Maria Jose Miguez

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.

Tobacco Smoking Increases Immune Activation and Impairs T-Cell Function in HIV Infected Patients on Antiretrovirals: A Cross-Sectional Pilot Study

Background The influence of tobacco smoking on the immune system of HIV infected individuals is largely unknown. We investigated the impact of tobacco smoking on immune activation, microbial translocation, immune exhaustion and T-cell function in HIV infected individuals. Method HIV infected smokers and non-smokers (n = 25 each) with documented viral suppression on combination antiretroviral therapy and HIV uninfected smokers and non-smokers (n = 15 each) were enrolled. Markers of immune activation (CD38 and HLA-DR) and immune exhaustion (PD1, Tim3 and CTLA4) were analyzed in peripheral blood mononuclear cells (PBMCs) by flow cytometry. Plasma markers of microbial translocation (soluble-CD14 - sCD14 and lipopolysaccharide - LPS) were measured. Antigen specific functions of CD4+ and CD8+ T-cells were measured, by flow cytometry, in PBMCs after 6 hours stimulation with Cytomegalovirus, Epstein-Barr virus and Influenza Virus (CEF) peptide pool. Results Compared to non-smokers, smokers of HIV infected and uninfected groups showed significantly higher CD4+ and CD8+ T-cell activation with increased frequencies of CD38+HLA-DR+ cells with a higher magnitude in HIV infected smokers. Expressions of immune exhaustion markers (PD1, Tim3 and CTLA4) either alone or in combinations were significantly higher in smokers, especially on CD4+ T-cells. Compared to HIV uninfected non-smokers, microbial translocation (sCD14 and LPS) was higher in smokers of both groups and directly correlated with CD4+ and CD8+ T-cell activation. Antigen specific T-cell function showed significantly lower cytokine response of CD4+ and CD8+ T-cells to CEF peptide-pool stimulation in smokers of both HIV infected and uninfected groups. Conclusions Our results suggest that smoking and HIV infection independently influence T-cell immune activation and function and together they present the worst immune profile. Since smoking is widespread among HIV infected individuals, studies are warranted to further evaluate the cumulative effect of smoking on impairment of the immune system and accelerated disease progression.

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.

Preventing mother-to-child HIV transmission in a developing country: the Dominican Republic experience.

Transmission of HIV in the Dominican Republic occurs primarily through heterosexual contact. As part of a continuing strategy to prevent and contain the spread of HIV infection, the Ministry of Health of the Dominican Republic established an integrated package of interventions to reduce HIV mother-to-child transmission that was initiated on May 15, 2000. The program was designed to be implemented in 3 phases. The 1st phase included 4 mother and child hospitals; the 2nd phase included 8 mother and child health institutions in Santo Domingo, the capital of the Dominican Republic, and 7 additional mother and child hospitals. The 3rd phase will include the remaining 12 mother and child health care institutions of the Dominican Republic. Evaluation of the 1st year of this program, involving 8 hospitals and >40,000 pregnant women, identified specific benefits and limitations. Low numbers of voluntary counseling sessions (6528/42,666 = 28%) and inadequate number of HIV rapid tests (23,067/42,666 = 54%) were the 2 main obstacles encountered. From the 23,067 pregnant women tested, 581 (2.5%) were HIV positive. Advantageous aspects included the successful administration of antiretroviral treatment to 89% (164/185) of the mothers and 98% (183/186) of the children. Cesarean section was performed in 67% (124/185) of the HIV-positive pregnant women, and infant formula was dispensed to 47% (87/186) of all cases. These findings demonstrate the feasibility of implementing a large-scale program to prevent mother-to-child transmission in a developing country.

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.

Cholesterol as a mediator of alcohol-induced risks for respiratory disease hospitalizations among people living with HIV.

We analyzed the role of cholesterol as a potential mediator of alcohol-increased risk of respiratory infections that required hospitalization in People Living with HIV (PLWH). Using a longitudinal clinic-based design, 346 PLWH were consecutively admitted and followed at Jackson Memorial Medical Center(enrolled in the study). Following national guidelines, PLWH were stratified according to cholesterol levels: <150 mg/dl (Hypocholesterolemia= HypoCHL), 151-200, and >200 mg/dl Hypercholesterolemia =HyperCHL), and compared on the basis of clinical outcomes, lymphocyte phenotypes and behavioral risks. Analyses indicated that compared to HyperCHL participants, HypoCHL subjects were more likely to be hospitalized, particularly for lower respiratory tract infections (LRTI). Excessive admissions were associated with more deviant lymphocyte profiles, particularly limited NK cells. In logistic regression analyses, smoking (OR=1.5), HypoCHL (OR=7.7), and alcohol (OR=1.2) were predictors of LRTI. These findings warrant further investigation of the potential use of HypoCHL as a risk marker, and the cost-effectiveness of switching prevention gears towards HypoCHL, alcohol and tobacco in PLWH.

