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1.  Isoniazid Hair Concentrations in Children with Tuberculosis: A Proof of Concept Study 
Assessing treatment adherence and quantifying tuberculosis drug exposure among children is challenging. We undertook a “proof of concept” study to assess the drug concentrations of isoniazid in hair as a therapeutic drug monitoring tool. Children <12 years of age initiated on thrice-weekly treatment including isoniazid (10 mg/kg) for newly diagnosed tuberculosis were enrolled. Isoniazid concentrations in hair were measured using liquid chromatography-tandem mass spectrometry at 1, 2, 4 and 6 months after tuberculosis treatment initiation. We found that isoniazid hair concentrations in all children on thrice weekly isoniazid were detectable and displayed variability across a dynamic range.
doi:10.5588/ijtld.15.0882
PMCID: PMC4889729  PMID: 27155191
Tuberculosis; Pediatric TB; therapeutic drug monitoring; Isoniazid drug concentrations; hair assays
3.  Strong Correlation Between Concentrations of Tenofovir (TFV) Emtricitabine (FTC) in Hair and TFV Diphosphate and FTC Triphosphate in Dried Blood Spots in the iPrEx Open Label Extension: Implications for Pre-exposure Prophylaxis Adherence Monitoring 
The Journal of Infectious Diseases  2015;212(9):1402-1406.
Self-reported adherence to pre-exposure prophylaxis (PrEP) has limitations, raising interest in pharmacologic monitoring. Drug concentrations in hair and dried blood spots (DBS) are used to assess long-term-exposure; hair shipment/storage occurs at room temperature. The iPrEx Open Label Extension collected DBS routinely, with opt-in hair collection; concentrations were measured with liquid chromatography/tandem mass spectrometry. In 806 hair-DBS pairs, tenofovir (TFV) hair levels and TFV diphosphate (DP) in DBS were strongly correlated (Spearman coefficient r = 0.734; P < .001), as were hair TFV/DBS emtricitabine (FTC) triphosphate (TP) (r = 0.781; P < .001); hair FTC/DBS TFV-DP (r = 0.74; P < .001); hair FTC/DBS FTC-TP (r = 0.587; P < .001). Drug detectability was generally concordant by matrix. Hair TFV/FTC concentrations correlate strongly with DBS levels, which are predictive of PrEP outcomes.
doi:10.1093/infdis/jiv239
PMCID: PMC4601920  PMID: 25895984
HIV prevention; pre-exposure prophylaxis; PrEP; pharmacologic monitoring; adherence; tenofovir/emtricitabine; hair concentrations; dried blood spot (DBS) concentrations; iPrEx Open Label Extension (OLE)
4.  A retrospective cohort analysis comparing pregnancy rates among HIV-positive women using contraceptives and efavirenz- or nevirapine-based antiretroviral therapy in Kenya 
The lancet. HIV  2015;2(11):e474-e482.
SUMMARY
Background
Given recent concerns of efavirenz reducing the efficacy of contraceptive implants, we sought to determine if pregnancy rates differ among HIV-positive women using various contraceptive methods and efavirenz- or nevirapine-based antiretroviral therapy (ART) regimens.
Methods
We conducted a retrospective cohort analysis of HIV-positive women aged 15–45 years enrolled in HIV care facilities in western Kenya from January 2011 to December 2013. Pregnancy was diagnosed clinically and the primary exposure was a combination of contraceptive method and ART regimen. We used Poisson models, adjusting for repeated measures, as well as demographic, behavioral and clinical factors, to compare pregnancy rates among women on different contraceptive/ART combinations.
Findings
24,560 women contributed 37,635 years of follow-up with 3,337 incident pregnancies. Among women using implants, adjusted pregnancy incidence for nevirapine- and efavirenz-based ART users were 1·1 (95% CI 0·72–1·5) and 3·3 (95% CI 1·8–4·8) per 100 women-years (w-y), respectively (adjusted incidence rate ratio (aIRR) 3·0, 95% CI 1·3–4·6). Among women using depomedroxyprogesterone acetate (DMPA), adjusted pregnancy incidence for nevirapine- and efavirenz-based ART users were 4·5 (95% CI 3·7–5·2) and 5·4 (95% CI 4·0–6·8) per 100 w-y, respectively (aIRR 1·2, 95% CI 0·91–1·5). Women using other contraceptive methods, except for intrauterine devices and permanent methods, experienced 3·1–4·1 higher rates of pregnancy than women using implants, with 1·6–2·8 higher rates specifically among women using efavirenz-based ART.
Interpretation
While HIV-positive women using implants on efavirenz-based ART faced three times higher risk of contraceptive failure than those on nevirapine-based ART, these women still experienced lower contraceptive failure rates than women on all other contraceptive methods, except for intrauterine devices and permanent methods. Guidelines for contraceptive and ART combinations should balance the failure rates for each contraceptive method and ART regimen combination against the high effectiveness of implants.
