The influence of neurocognitive impairment, alcohol and other drug (AOD) use, and psychosocial factors on antiretroviral treatment adherence, service utilization and viral load among HIV-seropositive adults

Among people living with HIV (PLWH), adherence to antiretroviral therapy (ART) can be affected by problems of neurocognitive (NC) impairment, stress, alcohol and other drug (AOD) abuse, and other barriers. The aims of this research were to: (1) examine factors associated with NC impairment, (2) explore relationships between psychosocial variables with ART adherence and viral load (VL), and (3) evaluate the efficacy of an evidence-based intervention in improving ART adherence, increasing service utilization, and decreasing VL. The first study (n=370) was cross sectional and used structural equation modeling to test whether AOD use, years living with HIV, and time from HIV diagnosis to seeking care were associated with poorer NC functioning. The second study (n=246) used similar methods to test the hypothesis that stress, barriers to adherence, NC impairment, poor social support, and AOD use were related to lower VL mediated by ART adherence. The third study (n=243) evaluated an evidence-based, eight-session program to improve ART adherence, reduce VL, and increase service utilization in a randomized controlled trial. Study participants were PLWH living in South Florida, 18 to 60 years old, with a history of alcohol abuse enrolled from January 2009 through November 2012. Secondary analysis of available data showed: (1) scores on interference with executive functioning increased by 0.32 for each day of marijuana use and 1.18 for each year living with HIV, but no association was found between alcohol use and NC functioning; (2) each barrier to adherence was associated with a 10% decrease in adherence to ART and a 0.42 unit increase in VL (log10) and the relationship between barriers and VL was partially mediated by ART adherence; (3) participants in the evidence-based program were more likely than the comparison group to report an undetectable VL (OR=2.25, p<0.01) at 6 months, but not 3 months, post-intervention. Psychosocial factors affect VL, but ART adherence is essential in achieving an undetectable VL in PLWH.

The Influence of Neurocognitive Impairment, Alcohol and other Drug (AOD) Use, and Psychosocial Factors on Antiretroviral Treatment Adherence, Service Utilization and Viral Load Among HIV-Seropositive Adults

Among people living with HIV (PLWH), adherence to antiretroviral therapy (ART) can be affected by problems of neurocognitive (NC) impairment, stress, alcohol and other drug (AOD) abuse, and other barriers. The aims of this research were to: (1) examine factors associated with NC impairment, (2) explore relationships between psychosocial variables with ART adherence and viral load (VL), and (3) evaluate the efficacy of an evidence-based intervention in improving ART adherence, increasing service utilization, and decreasing VL. The first study (n=370) was cross sectional and used structural equation modeling to test whether AOD use, years living with HIV, and time from HIV diagnosis to seeking care were associated with poorer NC functioning. The second study (n=246) used similar methods to test the hypothesis that stress, barriers to adherence, NC impairment, poor social support, and AOD use were related to lower VL mediated by ART adherence. The third study (n=243) evaluated an evidence-based, eight-session program to improve ART adherence, reduce VL, and increase service utilization in a randomized controlled trial. Study participants were PLWH living in South Florida, 18 to 60 years old, with a history of alcohol abuse enrolled from January 2009 through November 2012. Secondary analysis of available data showed: (1) scores on interference with executive functioning increased by 0.32 for each day of marijuana use and 1.18 for each year living with HIV, but no association was found between alcohol use and NC functioning; (2) each barrier to adherence was associated with a 10% decrease in adherence to ART and a 0.42 unit increase in VL (log10) and the relationship between barriers and VL was partially mediated by ART adherence; (3) participants in the evidence-based program were more likely than the comparison group to report an undetectable VL (OR=2.25, p Psychosocial factors affect VL, but ART adherence is essential in achieving an undetectable VL in PLWH.

