The role of alcohol on platelets, thymus and cognitive performance among HIV-infected subjects: are they related?

Our objective was to evaluate whether thrombocytopenia and small thymus volume, which may be associated with hazardous alcohol consumption, are predictors of cognitive performance after highly-active antiretroviral treatment (HAART). To achieve this goal 165 people living with HIV starting HAART underwent thymus magnetic resonance imaging, cognitive (HIV Dementia Score [HDS] and the California Verbal Learning Test [CVLT]), immune and laboratory assessments at baseline and after 6 months of HAART. At baseline, hazardous alcohol consumption was significantly correlated with both thymus size (r = -0.44, p = 0.003) and thrombocytopenia (r = 0.28, p = 0.001). Of interest, thrombocytopenic patients were characterized by a smaller thymus size. Individuals with and without cognitive impairment differed in alcohol consumption, platelet counts and thymus size, suggesting that they may be risk factors for neurological abnormalities. In fact, after HAART hazardous alcohol use associations with thrombocytopenia were related to cognitive decline (learning = -0.2 +/- 0.8, recall = -0.3 +/- 0.1 and HDS = -0.5). This contrasted with improvements on every cognitive measure (learning = 1.6 +/- 0.3, p = 0.0001, recall = 2.2 +/- 0.4, p = 0.0001 and HDS = 1.0, p = 0.05) in those with neither alcohol use nor thrombocytopenia. In adjusted analyses for sociodemographics, adherence and immune measurements, reduced thymus size was associated with a 90% and thrombocytopenia with a 70% increase in the risk of scoring in the demented range after HAART (RR = 1.9, p < 0.05 and RR = 1.7, p = 0.03) and with low CVLT scores (thymus volume RR = 2.0, p = 0.04, chronic alcohol use p = 0.05 and thrombocytopenia p = 0.06). Thymus volume and platelet counts were negatively affected by alcohol and were predictors of cognitive performance and improvements after HAART. These results could have important clinical and therapeutic implications.

The influence of different types of alcoholic beverages on disrupting highly active antiretroviral treatment (HAART) outcome.

AIMS: Studies have yielded conflicting results regarding alcohol's influence on HIV outcomes, particularly after highly active antiretroviral treatment (HAART). Discrepant findings may be related to confounding variables, including gender, patterns of alcohol abuse and type of alcohol beverage beyond the amount consumed. METHODS: Using a cohort study, differences in HAART effectiveness after 24 weeks of therapy were compared as a function of amount and preference for alcohol, drinking only liquor (LI, n = 55) or only wine or beer (BW, n = 110). Given the critical role of thymus on HAART response, changes in thymus size, CD4s, naïve lymphocytes and viral loads were assessed. RESULTS: After HAART, positive increases in both CD4s (+12 cell counts/mm(3)) and thymus size (+0.7 mm(3)) were evident in the BW group. In contrast, the LI subgroup exhibited a decline in both parameters (-4 CD4 cells/mm(3) and -0.6 mm(3) in thymus size). Women in the LI group exhibited significantly lower CD4 (163.4 +/- 46.2) and naïve counts (178 +/- 69.5) than LI men (CD4: 281.6 +/- 203, P = 0.05; lymphocytes: 301.4 +/- 198, P = 0.04). In adjusted regression models, the LI compared to the BW subgroup had greater odds of maintaining detectable viral loads (RR = 1.35, 95% CI 1.04-1.75; P = 0.03), increased thymus volumes (RR = 3.8, P = 0.04) and replenished naïve cells (RR = 13, P = 0.02). CONCLUSIONS: Liquor was associated with thymus deterioration and thus with poorer viro-immune outcomes after HAART. Subtyping participants by alcohol consumption patterns seems to be clinically relevant and needs to be accounted for in future studies.

Non-tuberculous mycobacteria disease as a cause of hospitalization in HIV-infected subjects.