Funding
Supported by the President’s Emergency Plan for AIDS Relief and the Centers for Disease Control and Prevention.
doi:10.1016/S2352-3018(15)00184-8
PMCID: PMC4632202  PMID: 26520927
5.  Age, baseline kidney function, and medication exposure are associated with declines in creatinine clearance on PrEP: an observational cohort study 
The lancet. HIV  2016;3(11):e521-e528.
SUMMARY
Background
As pre-exposure prophylaxis (PrEP) with tenofovir-disoproxil-fumarate/emtricitabine (TDF/FTC) for the prevention of HIV infection enters a phase of global roll-out, strategies to maintain effectiveness, but minimize adverse effects, merit close consideration. The aim of this study was to evaluate rates and predictors of renal toxicity in a large open-label study of PrEP to help provide guidance on safety monitoring with this important prevention strategy.
Methods
The iPrEx open-label-extension (OLE) study (NCT00458393) enrolled HIV-negative MSM/transgender participants from three previous PrEP trials from Brazil, Ecuador, Peru, South Africa, Thailand, and the U.S into an open-label PrEP study. There were no restrictions on current renal function for enrollment into iPrEx OLE.. Creatinine clearance (CrCl) on PrEP was estimated every 12 weeks and in a subset, hair samples were collected for measuring tenofovir (TFV)/FTC concentrations via liquid-chromatography/tandem-mass-spectrometry. Change in CrCl from baseline was calculated and predictors identified.
Findings
Baseline characteristics of participants in iPrEx-OLE (n=1224; 7475 person-visits) and its hair substudy (n=220; 1114 person-visits) were similar. Over 72 weeks (median), the average decline in CrCl was −2·9% (p<0.0001), but declines were significantly greater for those starting PrEP at older ages (−4·2% (95% CI −2·8%, −5·5%), baseline age 40–50 years; −4·9% (−3·1%, −6·8%), age ≥50). Besides age, baseline CrCl of <90ml/min in multivariate models predicted renal decline. There was a monotonic relationship between percent decrease in CrCl and number of doses of TDF/FTC taken per week as estimated by hair levels (p 0.008).
Interpretation
With the global roll-out of PrEP, our analysis suggests that the frequency of safety monitoring may differ by age group and that pharmacologic measures of adherence can additionally monitor for toxicities.
Funding
NIH
doi:10.1016/S2352-3018(16)30153-9
PMCID: PMC5085869  PMID: 27658870
HIV prevention; pre-exposure prophylaxis; PrEP; pharmacologic measures; tenofovir/emtricitabine; hair concentrations; iPrEx Open Label Extension (OLE); renal decline; creatinine clearance
6.  Behavioral Intervention Improves Treatment Outcomes Among HIV-Infected Individuals Who Have Delayed, Declined, or Discontinued Antiretroviral Therapy: A Randomized Controlled Trial of a Novel Intervention 
AIDS and behavior  2015;19(10):1801-1817.
Nationally up to 60 % of persons living with HIV are neither taking antiretroviral therapy (ART) nor well engaged in HIV care, mainly racial/ethnic minorities. This study examined a new culturally targeted multi-component intervention to address emotional, attitudinal, and social/structural barriers to ART initiation and HIV care. Participants (N = 95) were African American/Black and Latino adults with CD4<500 cells/mm3 not taking ART, randomized 1:1 to intervention or control arms, the latter receiving treatment as usual. Primary endpoints were adherence, evaluated via ART concentrations in hair samples, and HIV viral load suppression. The intervention was feasible and acceptable. Eight months post-baseline, intervention participants tended to be more likely to evidence “good” (that is, 7 days/week) adherence (60 vs. 26.7 %; p = 0.087; OR = 3.95), and had lower viral load levels than controls (t(22) = 2.29, p = 0.032; OR = 5.20), both large effect sizes. This highly promising intervention merits further study.
doi:10.1007/s10461-015-1054-6
PMCID: PMC4567451  PMID: 25835462
Antiretroviral therapy; Intervention; HIV/AIDS; Disparities; Motivational interviewing
7.  Using Lopinavir Concentrations in Hair Samples to Assess Treatment Outcomes on Second-Line Regimens Among Asian Children 
AIDS Research and Human Retroviruses  2015;31(10):1009-1014.
Abstract
We conducted a prospective monitoring study to determine whether antiretroviral (ARV) levels in hair of Asian children on second-line protease inhibitor-based ARV therapy (ART) are associated with virologic failure (VF), compared to plasma drug levels and self-reported adherence. HIV-infected Asian children on second-line ART regimens were enrolled into a longitudinal cohort. Traditional adherence measures, plasma, and hair samples were collected 24 weeks after study enrollment. Hair ARV levels were determined via liquid chromatography/tandem mass spectrometry. Among 149 children on lopinavir/ritonavir-based regimens, 47% were female; the median [interquartile range (IQR)] age was 10.3 (7.9–13.3) years. The median CD4% was 26% (IQR 21.7–32.1%) and the median CD4 cell count 754 (IQR 596–1,013) cells/mm3. The median duration of lopinavir-based ART prior to week 24 of the study was 2.9 (IQR 1.6–4.2) years. Adherence was >95% in 91% (135/148) by visual analogue scale and 89% (129/145) by pill count. The median lopinavir hair concentrations were 5.43 (IQR 3.21–9.01) ng/mg in children with HIV RNA >1,000 copies/ml and 9.96 (IQR 6.51–12.31) ng/mg in children with HIV RNA <1,000 copies/ml (p = 0.003). Plasma trough and lopinavir hair concentrations were not statistically significantly correlated (Pearson's correlation coefficient 0.20; p = 0.13). Increasing lopinavir hair concentrations in quartiles were strongly associated with virologic success (odds ratios ≥4.0, overall p = 0.02), while self-reported adherence, pill count, and plasma lopinavir levels were not. Based on this first report of hair ARV concentrations and virologic outcomes in children, ARV hair concentrations, representing longer-term adherence, may be useful to identify children at risk for VF.
