0.500 x 10(9) cells/L or more and HIV RNA levels of 400 copies/mL or less was 29% for participants initially assigned to episodic therapy and 66% for those assigned to continuous therapy. Participants who reinitiated continuous therapy experienced rapid suppression of HIV RNA levels (89.7% with HIV RNA levels < or =400 copies/mL after 6 months), but CD4+ cell counts after 6 months remained 0.140 x 10(9) cells/L below baseline. The hazard ratio (episodic versus continuous treatment) for opportunistic disease or death decreased after the recommendation to reinitiate continuous therapy (from 2.5 [CI, 1.8 to 3.5] to 1.4 [CI, 1.0 to 2.0]; P = 0.033 for difference). The residual excess risk was attributable to failure to reinitiate therapy by some participants and slow recovery of CD4+ cell counts for those who reinitiated therapy. LIMITATION: Follow-up was too short to assess the full effect of switching from episodic to continuous antiretroviral therapy. CONCLUSION: Reinitiating continuous antiretroviral therapy in patients previously assigned to episodic treatment reduced excess risk for opportunistic disease or death, but excess risk remained. Episodic antiretroviral therapy, as used in the SMART study, should be avoided.

CD4+ count-guided interruption of antiretroviral treatment.

BACKGROUND: Despite declines in morbidity and mortality with the use of combination antiretroviral therapy, its effectiveness is limited by adverse events, problems with adherence, and resistance of the human immunodeficiency virus (HIV). METHODS: We randomly assigned persons infected with HIV who had a CD4+ cell count of more than 350 per cubic millimeter to the continuous use of antiretroviral therapy (the viral suppression group) or the episodic use of antiretroviral therapy (the drug conservation group). Episodic use involved the deferral of therapy until the CD4+ count decreased to less than 250 per cubic millimeter and then the use of therapy until the CD4+ count increased to more than 350 per cubic millimeter. The primary end point was the development of an opportunistic disease or death from any cause. An important secondary end point was major cardiovascular, renal, or hepatic disease. RESULTS: A total of 5472 participants (2720 assigned to drug conservation and 2752 to viral suppression) were followed for an average of 16 months before the protocol was modified for the drug conservation group. At baseline, the median and nadir CD4+ counts were 597 per cubic millimeter and 250 per cubic millimeter, respectively, and 71.7% of participants had plasma HIV RNA levels of 400 copies or less per milliliter. Opportunistic disease or death from any cause occurred in 120 participants (3.3 events per 100 person-years) in the drug conservation group and 47 participants (1.3 per 100 person-years) in the viral suppression group (hazard ratio for the drug conservation group vs. the viral suppression group, 2.6; 95% confidence interval [CI], 1.9 to 3.7; P<0.001). Hazard ratios for death from any cause and for major cardiovascular, renal, and hepatic disease were 1.8 (95% CI, 1.2 to 2.9; P=0.007) and 1.7 (95% CI, 1.1 to 2.5; P=0.009), respectively. Adjustment for the latest CD4+ count and HIV RNA level (as time-updated covariates) reduced the hazard ratio for the primary end point from 2.6 to 1.5 (95% CI, 1.0 to 2.1). CONCLUSIONS: Episodic antiretroviral therapy guided by the CD4+ count, as used in our study, significantly increased the risk of opportunistic disease or death from any cause, as compared with continuous antiretroviral therapy, largely as a consequence of lowering the CD4+ cell count and increasing the viral load. Episodic antiretroviral therapy does not reduce the risk of adverse events that have been associated with antiretroviral therapy. (ClinicalTrials.gov number, NCT00027352 [ClinicalTrials.gov].).

Evolution of antifungal susceptibility among Candida species isolates recovered from human immunodeficiency virus-infected women receiving fluconazole prophylaxis.