OBJECTIVES: The present study characterized and determined the prevalence of mycobacterial diseases (tuberculosis (TB) and non-tuberculous mycobacteria (NTM)) as a cause of hospitalization among HIV-infected subjects consecutively admitted to a large metropolitan hospital during 2001/2002. METHODS: Hospital discharge diagnoses were established for 521 HIV-positive patients. RESULTS: Respiratory disease accounted for 49% of the admissions. Community acquired pneumonia (CAP) was the main cause of respiratory disease (52%) followed by Pneumocystis carinii (PCP, 24%), non-tuberculous mycobacteria (NTM, 11%) and Mycobacterium tuberculosis (TB, 9%). Mycobacterium tuberculosis disease was established using bacteriological, clinical and radiographic criteria. NTM disease was defined following the American Thoracic Society criteria. NTM was disseminated in the majority of cases (19 Mycobacterium avium complex (MAC), one Mycobacterium kansasii). Nine patients had respiratory disease (seven MAC, one Mycobacterium fortuitum, one Mycobacterium kansasii) and one had gastrointestinal disease caused by MAC. Mortality was 10% for NTM disseminated cases; none of the TB patients died over the course of the study. The length of hospitalization for NTM patients was longer (15+/-13 days) than for other respiratory cases (10+/-10, p=0.04). CONCLUSIONS: NTM disease along with its related mortality is a significant pathology as a cause of hospitalization among HIV-infected individuals.

Increased risk of Pneumocystis carinii and community-acquired pneumonia with tobacco use in HIV disease.

OBJECTIVES: Tobacco smoking-related diseases continue to be of great health concern for the public, in general, and may be particularly deleterious for immunosuppressed HIV-positive individuals, who exhibit widespread tobacco use. METHODS: A total of 521 HIV-infected subjects consecutively admitted to Jackson Memorial Hospital between 2001-2002 were enrolled in the study. Research data included a medical history, details of tobacco and illicit drug use and complete computerized hospital information. Blood was drawn to obtain T lymphocyte profiles and viral load levels. Statistical analysis methods included Pearson, Student's t- and Chi-square tests and SAS Proc CATMOD. RESULTS: Tobacco use was prevalent, with 65% of the 521 HIV-positive hospitalized patients being current smokers. Overall, current tobacco users reported smoking an average of 15+/-13 cigarettes per day for an average of 15+/-14 years, with 40% smoking more than one pack per day. Pulmonary infections accounted for 49% of the total hospital admissions: 52% bacterial pneumonias, 24% Pneumocystis carinii pneumonia (PCP), 12% non-tuberculous mycobacterial diseases (NTM), 11% tuberculosis and 1% bronchitis. Many of the respiratory patients (46%) had been on highly active antiretroviral therapy (HAART) for over six months and 42% had received PCP and/or NTM prophylaxis. After matching the cases by HAART and CDC stage, the hazardous risk of being hospitalized with a respiratory infection was significantly higher for smokers than non-smokers (95% CI 1.33-2.83; p=0.003). Respiratory infections were noted in (37%) of the HAART-treated patients, and most (67%) occurred in smokers. CATMOD analyses controlling for HAART, viral load and CD4, indicated that HIV-infected smokers were three times more likely to be hospitalized with PCP and twice as likely to be hospitalized with community-acquired pneumonia than non-smokers, with increased risk related to the number of cigarettes/day in a dose-dependent manner. CONCLUSIONS: Tobacco use, which is widespread among HIV-infected subjects, increases the risk of pulmonary diseases, particularly PCP and CAP, two respiratory infections with high prevalence and morbidity risks even in the era of HAART.

Impact of a selenium chemoprevention clinical trial on hospital admissions of HIV-infected participants.

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.

Evaluation of HIV prevention and counseling practices of obstetrician/gynecologists in Bogota, Colombia: impact on women's knowledge and risk practices.