doi:10.1089/aid.2015.0111
PMCID: PMC4576945  PMID: 26200586
8.  A mentor training program improves mentoring competency for researchers working with early-career investigators from underrepresented backgrounds 
Background
Mentoring is increasingly recognized as a critical element in supporting successful careers in academic research in medicine and related disciplines, particularly for trainees and early career investigators from underrepresented backgrounds. Mentoring is often executed ad hoc; there are limited programs to train faculty to become more effective mentors, and the few that exist have a dearth of empirical support of their impact.
Methods
In 2013, we recruited 34 faculty from across the U.S. engaged in HIV-related clinical research to participate in a two-day Mentoring the Mentors workshop. The workshop included didactic and interactive content focused on a range of topics, such as mentor-mentee communication, leadership styles, emotional intelligence, understanding the impact of diversity (unconscious bias, microaggressions, discrimination, tokenism) for mentees, and specific tools and techniques for effective mentoring.
Results
Pre- and post-workshop online evaluations documented high rates of satisfaction with the program and statistically significant improvements in self-appraised mentoring skills (e.g. addressing diversity in mentoring, communication with mentees, aligning mentor-mentee expectations), as assessed via a validated mentoring competency tool.
Discussion
This is the first mentoring training program focused on enhancing mentors’ abilities to nurture investigators of diversity, filling an important gap, and evaluation results offer support for its effectiveness. Results suggest a need for refinement and expansion of the program and for more comprehensive, long-term evaluation of distal mentoring outcomes for those who participate in the program.
doi:10.1007/s10459-014-9555-z
PMCID: PMC4383738  PMID: 25274417
Diversity; Mentoring Training; Underrepresented Minority Populations
9.  Pulling the network together: quasi-experimental trial of a patient-defined support network intervention for promoting engagement in HIV care and medication adherence on Mfangano Island, Kenya 
Background
Despite progress in the global scale-up of antiretroviral therapy, sustained engagement in HIV care remains challenging. Social capital is an important factor for sustained engagement, but interventions designed to harness this powerful social force are uncommon.
Methods
We conducted a quasi-experimental study evaluating the impact of the Microclinic social network intervention on engagement in HIV care and medication adherence on Mfangano Island, Kenya. The intervention was introduced into 1 of 4 similar communities served by this clinic; comparisons were made between communities using an intention-to-treat analysis. Microclinics, composed of patient-defined support networks, participated in ten bi-weekly discussion sessions covering topics ranging from HIV biology to group support, as well as group HIV status disclosure. Nevirapine concentrations in hair were measured pre-and-post study.
Results
113 (74%) intervention community participants joined a microclinic group, 86% of whom participated in group HIV status disclosure. Over 22-months of follow-up, intervention community participants experienced one-half the rate of ≥ 90-day clinic absence as those in control communities (adjusted hazard ratio 0.48, 95%CI 0.25–0.92). Nevirapine hair levels declined in both study arms; in adjusted linear regression analysis, the decline was 6.7 ng/mg less severe in the intervention arm than control arm (95% CI −2.7 to 16.1).
Conclusions
The microclinic intervention is a promising and feasible community-based strategy to improve long-term engagement in HIV care and possibly medication adherence. Reducing treatment interruptions using a social network approach has important implications for individual patient virologic suppression, morbidity and mortality, and for broader community empowerment and engagement in healthcare.
doi:10.1097/QAI.0000000000000664
PMCID: PMC4485532  PMID: 25984711
10.  HIV pre-exposure prophylaxis for women 
Journal of Virus Eradication  null;2(3):149-155.
Abstract
Women and girls comprise nearly half of HIV-infected individuals globally and 20% of new infections in the United States, indicating an urgent need to optimise HIV prevention options in this population. HIV pre-exposure prophylaxis (PrEP) – where antiretrovirals are administered to HIV-non-infected individuals at risk of HIV acquisition – is a promising, female-controlled HIV prevention strategy but has so far been underutilised in women. Clinical trial data demonstrate efficacy of daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for reduction of HIV acquisition among women when used consistently. Limited HIV risk perception and suboptimal PrEP awareness among women and healthcare personnel are among the challenges with PrEP delivery for women. Future research into the development of new drugs and delivery systems, and integrating PrEP delivery with reproductive healthcare services, provide opportunities to optimise this prevention strategy for women.