The effect of fluconazole on the susceptibility of Candida isolates recovered from women infected with human immunodeficiency virus (HIV) was evaluated in a randomized, double-blind, placebo-controlled trial. Women with CD4(+) cell counts of < or =300 cells/mm(3) received either fluconazole (200 mg/week) or placebo as prophylaxis. The antifungal susceptibility of specimens was evaluated. One patient who received fluconazole and 2 patients assigned to placebo had Candida albicans isolates recovered that were resistant to fluconazole (MIC, > or =64 microg/mL). Eleven patients assigned fluconazole and 4 patients assigned placebo had non-albicans Candida strains (all Candida glabrata) recovered that were resistant to fluconazole. There was significant azole cross-resistance among the non-albicans Candida species isolates. Although the rate of azole resistance did not significantly increase after fluconazole prophylaxis, there was a trend toward more in vitro azole resistance in C. glabrata isolates from patients assigned fluconazole. Moreover, the majority of resistant vaginal isolates of Candida species were recovered after initiation of open-label fluconazole use.

A randomized study of antiretroviral management based on plasma genotypic antiretroviral resistance testing in patients failing therapy. CPCRA 046 Study Team for the Terry Beirn Community Programs for Clinical Research on AIDS.

OBJECTIVE: To determine the short-term effects of using genotypic antiretroviral resistance testing (GART) with expert advice in the management of patients failing on a protease inhibitor and two nucleoside reverse transcriptase inhibitors. DESIGN: Prospective randomized controlled trial. SETTING: Multicenter community-based clinical trials network. PATIENTS: One-hundred and fifty-three HIV-infected adults with a threefold or greater rise in plasma HIV-1 RNA on at least 16 weeks of combination antiretroviral therapy. INTERVENTIONS: Randomization was either to a GART group, where genotype interpretation and suggested regimens were provided to clinicians, or to a no-GART group, where treatment choices were made without such input. MAIN OUTCOMES MEASURES: Plasma HIV-1 RNA levels and CD4 cell counts were measured at 4, 8, and 12 weeks following randomization. The primary endpoint was change in HIV-1 RNA levels from baseline to the average of the 4 and 8 week levels. RESULTS: The average baseline CD4 cell count was 230 x 10(6) cells/l and the median HIV-1 RNA was 28,085 copies/ml. At entry, 82 patients were failing on regimens containing indinavir, 51 on nelfinavir, 11 on ritonavir, and nine on saquinavir. HIV-1 RNA, averaged at 4 and 8 weeks, decreased by 1.19 log10 for the 78 GART patients and -0.61 log10 for the 75 no-GART patients (treatment difference: -0.53 log, 95% confidence interval, -0.77 to -0.29; P = 0.00001). Overall, the best virologic responses occurred in patients who received three or more drugs to which their HIV-1 appeared to be susceptible. CONCLUSION: In patients failing triple drug therapy, GART with expert advice was superior to no-GART as measured by short-term viral load responses.

Relationship of baseline serum cholesterol levels in 3 large cohorts of younger men to long-term coronary, cardiovascular, and all-cause mortality and to longevity.