The present community-based study in Bogotá, Colombia, investigated risk assessment and preventive counseling practices of obstetrician/gynecologists (ob/gyn n = 34) and their impact on women's (n = 230) knowledge and risk behaviors. The data indicate that physician education has a significant and positive impact on women's knowledge and behavior. After controlling for sociodemographic variables, women instructed by their ob/gyn were 11 times more likely to correctly identify preventive measures (p = 0.0001) and high-risk sexual practices for the HIV /sexually transmitted diseases (STDs) transmission (4x; p = 0.05) and were less likely to engage in high-risk sexual practices (OR = 2; p = 0.05). Few ob/gyns (17%), however, assess risk behaviors and provide risk reduction counseling, and only 6% frequently encouraged HIV testing. These findings highlight the potential public health impact of ob/gyn physicians and underscore the need to increase their involvement in halting the HIV/STD epidemic in Colombia.

Continued high risk behaviors in HIV infected drug abusers.

To characterize current risk behaviors of HIV drug abusers in the highly active antiretroviral therapy (HAART) era, socio-demographic, 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.

Mood Disorders and BDNF Relationship with Alcohol Drinking Trajectories among PLWH Receiving Care.

BACKGROUND: Despite the excessive rates of Hazardous Alcohol Use (HAU) among people living with HIV (PLWH), although largely speculated, psychological and physiological components associated with HAU, has not been actively measured. Therefore, the present study was geared toward determining: 1) the rates of mood disorders and its relationship with HAU, and 2) to assess the impact of Brain Derived Neurotrophic Factor (BDNF), a well-known regulator of alcohol and mood disorders. METHODS: For this study, participants of the longitudinal PADS Study n=400, were followed over time. Alcohol use (Alcohol Use Disorders Identification Test -AUDIT- and the Alcohol Dependence Scale -ADS) and moods (depression, anxiety, and stress) were assessed repeatedly. RESULTS: A cluster analyses shows three distinctive trajectories. The first one, revealed a group with increased drinking (Cluster 1: n=140), constant alcohol intake (Cluster 2: n = 60), and one with decreased consumption (Cluster 3: n =120). Analyses discovered higher AUDIT scores across the clusters with Cluster 1 being followed by Clusters 2 and 3 (1: 14.5 ± 8 vs. 2=8.7 ± 7.5 vs. 3= 6.6 ± 4.2, p = 0.001). Women in Clusters 1 and 2 had higher levels of stress (1:21 ± 7.5; 2:19.3 ± 7) and lower BDNF levels (7904 ± 1248 pg/ml and 10405 ± 909 pg/mL) than their counterparts in Cluster 3 (PSS: 3: 16.6 ±5, p = 0.02 BDNF: 10828 ± 1127 pg/mL, p = 0.08). Men in Cluster 1 differed in terms of stress (19.8 ± 7 vs. 21 ± 7.5 score) and BDNF levels (Cluster 1: 5204 ± 818 vs. Cluster 2: 7656 ± 843 pg/ml, p = 0.002) but not in the number of years living with HIV. The proportion of subjects with multiple mood comorbidities was disturbingly higher (26%), and all were members of Cluster 1. Multiple logistic regression analyses indicated that participants reporting high relative to low levels of perceived stress, dual mood comorbidity, altered BDNF levels and low income increased the likelihood of being a member of Cluster 1. CONCLUSION: This study found that stress and overlaying psychiatric comorbidities are linked with persistent alcohol use. Findings suggest that BDNF and social support seems to be a logical target as it seems to be the bridge linking mood disorders and alcohol consumption.

Are Serotonin Alterations the Link between Thrombocytopenia and Poor Immune Status among HIV Infected Individuals?

