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1.  HIV Drug Resistance Profiles and Clinical Outcomes in Patients with Viremia Maintained at Very Low Levels 
World journal of AIDS  2013;3(2):71-78.
We describe an observational study of clinical, virologic and drug resistance profiles in HIV-positive antiretroviral adherent subjects with stable low level viremia (LLV) 50–1,000 copies/mL for more than 12 months. Subjects were followed from time of first detectable viral load (VL). In total, 102 episodes of LLV were detected among 80 individuals. The median (mean, range) HIV copy number at genotyping was 250 (486, <50–3900) copies/mL after 14 (17.9, 0–58) months of LLV. Few patients maintained LLV for the entire 9 year period of observation, with half (52%) experiencing viremic progression following a stable period of LLV either spontaneously or after treatment interruption or failed regimen intensification. In the setting of prolonged periods of sustained LLV, mean duration 22 (range 8 – 106) months, drug resistance (DR) was almost universal. Resistance to ≥1 on-treatment drugs was defined in 97% of specimens and DR to all drugs in the treatment regimen in over half of all patients. Evolution of DR mutations during the period of LLV was observed in 20/28 (71%) subjects with specimens available for follow-up testing. This evolution was associated with viremic progression to levels >1000 copies/mL (p=0.03).
Our data suggest that DR present in patients with LLV is likely to impact long term clinical outcomes, highlighting the importance of optimizing techniques to detect the presence of drug resistant HIV in the setting of LLV and the need for larger prospective studies to assess the emergence of DR in the setting of sustained LLV and the impact of this DR on treatment outcomes.
doi:10.4236/wja.2013.32010
PMCID: PMC4319662
HIV; low level viremia; treatment experienced patients; HIV drug resistance
2.  Progression of Carotid Intima-Media Thickness and Coronary Artery Calcium over Six Years in an HIV-infected Cohort 
Journal of acquired immune deficiency syndromes (1999)  2013;64(1):10.1097/QAI.0b013e31829ed726.
Objective
To evaluate changes in cardiovascular disease risk surrogate markers in a longitudinal cohort of HIV-infected adults over 6 years.
Design
Internal and common carotid artery intima-media thickness, coronary artery calcium, vascular and HIV risk factors were prospectively examined over 6 years in HIV-infected adults from 2002 to 2010.
Setting
Longitudinal cohort study with participants from urban center and surrounding communities.
Subjects, participants
345 HIV-infected participants were recruited from a longitudinal cohort study. 211 participants completed the study and were included in this analysis.
Main Outcome Measures
Total and yearly internal and common carotid artery intima-media thickness change; coronary artery calcium score progression.
Results
Participants were 27% female and 49% non-white; mean age at start was 45 ± 7 years. The median change in internal and common carotid arteries over six years was 0.15mm (0.08,0.28) and 0.12mm (0.09,0.15), respectively. Age, baseline triglycerides ≥ 150mg/dL, and pack-years smoking were associated with internal carotid artery intima-media thickness change; age, cholesterol, nadir CD4+ count, and protease inhibitor use were associated with common carotid artery intima-media thickness change. Diabetes, HIV viral load, and HAART duration were associated with coronary artery calcium progression.
Conclusions
Carotid intima-media thickness and coronary artery calcium progressed in this HIV-infected cohort. Some HIV-specific characteristics were associated with surrogate marker changes, but the majority of risk factors continue to be traditional. Aggressive identification and management of modifiable risk factors may reduce progression of cardiovascular disease risk in this population.