CONTEXT: Based on observational and interventional data for middle-aged cohorts (aged 40-64 years), serum cholesterol level is known to be an established major risk factor for coronary heart disease (CHD). However, findings for younger people are limited, and the value of detecting and treating hypercholesterolemia in younger adults is debated. OBJECTIVE: To evaluate the long-term impact of unfavorable serum cholesterol levels on risk of death from CHD, cardiovascular disease (CVD), and all causes. DESIGN, SETTING, AND PARTICIPANTS: Three prospective studies, from which were selected 3 cohorts of younger men with baseline serum cholesterol level measurements and no history of diabetes mellitus or myocardial infarction. A total of 11,017 men aged 18 through 39 years screened in 1967-1973 for the Chicago Heart Association Detection Project in Industry (CHA); 1266 men aged 25 through 39 years examined in 1959-1963 in the Peoples Gas Company Study (PG); and 69,205 men aged 35 through 39 years screened in 1973-1975 for the Multiple Risk Factor Intervention Trial (MRFIT). MAIN OUTCOME MEASURES: Cause-specific mortality during 25 (CHA), 34 (PG), and 16 (MRFIT) years of follow-up; mortality risks; and estimated life expectancy in relation to baseline serum cholesterol levels. RESULTS: Death due to CHD accounted for 26%, 34%, and 28% of all deaths in the CHA, PG, and MRFIT cohorts, respectively; and CVD death for 34%, 42%, and 39% of deaths in the same cohorts, respectively. Men in all 3 cohorts with unfavorable serum cholesterol levels (200-239 mg/dL [5.17-6.18 mmol/L] and >/=240 mg/dL [>/=6.21 mmol/L]) had strong gradients of relative mortality risk. For men with serum cholesterol levels of 240 mg/dL or greater (>/=6.21 mmol/L) vs favorable levels (<200 mg/dL [<5.17 mmol/L]), CHD mortality risk was 2.15 to 3.63 times greater; CVD disease mortality risk was 2.10 to 2.87 times greater; and all-cause mortality was 1.31 to 1.49 times greater. Hypercholesterolemic men had age-adjusted absolute risk of CHD death of 59 per 1000 men in 25 years (CHA cohort), 90 per 1000 men in 34 years (PG cohort), and 15 per 1000 men in 16 years (MRFIT cohort). Absolute excess risk was 43.6 per 1000 men (CHA), 81.4 per 1000 men (PG), and 12.1 per 1000 men (MRFIT). Men with favorable baseline serum cholesterol levels had an estimated greater life expectancy of 3.8 to 8.7 years. CONCLUSIONS: These results demonstrate a continuous, graded relationship of serum cholesterol level to long-term risk of CHD, CVD, and all-cause mortality, substantial absolute risk and absolute excess risk of CHD and CVD death for younger men with elevated serum cholesterol levels, and longer estimated life expectancy for younger men with favorable serum cholesterol levels. JAMA. 2000;284:311-318

Frequency of antiretroviral drug resistance mutations in HIV-1 strains from patients failing triple drug regimens. The Terry Beirn Community Programs for Clinical Research on AIDS.

The frequency of protease and reverse transcriptase (RT) gene mutations was determined in HIV-1 strains from 153 patients entering the CPCRA 046 (GART) study who were failing triple-drug regimens consisting of one protease inhibitor (PI) and two RT inhibitors. Population-based sequence analyses showed that nearly all patients had similar RT gene mutations regardless of prior drug exposure, although the M184V mutation was significantly less prevalent in patients not recently treated with lamivudine. Whilst typical inhibitor-specific ('signature') protease gene mutations were found in patients failing their first PI, these mutations were significantly less likely to be found in patients exposed to two or more PIs. Protease gene mutations associated with multi-PI resistance were more likely to be observed in patients treated with more than one PI. These results suggest sequential treatment with PIs select for a relatively limited number of protease gene mutations that likely originated during early PI therapy. These protease gene mutations and a similarly limited set of RT gene mutations appear to be responsible for treatment failure in antiretroviral therapy.

Kaposi's sarcoma and central nervous system disease: a real association or an artifact of the control group? Terry Beirn Community Programs for Clinical Research on AIDS.

