Ximena Burbano

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.

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.

Psychological Burden in the Era of Haart: Impact of Selenium Therapy

Objective: To determine the impact of nutritional (selenium) chemo-prevention on levels of psychological burden (anxiety, depression, and mood state) in HIV/AIDS. Method: A randomized, double-blind, placebo-controlled selenium therapy (200 μ/day) trial was conducted in HIV+ drug users from 1998–2000. Psychosocial measures (STAI-State and Trait anxiety, BDI-depression, and POMS- mood state), clinical status (CD4 cell count, viral load), and plasma selenium levels were determined at baseline and compared with measurements obtained at the 12-month evaluation in 63 participants (32 men, 31 women). Results: The majority of the study participants reported elevated levels of both State (68%) and Trait (70%) anxiety. Approximately 25% reported overall mood distress (POMS >60) and moderate depression (BDI > 20). Psychological burden was not influenced by current drug use, antiretroviral treatment, or viral load. At the 12-month evaluation, participants who received selenium reported increased vigor (p = 0.004) and had less anxiety (State, p = 0.05 and Trait, p = 0.02), compared to the placebo-treated individuals. No apparent selenium-related affect on depression or distress was observed. The risk for state anxiety was almost four times higher, and nearly nine times greater for trait anxiety in the placebo-treated group, controlling for antiretroviral therapy, CD4 cell decline (> 50 cells) and years of education. Conclusions: Selenium therapy may be a beneficial treatment to decrease anxiety in HIV+ drug users who exhibit a high prevalence of psychological burden.

Thrombocytopenia in HIV-infected drug users in the HAART era.

The present case-control study compared 26 HIV+ drug users having persistent thrombocytopenia (TCP<150 000/mm 3 ) with 54 available age, gender and HIV CDC classification matched controls with normal platelet counts. Participants were followed longitudinally over a 2-year period (1998-2000), and hematological alterations evaluated in relationship to antiretroviral treatment, drug use and nutritional (selenium) status. Demographic information and medical history, including antiretroviral treatment were obtained. Blood was drawn for complete cell blood count, T lymphocytes and viral load. Sixty-nine percent of the individuals with persistent TCP and 49% of the controls were receiving antiretrovirals. At baseline, no significant differences in CD4 existed between the two groups. Over time, CD4 cell count declined in the cases ( P = 0.05) and a significantly higher proportion of the cases (38%) developed AIDS (CD4<200 cell/mm 3 ), as compared to the controls (18%, P = 0.004). A high risk for development of thrombocytopenia was observed with specific drug use (heroin 2.96 times, P = 0.0007), selenium levels below 145 w g/l (6 times, P = 0.008), and abnormal liver enzyme (SGOT) levels (2 times, P = 0.002). Together, these results indicate a number of factors that may be sensitive predictors of thrombocytopenia, which, despite antiretroviral treatment, appears to be related to more rapid disease progression in drug users.

Development of thrombocytosis in HIV+ drug users: impact of antiretroviral therapy

With the exception of hemolytic anemia, the potential hematological toxicity of antiretrovirals (ARV) and combination treatments in HIV treated individuals has not been well established. We report, for the first time, hematological toxicity defined as thrombocytosis in 9% of the HIV+ patients receiving highly active antiretroviral treatment (HAART) being followed in a nutritional clinical trial. Participants were evaluated every 6 months during a 2-year period (1998-2000) and blood drawn for biochemical, hematological and immunological parameters. NK cells were negatively correlated with platelet counts in the total cohort ( P = 0.018) and persistently elevated with ARVT. Chronic thrombocytosis was associated with significantly lower NK percentages ( P = 0.005). Twenty-five percent of the patients with thrombocytosis developed a cardiovascular disease. Together, these results support the proposal that HAART may increase the risk of hematological dysfunction and impact the risk of cardiovascular disease.

Continued High Risk Behaviors in HIV Infected Drug Abusers

ABSTRACT To characterize current risk behaviors of HIV drug abusers in the highly active antiretroviral therapy (HAART) era, socio-demo-graphic, medical and behavioral information were obtained and immune measurements determined. High-risk sexual practices were prevalent. Participants diagnosed before 1995 were 6 times more likely to have unprotected sex with HIV+ partners (p = 0.05) and 11 times more likely to use contaminated needles (p = 0.05) than participants with later diagnosis. Consistent condom use was reported by only 7% of the cohort. Many (43%) of the participants reported multiple HIV+ and HIV-concurrent partners. Most (65%), particularly women (OR = 3, p = 0.02), did so for drugs or money. Despite detectable viral loads, 36% reported unprotected anal sex. Antiretroviral-treated men, compared to non-treated, tended to have unprotected anal sex (OR = 2, p = 0.07). The continued high-risk behaviors of HIV drug users, particularly those diagnosed before 1995 and/or on antiretroviral therapy, indicates an urgent need for new public health strategies.

Low cholesterol? Don't brag yet ... hypocholesterolemia blunts HAART effectiveness: a longitudinal study

BackgroundIn vitro studies suggest that reducing cholesterol inhibits HIV replication. However, this effect may not hold in vivo, where other factors, such as cholesterols immunomodulatory properties, may interact.MethodsFasting blood samples were obtained on 165 people living with HIV at baseline and after 24 weeks on highly active antiretroviral therapy (HAART). Participants were classified as hypocholesterolemic (HypoCHL; <150 mg/dl) or non-HypoCHL (>150 mg/dl) and were compared on viro-immune outcomes.ResultsAt baseline, participants with HypoCHL (40%) exhibited lower CD4 (197 ± 181 vs. 295 ± 191 cells/mm3, p = 0.02) and CD8 (823 ± 448 vs. 1194 ± 598 cells/mm3, p = 0.001) counts and were more likely to have detectable viral loads (OR = 3.5, p = 0.01) than non-HypoCHL controls. After HAART, participants with HypoCHL were twice as likely to experience a virological failure >400 copies (95% CI 1-2.6, p = 0.05) and to exhibit <200 CD4 (95% CI 1.03-2.9, p = 0.04) compared with non-HypoCHL. Low thymic output was related to poorer CD4 cell response in HypoCHL subjects. Analyses suggest a dose-response relationship with every increase of 50 mg/dl in cholesterol related to a parallel rise of 50 CD4 cells.ConclusionsThe study implicates, for the first time, HypoCHL with impaired HAART effectiveness, including limited CD4 repletion by the thymus and suboptimal viral clearance.

High-risk behaviours in men from Bogotá, Colombia and the spread of HIV

Our objective was to identify sexual behaviours related to risk of HIV infection. A cluster survey of sexually experienced men from diverse socio-demographic settings in Bogotá, Colombia was carried out using a standardized self-administered questionnaire. A high response rate (96%) resulted in the enrolment of 553 men. Most participants 129/442 reported having intercourse with women and 51/111 reported having sex with other men. Most respondents (90%) engaged in high-risk sexual practices; only 2% knew their HIV-1 serostatus. Consistent condom use was reported by 20% of those who practised anal sex, and was even lower (5%) among men who had sex with women during menses. Heterosexuals exhibited a higher degree of risky sexual patterns than homosexual/bisexuals (P=0.01). In conclusion, high-risk sexual practices are prevalent among men in Bogotá, particularly heterosexuals, attesting to the urgent need for effective and specific interventions to prevent HIV transmission.