OBJECTIVE: Thrombocytopenia (TCP<150 × 103 cells/mm3) has emerged as a relevant factor in the clinical course of HIV. However, the mechanisms mediating such observations have not been well characterized, limiting the possibility of creating targeted interventions. Notably, platelets are the storage and transporter system for serotonin and Brain derived neurotrophic factor (BDNF), which recent laboratory studies associated with viral replication and lymphocyte survival. Thus, we posit that (1) TCP will be associated with reduced levels of BDNF and serotonin (2) That these alterations will lead to poor viro-immune responses to antiretroviral therapy. METHODS: To achieve this goal, a total of 400 people living with HIV were consecutively enrolled to characterize the frequency of thrombocytopenia in hazardous and non-hazardous alcohol user populations in the HAART era. Then, participants underwent immune and laboratory assessments, to determine if TCP was associated with alterations in serotonin (5-HT) and brain derived neurotrophic factor (BDNF). RESULTS: The prevalence of thrombocytopenia in this antiretroviral treated cohort was 14%. Rates were significantly higher in the heavy alcohol users, HAU versus the non HAU group (Heavy: 25% versus HAU: 15% versusnon-HAU: 10%). Multivariate model analyses indicated that having TCP, low BDNF levels (<5000 pg/ml), and number of drinks per day were predictors of serotonin levels. PLWH with TCP had about 2-fold lower PPP-BDNFlevels (5037.4 ± 381 vs. 9137.5 ± 7062 pg/ml p=0.0001). Other significant predictors of BDNF levels at the last visit included receiving selective serotonin reuptake inhibitors and PPP serotonin levels. Multivariate analyses also confirmed that altered serotonin levels were associated withhigh viral loadsboth low CD4 cell counts. CONCLUSIONS: Thrombocytopenia is a relatively frequent complication of HIV, andis particularly prevalent among hazardous alcohol users (HAU). These findings suggest that TCP is associated with altered levels of BDNF and serotonin, suggesting that they may be the bridge linking TCP and poor viro-immune responses observed in this group. These results could have important clinical and therapeutic implications.

Menthol cigarettes and the cardiovascular risks of people living with HIV.

The possibility that menthol cigarettes add to the deleterious cardiovascular effects of smoking has been barely discussed. Although cardiovascular diseases (CVD) are at the forefront of medical concerns of people living with HIV (PLWH), an important, yet unknown, issue for clinicians and public health authorities is whether use of menthol-flavored cigarettes heightens CVD risk factors. Our study aims to assess traditional (10-year risk using the Framingham Risk Model) and nontraditional CVD risk factors and to contrast the effects of menthol-flavored versus non-menthol-flavored cigarettes on these risk factors. Compared to controls, menthol smokers were twice as likely to have hypertension. Users of menthol-flavored cigarettes had higher body mass index values, and increased risk of abdominal obesity. Multivariate analyses indicated that menthol smokers doubled the odds of having moderate to high CVD risk. This finding is highly significant given the widespread use of menthol-flavored cigarettes, particularly among women, minorities, and PLWH.

Gender differences in the association of hazardous alcohol use with hypertension in an urban cohort of people living with HIV in South Florida.

OBJECTIVE: Industrialized countries are currently experiencing an epidemic of high blood pressure (HBP) extending to people living with HIV (PLWH). Given the prevalence of hazardous alcohol use (HAU), this study examines the relationship between alcohol consumption and hypertension in PLWH. Including a gender analysis is critical, given the high rates of HAU and HIV among females. METHOD: We followed PLWH including both HAU and non-HAU (200 each). Participants were assessed twice for body weight, blood pressure, alcohol consumption, and other BP-associated lifestyle factors. High blood pressure (defined as systolic/diastolic blood pressure above 140/90 mmHg and/or treatment of HBP) was the primary outcome. RESULTS: Overall prevalence of hypertension was 38% and higher among HAU compared to non-HAU (42% vs. 34%, p = 0.02). Less than half with HBP (42%) were receiving treatment for hypertension. Overall, males had a 50% higher risk of HBP than women (odds ratio: 1.5, 95% CI: 1-2.6, p = 0.05). However among HAU, females were twice as likely to suffer HBP as their male counterparts (95% CI: 1-3.9, p = 0.02). Those HAU who preferred liquor, versus wine, had higher adjusted mean BP (132.6±18 vs. 122.3±14 mm Hg, p = 0.05). Additional analyses indicated that consumption of >1 standard drink of liquor or beer/day was associated with HBP. Risk of hypertension was noted in those with daily consumption of >3 glasses of wine. For those reporting <1 drink per day, the odds ratio of having HBP was 0.97 (CI: 0.6-0.99, p = 0.05). Factors associated with hypertension in the multivariate model included increased age, gender, BMI, HAU particularly of liquor, and smoking. CONCLUSIONS: Excessive hypertension burden in this population and its association with HAU and sub-optimal care indicate the need for preventive and educational intervention in PLWH. Analyses highlight the necessity of gender and type-of-beverage specific approaches.