OBJECTIVES: To test the hypothesis that Kaposi's sarcoma (KS) protects against four central nervous system (CNS) diseases in HIV-1-infected individuals. STUDY POPULATION AND DESIGN: The study population of 9404 subjects included participants in Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA) protocols who were enrolled between September 1990 and September 1998. This was an observational study. METHODS: Proportional hazards regression was used to estimate adjusted relative risks for predictors of four central nervous system diseases. Covariates included occurrence of Kaposi's sarcoma, occurrence of other opportunistic infections or malignancies, baseline CD4+ count, and other baseline characteristics. RESULTS: Among the 5944 participants without progression to AIDS at entry, 451 developed a CNS disease. The adjusted relative risk of any CNS disease for those who developed Kaposi's sarcoma versus those who did not develop any AIDS-defining event was 1.41 [95% confidence interval (CI), 0.98-2.03; P = 0.06]. In contrast, the adjusted relative risk of any CNS disease for those with Kaposi's sarcoma versus those with some other non-Kaposi's sarcoma AIDS-defining event was 0.37 (95% CI, 0.24-0.57; P < 0.0001). Among the 3460 participants with progression to AIDS at entry, the adjusted relative risk of any CNS disease for those with Kaposi's sarcoma versus those with some other non-Kaposi's sarcoma AIDS-defining event was 0.71 (95% CI, 0.40-1.25; P = 0.23). CONCLUSIONS: Our analyses indicate that the risk of CNS disease associated with Kaposi's sarcoma depends strongly on the reference or control group chosen. When compared to individuals with other non-Kaposi's sarcoma AIDS-defining diseases, Kaposi's sarcoma is associated with a lower risk of CNS disease in HIV-1 positive individuals. However, when compared to individuals with no AIDS-defining disease or with a similarly mild AIDS-defining disease such as invasive candidiasis, Kaposi's sarcoma is associated with an equivalent risk of CNS disease.

Low risk-factor profile and long-term cardiovascular and noncardiovascular mortality and life expectancy: findings for 5 large cohorts of young adult and middle-aged men and women.

CONTEXT: Three major coronary risk factors-serum cholesterol level, blood pressure, and smoking-increase incidence of coronary heart disease (CHD) and related end points. In previous investigations, risks for low-risk reference groups were estimated statistically because samples contained too few such people to measure risk. OBJECTIVE: To measure long-term mortality rates for individuals with favorable levels for all 3 major risk factors, compared with others. DESIGN: Two prospective studies, involving 5 cohorts based on age and sex, that enrolled persons with a range of risk factors. Low risk was defined as serum cholesterol level less than 5.17 mmol/L (<200 mg/dL), blood pressure less than orequal to 120/80 mm Hg, and no current cigarette smoking. All persons with a history of diabetes, myocardial infarction (MI), or, in 3 of 5 cohorts, electrocardiogram (ECG) abnormalities, were excluded. SETTING AND PARTICIPANTS: In 18 US cities, a total of 72144 men aged 35 through 39 years and 270671 men aged 40 through 57 years screened (1973-1975) for the Multiple Risk Factor Intervention Trial (MRFIT); in Chicago, a total of 10025 men aged 18 through 39 years, 7490 men aged 40 through 59 years, and 6229 women aged 40 through 59 years screened (1967-1973) for the Chicago Heart Association Detection Project in Industry (CHA) (N = 366559). MAIN OUTCOME MEASURES: Cause-specific mortality during 16 (MRFIT) and 22 (CHA) years, relative risks (RRs) of death, and estimated greater life expectancy, comparing low-risk subcohorts vs others by age strata. RESULTS: Low-risk persons comprised only 4.8% to 9.9% of the cohorts. All 5 low-risk groups experienced significantly and markedly lower CHD and cardiovascular disease death rates than those who had elevated cholesterol level, or blood pressure, or smoked. For example, age-adjusted RRs of CHD mortality ranged from 0.08 for CHA men aged 18 to 39 years to 0.23 for CHA men aged 40 through 59 years. The age-adjusted relative risks (RRs) for all cardiovascular disease mortality ranged from 0.15 for MRFIT men aged 35 through 39 years to 0.28 for CHA men aged 40 through 59 years. The age-adjusted RR for all-cause mortality rate ranged from 0.42 for CHA men aged 40 through 59 years to 0.60 for CHA women aged 40 through 59 years. Estimated greater life expectancy for low-risk groups ranged from 5.8 years for CHA women aged 40 through 59 years to 9.5 years for CHA men aged 18 through 39 years. CONCLUSIONS: Based on these very large cohort studies, for individuals with favorable levels of cholesterol and blood pressure who do not smoke and do not have diabetes, MI, or ECG abnormalities, long-term mortality is much lower and longevity is much greater. A substantial increase in the proportion of the population at lifetime low risk could contribute decisively to ending the CHD epidemic.

