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1.  The Association of Self-perception of Body Fat Changes and Quality of Life in the Women’s Interagency HIV Study 
AIDS care  2013;25(12):10.1080/09540121.2013.793265.
Body fat changes are of concern to HIV-seropositive adults on highly active antiretroviral therapy (HAART). Studies examining the association of body fat changes and quality of life (QOL) in the setting of HIV infection have been conducted predominately in men. We examined the relationship of self-perceived body fat change with QOL among 1,671 HAART-using HIV-seropositive women (mean age 40 ± 8 years; 54% African American, 24% reporting ≤ 95% HAART adherence) from the Women’s Interagency HIV Study. Self-perception of any fat loss was associated with lower overall QOL. Report of any peripheral fat loss was strongly associated with nearly all QOL domains (i.e., physical functioning, role functioning, energy/fatigue, social functioning, pain, emotional well-being, health perception, and perceived health index) except cognitive functioning, whereas report of any central fat loss was significantly associated with lower social and cognitive functioning. Report of any central fat gain was associated with lower overall QOL, but only physical functioning, energy/fatigue, and cognitive functioning were significantly affected. A significant association of report of any peripheral fat gain with overall QOL was not observed, however peripheral fat gain was significantly associated with lower physical functioning and pain. We found that any report of fat loss, especially in peripheral body sites is associated with lower QOL, as was any report of central fat gain. Ultimately health providers and patients need to be informed of these associations so as to better support HIV-seropositive women who live with these effects.
doi:10.1080/09540121.2013.793265
PMCID: PMC3769511  PMID: 23656440
body image perception; lipoatrophy; lipohypertrophy; Quality of life; HIV-seropositive women; HAART
2.  A Single-Nucleotide Polymorphism in CYP2B6 Leads to >3-Fold Increases in Efavirenz Concentrations in Plasma and Hair Among HIV-Infected Women 
The Journal of Infectious Diseases  2012;206(9):1453-1461.
Background. Efavirenz exhibits marked interindividual variability in plasma levels and toxicities. Prior pharmacogenetic studies usually measure exposure via single plasma levels, examine limited numbers of polymorphisms, and rarely model multiple contributors. We analyzed numerous genetic and nongenetic factors impacting short-term and long-term exposure in a large heterogeneous population of human immunodeficiency virus (HIV)–infected women.
Methods. We performed 24-hour intensive pharmacokinetic studies in 111 women receiving efavirenz under actual-use conditions and calculated the area-under-the-concentration-time curve (AUC) to assess short-term exposure; the efavirenz concentration in hair was measured to estimate long-term exposure. A total of 182 single-nucleotide polymorphisms (SNPs) and 45 haplotypes in 9 genes were analyzed in relationship to exposure by use of multivariate models that included a number of nongenetic factors.
Results. Efavirenz AUCs increased 1.26-fold per doubling of the alanine aminotransferase level and 1.23-fold with orange and/or orange juice consumption. Individuals with the CYP2B6 516TT genotype displayed 3.5-fold increases in AUCs and 3.2-fold increases in hair concentrations, compared with individuals with the TG/GG genotype. Another SNP in CYP2B6 (983TT) and a p-glycoprotein haplotype affected AUCs without substantially altering long-term exposure.
Conclusions. This comprehensive pharmacogenomics study showed that individuals with the CYP2B6 516TT genotype displayed >3-fold increases in both short-term and long-term efavirenz exposure, signifying durable effects. Pharmacogenetic testing combined with monitoring of hair levels may improve efavirenz outcomes and reduce toxicities.
doi:10.1093/infdis/jis508
PMCID: PMC3466997  PMID: 22927450
3.  Insulin Resistance and Cognition Among HIV-Infected and HIV-Uninfected Adult Women: The Women's Interagency HIV Study 
Abstract
Cognitive impairment remains prevalent in the era of combination antiretroviral therapy (cART) and may be partially due to comorbidities. We postulated that insulin resistance (IR) is negatively associated with cognitive performance. We completed a cross-sectional analysis among 1547 (1201 HIV+) women enrolled in the Women's Interagency HIV Study (WIHS). We evaluated the association of IR with cognitive measures among all WIHS women with concurrent fasting bloods and cognitive testing [Trails A, Trails B, and Symbol Digit Modalities Test (SDMT)] using multiple linear regression models. A smaller subgroup also completed the Stroop test (n=1036). IR was estimated using the Homeostasis Model Assessment (HOMA). Higher HOMA was associated with poorer performance on the SDMT, Stroop Color-Naming (SCN) trial, and Stroop interference trial, but remained statistically significant only for the SCN in models adjusting for important factors [β=3.78 s (95% CI: 0.48–7.08), p=0.025, for highest vs. lowest quartile of HOMA]. HIV status did not appear to substantially impact the relationship of HOMA with SCN. There was a small but statistically significant association of HOMA and reduced neuropsychological performance on the SCN test in this cohort of women.
