Platelet decline as a predictor of brain injury in HIV infection.

An association between platelet decline and increased risk of progression to dementia has been observed in an advanced HIV infection cohort study. This investigation evaluated the prognostic significance of platelet decline for dementia, for psychomotor slowing, and for brain injury, as quantified in vivo, in a much larger population of HIV+ men. Platelet counts and neurocognitive data were available from biannual visits of 2,125 HIV+ men participating in the prospective, Multicenter AIDS Cohort Study from 1984 to 2009. Brain volumetric data were also available from an imaging substudy of 83 seropositive participants aged 50 and older. The association of platelet counts with neurocognitive outcome was assessed using Cox proportional hazard models where change in platelet count from baseline was a time-updated variable. Marked platelet decline was associated with increased risk of dementia in univariate analysis (hazard ratio [HR] = 2.5, 95% confidence interval [CI] = 1.8-3.5), but not after adjustment for CD4 cell count, HIV viral load, age, study site, hemoglobin, race, education, smoking, and alcohol use (HR = 1.4, 95% CI = 0.78-2.5). Platelet decline did not predict psychomotor slowing in either univariate (HR = 0.79, 95% CI = 0.58-1.08) or multivariate (HR = 1.10, 95% CI = 0.73-1.67) analysis. Analysis of brain volumetric data, however, indicated a relationship between platelet decline and reduced gray matter volume fraction in univariate (p = 0.06) and multivariate (p < 0.05) analyses. Platelet decline was not an independent predictor of dementia or psychomotor slowing, after adjusting for stage of disease. Findings from a structural brain imaging substudy of older participants, however, support a possible relationship between platelet decline and reduced gray matter.

Cumulative exposure to nucleoside analogue reverse transcriptase inhibitors is associated with insulin resistance markers in the Multicenter AIDS Cohort Study.

OBJECTIVE: To estimate insulin resistance and its relationship to antiretroviral therapy (ART) in a cohort of HIV-infected persons with comparison to HIV-seronegative controls. DESIGN: Prospective cohort of 533 HIV-infected and 755 HIV-seronegative men in the Multicenter AIDS Cohort Study evaluated at 6-month intervals between 1999 and 2003. METHODS: Recent ART exposure was assessed by type of treatment in the preceding 6 months [i.e., no ART, monotherapy, combination ART, or highly active antiretroviral therapy (HAART) with and without a protease inhibitor (PI)]. Cumulative exposure was determined for the three major ART classes and for individual medications within each class. Two endpoints, a modified QUICKI index, 100 x 1/[log10(glucose) + log10(insulin)] and fasting hyperinsulinemia (insulin > 15 microU/ml), were assessed. All statistical models were adjusted for age, body mass index, race, nadir CD4 cell count, hepatitis C serostatus and family history of diabetes mellitus. RESULTS: Each of the HIV-infected groups had higher odds of hyperinsulinemia and lower mean QUICKI than the HIV-seronegative men. Each additional year of exposure to nucleoside analogue reverse transcriptase inhibitors (NRTI) was associated with increased odds of hyperinsulinemia [odds ratio (OR), 1.08; 95% confidence interval (CI), 1.02-1.13) and a lower QUICKI (-0.04; 95% CI, -0.07 to -0.01). Cumulative exposure to non-nucleoside analogue reverse transcriptase inhibitors or PI drugs was not associated with either insulin resistance marker. Of individual medications examined, stavudine was associated with the highest risk of hyperinsulinemia (OR, 1.2; 95% CI, 1.2-1.3). CONCLUSIONS: Fasting surrogate markers suggest increased insulin resistance in HIV-infected men, which is related to cumulative NRTI exposure.

Antiretroviral therapy and the prevalence and incidence of diabetes mellitus in the multicenter AIDS cohort study.