The relationship of thymulin activity, immune parameters of HIV disease progression and substance use in a cohort of HIV seropositive alcohol and drug users

Zinc is essential for the activity of thymulin, a thymic hormone involved in T-lymphocyte differentiation and activation. Zinc deficiency is widespread in populations with HIV infection, and HIV+ drug users are particularly susceptible to zinc deficiency and immune suppression. This dissertation explored the relationship of zinc-bound active thymulin to plasma zinc, CD4+ and CD8+ cell count, the CD4+/CD8+ ratio, and drug use in HIV-infected drug users. Zinc-bound active thymulin was assessed in plasma of HIV+ drug users who were participating in a 30 month zinc supplementation trial. Plasma from 80 participants at the 12 month visit, and 40 of these same participants, randomly selected, at the baseline visit were assessed for zinc-bound active thymulin levels using a modification of the rosette inhibition assay. Thymulin activity was directly associated with CD4+ cell count (β = 0.127, p = 0.002) and inversely associated with cocaine use (β = −0.908, p = 0.026; R2 = 0.188, p = 0.019) independent of HIV viral load, age, gender and antiretroviral use. An increase in thymulin activity was 1.4 times more likely when CD4+ cell count increased (OR = 1.402, 95%CI: 1.006–1.956), independent of change in viral load, antiretroviral use, and age. Participants who used cocaine consistently, were 7.6 times less likely to have an increase in thymulin activity (OR = 0.133, 95%CI: 0.017–1.061). There was a direct correlation between change in plasma zinc and change in zinc-bound active thymulin (r = 0.243, p = 0.13). Analysis of CD4+ cell count decline in 222 participants in the zinc supplementation trial across the 30 months showed that both crack cocaine use and heavy alcohol use accelerated CD4+ cell count decline. Thymulin activity is directly associated with HIV disease progression, measured by CD4+ cell count, and is depressed with cocaine use independent of antiretroviral use and HIV viral load. Cocaine and heavy alcohol accelerate CD4+ cell count decline. The effect of cocaine on thymic output requires further evaluation as a mechanism for the association of cocaine use with faster HIV disease progression.

Serial evolutionary networks of within-patient HIV-1 sequences reveal patterns of evolution of X4 strains

Background The HIV virus is known for its ability to exploit numerous genetic and evolutionary mechanisms to ensure its proliferation, among them, high replication, mutation and recombination rates. Sliding MinPD, a recently introduced computational method [1], was used to investigate the patterns of evolution of serially-sampled HIV-1 sequence data from eight patients with a special focus on the emergence of X4 strains. Unlike other phylogenetic methods, Sliding MinPD combines distance-based inference with a nonparametric bootstrap procedure and automated recombination detection to reconstruct the evolutionary history of longitudinal sequence data. We present serial evolutionary networks as a longitudinal representation of the mutational pathways of a viral population in a within-host environment. The longitudinal representation of the evolutionary networks was complemented with charts of clinical markers to facilitate correlation analysis between pertinent clinical information and the evolutionary relationships. Results Analysis based on the predicted networks suggests the following:: significantly stronger recombination signals (p = 0.003) for the inferred ancestors of the X4 strains, recombination events between different lineages and recombination events between putative reservoir virus and those from a later population, an early star-like topology observed for four of the patients who died of AIDS. A significantly higher number of recombinants were predicted at sampling points that corresponded to peaks in the viral load levels (p = 0.0042). Conclusion Our results indicate that serial evolutionary networks of HIV sequences enable systematic statistical analysis of the implicit relations embedded in the topology of the structure and can greatly facilitate identification of patterns of evolution that can lead to specific hypotheses and new insights. The conclusions of applying our method to empirical HIV data support the conventional wisdom of the new generation HIV treatments, that in order to keep the virus in check, viral loads need to be suppressed to almost undetectable levels.