doi:10.1097/QAI.0b013e31829ed726
PMCID: PMC3815556  PMID: 23945252
3.  Changes in HIV-1 Subtypes B and C Genital Tract RNA in Women and Men After Initiation of Antiretroviral Therapy 
Fiscus, Susan A. | Cu-Uvin, Susan | Eshete, Abel Tilahun | Hughes, Michael D. | Bao, Yajing | Hosseinipour, Mina | Grinsztejn, Beatriz | Badal-Faesen, Sharlaa | Dragavon, Joan | Coombs, Robert W. | Braun, Ken | Moran, Laura | Hakim, James | Flanigan, Timothy | Kumarasamy, N. | Campbell, Thomas B. | Klingman, Karin L. | Nair, Apsara | Walawander, Ann | Smeaton, Laura M. | De Gruttola, Victor | Martinez, Ana I. | Swann, Edith | Barnett, Ronald L. | Brizz, Barbara | Delph, Yvette | Gettinger, Nikki | Mitsuyasu, Ronald T. | Eshleman, Susan | Safren, Steven | Andrade, Adriana | Haas, David W. | Amod, Farida | Berthaud, Vladimir | Bollinger, Robert C. | Bryson, Yvonne | Celentano, David | Chilongozi, David | Cohen, Myron | Collier, Ann C. | Currier, Judith Silverstein | Eron, Joseph | Firnhaber, Cynthia | Flexner, Charles | Gallant, Joel E. | Gulick, Roy M. | Hammer, Scott M. | Hoffman, Irving | Kazembe, Peter | Kumwenda, Johnstone | Kumwenda, Newton | Lama, Javier R. | Lawrence, Jody | Maponga, Chiedza | Martinson, Francis | Mayer, Kenneth | Nielsen, Karin | Pendame, Richard B. | Ramratnam, Bharat | Rooney, James F. | Sanchez, Jorge | Sanne, Ian | Schooley, Robert T. | Snowden, Wendy | Solomon, Suniti | Tabet, Steve | Taha, Taha | Uy, Jonathan | van der Horst, Charles | Wanke, Christine | Gormley, Joan | Marcus, Cheryl J. | Putnam, Beverly | Ntshele, Smanga | Loeliger, Edde | Pappa, Keith A. | Webb, Nancy | Shugarts, David L. | Winters, Mark A. | Descallar, Renard S. | Sharma, Jabin | Poongulali, S. | Cardoso, Sandra Wagner | Faria, Deise Lucia | Berendes, Sima | Burke, Kelly | Kanyama, Cecelia | Kayoyo, Virginia | Samaneka, Wadzanai P. | Chisada, Anthony | Santos, Breno | La Rosa, Alberto | Infante, Rosa | Balfour, Henry H. | Mullan, Beth | Kim, Ge-Youl | Klebert, Michael K. | Mildvan, Donna | Revuelta, Manuel | Jan Geiseler, P. | Santos, Bartolo | Daar, Eric S. | Lopez, Ruben | Frarey, Laurie | Currin, David | Haas, David H. | Bailey, Vicki L. | Tebas, Pablo | Zifchak, Larisa | Sha, Beverly E. | Fritsche, Janice M.
Women with human immunodeficiency virus (HIV)–1 subtype C had significantly higher genital tract viral loads compared to women with HIV-1 subtype B and men with HIV-1 subtype C or B. Women in general were significantly less likely to have genital tract viral load below the lower limit of quantification compared to men.
Background. Combination antiretroviral therapy (cART) reduces genital tract human immunodeficiency virus type 1 (HIV-1) load and reduces the risk of sexual transmission, but little is known about the efficacy of cART for decreasing genital tract viral load (GTVL) and differences in sex or HIV-1 subtype.
Methods. HIV-1 RNA from blood plasma, seminal plasma, or cervical wicks was quantified at baseline and at weeks 48 and 96 after entry in a randomized clinical trial of 3 cART regimens.
Results. One hundred fifty-eight men and 170 women from 7 countries were studied (men: 55% subtype B and 45% subtype C; women: 24% subtype B and 76% subtype C). Despite similar baseline CD4+ cell counts and blood plasma viral loads, women with subtype C had the highest GTVL (median, 5.1 log10 copies/mL) compared to women with subtype B and men with subtype C or B (4.0, 4.0, and 3.8 log10 copies/mL, respectively; P < .001). The proportion of participants with a GTVL below the lower limit of quantification (LLQ) at week 48 (90%) and week 96 (90%) was increased compared to baseline (16%; P < .001 at both times). Women were significantly less likely to have GTVL below the LLQ compared to men (84% vs 94% at week 48, P = .006; 84% vs 97% at week 96, P = .002), despite a more sensitive assay for seminal plasma than for cervical wicks. No difference in GTVL response across the 3 cART regimens was detected.
