Gail Shor-Posner

High risk of HIV-related mortality is associated with selenium deficiency

To determine the independent contribution of specific immunologic and nutritional factors on survival in HIV-1 disease, CD4 cell count, antiretroviral treatment, plasma levels of vitamins A, E, B6, and B12 and minerals selenium and zinc were considered in relation to relative risk for HIV-related mortality. Immune parameters and nutrients known to affect immune function were evaluated at 6-month intervals in 125 HIV-1-seropositive drug-using men and women in Miami, FL, over 3.5 years. A total of 21 of the HIV-1-infected participants died of HIV-related causes during the 3.5-year longitudinal study. Subclinical malnutrition (i.e., overly low levels of prealbumin, relative risk [RR] = 4.01, p < 0.007), deficiency of vitamin A (RR = 3.23, p < 0.03), vitamin B12 deficiency (RR = 8.33, p < 0.009), zinc deficiency (RR = 2.29.1, p < 0.04), and selenium deficiency (RR = 19.9, p < 0.0001) over time, but not zidovudine treatment, were shown to each be associated with HIV-1-related mortality independent of CD4 cell counts <200/mm3 at baseline, and CD4 counts over time. When all factors that could affect survival, including CD4 counts <200/mm3 at baseline, CD4 levels over time, and nutrient deficiencies were considered jointly, only CD4 counts over time (RR = 0.69, p < 0.04) and selenium deficiency (RR = 10.8, p < 0.002) were significantly associated with mortality. These results indicate that selenium deficiency is an independent predictor of survival for those with HIV-1 infection.

Specific nutrient abnormalities in asymptomatic HIV-1 infection.

ObjectiveTo determine whether specific nutrient abnormalities occur in earlier stages of HIV-1 infection, thereby preceding the marked wasting and malnutrition that accompany later stages of the infection. DesignA longitudinal investigation to determine biological, psychological and social factors thought to influence the progression and outcome of HIV-1 infection. Nutritional status was assessed using biochemical measurement of nutrient levels, dietary history, anthropometry and clinical examination for the signs and symptoms of nutritional deficiency or excess. SettingThe study was performed on an outpatient basis at the University of Miami School of Medicine. ParticipantsOne hundred homosexual men, aged between 20 and 55 years, who were asymptomatic other than persistent generalized lymphadenopathy (Centers for Disease Control stage III) and 42 age-matched homosexual men demonstrated to be free of HIV-1 infection at two 6-month intervals. Main outcome measuresBiochemical measurement of nutrient status, dietary history, anthropometry, clinical signs or symptoms of nutritional excess or deficiency were obtained for all participants. ResultsDespite few differences in mean blood levels of specific nutrients, prevalence of specific nutrient abnormalities was widespread among HIV-1-infected subjects, compared with non-infected male homosexual controls. Overtly and marginally low blood levels of vitamins A (18%), E (27%), riboflavin (26%), B6 (53%), and B12 (23%), together with copper (74%) and zinc (50%) were documented in HIV-1-seropositive subjects. With the exception of riboflavin, zinc, and copper, a similar prevalence of abnormalities among HIV-1-seronegative controls was not observed. ConclusionSpecific nutrient abnormalities occur with relative frequency in asymptomatic HIV-1 infection and may contribute to the rate and form of HIV-1 disease progression.