PMCID: PMC4967966  PMID: 27482454
Pre-exposure prophylaxis; women's health; HIV prevention
11.  Quantifying Isoniazid Levels in Small Hair Samples: A Novel Method for Assessing Adherence during the Treatment of Latent and Active Tuberculosis 
PLoS ONE  2016;11(5):e0155887.
Background
Tuberculosis (TB) is the leading cause of death from an infectious pathogen worldwide and the most prevalent opportunistic infection in people living with HIV. Isoniazid preventive therapy (IPT) reduces the incidence of active TB and reduces morbidity and mortality in HIV-infected patients independently of antiretroviral therapy. However, treatment of latent or active TB is lengthy and inter-patient variability in pharmacokinetics and adherence common. Current methods of assessing adherence to TB treatment using drug levels in plasma or urine assess short-term exposure and pose logistical challenges. Drug concentrations in hair assess long-term exposure and have demonstrated pharmacodynamic relevance in HIV.
Methods
A large hair sample from a patient with active TB was obtained for assay development. Methods to pulverize hair and extract isoniazid were optimized and then the drug detected by liquid chromatography/ tandem mass spectrometry (LC/MS-MS). The method was validated for specificity, accuracy, precision, recovery, linearity and stability to establish the assay’s suitability for therapeutic drug monitoring (TDM). Hair samples from patients on directly-observe isoniazid-based latent or active TB therapy from the San Francisco Department of Public Health TB clinic were then tested.
Results
Our LC/MS-MS-based assay detected isoniazid in quantities as low as 0.02ng/mg using 10–25 strands hair. Concentrations in spiked samples demonstrated linearity from 0.05–50ng/mg. Assay precision and accuracy for spiked quality-control samples were high, with an overall recovery rate of 79.5%. In 18 patients with latent or active TB on treatment, isoniazid was detected across a wide linear dynamic range.
Conclusions
An LC-MS/MS-based assay to quantify isoniazid levels in hair with performance characteristics suitable for TDM was developed and validated. Hair concentrations of isoniazid assess long-term exposure and may be useful for monitoring adherence to latent or active TB treatment in the setting of HIV.
doi:10.1371/journal.pone.0155887
PMCID: PMC4871544  PMID: 27191185
12.  Longitudinal Trends in Sexual Behaviors with Advancing Age and Menopause Among Women With and Without HIV-1 Infection 
AIDS and behavior  2015;19(5):931-940.
We assessed changes in self-reported sexual activity (SA) over 13 years among HIV-infected and uninfected women. The impact of aging and menopause on SA and unprotected anal or vaginal intercourse (UAVI) was examined among women in the Women’s Interagency HIV Study (WIHS), stratifying by HIV status and detectable viral load among HIV-infected women. Generalized mixed linear models were fitted for each outcome, adjusted for relevant covariates. HIV-uninfected women evidenced higher levels of SA and UAVI than HIV-infected. The odds of SA declined by 62–64 % per decade of age. The odds of SA in a 6-month interval for women aged 40–57 declined by 18–22 % post-menopause (controlling for age). Among HIV+/detectable women only, the odds of any UAVI decreased by 17 % per decade of age; the odds of UAVI were unchanged pre-menopause, and then decreased by 28 % post-menopause. Elucidating the factors accounting for ongoing unprotected sex among older women should inform interventions.
doi:10.1007/s10461-014-0901-1
PMCID: PMC4370800  PMID: 25245474
Sexual activity; Sexual risk behaviors; Aging; Menopause; Women’s Interagency HIV Study (WIHS)
13.  Hair Concentrations of Antiretrovirals Predict Viral Suppression in HIV-Infected Pregnant and Breastfeeding Ugandan Women 
AIDS (London, England)  2015;29(7):825-830.
Objective
Hair concentrations are a non-invasive measure of cumulative antiretroviral (ARV) exposure and the strongest predictor of viral suppression in large cohorts of non-pregnant patients. We examined hair concentrations of ARVs in relation to virologic outcomes in pregnant and breastfeeding women for the first time.
Design/Methods
The PROMOTE trial (NCT00993031) enrolled HIV-infected pregnant Ugandan women at 12–28 weeks gestation who were randomized to lopinavir or efavirenz-based antiretroviral therapy (ART). Small hair samples were collected at 30–34 weeks gestation and 10–25 weeks postpartum. Efavirenz and lopinavir hair concentrations were measured via liquid chromatography/tandem mass spectrometry. Multivariate logistic regression models examined predictors of viral suppression (HIV-1 RNA ≤400 copies/ml) at delivery and 24 weeks postpartum.
Results
Among 325 women, median CD4 cell count was 366 cells/mm3 (IQR 270–488) at ART initiation. Mean self-reported 3-day adherence was >97% in each arm. Viral suppression was achieved by 98.0% (efavirenz) and 87.4% (lopinavir) at delivery. At 24 weeks postpartum, 92.5% (efavirenz) and 90.6% (lopinavir) achieved viral suppression; 88% of women were breastfeeding. In multivariate models including self-reported adherence and pretreatment HIV-1 RNA, ARV hair concentrations were the strongest predictors of viral suppression at delivery (efavirenz: aOR 1.86 per doubling in concentration, 95% CI 1.14–3.1, P=0.013; lopinavir: aOR 1.90, 95% CI 1.33–2.7, P=0.0004) and 24 weeks postpartum (efavirenz: aOR 1.81, 95% CI 1.22–2.7, P=0.003; lopinavir: aOR 1.53, 95% CI: 1.05–2.2, P=0.026).