Beyond the Brain: The Role of Brain-Derived Neurotrophic Factor in Viroimmune Responses to Antiretroviral Therapy among People Living with HIV with and without Alcohol Use.

OBJECTIVE: Given the emerging data suggesting the key role of brain-derived neurotrophic factor (BDNF) in the immune system, we assessed longitudinally whether BDNF depletions induced by hazardous alcohol use (HAU) would impact a response to antiretroviral therapy (ART). METHODS: In a prospective single-site cohort, virological and immunological responses to ART in 200 hazardous and 200 nonhazardous users were obtained, along with plasma BDNF levels. RESULTS: Hazardous drinkers were more likely to have BDNF levels <4000 pg/mL (odds ratio [OR] = 1.6, P = .01). Participants with BDNF <4000 pg/mL were less likely to have CD4 counts of more than 500 cells/mm(3) (P = .02) and to achieve viral suppression over the follow-up period (OR = 1.5, P = .03). Multivariate analysis confirmed the significant role of HAU and low BDNF in predicting viroimmune responses. CONCLUSION: Hazardous alcohol use was associated with BDNF alterations, which in turn were linked to a limited response to ART in terms of viral suppression and CD4 count improvements.

Brain derived neurotrophic factor and cognitive status: the delicate balance among people living with HIV, with and without alcohol abuse.

INTRODUCTION: The advent of combination antiretroviral therapy(cART) has lead to a significant reduction in morbidity and mortality among people living with HIV(PLWH). However, HIV-associated neurocognitive disorders (HAND) still remain a significant problem. One possible mechanism for the persistence of these disorders is through the effect of HIV on brain-derived neurotrophic factor (BDNF). BDNF is influenced by various factors including hazardous alcohol use (HAU), which is prevalent among PLWH. This study attempts to elucidate the relationships between HAU, BDNF and HAND. METHODS: Cross-sectional analyses were conducted on a sample of 199 hazardous alcohol users and 198 non-HAU living with HIV. Members of each group were matched according to sociodemographic characteristics and CD4 count. Research procedures included validated questionnaires, neuropsychological assessments and a blood sample to obtain BDNF and immune measurements. RESULTS: Hazardous alcohol users showed either significantly lower or significantly higher BDNF levels compared to the Non-hazardous (OR=1,4; 95% CI: 1-2.1, p = 0.003). Therefore, for additional analyses, subjects were categorized based on BDNF values in: Group 1 < 4000, Group 2: 4001-7,999 (reference group), and Group 3 for those >8,000 pg/mL. Groups 1 and 3 performed significantly worse than those in Group 2 in the domains of processing speed, auditory-verbal and visuospatial learning and memory. Multivariate analyses confirmed that HAU and BDNF are significant contributors of HAND. CONCLUSION: Our findings offer novel insights into the relationships between BDNF, and alcohol use among PLWH. Our results also lend support to expanding clinical movement to use BDNF as an intervention target for PLWH, in those with evidence of deficiencies, and highlight the importance of including HAUat the inception of clinical trials.

Alcohol, Brain Derived Neurotrophic Factor and Obesity among People Living with HIV.