Overweight/Obesity and HIV Disease Progression in HIV+ Adults in Botswana

Studies indicate that overweight and obesity protect against HIV-disease progression in antiretroviral therapy (ART)-naïve patients. We examined retrospectively the relationship of overweight/obesity with HIV-disease progression in ART-naïve HIV+ adults in Botswana in a case-control study with 18-month follow-up, which included 217 participants, 139 with BMI 18.0-24.9 kg/m2 and 78 with BMI ≥25 kg/m2. Archived plasma samples were used to determine inflammatory markers: leptin and bacterial endotoxin lipopolysaccharide (LPS), and genotype single nucleotide polymorphisms (SNPs) of the Fat Mass and Obesity Associated Gene (FTO). At baseline, BMI was inversely associated with risk for AIDS-defining conditions (HR=0.218; 95%CI=0.068, 0.701, P=0.011), and higher fat mass was associated with reduced risk of the combined outcome of CD4+cell count ≤250/µL and AIDS-defining conditions, whichever occurred earlier (HR=0.918; 95%CI=0.847, 0.994, P=0.036) over 18 months, adjusting for age, gender, marriage, children, and baseline CD4+cell count and HIV-viral load. FTO-SNP rs17817449 was associated with BMI (OR=1.082; 95%CI=1.001, 1.169; P=0.047). Fat mass was associated with the risk alleles of rs1121980 (OR=1.065; 95%CI=1.009, 1.125, P=0.021), rs8050136 (OR=1.078; 95%CI=1.021, 1.140; P=0.007), and rs17817449 (OR=1.086; 95%CI=1.031, 1.145; P=0.002), controlling for age, gender, tribe, total energy intake, and activity. There were no associations of SNPs with markers of disease progression. Leptin levels were positively associated with BMI (β=1.764; 95%CI=0.788, 2.739; P=0.022) and fat mass (β=0.112; 95%CI=0.090, 0.135; P<0.001), but inversely with viral load (β=-0.305; 95%CI=-0.579, -.031; P=0.030). LPS levels were inversely associated with BMI (OR=0.790, 95%CI=0.630, 0.990; P=0.041), and fat mass (OR=0.852, 95%CI=0.757, 0.958; P=0.007) and directly with viral load (OR=2.608, 95%CI=1.111, 6.124; P=0.028), adjusting for age, gender, smoking and %fat mass. In this cohort, overweight/obesity predicted slower HIV-disease progression. Obesity may confer an advantage in maintaining fat stores to support the overactive immune system. FTO-SNPs may contribute to the variation in fat mass; however, they were not associated with HIV-disease progression. Our findings suggest that the obesity paradox may be explained by the association of increased LPS with lower BMI and higher viral load; while viral load decreased with increasing leptin levels. Studies in African populations are needed to clarify whether genetic variation and inflammation mediate the obesity paradox in HIV-disease progression.