Conclusions
ARV hair concentrations represent an innovative tool that strongly predicts viral suppression among HIV-infected childbearing women during the critical periods of delivery and breastfeeding.
doi:10.1097/QAD.0000000000000619
PMCID: PMC4438773  PMID: 25985404
Antiretroviral therapy; hair concentrations; adherence; perinatal transmission; pharmacokinetics; pregnancy; breastfeeding
14.  Increase of perceived frequency of neighborhood domestic violence is associated with increase of women's depression symptoms in a nationally representative longitudinal study in South Africa 
Studies that examine the effects of neighborhood characteristics on mental health show that perceptions of general neighborhood violence are associated with depression across diverse populations (Clark et al., 2008; Velez-Gomez et al., 2013; Wilson-Genderson & Pruchno, 2013). However, to our knowledge, none have examined the specific effect of perceived frequency of neighborhood domestic violence (PFNDV) on residents' mental health, despite knowledge that domestic violence is a potent predictor of depression at the level of the individual. This study investigates the impact of PFNDV on mental health using the South African National Income Dynamics Study (SA-NIDS). NIDS Waves 2 and 3 measure the perceived frequency of six neighborhood violence subtypes through the NIDS household respondent questionnaire and depression through a questionnaire administered to all NIDS participants. Linear regression was used to model the relationship between change in depression symptoms and change in violence subtypes between Waves 2 and 3. We found that two-year increase in PFNDV was significantly correlated with increase of depression symptoms over the same time period for women, independently of individual, household and neighborhood level characteristics, including five other types of neighborhood violence. No other type of violence was associated with increased depression in women in the fully adjusted model. Research and policy implications are discussed.
doi:10.1016/j.socscimed.2015.03.008
PMCID: PMC4382311  PMID: 25769107
Depression; Domestic violence; Women's mental health; Longitudinal; Neighborhood violence; Mental health; South Africa; National income dynamics study
15.  Assessment of HIV antiretroviral therapy adherence by measuring drug concentrations in hair among children in rural Uganda 
AIDS care  2014;27(3):327-332.
Current tools for measuring medication adherence have significant limitations, especially among pediatric populations. We conducted a prospective observational study to assess the use of antiretroviral (ARV) drug levels in hair for evaluating antiretroviral therapy (ART) adherence among HIV-infected children in rural Uganda. Three-day caregiver recall, 30-day visual analog scale (VAS), Medication Event Monitoring System (MEMS), and unannounced pill counts and liquid formulation weights (UPC) were collected monthly over a one-year period. Hair samples were collected quarterly and analyzed for nevirapine (NVP) levels, and plasma HIV RNA levels were collected every six months. Among children with at least one hair sample collected, we used univariable random intercept linear regression models to compare log transformed NVP concentrations with each adherence measure, and the child’s age, sex, and CD4 count percentage (CD4%). 121 children aged 2–10 years were enrolled in the study; 74 (61%) provided at least one hair sample, and the mean number of hair samples collected per child was 1.9 (standard deviation [SD] 1.0). Three-day caregiver recall, VAS, and MEMS were found to be positively associated with increasing NVP concentration in hair, although associations were not statistically significant. UPC was found to have a non-significant negative association with increasing hair NVP concentration. In conclusion, NVP drug concentrations in hair were found to have non-significant, although generally positive, associations with other adherence measures in a cohort of HIV-infected children in Uganda. Hair collection in this population proved challenging, suggesting the need for community education and buy-in with the introduction of novel methodologies.
doi:10.1080/09540121.2014.983452
PMCID: PMC4305465  PMID: 25483955
16.  Efficacy and Safety of Lopinavir/ritonavir- versus Efavirenz-based Antiretroviral Therapy in HIV-Infected Pregnant Ugandan Women 
AIDS (London, England)  2015;29(2):183-191.
Objective
Combination antiretroviral therapy (ART) is now the global standard for HIV-infected pregnant and breastfeeding women at all CD4 cell counts. We compared the efficacy and safety of an efavirenz versus lopinavir/ritonavir regimen for HIV-infected pregnant women initiating ART in rural Uganda.
Design
Randomized clinical trial.
Methods
We performed a planned secondary analysis comparing viral load suppression (HIV-1 RNA ≤400 copies/ml), safety, and HIV transmission to infants in a trial designed to test the hypothesis that lopinavir/ritonavir- versus efavirenz-based ART would reduce placental malaria (PROMOTE, ClinicalTrials.gov, NCT00993031). HIV-infected, ART-naïve pregnant women at 12–28 weeks gestation and any CD4 cell count were randomized. ART was provided and participants were counseled to breastfeed for one year postpartum.