Evolution of vaginal Candida species recovered from human immunodeficiency virus-infected women receiving fluconazole prophylaxis: the emergence of Candida glabrata? Terry Beirn Community Programs for Clinical Research in AIDS (CPCRA).

The effect of fluconazole prophylaxis on the vaginal flora of 323 human immunodeficiency virus-infected women was evaluated in a multicenter, randomized, double-blind, placebo-controlled trial. Women with CD4 cell counts of < or = 300/mm3 received either 200 mg of fluconazole per week or placebo. Vaginal surveillance cultures were performed every 3 months. After a follow-up of 29 months, Candida albicans was recovered from 53% of patients receiving fluconazole and 68% of patients assigned placebo. Fluconazole was associated with a 50% reduction in the odds of being colonized with C. albicans but with higher rates for non-albicans Candida species. Candida glabrata was recovered from 40 women assigned fluconazole and 29 assigned placebo (relative odds, 1.96; 95% confidence interval, 0.98-3.94). Fluconazole had an early and persistent effect on the vaginal mycoflora, with the emergence of C. glabrata vaginal colonization within the first 6 months. The effect of fluconazole prophylaxis can be attributed to the reduction in vaginal C. albicans colonization; however, C. glabrata colonization rapidly supervened.

Experience with a cross-study endpoint review committee for AIDS clinical trials. Terry Beirn Community Programs for Clinical Research on AIDS.

OBJECTIVES: To describe the methods and results of a standardized system for clinical endpoint determination for defining and reviewing endpoints in clinical trials for HIV-infected individuals. DESIGN: A system was developed utilizing standard definitions for the 24 diagnoses or clinical events that serve as trial endpoints and together define the combined endpoint 'progression of HIV disease. A common set of case report forms were used for all trials. Thus, an event of Pneumocystis carinii pneumonia (PCP), for example, for a subject co-enrolled in an antiretroviral trial and a PCP prophylaxis trial was only reported once. METHODS: A central committee was established to define clinical events and review endpoints across all studies. Events were classified according to established criteria for confirmed, probable and possible levels of certainty. RESULTS: This report describes the methods used to ascertain and review endpoints, and summarized 2299 clinical events for 8097 subjects enrolled in one or more of nine clinical trials. Data on the diagnostic certainty of events and agreement between site clinicians and the endpoint committee are presented. CONCLUSIONS: Uniform classification of endpoints across AIDS clinical trials can be accomplished by multicenter, multitrial organizations with standardized definitions and review of endpoint documentation. Our experience suggests that nurse coordinators reviewing all submitted endpoints for every trial are warranted and the need for external review by a clinical events committee may depend on the type of trial conducted.

Sexually transmitted infections in women infected with the human immunodeficiency virus. Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA).

BACKGROUND AND OBJECTIVES: Limited prospective data are available on sexually transmitted infections (STIs) among HIV-infected patients. The incidence and predictors of STIs were assessed among HIV-infected women enrolled in a clinical trial. STUDY DESIGN: Prospective cohort of 323 women. RESULTS: Sixty-five percent had at least one STI based on history and/or examination at baseline. Most conditions identified at baseline were based on patient history; only 10 of 123 women with no history of an STI (8.1%) had one identified upon examination. During a median follow-up of 2.1 years, 25% developed a new/recurrent STI. Being African-American (odds ratio [OR] = 4.22, 95% confidence interval [CI]: 1.45-12.26), reporting sex with an intravenous drug user as an HIV risk behavior (OR = 2.29, 95% CI: 1.34-3.92), and a history/presence of STIs at baseline (OR = 1.79, 95% CI: 1.01-3.19) were factors associated with significantly increased risk of STI's. CONCLUSIONS: A substantial proportion of women developed new STIs during the course of the clinical trial. Prevention efforts should be emphasized among high risk HIV-infected patients.