doi:10.1089/aid.2011.0159
PMCID: PMC3332367  PMID: 21878059
4.  Self-Perception of Body Fat Changes and HAART Adherence in the Women’s Interagency HIV Study 
AIDS and behavior  2008;13(1):53-59.
To determine the association of self-perceived fat gain or fat loss in central and peripheral body sites with adherence to highly active antiretroviral therapy (HAART) in HIV-seropositive women. 1,671 women from the Women’s Interagency HIV Study who reported HAART use between April 1999 and March 2006 were studied. Adherence was defined as report of taking HAART ≥ 95% of the time during the prior 6 months. Participant report of any increase or decrease in the chest, abdomen, or upper back in the prior 6 months defined central fat gain and central fat loss, respectively. Report of any increase or decrease in the face, arms, legs or buttocks in the prior 6 months defined peripheral fat gain or peripheral fat loss. Younger age, being African-American (vs. White non-Hispanic), a history of IDU, higher HIV RNA at the previous visit, and alcohol consumption were significant predictors of HAART non-adherence (P <0.05). After multivariate adjustment, self-perception of central fat gain was associated with a 1.5-fold increased odds of HAART non-adherence compared to no change. Perception of fat gain in the abdomen was the strongest predictor of HAART non-adherence when the individual body sites were studied. Women who perceive central fat gain particularly in the abdomen are at risk for decreased adherence to HAART despite recent evidence to suggest that HIV and specific antiretroviral drugs are more commonly associated with fat loss than fat gain.
doi:10.1007/s10461-008-9444-7
PMCID: PMC2902995  PMID: 18688706
Lipodystrophy; HIV; Women; HAART adherence; body image perception
5.  NNRTI pharmacokinetics in a large unselected cohort of HIV-infected women 
Background
Small intensive pharmacokinetic (PK) studies of medications in early-phase trials cannot identify the range of factors that influence drug exposure in heterogeneous populations. We performed PK studies in large numbers of HIV-infected women on nonnucleoside-reverse-transcriptase-inhibitors (NNRTIs) under conditions of actual use to assess patient characteristics that influence exposure and evaluated the relationship between exposure and response.
Methods
225 women on NNRTI-based antiretroviral regimens from the Women’s Interagency HIV Study (WIHS) were enrolled into 12 or 24-hour PK studies. Extensive demographic, laboratory and medication covariate data was collected before and during the visit to be used in multivariate models. Total NNRTI drug exposure was estimated by area-under-the-concentration-time curves (AUC).
Results
Hepatic inflammation and renal insufficiency were independently associated with increased nevirapine (NVP) exposure in multivariate analyses; crack cocaine, high fat diets, and amenorrhea were associated with decreased levels (n=106). Higher efavirenz (EFV) exposure was seen with increased transaminase, albumin levels, and orange juice consumption; tenofovir use, increased weight, being African-American and amenorrhea were associated with decreased exposure (n=119). With every 10-fold increase in NVP or EFV exposure, participants were 3.3 and 3.6 times as likely to exhibit virologic suppression, respectively. Patients with higher drug exposure were also more likely to report side effects on therapy.
Conclusions
Our study identifies and quantitates previously unrecognized factors modifying NNRTI exposure in the “real-world” setting. Comprehensive PK studies in representative populations are feasible and may ultimatley lead to dose optimization strategies in patients at risk for failure or adverse events.
PMCID: PMC2700138  PMID: 19408353
HIV; antiretrovirals; nevirapine; efavirenz; pharmacokinetics; drug exposure; women
6.  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 1-6 (6)