Results
The median age of the 389 study participants was 29 years; median CD4 cell count was 370 cells/mm3. At delivery, virologic suppression was 97.6% in the efavirenz arm and 86.0% in the lopinavir/ritonavir arm, p <0.001. At 48 weeks postpartum, 91.0% of women on efavirenz and 88.4% on lopinavir/ritonavir had viral suppression, p = 0.49. Grade 1 or 2 gastrointestinal adverse events were higher among women on lopinavir/ritonavir versus efavirenz. Only two infants acquired HIV (both in the lopinavir/ritonavir arm) and HIV-free infant survival was similar between study arms: 92.9% (lopinavir/ritonavir) versus 97.2% (efavirenz), p = 0.10.
Conclusions
Virologic suppression at delivery was higher with an efavirenz- versus lopinavir/ritonavir-based regimen. However, women in both arms achieved high levels of virologic suppression through one year postpartum and the risk of transmission to infants was low.
doi:10.1097/QAD.0000000000000531
PMCID: PMC4428759  PMID: 25426808
Prevention of mother-to-child transmission of HIV; pregnancy; breastfeeding; efavirenz; lopinavir/ritonavir
17.  Comparing the Novel Method of Assessing PrEP Adherence/Exposure using Hair Samples to other Pharmacologic and Traditional Measures 
Objective
The efficacy of pre-exposure-prophylaxis (PrEP) in HIV can diminish with poor adherence; pharmacologic measures of drug exposure have proven critical to PrEP trial interpretation. We assessed drug exposure in hair against other pharmacologic and more routinely-used measures to assess pill-taking.
Design
Participants were randomized to placebo, daily PrEP or intermittent PrEP in order to evaluate safety and tolerability of daily-versus-intermittent tenofovir/emtricitabine (TFV/FTC) in two phase-II PrEP clinical trials conducted in Africa. Different measures of drug exposure, including self-report, medication-electronic-monitoring-system (MEMS)-cap openings, and TFV/FTC levels in hair and other biomatrices, were compared.
Methods
At weeks 8 and 16, self-reported pill-taking, MEMS-cap openings, and TFV/FTC levels in hair, plasma, and peripheral-blood-mononuclear-cells (PBMCs) were measured. Regression models evaluated predictors of TFV/FTC concentrations in the three biomatrices; correlation coefficients between pharmacologic and non-pharmacologic measures were calculated. Both trials were registered on ClinicalTrials.gov (NCT00931346/NCT00971230).
Results
Hair collection was highly feasible and acceptable (100% week 8; 96% week 16). In multivariate analysis, strong associations were seen between pharmacologic measures and MEMS-caps openings (all p<0.001); self-report was only weakly associated with pharmacologic measures. TFV/FTC hair concentrations were significantly correlated with levels in plasma and PBMCs (correlation coefficients 0.41–0.86, all p<0.001).
Conclusions
Measuring TFV/FTC exposure in small hair samples in African PrEP trials was feasible and acceptable. Hair levels correlated strongly with PBMC, plasma concentrations, and MEMS-caps openings. As in other PrEP trials, self-report was the weakest measure of exposure. Further study of hair TFV/FTC levels in PrEP trials and demonstration projects to assess adherence/exposure is warranted.
doi:10.1097/QAI.0000000000000386
PMCID: PMC4262724  PMID: 25296098
Tenofovir; preventive therapy; hair; self-report; HIV; medication adherence
18.  A qualitative assessment of barriers and facilitators to antiretroviral adherence in Thai patients 
Journal of Virus Eradication  null;2(1):22-27.
Abstract
Objectives
Excellent adherence to combination antiretroviral therapy can suppress HIV replication and produce life expectancies nearing those of individuals without HIV infection. This qualitative study sought to identify the barriers and facilitators to good antiretroviral medication adherence in Thai patients living with HIV.
Methods
Semi-structured interviews were conducted with a convenience sample (n=21) of patients attending routine clinic visits at Srinagarind Hospital in Khon Kaen, or HIV-NAT, the Thai Red Cross AIDS Research Centre in Bangkok.
Results
Median informant age was 43 years (range 27–60 years) and 43% were female. We identified key facilitators and barriers to adherence among HIV-infected Thai patients along three major themes (patient-related, health system-related and medication-related). Stigma was a primary concern for most informants, operating throughout Thai society to induce feelings of shame for Thai people living with HIV. Determination to stay healthy and incorporate taking cART into their daily routine were key components of good adherence. Supportive and trusting relationships, particularly with the clinic team, empowered patients to maintain good medication adherence.
Conclusions
Changing public perceptions about HIV, and training of HIV clinic staff on the importance of trusting and supportive provider–patient relationships in promoting good health outcomes, will help Thailand achieve its aim of having zero new HIV infections, zero discrimination and zero AIDS-related deaths by 2030.
PMCID: PMC4946691  PMID: 27482431
adherence, HIV, Thailand, Southeast Asia, antiretroviral agents
19.  HPV knowledge, vaccine acceptance, and vaccine series completion among female entertainment and sex workers in Phnom Penh, Cambodia: the Young Women's Health Study 
International journal of STD & AIDS  2014;26(12):893-902.