BACKGROUND: The risk of diabetes mellitus (DM) in human immunodeficiency virus (HIV)-infected patients receiving highly active antiretroviral therapy (HAART) has not been well defined. METHODS: We conducted an analysis in the Multicenter AIDS Cohort Study to determine the prevalence and incidence of DM in this cohort of HIV-infected and HIV-seronegative men. Prevalence analysis included 1278 men (710 HIV seronegative and 568 HIV infected, 411 receiving HAART) with fasting glucose concentration determinations at baseline. Incidence analysis included 680 of these 1278 men who at the baseline visit had a fasting glucose concentration of 98 mg/dL (5.4 mmol/L) or less, no self-reported history of DM, and no self-reported use of antidiabetic medication. Diabetes mellitus was defined as a fasting glucose concentration of 126 mg/dL (7 mmol/L) or higher, self-reported diagnosis of DM, or self-reported use of antidiabetic medication. RESULTS: Fifty-seven (14%) of the 411 HIV-infected men using HAART at the baseline visit had prevalent DM compared with 33 (5%) of the 711 HIV-seronegative men (prevalence ratio = 4.6; 95% confidence interval, 3.0-7.1, adjusted for age and body mass index [calculated as weight in kilograms divided by the square of height in meters]). The rate of incident DM was 4.7 cases per 100 person-years among HIV-infected men using HAART compared with 1.4 cases per 100 person-years among HIV-seronegative men (rate ratio = 4.11; 95% confidence interval, 1.85-9.16, adjusted for age and body mass index), during the 4-year observation period, based on a median follow-up of 2.3 years. CONCLUSION: The incidence of DM in HIV-infected men with HAART exposure was greater than 4 times that of HIV-seronegative men, representing a risk that is higher than previous estimates.

Psychosocial risk factors of HIV morbidity and mortality: findings from the Multicenter AIDS Cohort Study (MACS).

Despite the use of laboratory markers in estimating HIV prognosis, significant variation in the natural history of HIV-1 infection remains unexplained. Recent studies suggest psychosocial risk factors have important prognostic significance in HIV disease. The objective of the present study was to examine the prognostic influence of age, general intellectual functioning, and emotional distress across the spectrum of HIV disease progression. The study sample was drawn from the Multicenter AIDS Cohort Study (MACS), a 13-year, prospective study of HIV-seropositive men recruited from four study centers across the country. The participants were 1,231 HIV-seropositive MACS participants, followed from baseline (median 8/15/87) to the end of the observation period (12/15/98). HIV disease progression was evaluated with respect to three outcome measures: (1) number of years from baseline testing to the first AIDS defining illness (progression to AIDS), (2) years from baseline to HIV-dementia (progression to dementia), and (3) years from baseline to death (survival). The influence of psychosocial risk factors on outcome measures was evaluated using survival analyses. General intellectual functioning, age, and somatic symptoms of depression, were found to be significant predictors of HIV disease progression and survival. Older age at baseline was associated with a more rapid progression to dementia and death. Lower Shipley IQ estimates were associated with a more rapid disease progression (AIDS and dementia) and shortened survival. Somatic symptoms of depression were associated with shortened survival. In addition, age, IQ, and somatic symptoms of depression, had an additive effect with an increase in the number of risk factors associated with accelerated disease progression and shortened time to death. These findings remained consistent, despite controlling for baseline CD4 and HIV medication use. Psychosocial cofactors are important in understanding HIV disease progression. Methods for estimating HIV prognosis may become more reliable if psychosocial factors are considered. Future research will clarify if psychosocial risk factors reflect central nervous system integrity, brain reserve capacity or mediate morbidity and mortality through social economic status, access to health care and other social correlates.

Changes in the incidence and predictors of wasting syndrome related to human immunodeficiency virus infection, 1987-1999.