INTRODUCTION: In an expanding HAART era, obesity has become a health problem among persons living with HIV (PLWH). Whereas the rising level of obesity has been largely attributed to poor nutrition and exercise habits, differences in biological factors may explain why some individuals gain more weight than others. Thus, our main goal is to prospectively determine in PLWH whether plasma brain-derived neurotrophic factor (BDNF), and hazardous alcohol use (HAU), two overlooked but highly prevalent conditions among PLWH, correlate with an adverse anthropometric profile. Also to test whether these relationships varied in men and women. METHODS: The Platelets mediating Alcohol and HIV Damage Study (PADS) is an ongoing multiethnic study of 400 PLWH receiving regular medical care in South Florida (37% females and 63% males). Semi-annual visits consisted of a medical exam, including anthropometrics to assess both general (body mass index: BMI) and central obesity (waist and hip circumferences). Participants also completed health history questionnaires, and provided a fasting blood sample to obtain BDNF and immune and biochemical assessments. RESULTS: 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%). Women were more likely to be obese than men (OR=4.9, 95% CI=2.9-8.2, p=0.0001). Compared to men, women also exhibited the highest mean plasma BDNF levels (9,959 ± 6,578 vs. 7,470 ± 6,068 pg/ml, p=0.0001). Additional analyses indicated that HAU, particularly heavy drinkers, had the smallest waist and hip circumferences if they were males, but the opposite if they were females. High BDNF levels were positively correlated with BMI. Linear regression analysis revealed that gender, BDNF, and HAU were the best predictors of BMI. CONCLUSION: In summary, our findings offer novel insights into the relationships between BDNF, and alcohol use among overweight and obese PLWH. Our results also suggest that these relationships may be inherently different by gender.

Ignoring the obvious missing piece of chronic kidney disease in HIV: cigarette smoking.

The impact of tobacco use on the development of chronic kidney disease (CKD) in people living with HIV (PLWH) has been overlooked, despite remarkably higher rates of smoking in these individuals. The authors examined the association between smoking and the risk of CKD in a case-controlled study that included 75 PLWH with CKD and 461 PLWH consecutively admitted to the hospital for other causes. Significant differences in gender, race/ethnicity, hypertension, hepatitis B, CD4 cell counts, and smoking between cases and controls were reported, suggesting that these variables may be risk factors for CKD. In logistic regression analyses, smoking (OR=1.97, p=.003), hypertension (OR=2), and African ancestry, particularly for Black Caribbeans (OR=2.6), were independent factors associated with CKD. Moreover, the results pointed to a dose-response relationship between packs smoked per day and CKD. Smoking was reported to contribute a significant risk for CKD in these subjects.

Methamphetamine enhances HIV-1 infectivity in monocyte derived dendritic cells.

The US is currently experiencing an epidemic of methamphetamine (Meth) use as a recreational drug. Recent studies also show a high prevalence of HIV-1 infection among Meth users. We report that Meth enhances HIV-1 infectivity of dendritic cells as measured by multinuclear activation of a galactosidase indicator (MAGI) cell assay, p24 assay, and LTR-RU5 amplification. Meth induces increased HIV-1 infection in association with an increase in the HIV-1 coreceptors, CXCR4 and CCR5, and infection is mediated by downregulation of extracellular-regulated kinase (ERK2) and the upregulation of p38 mitogen-activated protein kinase (MAPK). A p38 inhibitor (SB203580) specifically reversed the Meth-induced upregulation of the CCR5 HIV-1 coreceptor. The dopamine D2 receptor antagonist RS +/- sulpiride significantly reversed the Meth-induced upregulation of CCR5, demonstrating that the Meth-induced effect is mediated via the D2 receptor. These studies report for the first time that Meth fosters HIV-1 infection, potentially via upregulating coreceptor gene expression. Further, Meth mediates its regulatory effects via dopamine receptors and via downregulating ERK2 with a reciprocal upregulation of p38 MAPK. Elucidation of the role of Meth in HIV-1 disease susceptibility and the mechanism through which Meth mediates its effects on HIV-1 infection may help to devise novel therapeutic strategies against HIV-1 infection in high-risk Meth-using HIV-1-infected subjects.