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1.  Decreased limb muscle and increased central adiposity are associated with 5-year all-cause mortality in HIV infection 
AIDS (London, England)  2011;25(11):1405-1414.
Background
Unintentional loss of weight and muscle due to aging and disease has been associated with increased mortality. Wasting and weight loss occur in HIV infection even in the modern era of effective antiretroviral therapy.
Methods
We determined the association of MRI-measured regional and total skeletal muscle and adipose tissue with 5-year, all-cause mortality in 922 HIV-infected persons in the study of Fat Redistribution and Metabolic Change in HIV Infection (FRAM).
Results
After 5 years of follow-up, HIV-infected participants with arm skeletal muscle in the lowest tertile had a mortality rate of 23%, compared with 11 and 8% for those in the middle and highest tertiles. After multivariable adjustment for demographics, cardiovascular risk factors, HIV-related factors, inflammatory markers, and renal disease, we found that lower arm skeletal muscle, lower leg skeletal muscle and higher visceral adipose tissue (VAT) were each independently associated with increased mortality. Those in the lowest tertile of arm or leg skeletal muscle had higher odds of death [arm: odds ratio (OR)=2.0, 95% confidence interval (CI) 0.96–4.0; leg: OR=2.4, 95% CI 1.2–4.8] compared with the highest respective tertiles. Those in the highest tertile of VAT had 2.1-fold higher odds of death (95% CI 1.1–4.0) compared with the lowest VAT tertile.
Conclusion
Lower muscle mass and central adiposity appear to be important risk factors for mortality in HIV-infected individuals. A substantial proportion of this risk may be unrecognized because of the current reliance on body mass index in clinical practice.
doi:10.1097/QAD.0b013e32834884e6
PMCID: PMC3933309  PMID: 21572308
body composition; cachexia; fat redistribution; HIV infection; lipoatrophy; lipodystrophy; mortality; sarcopenia
2.  HIV viremia and changes in kidney function 
AIDS (London, England)  2009;23(9):1089-1096.
Objective
To evaluate the effect of HIV infection on longitudinal changes in kidney function and to identify independent predictors of kidney function changes in HIV-infected individuals.
Design
A prospective cohort.
Methods
Cystatin C was measured at baseline and at the 5-year follow-up visit of the Study of Fat Redistribution and Metabolic Change in HIV infection in 554 HIV-infected participants and 230 controls. Control participants were obtained from the Coronary Artery Risk Development in Young Adults study. Glomerular filtration rate (eGFRcys) was estimated using the formula 76.7 × cysC−1.19.
Results
Compared with controls, HIV-infected participants had a greater proportion of clinical decliners (annual decrease in eGFRcys > 3 ml/min per 1.73 m2; 18 versus 13%, P=0.002) and clinical improvers (annual increase in eGFRcys > 3 ml/min per 1.73 m2; 26 versus 6%, P< 0.0001). After multivariable adjustment, HIV infection was associated with higher odds of both clinical decline (odds ratio 2.2; 95% confidence interval 1.3, 3.9, P = 0.004) and clinical improvement (odds ratio 7.3; 95% confidence interval 3.9, 13.6, P ≤ 0.0001). Among HIV-infected participants, a decrease in HIV viral load during follow-up was independently associated with clinical improvement; conversely, higher baseline and an increase in viral load during follow-up were associated with clinical decline. No individual antiretroviral drug or drug class appeared to be substantially associated with clinical decline or improvement.
Conclusion
Compared with controls, HIV-infected persons were more likely both to have clinical decline and clinical improvement in kidney function during 5 years of follow-up. The extent of viremic control had a strong association with longitudinal changes in kidney function.
doi:10.1097/QAD.0b013e32832a3f24
PMCID: PMC3725756  PMID: 19352136
cystatin C; glomerular filtration rate; HIV; kidney; viral load
4.  Associations of antiretroviral drug use and HIV-specific risk factors with carotid intima–media thickness 
AIDS (London, England)  2010;24(14):2201-2209.
Background
Previous research has demonstrated an increase in carotid intima–media thickness (cIMT) in HIV-infected individuals compared to controls. However, the reason for this increased level of subclinical vascular disease is unknown.
Objective
To identify HIV-related risk factors for increased cIMT.
Methods
We evaluated the relationship between HIV-related characteristics (including markers of HIV disease severity and use of antiretroviral therapy) and cIMT measurements in the internal/bulb and common carotid regions among 538 HIV-infected participants from the Study of Fat Redistribution and Metabolic Change in HIV Infection (FRAM). We used Bayesian model averaging to estimate the posterior probability of candidate HIV and non-HIV-related risk factors being true predictors of increased cIMT. Variables with a posterior probability of more than 50% were used to develop a selected regression model for each of the anatomic regions.