The authors examined the impact of potent antiretroviral therapy (ART) on the diagnosis of wasting syndrome in the Multicenter AIDS Cohort Study. Study time was divided into the periods 1988-1990, 1991-1993, 1994-1995, and 1996-1999 to correspond to different treatment eras. The proportion of acquired immunodeficiency syndrome diagnoses in which wasting was present increased from 5% in 1988-1990 to 7.1% in 1991-1993, 7.7% in 1994-1995, and 18.9% in 1996-1999. The incidence of wasting per 1,000 person-years increased from 7.5 in 1988-1990 to 14.4 in 1991-1993 and 22.1 in 1994-1995; it decreased to 13.4 in 1996-1999. Fewer patients with wasting had low hemoglobin and hematocrit levels and reported oral thrush in 1996-1999 than in any other period. Analysis of change in body mass index (weight (kg)/height (m)(2)) after wasting showed a faster return to prewasting levels in 1994-1995 and 1996-1999 than in earlier periods. Case-control analysis showed that wasting prior to 1996 was weakly associated with fatigue (p = 0.10), low hemoglobin (p = 0.11), and CD4-positive T-lymphocyte count (p = 0.04). During 1996-1999, wasting was weakly associated with diarrhea (p = 0.05) and potent ART (p = 0.097). Predictors of wasting have changed with potent ART. Further research is needed to determine whether lipodystrophy may be misdiagnosed as wasting syndrome.

Validity of self-reporting of episodes of external genital warts.

To determine whether men are able to self-diagnose external genital warts (EGWs), we studied data from 1115 men with and without human immunodeficiency virus infection. Men were largely unable to accurately assess the presence of EGWs. Self-reporting of EGWs was not a sensitive tool; only 38% of men who had EGWs diagnosed by a trained examiner who used bright light and visual inspection also reported having them. When we controlled for other covariates in a multivariate model, men who had EGWs diagnosed by an examiner were 14 times less likely to show concordance between examiner findings and self-report than were men who did not have EGWs diagnosed by an examiner (odds ratio, 0.07; 95% confidence interval, 0.06-0.09). Self-diagnosis and self-assessment may not accurately reflect the presence of EGWs, and self-diagnosis should not be used in place of an examiner's findings for epidemiologic studies that seek to determine the cause of disease.

Attitudes towards highly active antiretroviral therapy are associated with sexual risk taking among HIV-infected and uninfected homosexual men.

OBJECTIVE: To determine whether attitudes towards highly active antiretroviral therapy (HAART) are associated with unprotected anal sex among sexually active homosexual men. DESIGN: Cross-sectional study nested within an ongoing prospective cohort study. SETTING: Multicenter AIDS Cohort Study, from April through September 1999. PARTICIPANTS: Five-hundred and forty-seven homosexual men reporting anal sex (218 HIV-negative and 329 HIV-positive) during study interviews in 1999, including a 20-item validated scale on attitudes toward HAART and HIV risk behaviors (e.g., 'Because of HAART, I am less concerned about becoming HIV-infected or infecting someone'), and safer sex fatigue (e.g., 'I am tired of always having safer sex'). MAIN OUTCOME MEASURES: Self-reported unprotected receptive anal sex (RAS) and insertive anal sex (IAS) in the prior 6 months. RESULTS: More than 50% of HIV-negative and HIV-positive men who reported having anal sex also reported recent unprotected RAS and/or IAS. HIV-negative men who most agreed that HAART reduced concern about becoming infected were more likely to report unprotected RAS compared to other HIV-negative men [adjusted odds ratio (AOR), 3.31; 95% confidence interval (CI), 1.27-8.62]. Moreover, HIV-positive men with greatest reduced concern due to HAART or safer sex fatigue were more likely to report unprotected IAS (AOR, 6.05; 95% CI, 2.24-16.63 and AOR, 4.57; 95% CI, 1.70-12.24, respectively) compared to other HIV-positive men. CONCLUSIONS: Among sexually active homosexual men, lessened concern about HIV transmission due to HAART was strongly associated with sexual risk taking, as was safer sex fatigue among HIV-positive men. Prevention programs should take into account underlying attitudes for unprotected sex in the era of HAART among both HIV-infected and uninfected men.