The Importance of HIV Status and Gender When Designing Prevention Strategies for Anal Cancer

&NA; Our objective is to review and summarize relevant aspects of the literature regarding human papillomavirus (HPV), the most common sexually transmitted infection in the United States, and to compare how the trajectory of HPV may differ in persons who are and who are not co‐infected with HIV. This comparison is particularly important because the literature on HPV has been largely based on individuals who are not co‐infected with HIV. Also, HPV findings may differ in HIV‐uninfected individuals versus HIV‐infected individuals. In addition, many reviews ignore gender differences, although in HIV‐uninfected individuals, anal cancers are up to 4 times more prevalent in women than men. Clinical decision making may be problematic if such critical factors as HIV status and gender are neglected. Therefore, we will review existing information on how HIV status and gender may affect the manifestation of HPV, particularly focusing on epidemiology, screening, and treatment issues.

Interleukin-6 and platelet protagonists in T lymphocyte and virological response.

The present cross-sectional study evaluated the status and relationship of interleukin-6, a platelet growth factor, with platelet counts, viral load, CD4 counts, and antiretroviral treatment in 75 HIV-infected subjects with thrombocytopenia and 50 gender-, race-, age- and antiretroviral treatment-matched controls without thrombocytopenia. Mean IL-6 production was significantly higher in thrombocytopenic participants (13 432 ± 8596) than in non-thrombocytopenic subjects (12 859 ± 3538 pg/105 Lym). Univariate analyses indicated, however, that thrombocytopenic patients were more likely to have <3000 pg of IL-6 than non-thrombocytopenic patients (OR = 7 95% CI 1.3–12; P = 0.01). For additional analyses, participants were dichotomized above and below 3000 pg of IL-6. Despite similar age, gender, drug use and antiretroviral treatment, thrombocytopenic participants had lower CD4 counts (186.5 ± 149 vs. 401 ± 286, P = 0.005) than non-thrombocytopenic subjects. Thrombocytopenic participants with elevated IL-6, with or without HAART, were more likely to have higher HIV-replication (496 273 ± 210 416; 34 656 ± 25 332) than thrombocytopenic individuals with low IL-6 levels (105 332 ± 42 699; 19 015 ± 14 296 P = 0.05). Non-thrombocytopenic patients with high IL-6 levels exhibited the highest CD4s (466.7 ± 333) and the lowest viral burden (63 094 ± 53 300) of the groups. Two distinct categories of HIV-associated thrombocytopenia exist: one accompanied by low IL-6, and another with compensatory elevations of IL-6. In thrombocytopenic individuals, the latter was associated with the poorest immunological and virological responses.

Body mass index, inflammatory biomarkers and neurocognitive impairment in HIV-infected persons

Abstract To determine the relationships among body mass index (BMI), and HIV-associated neurocognitive impairment and the potential mediating effects of inflammatory cytokines. Among the HIV-infected individuals (N = 90) included in this study, obesity was associated with slower processing speed (β = −.229, standard error (SE) = 2.15, p = .033), compared to participants with a normal BMI, after controlling for psychosocial and HIV clinical factors. Serum concentrations of the interleukin-16 (IL-16) cytokine were significantly associated with slowed processing speed (β = −.235, SE = 1.62, p = .033) but did not mediate the relationship between obesity and processing speed These findings suggest that obesity may contribute to cognitive processing speed deficits in HIV-infected adults. Elevated concentrations of IL-16 are also associated with slowing, though the results suggest that obesity and IL-16 may exert independent effects.

Obesity, Cytokines and Cognition across the Lifespan among People Living with HIV

Background/objective: Neurocognitive Impairment (NCI) remains prevalent among people living with HIV (PLWH/AIDS), and may be exacerbated by body core changes. Waist circumference, a metabolic syndrome (MetSy) criterion, is not routinely measured, yet could be particularly useful when considering that both antiretroviral therapy (ART) and Hazardous alcohol use (HAU) have been associated with central fat accumulation. The purpose of this work was to examine the longitudinal associations between body mass index (BMI), waist circumference (WC), and cognitive performance in PLWH/AIDS, and to explore their modifications by age. Methods: Using a prospective cohort study, we obtained participants’ anthropometrics, along with a comprehensive cognitive assessment over one year. Subjects were classified as overweight if BMI was 25-29.9 kg/m2, and obese if BMI was ≥ 30 kg/m2. Central obesity was defined as a waist >35 inches for females and >40 inches for males. Neurocognitive Impairment was defined using individual and global deficit corrected scores. Results/conclusion: A sizable proportion of participants met the National Institutes of Health definition of overweight (BMI=25-29.9 kg/m2; 26%) and obese (BMI ≥ 30 kg/m2; 35%). Central obesity was present in more than half of the population (52%) and was higher in males than females (OR=5). Higher BMI and higher WC, both in young individuals and in the elderly, were related to worse cognitive performance. Cognitive performance across different tests was worst in obese individuals. Central obesity subtly impacts mood and motor skills. Analyses uncovered a likely mechanism for these cognitive deficits, as interleukin (IL)-9, 10, 17, 20, 23 and TNF were significantly associated with most cognitive variables. Age has a substantial impact on the relationship between cytokines and cognitive performance as most correlations became non-significant among the older individuals. The results indicate the importance of cytokines and obesity to neurocognitive status.