Human papillomavirus (HPV) is a common sexually transmitted infection (STI) and the causative agent for cervical cancer, a frequently occurring malignant disease among women in developing countries. We assessed HPV awareness prior to the delivery of a brief information and education intervention, and HPV vaccine provision to female entertainment and sex workers (N=220). At baseline, only 23.6% of women had heard of HPV. Following the educational intervention, 90% answered all the HPV knowledge questions correctly. Of 192 participants attending the first quarterly cohort visit where vaccine was offered, 149 (78%) were eligible for vaccination; HIV-positive (n=32) and pregnant (n=11) women were excluded. Acceptance of vaccine among eligible women was universal, and 79.2% completed the three-dose vaccination series. Women who reported use of amphetamine type stimulants (ATS) had significantly and independently lower odds of vaccine completion (Adjusted OR 0.24; 95% CI 0.08, 0.69). New pregnancies also had an impact on vaccine completion: 5.4% (8/149 5.4%) who started the series had to stop due to new pregnancy. Results demonstrate the effectiveness of a simple education intervention designed to increase HPV knowledge and the feasibility of successful HPV vaccine in a population that is often difficult to engage in preventive health care.
doi:10.1177/0956462414563626
PMCID: PMC4506266  PMID: 25505042
HPV; vaccine; knowledge; attitudes; brief intervention; Cambodia; female sex workers; HIV
20.  Development and Implementation of a Workshop to Enhance the Effectiveness of Mentors Working with Diverse Mentees in HIV Research 
Abstract
A growing body of evidence highlights the importance of competent mentoring in academic research in the field of HIV, particularly for early stage investigators from diverse, underrepresented backgrounds. We describe the development and implementation of a 2-day intensive workshop to train mid-level and senior-level investigators conducting HIV-related clinical and translational research across multiple academic institutions on more effective mentoring, with an emphasis on techniques to foster mentees of diversity. The workshop was focused on training mentors in techniques designed to improve the effectiveness of the mentor–mentee relationship, and included didactic presentations, interactive discussions, and small-group problem-based learning activities. Mid-level or senior-level faculty involved or planning to be involved in significant mentorship activities related to HIV research were eligible. Surveys and formal actions plans allowed for workshop evaluation and laid the groundwork for subsequent workshops. Twenty-six faculty from 16 U.S.-based institutions participated, with good representation across discipline, gender, and race/ethnicity. The sessions were highly rated and discussions and evaluations revealed important barriers and facilitators to mentoring, challenges and solutions related to mentoring mentees from diverse backgrounds, and specific tools to enhance mentoring effectiveness. The Mentoring the Mentors training program for HIV researchers focusing on early career investigators of diversity was the first of its kind and was well attended, was rated highly, and provided guidance for improving the program in the future. This training program fills an important gap in the HIV researcher community and offers guidance for training mentors interested in diversity issues in settings outside of HIV.
doi:10.1089/aid.2014.0018
PMCID: PMC4118696  PMID: 24735004
21.  Smoking Cessation and Recidivism in the Women's Interagency Human Immunodeficiency Virus Study 
Background
Smoking increases the risk of morbidity and mortality and is particularly harmful to HIV-infected people.
Purpose
To explore smoking trends and longitudinal factors associated with smoking cessation and recidivism among participants in the Women's Interagency HIV Study.
Methods
From 1994 through 2011, 2,961 HIV-infected and 981 HIV-uninfected women were enrolled and underwent semi-annual interviews and specimen collection. Smoking prevalence was evaluated annually and risk factors associated with time to smoking cessation and recidivism were analyzed in 2013 using survival models.
Results
The annual cigarette smoking prevalence declined from 57% in 1995 to 39% in 2011 (p-trend<0.0001). Among smokers, factors significantly associated with a longer time to smoking cessation included less education, alcohol use, having health insurance, >10-year smoking duration, self-reported poor health rating, and having hypertension. Pregnancy in the past 6 months was associated with a shorter time to cessation. Among HIV-infected women, additional risk factors for longer time to cessation included lower household income, use of crack/cocaine/heroin, CD4 cell count ≤200, and highly active antiretroviral therapy (HAART) use. Predictors of smoking recidivism included marijuana use, enrollment in 1994–1996, and not living in one's own place. Among HIV-infected women, enrollment in 2001-2002 and crack/cocaine/heroin use were associated with a shorter time to recidivism, whereas older age and HAART use were associated with a longer time to recidivism.