Micronutrients and HIV-1 disease progression

ObjectiveTo determine whether nutritional status affects immunological markers of HIV-1 disease progression. DesignA longitudinal study, to evaluate the relationship between plasma levels of nutrients and CD4 cell counts, along and in combination with β2-microglobulin (β2M; AIDS index) over an 18-month follow-up. MethodsBicohemical measurements of nutritional status including plasma proteins, zinc, iron and vitamins B,, B2/ Be, B12 (cobalamin), A, E, C and folate and immunological markers [lymphocyte subpopulations (CD4) and β2M] were obtained in 108 HIV-1-seropositive homosexual men at baseline and over three 6-month time periods. Changes in nutrient status (e.g., normal to deficient, deficient to normal), were compared with immunological parameters in the same time periods using an autoregressive model. ResultsDevelopment of deficiency of vitamin A or vitamin B12 was associated with a decline in CD4 cell count (P= 0.0255 and 0.0377, respectively), while normalization of vitamin A, vitamin B12 and zinc was associated with higher CD4 cell counts (P= 0.0492, 0.0061 and 0.0112, respectively). These findings were largely unaffected by ziddvudine use. For vitamin B12, low baseline status significantly predicted accelerated HIV-1 disease progression determined by CD4 cell count (P= 0.041) and the AIDS index (P= 0.005). ConclusionsThese data suggest that micronutrient deficiencies are associated with HIV-1 disease progression and raise the possibility that normalization might increase symptom-free survival.

Hypocholesterolemia is associated with immune dysfunction in early human immunodeficiency virus-1 infection

PURPOSE Patients with the acquired immunodeficiency syndrome exhibit marked disturbances in lipid metabolism. Because altered lipid metabolism may affect immune processes, this study characterized the lipid profile of asymptomatic individuals infected with the human immunodeficiency virus (HIV-1), in relationship to immune function. PATIENTS AND METHODS Serum levels of triglycerides and cholesterol were determined in 94 asymptomatic HIV-1-infected (Centers for Disease Control stage II, III) homosexual men and 42 healthy seronegative control subjects. Immune assessment included measurements of lymphocyte subpopulations (CD4), immune activation (beta 2-microglobulin), natural killer cell function, and lymphocyte proliferation in response to mitogens phytohemagglutinin and pokeweed. Dietary intake was determined using a semiquantitative food frequency questionnaire. RESULTS Despite greater consumption of saturated fat and cholesterol, significantly lower levels of total, high-density, and low-density lipoprotein cholesterol were observed in HIV-1-seropositive men, relative to seronegative controls (p < 0.05), with 40% of the HIV-1-infected group demonstrating hypocholesterolemia (less than 150 mg/dL). Low values of total, high-density, and low-density cholesterol were associated with elevated levels of beta 2-microglobulin in HIV-1-seropositive men. No difference between the groups was noted for serum triglycerides. HIV-1-infected subjects did not demonstrate the significant inverse relationship between cholesterol and mitogen response observed in seronegative controls. CONCLUSIONS These findings indicate that low levels of cholesterol are prevalent during the early stages of HIV-1 infection and associated with specific alterations in immune function, suggesting that hypocholesterolemia may be a useful marker of disease progression.

Mortality risk in selenium-deficient HIV-positive children

OBJECTIVE To determine the independent contribution of specific nutritional factors on disease progression and survival in HIV-1-infected children. POPULATION HIV-infected children (N = 24), who were perinatally exposed to the virus and symptomatic, were recruited between October and December of 1990 from the Jackson Memorial Pediatric Immunology Clinic, Miami, Florida, and observed for 5 years. METHODS Immune status was measured by CD4 cell count; nutritional status was determined using serum albumin and plasma trace elements including iron, zinc, and selenium. Cox proportional hazards regression models were used to evaluate the relationship of these parameters to survival. Use of antiretroviral treatment was considered in the statistical model, and age at death was considered a parameter of disease progression. RESULTS Over the course of the study, 12 children died of HIV-related causes. The final Cox multivariate analysis indicated that, of the variables evaluated, only CD4 cell count below 200 (risk ratio [RR] = 7.05; 95% confidence interval [CI], 1.87-26.5); p = .004], and low levels of plasma selenium (RR = 5.96; 95% CI, 1.32-26.81; p = .02) were significantly and independently related to mortality. Among the children who died, those with low selenium levels (< or =85 microg/L), died at a younger age, suggesting more rapid disease progression. CONCLUSIONS In pediatric HIV-infection, low plasma level of selenium is an independent predictor of mortality, and appears to be associated with faster disease progression.

