Alice M. Tang

Long-term effects of androgen deprivation therapy in prostate cancer patients

background Prostate cancer (PCa) is one of the most common cancers in men and has an increasing incidence. In 1999, 37 000 men died from PCa in the USA. Androgen deprivation therapy (ADT) with GnRH agonists is frequently employed in the treatment of recurrent and metastatic PCa by inducing medical castration, rendering these men hypogonadal. Because hypogonadism in men is associated with a wide range of complications, we attempted to determine the effects of long‐term ADT in men with PCa.

Micronutrients and the pathogenesis of human immunodeficiency virus infection

Micronutrient deficiencies may be common during human immunodeficiency virus (HIV) infection. Insufficient dietary intake, malabsorption, diarrhoea, and impaired storage and altered metabolism of micronutrients can contribute to the development of micronutrient deficiencies. Low plasma or serum levels of vitamins A, E, B6, B12 and C, carotenoids, Se, and Zn are common in many HIV-infected populations. Micronutrient deficiencies may contribute to the pathogenesis of HIV infection through increased oxidative stress and compromised immunity. Low levels or intakes of micronutrients such as vitamins A, E, B6 and B12, Zn and Se have been associated with adverse clinical outcomes during HIV infection, and new studies are emerging which suggest that micronutrient supplementation may help reduce morbidity and mortality during HIV infection.

Association between serum vitamin A and E levels and HIV-1 disease progression

Objective:To examine the associations between serum vitamin A and E levels and risk of progression to three key outcomes in HIV-1 infection: first AIDS diagnosis, CD4+ cell decline to < 200 cells × 106/l, and mortality. Design:Non-concurrent prospective study. Methods:Serum levels of vitamins A and E were measured at the enrollment visit of 311 HIV-seroprevalent homo-/bisexual men participating in the Baltimore/Washington DC site of the Multicenter AIDS Cohort Study. Cox proportional hazards models were used to estimate the relative hazard of progression to each outcome over the subsequent 9 years, adjusting for several independent covariates. Results:Men in the highest quartile of serum vitamin E levels (≥ 23.5 µmol/l) showed a 34% decrease in risk of progression to AIDS compared with those in the lowest quartile [relative hazard (RH), 0.66; 95% confidence interval (CI), 0.41–1.06)]. This effect was statistically significant when comparing the highest quartile of serum vitamin E to the remainder of the cohort (RH, 0.67; 95% CI, 0.45–0.98). Associations between serum vitamin A levels and risk of progression to AIDS were less clear, but vitamin A levels were uniformly in the normal to high range (median = 2.44 µmol/l). Similar trends were observed for each vitamin with mortality as the outcome, but neither vitamin was associated with CD4+ cell decline to < 200 cells × 106/l. Men who reported current use of multivitamin or single vitamin E supplements had significantly higher serum tocopherol levels than those who were not taking supplements (P = 0.0001). Serum retinol levels were unrelated to intake of multivitamin or single vitamin A supplements. Conclusions:These data suggest that high serum levels of vitamin E may be associated with slower HIV-1 disease progression, but no relationship was observed between retinol levels and disease progression in this vitamin A-replete population.

Weight loss and survival in HIV-positive patients in the era of highly active antiretroviral therapy.

Weight loss and wasting have long been established as strong predictors of mortality in HIV-infected patients. Today, despite the effectiveness of highly active antiretroviral therapy (HAART), there is evidence that HIV-related wasting is still an important comorbidity in many patients. We conducted a study to determine if wasting is still associated with decreased survival in patients receiving HAART and which parameter (weight, fat-free mass [FFM], body cell mass [BCM], or fat mass [FM]) is most strongly associated with mortality. The study population consisted of 678 HIV-positive participants enrolled in the Nutrition for Healthy Living study. Weight, FFM, BCM, and FM were assessed for all participants at 6-month intervals. At each follow-up visit, percent losses of each parameter were calculated from values at baseline and the previous visit. Cox proportional hazards models were used to estimate and compare the relative risks of death for each parameter, adjusting for potential confounders such as HAART use, body mass index, and CD4 cell counts. In analyses examining the parameters separately and together in the same model, weight loss emerged as the strongest independent predictor of mortality. Weight loss of >or=10% from baseline or the previous visit was significantly associated with a four- to sixfold increase in mortality compared with maintenance or gaining of weight. Even one episode of weight loss of >or=3% from baseline or >or=5% from the previous visit was predictive of mortality. In summary, despite the apparent benefits of HAART use on HIV-related survival, weight loss remains an independent predictor of mortality. In addition, FFM or BCM estimated using bioelectrical impedance analysis does not add further prognostic value over weight loss.