Conclusions
Despite declining rates of cigarette smoking, integrated interventions are needed to help women with and at risk for HIV infection to quit smoking and sustain cessation.
doi:10.1016/j.amepre.2014.02.010
PMCID: PMC4065848  PMID: 24746376
22.  Antiretroviral concentrations in small hair samples as a feasible marker of adherence in rural Kenya 
Antiretroviral hair levels objectively quantify drug exposure over time and predict virologic responses. We assessed the acceptability and feasibility of collecting small hair samples in a rural Kenyan cohort. 95% of participants (354/373) donated hair. Although median self-reported adherence was 100% (IQR 96–100%), a wide range of hair concentrations likely indicates overestimation of self-reported adherence and the advantages of a pharmacologic adherence measure. Higher nevirapine (NVP) hair concentrations observed in women and older adults require further study to unravel behavioral versus pharmacokinetic contributors. In resource-limited settings, hair antiretroviral levels may serve as a low-cost quantitative biomarker of adherence.
doi:10.1097/QAI.0000000000000154
PMCID: PMC4146734  PMID: 24694932
Adherence; nevirapine; hair concentrations; resource-limited setting; feasibility and acceptability; pharmacologic measure
23.  Nevirapine Concentration in Hair Samples Is a Strong Predictor of Virologic Suppression in a Prospective Cohort of HIV-Infected Patients 
PLoS ONE  2015;10(6):e0129100.
Effective antiretroviral (ARV) therapy depends on adequate drug exposure, yet methods to assess ARV exposure are limited. Concentrations of ARV in hair are the product of steady-state pharmacokinetics factors and longitudinal adherence. We investigated nevirapine (NVP) concentrations in hair as a predictor of treatment response in women receiving ARVs. In participants of the Women’s Interagency HIV Study, who reported NVP use for >1 month from 2003–2008, NVP concentrations in hair were measured via liquid-chromatography-tandem mass-spectrometry. The outcome was virologic suppression (plasma HIV RNA below assay threshold) at the time of hair sampling and the primary predictor was nevirapine concentration categorized into quartiles. We controlled for age, race/ethnicity, pre-treatment HIV RNA, CD4 cell count, and self-reported adherence over the 6-month visit interval (categorized ≤ 74%, 75%–94% or ≥ 95%). We also assessed the relation of NVP concentration with changes in hepatic transaminase levels via multivariate random intercept logistic regression and linear regression analyses. 271 women contributed 1089 person-visits to the analysis (median 3 of semi-annual visits). Viral suppression was least frequent in concentration quartile 1 (86/178 (48.3%)) and increased in higher quartiles (to 158/204 (77.5%) for quartile 4). The odds of viral suppression in the highest concentration quartile were 9.17 times (95% CI 3.2–26, P < 0.0001) those in the lowest. African-American race was associated with lower rates of virologic suppression independent of NVP hair concentration. NVP concentration was not significantly associated with patterns of serum transaminases. Concentration of NVP in hair was a strong independent predictor of virologic suppression in women taking NVP, stronger than self-reported adherence, but did not appear to be strongly predictive of hepatotoxicity.
doi:10.1371/journal.pone.0129100
PMCID: PMC4460031  PMID: 26053176
24.  An Incidental Abscess in a Patient with Acquired Immunodeficiency Syndrome 
doi:10.1097/IPC.0b013e318264132a
PMCID: PMC4423602  PMID: 25960626
Abscess; HIV; AIDS; Immunocompromised
25.  Common Clinical Conditions – Age, Low BMI, Ritonavir Use, Mild Renal Impairment - Affect Tenofovir Pharmacokinetics in a Large Cohort of HIV-Infected Women 
AIDS (London, England)  2014;28(1):59-66.
Objective
Tenofovir is used commonly in HIV treatment and prevention settings, but factors that correlate with tenofovir exposure in real-world setting are unknown.
Design
Intensive pharmacokinetic (PK) studies of tenofovir in a large, diverse cohort of HIV-infected women over 24-hours at steady-state were performed and factors that influenced exposure (assessed by areas-under-the-time-concentration curves, AUCs) identified
Methods
HIV-infected women (n=101) on tenofovir-based therapy underwent intensive 24-hour PK sampling. Data on race/ethnicity, age, exogenous steroid use, menstrual cycle phase, concomitant medications, recreational drugs and/or tobacco, hepatic and renal function, weight and body mass index (BMI) were collected. Multivariable models using forward stepwise selection identified factors associated with effects on AUC. Glomerular filtration rates (GFR) prior to starting tenofovir were estimated by the CKD-EPI equation using both creatinine and cystatin-C measures
Results
The median (range) of tenofovir AUCs was 3350 (1031–13,911) ng x h/mL. Higher AUCs were associated with concomitant ritonavir use (1.33-fold increase, p 0.002), increasing age (1.21-fold increase per decade, p=0.0007) and decreasing BMI (1.04-fold increase per 10% decrease in BMI). When GFR was calculated using cystatin-C measures, mild renal insufficiency prior to tenofovir initiation was associated with higher subsequent exposure (1.35-fold increase when pre-tenofovir GFR <70mL/min, p=0.0075).
Conclusions
Concomitant ritonavir use, increasing age, decreasing BMI and lower GFR prior to tenofovir initiation as estimated by cystatin C were all associated with elevated tenofovir exposure in a diverse cohort of HIV-infected women. Clinicians treating HIV-infected women should be aware of common clinical conditions that affect tenofovir exposure when prescribing this medication.
doi:10.1097/QAD.0000000000000033
PMCID: PMC3956315  PMID: 24275255
Tenofovir; pharmacokinetics; HIV-infected women; diverse populations; GFR; cystatin C

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