HIV treatment in drug abusers: impact of alcohol use

Studies of alcohol use in HIV‐1 infected patients have resulted in conflicting and limited information regarding prevalence, as well as impact on HIV replication, disease progression and response to antiretroviral therapy. Alcohol, drug abuse and past medical information, including antiretroviral treatment, were obtained using research questionnaires and medical chart review in 220 HIV‐1 infected drug users. A physical examination was conducted and blood was drawn to evaluate immune measures and nutritional status. Heavy alcohol consumption, defined as daily or 3‐4 times per/week, was reported in 63% of the cohort. Men (odds ratio (OR)=2.6, 95% CI 1.13‐5.99, p =0.013), and participants between 35 and 45 years of age were three times more likely to be heavy alcohol users (p =0.006 and 0.0009, respectively). Low serum albumin levels were more evident in heavy alcohol users than non‐drinkers (p =0.003). Heavy alcohol users receiving antiretroviral therapy were twice as likely to have CD4 counts below 500 than light or non‐drinkers (95% CI, 1‐5.5, p =0.03), and highly active antiretroviral therapy (HAART)‐treated heavy alcohol users were four times less likely to achieve a positive virological response (95% CI, 1.2‐17, p =0.04). Alcohol consumption is prevalent in our HIV‐1 infected drug user cohort and significantly impacts both immunological and virological response to HAART treatment.

Impact of tobacco use on the development of opportunistic respiratory infections in HIV seropositive patients on antiretroviral therapy

The increased risk of developing lung diseases in cigarette smokers has been well recognized. The association between smoking and the risk of developing pulmonary infections in HIV‐1‐infected patients, however, which has not been established, was evaluated in the present study. Twenty‐seven cases with lower respiratory infections (15 Pneumocystis carinii pneumonia (PCP), 12 TB cases) were compared with 27 age, gender, socio‐economic and HIV status‐matched patients, without history of respiratory diseases. Medical history and physical examinations were obtained every 6 months. Blood was drawn for CD4 and viral load measurements. A substantial number of HIV+ smokers who developed PCP (one‐third) had been on highly active retroviral therapy (HAART) for more than 6 months and prophylaxis had been discontinued. Multivariate analyses indicated that in HIV‐infected people, after controlling for HIV status and antiretrovirals, cigarette smoking doubled the risk for developing PCP (p =0.01). Multivariate analyses demonstrated that long‐term smoking also increased the risk (2×) of developing tuberculosis (p =0.04). Moreover, daily tobacco use seemed to attenuate by 40% the immune and virological response to antiretroviral therapies. These findings indicate that tobacco use significantly increases the risk of pulmonary diseases in HIV infected subjects and has a potential deleterious impact on antiretroviral treatment.

Impact of a Selenium Chemoprevention Clinical Trial on Hospital Admissions of HIV-Infected Participants