Incidence of metabolic syndrome in a cohort of HIV-infected adults and prevalence relative to the US population (National Health and Nutrition Examination Survey).

Background:Metabolic syndrome increases the risk of cardiovascular outcomes and type II diabetes. Most of the metabolic abnormalities defining metabolic syndrome are observed in HIV. Objective:To determine the incidence and risk factors for metabolic syndrome in HIV-infected adults in the Nutrition for Healthy Living (NFHL) study (2000-2003) and prevalence relative to the findings of the National Health and Nutrition Examination Survey (NHANES) (1999-2002). Methods:Metabolic syndrome is ≥3 of the following: hypertriglyceridemia, low high-density lipoprotein (HDL) cholesterol, hypertension, abdominal obesity, and high serum glucose. The baseline prevalence of metabolic syndrome in the NFHL study (n = 477) was compared to that in the NHANES (n = 1876), adjusted for age, race, gender, poverty, exercise, and diet. Results:Almost one quarter of NFHL subjects had metabolic syndrome. Most with metabolic syndrome (77%) had low HDL and hypertriglyceridemia plus ≥1 additional abnormality. The prevalence of metabolic syndrome was significantly lower in HAART and non-HAART users compared with NHANES participants unadjusted for body mass index (BMI). After adjustment for BMI, it was no longer significant but the trend remained. The incidence of metabolic syndrome in the NFHL study was higher with increasing viral load, higher BMI, higher trunk-to-limb fat ratio, and Kaletra (lopinavir/ritonavir) or didanosine (ddI) use and lower among college-educated persons. Conclusions:Metabolic syndrome is mostly diagnosed through low HDL and high triglycerides in HIV. The risk of developing the syndrome is related to HIV, specific medications, and body fat.

Risk of Cardiovascular Disease in a Cohort of HIV-Infected Adults: A Study Using Carotid Intima-Media Thickness and Coronary Artery Calcium Score

BACKGROUND There is concern that human immunodeficiency virus (HIV) infection and the use of highly active antiretroviral therapy lead to accelerated atherosclerosis and increased risk of cardiovascular disease. We measured 2 surrogate markers of subclinical atherosclerosis, carotid intima-media thickness (c-IMT) and coronary artery calcium (CAC) scores, in HIV-infected adults. METHODS A cross-sectional analysis of 242 men and 85 women with HIV infection was used. Carotid ultrasonography and coronary computed tomography were performed, and their associations with cardiovascular risk factors were examined. RESULTS Among men, the mean (+/- standard deviation [SD]) common c-IMT was 0.62+/-0.2 mm, the mean (+/-SD) internal c-IMT was 0.76+/-0.5 mm, and 136 patients (56.1%) had detectable CAC. Among women, the mean (+/-SD) common c-IMT was 0.59+/-0.2 mm, the mean (+/-SD) internal c-IMT was 0.66+/-0.4 mm, and 40 patients (47.1%) had detectable CAC. Neither the c-IMT nor the CAC score differed by antiretroviral therapy class or individual medications for either sex. For men, age and waist circumference independently predicted common c-IMT; age, systolic blood pressure, and high-sensitivity C-reactive protein level independently predicted internal c-IMT; and age, apolipoprotein B level, and high-sensitivity C-reactive protein level independently predicted CAC score. For women, age and body mass index independently predicted common c-IMT; age independently predicted internal c-IMT; and age and glucose level independently predicted CAC score. CONCLUSIONS Our participants had more abnormal surrogate markers than expected at a relatively young age, but those were not associated with use of highly active antiretroviral therapy or protease inhibitors. At present, the positive associations were primarily with traditional and novel cardiovascular risk factors. Some HIV-specific (not treatment-specific) factors were observed; they may become more evident with prolonged HIV infection and treatment.

