Publications
2015
BACKGROUND
Alcohol use may accelerate HIV disease progression, but the plausible biological mechanisms have not been clearly elucidated.
METHODS
HIV-positive persons who were not on antiretroviral therapy (ART) completed the baseline assessment for a longitudinal study examining the association of alcohol use with HIV disease markers. Oversampling drinkers, baseline samples were tested for markers of monocyte activation (soluble CD14 [sCD14]), inflammation (interleukin-6 [IL-6]-6), and coagulation (d-dimer). We defined "unhealthy alcohol use" as testing positive using the Alcohol Use Disorders Identification Test-Consumption (≥3 for women and ≥4 for men) in the past 3 months or testing positive using a biomarker of heavy drinking, phosphatidylethanol (≥50 ng/ml). Multiple linear regression was used to examine the associations of unhealthy alcohol use with sCD14, log10 IL-6, and d-dimer.
RESULTS
Compared to those who were abstinent from alcohol, unhealthy drinkers had significantly higher sCD14 levels (mean = 1,676 vs. 1,387 ng/ml; mean difference [95% confidence interval (CI)] = 289 [83, 495], p < 0.01). In analyses adjusted for demographic factors, current cigarette smoking, and HIV disease markers, unhealthy drinkers continued to display significantly higher sCD14 levels compared to those who were abstinent from alcohol (adjusted mean = 1,670 vs. 1,406 ng/ml; adjusted mean difference [95% CI] = 264 [47, 480], p = 0.02). Unhealthy alcohol use was not significantly associated with IL-6 or d-dimer levels.
CONCLUSIONS
Unhealthy alcohol use was independently associated with a marker of monocyte activation (i.e., higher sCD14) that predicts mortality in treated HIV infection. Longitudinal research should examine whether unhealthy alcohol use predicts changes in sCD14 prior to and following ART initiation.
View on PubMed2015
2015
2015
OBJECTIVE
The successful scale-up of antiretroviral therapy (ART) in sub-Saharan Africa has led to increasing life expectancy, and thus increased risk of hypertension. We aimed to describe the incidence and predictors of hypertension in HIV patients receiving ART at a publicly funded clinic in rural Uganda.
METHODS
We abstracted data from medical records of adult patients who initiated ART at an HIV clinic in south-western Uganda during 2010-2012. We defined hypertension as at least two consecutive clinical visits, with a SBP at least 140 mmHg and/or SBP of at least 90 mmHg, or prescription for an antihypertensive medication. We calculated the incidence of hypertension and fit multivariable Cox proportional-hazards models to identify predictors of hypertension.
RESULTS
A total of 3389 patients initiated ART without a prior diagnosis of hypertension during the observation period. Over 3990 person-years of follow-up, 445 patients developed hypertension, for a crude incidence of 111.5/1000 (95% confidence interval 101.9-121.7) person-years. Rates were highest among men aged at least 40 years (158.8 per/1000 person-years) and lowest in women aged 30-39 years (80/1000 person-years). Lower CD4 cell count at ART initiation, as well as traditional risk factors including male sex, increasing age, and obesity, were independently associated with hypertension.
CONCLUSION
We observed a high incidence of hypertension in HIV-infected persons on ART in rural Uganda, and increased risk with lower nadir CD4 cell counts. Our findings call for increased attention to screening of and treatment for hypertension, along with continued prioritization of early ART initiation.
View on PubMed2015
2015
2015
2015
BACKGROUND
Persistent CD8 T-cell expansion, low CD4/CD8 T-cell ratios, and heightened inflammation persist in antiretroviral therapy (ART)-treated human immunodeficiency virus (HIV) infection and are associated with increased risk of morbid outcomes. We explored the role of cytomegalovirus (CMV) infection in CD8 lymphocytosis and inflammation in ART-treated HIV infection.
METHODS
Absolute CD4 and CD8 T-cell counts were abstracted from clinical records and compared among 32 HIV-infected CMV-seronegative subjects, 126 age, CD4 and gender-matched HIV-infected CMV-seropositive subjects, and among 21 HIV-uninfected controls (9 CMV-negative, 12 CMV-positive). Plasma inflammatory indices were measured in a subset by ELISA.
RESULTS
Median CD8 counts/µL were higher in HIV-positive/CMV-positive patients (795) than in HIV-positive/CMV-negative subjects (522, P = .006) or in healthy controls (451, P = .0007), whereas CD8 T-cell counts were similar to controls' levels in HIV-positive/CMV-negative subjects. Higher plasma levels of IP-10 (P = .0011), TNF-RII (P = .0002), and D-dimer (P = .0444) were also found in coinfected patients than in HIV-positive/CMV-negative subjects.
CONCLUSIONS
CMV infection is associated with higher CD8 T-cell counts, resultant lower CD4/CD8 ratios, and increased systemic inflammation in ART-treated HIV infection. CMV infection may contribute to risk for morbid outcomes in treated HIV infection.
View on PubMed2015
2015
BACKGROUND
Human immunodeficiency virus (HIV) infection and associated immune activation predict the risk of cardiovascular disease in resource-rich areas. Less is known about these relationships in sub-Saharan Africa.
METHODS
Beginning in 2005, we enrolled subjects in southwestern Uganda into a cohort at the time of antiretroviral therapy (ART) initiation. Multiple immune activation measures were assessed before and 6 months after ART initiation. Beginning in 2013, participants aged >40 years underwent metabolic profiling, including measurement of hemoglobin A1c and lipid levels and carotid ultrasonography. We fit regression models to identify traditional and HIV-specific correlates of common carotid intima media thickness (CCIMT).
RESULTS
A total of 105 participants completed carotid ultrasonography, with a median completion time of 7 years following ART initiation. Age, low-density lipoprotein cholesterol level, and pre-ART HIV load were correlated with CCIMT. No association was found between CCIMT and any pre-ART biomarkers of immune activation. However, in multivariable models adjusted for cardiovascular disease risk factors, lower absolute levels of soluble CD14 and interleukin 6 and greater declines in the CD14 level and kynurenine-tryptophan ratio after 6 months of ART predicted a lower CCIMT years later (P < .01).
CONCLUSIONS
Persistent immune activation despite ART-mediated viral suppression predicts the future atherosclerotic burden among HIV-infected Ugandans. Future work should focus on clinical correlates of these relationships, to elucidate the long-term health priorities for HIV-infected people in the region.
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