Sixteen-year coronary mortality in black and white men with diabetes screened for the Multiple Risk Factor Intervention Trial (MRFIT).

BACKGROUND: Risk of coronary heart disease (CHD) mortality associated with diabetes is high and it is unclear to what extent the high mortality is due to modifiable risk factors. To explore this, mortality and predictors of CHD death are compared in a large cohort of black and white men with diabetes. METHODS: In all, 610 black and 3997 white men who reported taking medication for diabetes and had no history of hospitalization for heart attack were screened by 22 centres for the Multiple Risk Factor Intervention Trial (MRFIT). At screening major risk factors for CHD were determined. Participants have been followed for an average of 16 years for vital status. Cause-specific mortality and predictors of CHD are compared for blacks and whites using proportional hazards regression. RESULTS: Serum cholesterol and systolic blood pressure levels were similar in blacks and whites with diabetes, while diastolic blood pressure and percentage of smokers were higher in blacks (89 versus 86 mmHg and 47% versus 34%) and median income was lower. Coronary heart disease was the leading cause of death, accounting for 31% (68/221) and 44% (564/1293) of deaths among blacks and whites, respectively. Adjusted relative risks of CHD death and all cause mortality for blacks compared to whites were 0.71 (95% CI: 0.53-0.95) and 0.94 (95% CI: 0.75-1.11). Differences in reporting cause of death probably account for some of the black/white difference in CHD. High serum cholesterol, high blood pressure, and smoking increased risk of CHD death similarly in blacks and whites. CONCLUSIONS: Serum cholesterol, blood pressure, and smoking are major influences on CHD mortality risk in both white and black men with diabetes. High prevalence of these factors indicates substantial potential for CHD prevention in both ethnic groups.

Mortality differences between black and white men in the USA: contribution of income and other risk factors among men screened for the MRFIT. MRFIT Research Group. Multiple Risk Factor Intervention Trial.

BACKGROUND: Studies of underlying differences in adult mortality between black and white individuals in the USA have been constrained by limitations of data or small study size. We investigated the extent to which differences in socioeconomic position between black and white men contribute to differences in all-cause and cause-specific mortality. METHODS: 361,662 men were screened for the Multiple Risk Factor Intervention Trial between 1973 and 1975, in 22 sites. Median family income of households by zipcode (postal) area of residence was available for 20,224 black and 300,685 white men as well as data on age, cigarette smoking, blood pressure, serum cholesterol, previous heart attack, and treatment for diabetes. We classified deaths during 16 years of follow-up into specific causes and compared differences in death rates between black men and white men, before and after adjustment for differences in income and other risk factors. FINDINGS: Age-adjusted relative risk of death (black vs white) was 1.47 (95% CI 1.42-1.53). Adjustment for diastolic blood pressure, serum cholesterol, cigarette smoking, medication for diabetes, and previous admission to hospital for heart attack decreased the relative risk to 1.40 (1.35-1.46). Adjustment for income but not the other risk factors decreased the risk to 1.19 (1.14-1.24) and adjustment for other risk factors did not alter this estimate. For cardiovascular death, relative risk on adjustment for income was decreased from 1.36 to 1.09; for cancer from 1.47 to 1.25; and for non-cardiovascular and non-cancer deaths from 1.71 to 1.26. For some specific causes of death, including prostate cancer, myeloma, and hypertensive heart disease, the higher death rates among black men did not seem to reflect differences in income. Rates of death for suicide and melanoma were lower among black than white men, as were those for coronary heart disease after adjustment for income. INTERPRETATION: Socioeconomic position is the major contributor to differences in death rates between black and white men. Differentials in mortality from some specific causes do not simply reflect differences in income, however, and more detailed investigations are needed of how differences are influenced by environmental exposures, lifetime socioeconomic conditions, lifestyle, racism, and other sociocultural and biological factors.