Micronutrient levels and HIV disease status in HIV-infected patients on highly active antiretroviral therapy in the Nutrition for Healthy Living cohort.

Background:Low serum micronutrient levels were common before widespread use of highly active antiretroviral therapy (HAART) and were associated with adverse outcomes. Few data are available on micronutrient levels in subjects taking HAART. Objective:To determine the prevalence of low serum retinol, α-tocopherol, zinc, and selenium in HIV-infected subjects taking HAART and to assess the association of micronutrient levels with HIV disease status. Design:Cross-sectional. Setting:Nutrition for Healthy Living (NFHL) study. Participants:HIV-infected subjects on HAART. Methods:Retinol, α-tocopherol, zinc, and selenium were determined in frozen serum samples from 171 men and 117 women. Low serum levels were defined as retinol <30 μg/dL, selenium <85 μg/L, α-tocopherol <500 μg/dL, and zinc <670 μg/L. Association of micronutrient quartiles with CD4 cell count, CD4 count <200 cells/mm3, HIV viral load (VL), and undetectable VL was assessed using adjusted multivariate regression. Results:Five percent of men and 14% of women had low retinol, 8% of men and 3% of women had low selenium, and 7% of men and no women had low α-tocopherol. Forty percent of men and 36% of women had low zinc, however. Subjects in the upper quartiles of zinc had lower log VL levels than those in the lowest quartile (significant for women). Subjects in the upper quartiles of selenium also tended to have lower VL levels compared with those in the lowest quartile. Surprisingly, women in the upper quartiles of retinol had higher log VLs than those in the lowest quartile. There was no significant association of any micronutrient with CD4 cell count or likelihood of CD4 count <200 cells/mm3. The level of CD4 cell count influenced the association of retinol with log VL in men, however. In men with CD4 counts >350 cells/mm3, those with higher retinol had higher log VLs compared with the lowest quartile, whereas in men with CD4 counts <350, those with higher retinol levels had lower log VLs compared with the lowest quartile. Conclusions:Low retinol, α-tocopherol, and selenium are uncommon in HIV-infected subjects on HAART. Zinc deficiency remains common, however. Decreased retinol levels in women and in men with CD4 counts >350 cells/mm3 and increased zinc and selenium levels in both genders may be associated with improved virologic control.

Increasing risk of 5% or greater unintentional weight loss in a cohort of HIV-infected patients, 1995 to 2003.

Although the incidence of most AIDS-defining opportunistic infections, including HIV wasting syndrome, has dramatically decreased since the introduction of highly active antiretroviral therapy (HAART), previous studies have shown that weight loss and wasting are still common in HIV-infected persons. We examined the 6-month risk and determinants of ≥5% weight loss during the period when the use of combination antiretroviral therapy and HAART was commonplace among 713 participants enrolled in the Nutrition for Healthy Living cohort in Boston, Massachusetts between 1995 and 2003. There was a significant 50% increase in the 6-month risk of ≥5% weight loss in the later HAART years (1998-2003) compared with the early HAART years (1995-1997) among most of the participants who reported they were not trying to lose weight (P = 0.002). In addition to calendar time, several other variables were significantly independently associated with risk of ≥5% weight loss, including use of injection drugs; living below the federal poverty level; higher body mass index (BMI; ≥25 kg/m2); lower CD4+ cell count; higher HIV viral load; and presence of diarrhea, nausea, or fever. The characteristics of weight loss in the later HAART years did not differ from the early HAART years with respect to initial body composition (eg, weight, BMI, triceps skinfold thickness) or changes in body composition during the periods of weight loss. In summary, we have found that the risk of ≥5% unintentional weight loss over 6-month intervals is on the rise in our cohort of HIV-infected participants, despite better control of HIV infection in recent years. Although we still do not know the exact cause of this increase, the fact that it exists indicates the need for clinicians who take care of HIV-infected patients to continue to pay attention to weight loss among particular segments of their patient population. This is particularly important because recent studies have shown that even a 5% weight loss in 6 months markedly increases the risk of death.