Overweight/obesity and HIV disease progression in HIV+ adults in Botswana

Studies indicate that overweight and obesity protect against HIV-disease progression in antiretroviral therapy (ART)-naïve patients. We examined retrospectively the relationship of overweight/obesity with HIV-disease progression in ART-naïve HIV+ adults in Botswana in a case-control study with 18-month follow-up, which included 217 participants, 139 with BMI 18.0-24.9 kg/m 2 and 78 with BMI ≥25 kg/m2. Archived plasma samples were used to determine inflammatory markers: leptin and bacterial endotoxin lipopolysaccharide (LPS), and genotype single nucleotide polymorphisms (SNPs) of the Fat Mass and Obesity Associated Gene (FTO). ^ At baseline, BMI was inversely associated with risk for AIDS-defining conditions (HR=0.218; 95%CI=0.068, 0.701, P=0.011), and higher fat mass was associated with reduced risk of the combined outcome of CD4+cell count ≤250/µL and AIDS-defining conditions, whichever occurred earlier (HR=0.918; 95%CI=0.847, 0.994, P=0.036) over 18 months, adjusting for age, gender, marriage, children, and baseline CD4+cell count and HIV-viral load. ^ FTO-SNP rs17817449 was associated with BMI (OR=1.082; 95%CI=1.001, 1.169; P=0.047). Fat mass was associated with the risk alleles of rs1121980 (OR=1.065; 95%CI=1.009, 1.125, P=0.021), rs8050136 (OR=1.078; 95%CI=1.021, 1.140; P=0.007), and rs17817449 (OR=1.086; 95%CI=1.031, 1.145; P=0.002), controlling for age, gender, tribe, total energy intake, and activity. There were no associations of SNPs with markers of disease progression. ^ Leptin levels were positively associated with BMI (β=1.764; 95%CI=0.788, 2.739; P=0.022) and fat mass (β=0.112; 95%CI=0.090, 0.135; P<0.001), but inversely with viral load (β=-0.305; 95%CI=-0.579, -.031; P=0.030). LPS levels were inversely associated with BMI (OR=0.790, 95%CI=0.630, 0.990; P=0.041), and fat mass (OR=0.852, 95%CI=0.757, 0.958; P=0.007) and directly with viral load (OR=2.608, 95%CI=1.111, 6.124; P=0.028), adjusting for age, gender, smoking and %fat mass. ^ In this cohort, overweight/obesity predicted slower HIV-disease progression. Obesity may confer an advantage in maintaining fat stores to support the overactive immune system. FTO-SNPs may contribute to the variation in fat mass; however, they were not associated with HIV-disease progression. Our findings suggest that the obesity paradox may be explained by the association of increased LPS with lower BMI and higher viral load; while viral load decreased with increasing leptin levels. Studies in African populations are needed to clarify whether genetic variation and inflammation mediate the obesity paradox in HIV-disease progression.^

Caffeine Intake and its Association with Disease Progression, Sleep Quality and Anxiety Symptoms and Nutritional Alterations in People Living with HIV in the Miami Adult Studies on HIV Cohort

Miami-Dade County has approximately 27,000 people living with HIV (PLWH), and the highest HIV incidence in the nation. PLWH have reported several types of sleep disturbances. Caffeine is an anorexic and lipolytic stimulant that may adversely affect sleep patterns, dietary intakes and body composition. High caffeine consumption (>250 mg. per day or the equivalent of >4 cups of brewed coffee) may also affect general functionality, adherence to antiretroviral treatment (ART) and HIV care. This study assess the relationship of high caffeine intake with markers of disease progression, sleep quality, insomnia, anxiety, nutritional intakes and body composition. A convenience sample of 130 PLWH on stable ART were recruited from the Miami Adult Studies on HIV (MASH) cohort, and followed for three months. After consenting, questionnaires on Modified Caffeine Consumption (MCCQ), Pittsburg Insomnia Rating Scale (PIRS), Pittsburg Sleep Quality Index (PSQI), Generalized Anxiety Disorder-7 (GAD-7), socio-demographics, drug and medication use were completed. CD4 count, HIV viral load, anthropometries, and body composition measures were obtained. Mean age was 47.89±6.37 years, 60.8% were male and 75.4% were African-Americans. Mean caffeine intake at baseline was 337.63 ± 304.97 mg/day (Range: 0-1498 mg/day) and did not change significantly at 3 months. In linear regression, high caffeine consumption was associated with higher CD4 cell count (β=1.532, P=0.049), lower HIV viral load (β=-1.067, P=0.048), higher global PIRS (β=1.776, P=0.046), global PSQI (β=2.587, P=0.038), and GAD-7 scores (β=1.674, P=0.027), and with lower fat mass (β=-0.994, P=0.042), energy intakes (β=-1.643, P=0.042) and fat consumption (β=-1.902, P=0.044), adjusting for relevant socioeconomic and disease progression variables. Over three months, these associations remained significant. The association of high caffeine with lower BMI weakened when excluding users of other anorexic and stimulant drugs such as cocaine and methamphetamine, suggesting that caffeine in combination, but not alone, may worsen their action. In summary, high caffeine consumption was associated with better measures of disease progression; but was also detrimental on sleep quality, nutritional intakes, BMI and body composition and associated with insomnia and anxiety. Large scale studies for longer time are needed to elucidate the contribution of caffeine to the well-being of PLWH.