Marianna K. Baum

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.

Crack-cocaine Use Accelerates Hiv Disease Progression in a Cohort of Hiv-positive Drug Users

Background:HIV infection is prevalent among substance abusers. The effects of specific illicit drugs on HIV disease progression have not been established. We evaluated the relationship between substances of abuse and HIV disease progression in a cohort of HIV-1-positive active drug users. Methods:A prospective, 30-month, longitudinal study was conducted on 222 HIV-1 seropositive drug users in Miami, FL. History of illicit drug, alcohol, and medication use, CD4+ cell count, and viral load were performed every 6 months. Results:Crack-cocaine users were 2.14 times [95% confidence interval (CI): 1.08 to 4.25, P = 0.029] more likely to present a decline of CD4 to ≤200 cells/mL, independent of antiretroviral use. Viral load over 30 months was significantly higher in crack users (β = 0.315, P = 0.037) independent of highly active antiretroviral therapy (HAART) over time. The only multidrug combination that significantly increased the risk of disease progression was crack cocaine with marijuana (hazard ratio = 2.42; 95% CI: 1.042 to 5.617, P = 0.04). Of those on HAART, a significantly lower proportion of crack-cocaine users versus nonusers had controlled viral load (P < 0.001), suggesting lower medication adherence, whereas crack-cocaine users not on HAART showed a greater risk for HIV disease progression than nonusers (hazard ratio = 3.946; 95% CI: 1.049 to 14.85, P = 0.042). Conclusions:Crack-cocaine use facilitates HIV disease progression by reducing adherence in those on HAART and by accelerating disease progression independently of HAART.

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.

Alcohol Use Accelerates HIV Disease Progression

The effects of alcohol abuse on HIV disease progression have not been definitively established. A prospective, 30-month, longitudinal study of 231 HIV(+) adults included history of alcohol and illicit drug use, adherence to antiretroviral therapy (ART), CD4(+) cell count, and HIV viral load every 6 months. Frequent alcohol users (two or more drinks daily) were 2.91 times (95% CI: 1.23-6.85, p = 0.015) more likely to present a decline of CD4 to <or=200 cells/microl, independent of baseline CD4(+) cell count and HIV viral load, antiretroviral use over time, time since HIV diagnosis, age, and gender. Frequent alcohol users who were not on ART also increased their risk for CD4 cell decline to <or=200 cells/mm(3) (HR = 7.76: 95% CI: 1.2-49.2, p = 0.03). Combined frequent alcohol use with crack-cocaine showed a significant risk of CD4(+) cell decline (HR = 3.57: 95% CI: 1.24-10.31, p = 0.018). Frequent alcohol intake was associated with higher viral load over time (beta = 0.259, p = 0.038). This significance was maintained in those receiving ART (beta = 0.384, p = 0.0457), but not in those without ART. Frequent alcohol intake and the combination of frequent alcohol and crack-cocaine accelerate HIV disease progression. The effect of alcohol on CD4(+) cell decline appears to be independent of ART, through a direct action on CD4 cells, although alcohol and substance abuse may lead to unmeasured behaviors that promote HIV disease progression. The effect of alcohol abuse on viral load, however, appears to be through reduced adherence to ART.

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.

Active coping style is associated with natural killer cell cytotoxicity in asymptomatic HIV-1 seropositive homosexual men

The aim of this study was to examine the hypothesis that a psychosocial model was associated with natural killer cell cytotoxicity (NKCC) in HIV-1 infection. A sample of 62 HIV-1 seropositive homosexual men at CDC stages II and III were given a psychosocial battery assessing life stressors, social support, and coping style. A regression model quantifying these variables along with control variables for alcohol use, substance use and nutritional status was estimated. Active coping style was directly and positively associated with NKCC, and trends toward a negative relationship of life stressors and a buffering effect of social support on lives stressors were also observed. The results suggest that (1) control variables should be included with psychosocial models and that (2) psychosocial factors, especially active coping, may have a deterrent effect on loss of NK cell function. Active coping style may merit a specific focus in future research of life stressors and the immune system.

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.