Dietary intake of community-based HIV-1 seropositive and seronegative injecting drug users

Dietary intake was assessed in a subsample of a cohort of inner-city injecting drug users (IDUs). In this population of predominantly African-American IDUs, including both HIV -1-infected and noninfected men and women, a food frequency questionnaire (FFQ) and a 24-h recall were administered. One hundred seven volunteers participated. Although total caloric intake was consistently higher with the food frequency method, percent of total calories from fat, protein, and carbohydrates were similar between the FFQ and 24-h recall. Spearmans correlations for agreement between the 24-h recall and the FFQ ranged from 0.22 for vitamin E to 0.52 for carbohydrates. HIV-1 seropositives reported higher protein (p = 0.05) and fat (p = 0.02) consumption than seronegatives according to the 24-h recall. The difference in total fat consumption was due to higher intakes of saturated and monounsaturated fats (p = 0.01). Median intakes of vitamins B2 and B12, pantothenic acid (p < or = 0.05), phosphorous (p < or = 0.01), and selenium (p < or = 0.005) were also greater in HIV-1 seropositives. Reported intake of vitamins A and E, calcium, and zinc were below the recommended daily allowances for both HIV-1 seropositives and seronegatives. Although intakes of most nutrients appeared adequate for the group as a whole, extreme ranges were observed and may be the result of imbalanced food selections and day to day variation. Food group analysis indicated low intakes of fruits, vegetables, milk, and milk products. More research is needed to fully understand the implication of dietary habits and nutritional status in the free-living HIV-1-infected and noninfected IDUs.

Use of Complementary and Alternative Therapies by Patients With Human Immunodeficiency Virus Disease in the Era of Highly Active Antiretroviral Therapy

BACKGROUND Complementary and alternative medical therapies (CAM) are popular with patients who are human immunodeficiency virus (HIV) seropositive, despite effective drug treatments, potential drug interactions, and overlapping toxicities. OBJECTIVE To determine rates and correlates of ingested and noningested CAM use, and to examine temporal changes in the rates of ingested CAM use during the introduction of highly active antiretroviral therapy (HAART). DESIGN Cross-sectional analysis with repeated measures from a cohort study, with the study visit as the unit of analysis. SETTING Eastern Massachusetts and Rhode Island. PARTICIPANTS Adults who are HIV seropositive followed semiannually (n = 642) in Nutrition for Healthy Living (NFHL) study. MEASUREMENTS Rates of ingested and noningested CAM use were assessed by interview every 6 months between 1995 and 1999. RESULTS Ingested CAM use was reported at 60% of visits. Between 1995 and 1999, HAART use increased from 0% to 70%, and ingested CAM use decreased from 71% to 52%. In multivariate analyses, users of ingested complementary therapies were more likely to be gay men (prevalence ratio [PR] 1.40, 95% confidence interval [CI] 1.23-1.58; p < 0.0001), at least high school educated (PR 1.37, 95% CI 1.12-1.68, p = 0.002), and with secure housing (PR 0.75, 95% CI 0.61-0.92; p = 0.007). Even in the lowest risk group (less educated, nongay males with insecure housing), CAM use rates were 27% (95% CI 21%-34%). There was no association between HAART and CAM use. CONCLUSIONS CAM therapies complement, rather than replace, HAART. Even among poorly educated, nongay male patients with insecure housing, rates of ingested CAM use were substantial. Physicians should routinely ask about ingested CAM therapy use and become knowledgeable about potential hazards.