Results
For common cIMT, the Bayesian model selection process identified age, African-American race, and systolic and diastolic blood pressure with probability more than 95%, HDL cholesterol with probability 85% and Hispanic ethnicity with probability 51%. Among the HIV-related factors included in the analysis, only tenofovir use was selected (51% probability). In the selected model, duration of tenofovir use was associated with lower common cIMT (−0.0094 mm/year of use; 95% confidence interval: −0.0177 to −0.0010). For internal cIMT, no HIV-related risk factors were above the 50% posterior probability threshold.
Conclusion
We observed an inverse association between duration of tenofovir use and common carotid cIMT. Whether this association is causal or due to confounding by indication needs further investigation.
doi:10.1097/QAD.0b013e32833d2132
PMCID: PMC3224487  PMID: 20671544
atherosclerosis; carotid intima–media thickness; HIV; tenofovir
5.  Association of Antiretroviral Therapy with Fibrinogen Levels in HIV Infection 
AIDS (London, England)  2008;22(6):707-715.
doi:10.1097/QAD.0b013e3282f560d9
PMCID: PMC3156620  PMID: 18356600
fibrinogen; HIV; protease inhibitors; non-nucleoside reverse transcriptase inhibitors
6.  HIV RNA level in early infection is predicted by viral load in the transmission source 
AIDS (London, England)  2010;24(7):941-945.
Objective
HIV-1 viral load in early infection predicts the risk of subsequent disease progression but the factors responsible for the differences between individuals in viral load during this period have not been fully identified. We sought to determine the relationship between HIV-1 RNA levels in the source partner and recently infected recipient partners within transmission pairs.
Methods
We recruited donor partners of persons who presented with acute or recent (< 6 months) HIV infection. Transmission was confirmed by phyologenetic comparison of virus sequence in the donor and recipient partners. We compared viral load in the donor partner and the recipient in the first 6 months of HIV infection.
Results
We identified 24 transmission pairs. The median estimated time from infection to evaluation in acutely/recently infected recipient individuals was 72 days. The viral load in the donor was closely associated with viral load at presentation in the recipient case (r=0.55, P=0.006).
Conclusion
The strong correlation between HIV-1 RNA levels within HIV transmission pairs indicates that virus characteristics are an important determinant of viral load in early HIV infection.
doi:10.1097/QAD.0b013e328337b12e
PMCID: PMC2887742  PMID: 20168202
HIV-1 RNA; acute HIV-1 infection; HIV-1 transmission; viral load set-point; HIV-1 pathogenesis
7.  Protease Inhibitor Levels in Hair Samples Strongly Predict Virologic Responses to HIV Treatment 
AIDS (London, England)  2009;23(4):471-478.
Objective
Antiretroviral (ARV) therapies fail when behavioral or biologic factors lead to inadequate medication exposure. Currently available methods to assess ARV exposure are limited. Levels of ARVs in hair reflect plasma concentrations over weeks to months and may provide a novel method for predicting therapeutic responses.
Design/methods
The Women's Interagency HIV Study, a prospective cohort of HIV-infected women, provided the basis for developing and assessing methods to measure commonly-prescribed protease inhibitors (PIs) - lopinavir (LPV) and atazanavir (ATV) - in small hair samples. We examined the association between hair PI levels and initial virologic responses to therapy in multivariate logistic regression models.
Results
ARV concentrations in hair were strongly and independently associated with treatment response for 224 women starting a new PI-based regimen. For participants initiating LPV/RTV, the odds ratio (OR) for virologic suppression was 39.8 (95%CI 2.8–564) for those with LPV hair levels in the top tertile (>1.9ng/mg) compared to the bottom (≤0.41ng/mg) when controlling for self-reported adherence, age, race, starting viral load and CD4, and prior PI experience. For women starting ATV, the adjusted OR for virologic success was 7.7 (95%CI 2.0-29.7) for those with hair concentrations in the top tertile (>3.4ng/mg) compared to the lowest (≤1.2ng/mg).
Conclusions
PI levels in small hair samples were the strongest independent predictor of virologic success in a diverse group of HIV-infected adults. This noninvasive method for determining ARV exposure may have particular relevance for the epidemic in resource-poor settings due to the ease of collecting and storing hair.
doi:10.1097/QAD.0b013e328325a4a9
PMCID: PMC2654235  PMID: 19165084
Hair levels; therapeutic drug monitoring; antiretroviral exposure; virologic response; protease inhibitors; atazanavir; lopinavir; WIHS cohort

Results 1-7 (7)