Abstract Purpose: To evaluate the impact of selenium chemoprevention (200μg/day) on hospitalizations in HIV-positive individuals. Method: Data were obtained from 186 HIV+ men and women participating in a randomized, double-blind, placebo-controlled selenium clinical trial (1998-2000). Supplements were dispensed monthly, and clinical evaluations were conducted every 6 months. Inpatient hospitalizations, hospitalization costs, and rates of hospitalization were determined 2 years before and during the trial. Results: At enrollment, no significant differences in CD4 cell counts or viral burden were observed between the two study arms. Fewer placebo-treated participants were using antiretrovirals (p < .05). The total number of hospitalizations declined from 157 before the trial to 103 during the 2 year study. A marked decrease in total admission rates (RR = 0.38; p = .002) and percent of hospitalizations due to infection/100 patients for those receiving selenium was observed (p = .01). As a result, the cost for hospitalization decreased 58% in the selenium group, compared to a 30% decrease in the placebo group (p = .001). In the final analyses, selenium therapy continued to be a significant independent factor associated with lower risk of hospitalization (p = .001). Conclusion: Selenium supplementation appears to be a beneficial adjuvant treatment to decrease hospitalizations as well as the cost of caring for HIV-1--infected patients.PURPOSE To evaluate the impact of selenium chemoprevention (200 microg/day) on hospitalizations in HIV-positive individuals. METHOD Data were obtained from 186 HIV+ men and women participating in a randomized, double-blind, placebo-controlled selenium clinical trial (1998-2000). Supplements were dispensed monthly, and clinical evaluations were conducted every 6 months. Inpatient hospitalizations, hospitalization costs, and rates of hospitalization were determined 2 years before and during the trial. RESULTS At enrollment, no significant differences in CD4 cell counts or viral burden were observed between the two study arms. Fewer placebo-treated participants were using antiretrovirals (p <.05). The total number of hospitalizations declined from 157 before the trial to 103 during the 2 year study. A marked decrease in total admission rates (RR = 0.38; p =.002) and percent of hospitalizations due to infection/100 patients for those receiving selenium was observed (p =.01). As a result, the cost for hospitalization decreased 58% in the selenium group, compared to a 30% decrease in the placebo group (p =.001). In the final analyses, selenium therapy continued to be a significant independent factor associated with lower risk of hospitalization (p =.001). CONCLUSION Selenium supplementation appears to be a beneficial adjuvant treatment to decrease hospitalizations as well as the cost of caring for HIV-1-infected patients.

HIV-1 infection in women is associated with severe nutritional deficiencies

Nutritional deficiencies may contribute to immune dysregulation, and have been shown to be sensitive markers of HIV-1 disease progression. Only limited information exists, however, regarding the nutritional profile of HIV-1-seropositive drug abusers. Immune and nutritional measurements were obtained in a subsample of 125 subjects from a larger cohort of drug users being followed for HIV-1 infection and cofactors of disease progression. Nutritional deficiencies, particularly vitamins A, E, and zinc, were widespread with up to 86% of the drug users exhibiting at least one nutritional alteration. Although immune parameters (CD4 count, CD8 count, beta2-microglobulin) were similar in the HIV-1-infected men and women, women had significantly poorer overall nutritional status, as measured by plasma proteins, which are considered to be sensitive markers of malnutrition. A comparison of individuals with advanced disease (CD4 count <200/mm3) revealed significantly lower levels of plasma prealbumin (p < .01), selenium, (p < .05), and greater deficiency of vitamins A (p < .01) and E (p < .05) in women than in men. The greater severity of nutritional deficiencies noted in HIV-1-infected women may be an important determinant of disease progression and survival.

Impact of selenium status on the pathogenesis of mycobacterial disease in HIV-1-infected drug users during the era of highly active antiretroviral therapy

&NA; The risk of mycobacterial disease is significantly increased in drug abusers as well as in immunocompromised HIV‐1‐infected individuals. The essential trace element selenium has an important function in maintaining immune processes and may, thus, have a critical role in clearance of mycobacteria. The impact of selenium status on the development of mycobacterial diseases in HIV‐1‐seropositive drug users was investigated over a 2‐year period (1999‐2001). Twelve cases of mycobacterial disease (tuberculosis, 9; infection due to atypical Mycobacterium species, 3) occurred; these 12 cases were compared with 32 controls with no history of respiratory infections who were matched on age, sex, and HIV status. Significant risk for development of mycobacterial disease was associated with a CD4 cell count of <200/mm3, malnutrition, and selenium levels of ⩽135 μg/L (patients with these levels were 13 times more likely to develop mycobacterial disease). Multivariate analyses controlling for antiretroviral treatment and CD4 cell count revealed that both body mass index and selenium level remained significant factors in the relative risk for developing mycobacterial disease (relative risk, 3; p = .015); these findings suggest that selenium status may have a profound impact on the pathogenesis of mycobacterial disease.