Conclusions. The female genital tract may serve as a reservoir of persistent HIV-1 replication during cART and affect the use of cART to prevent sexual and perinatal transmission of HIV-1.
doi:10.1093/cid/cit195
PMCID: PMC3689341  PMID: 23532477
HIV-1 genital tract RNA; HIV-1 subtypes B and C; antiretroviral drugs
4.  Contribution of Genetic Background, Traditional Risk Factors, and HIV-Related Factors to Coronary Artery Disease Events in HIV-Positive Persons 
Rotger, Margalida | Glass, Tracy R. | Junier, Thomas | Lundgren, Jens | Neaton, James D. | Poloni, Estella S. | van 't Wout, Angélique B. | Lubomirov, Rubin | Colombo, Sara | Martinez, Raquel | Rauch, Andri | Günthard, Huldrych F. | Neuhaus, Jacqueline | Wentworth, Deborah | van Manen, Danielle | Gras, Luuk A. | Schuitemaker, Hanneke | Albini, Laura | Torti, Carlo | Jacobson, Lisa P. | Li, Xiuhong | Kingsley, Lawrence A. | Carli, Federica | Guaraldi, Giovanni | Ford, Emily S. | Sereti, Irini | Hadigan, Colleen | Martinez, Esteban | Arnedo, Mireia | Egaña-Gorroño, Lander | Gatell, Jose M. | Law, Matthew | Bendall, Courtney | Petoumenos, Kathy | Rockstroh, Jürgen | Wasmuth, Jan-Christian | Kabamba, Kabeya | Delforge, Marc | De Wit, Stephane | Berger, Florian | Mauss, Stefan | de Paz Sierra, Mariana | Losso, Marcelo | Belloso, Waldo H. | Leyes, Maria | Campins, Antoni | Mondi, Annalisa | De Luca, Andrea | Bernardino, Ignacio | Barriuso-Iglesias, Mónica | Torrecilla-Rodriguez, Ana | Gonzalez-Garcia, Juan | Arribas, José R. | Fanti, Iuri | Gel, Silvia | Puig, Jordi | Negredo, Eugenia | Gutierrez, Mar | Domingo, Pere | Fischer, Julia | Fätkenheuer, Gerd | Alonso-Villaverde, Carlos | Macken, Alan | Woo, James | McGinty, Tara | Mallon, Patrick | Mangili, Alexandra | Skinner, Sally | Wanke, Christine A. | Reiss, Peter | Weber, Rainer | Bucher, Heiner C. | Fellay, Jacques | Telenti, Amalio | Tarr, Philip E.
We show in human immunodeficiency virus–positive persons that the coronary artery disease effect of an unfavorable genetic background is comparable to previous studies in the general population, and comparable in size to traditional risk factors and antiretroviral regimens known to increase cardiovascular risk.
Background Persons infected with human immunodeficiency virus (HIV) have increased rates of coronary artery disease (CAD). The relative contribution of genetic background, HIV-related factors, antiretroviral medications, and traditional risk factors to CAD has not been fully evaluated in the setting of HIV infection.
Methods In the general population, 23 common single-nucleotide polymorphisms (SNPs) were shown to be associated with CAD through genome-wide association analysis. Using the Metabochip, we genotyped 1875 HIV-positive, white individuals enrolled in 24 HIV observational studies, including 571 participants with a first CAD event during the 9-year study period and 1304 controls matched on sex and cohort.
Results A genetic risk score built from 23 CAD-associated SNPs contributed significantly to CAD (P = 2.9×10−4). In the final multivariable model, participants with an unfavorable genetic background (top genetic score quartile) had a CAD odds ratio (OR) of 1.47 (95% confidence interval [CI], 1.05–2.04). This effect was similar to hypertension (OR = 1.36; 95% CI, 1.06–1.73), hypercholesterolemia (OR = 1.51; 95% CI, 1.16–1.96), diabetes (OR = 1.66; 95% CI, 1.10–2.49), ≥1 year lopinavir exposure (OR = 1.36; 95% CI, 1.06–1.73), and current abacavir treatment (OR = 1.56; 95% CI, 1.17–2.07). The effect of the genetic risk score was additive to the effect of nongenetic CAD risk factors, and did not change after adjustment for family history of CAD.
Conclusions In the setting of HIV infection, the effect of an unfavorable genetic background was similar to traditional CAD risk factors and certain adverse antiretroviral exposures. Genetic testing may provide prognostic information complementary to family history of CAD.
doi:10.1093/cid/cit196
PMCID: PMC3669528  PMID: 23532479
HIV infection; coronary artery disease; genetics; traditional risk factors; antiretroviral therapy
5.  Pharmacy and self-report adherence measures to predict virological outcomes for patients on free antiretroviral therapy in Tamil Nadu, India 
AIDS and behavior  2013;17(6):2253-2259.
Over 480,000 individuals receive free antiretroviral therapy (ART) in India yet data associating ART adherence with HIV viral load for populations exclusively receiving free ART are not available. Additionally estimates of adherence using pharmacy data on ART pick-up are not available for any population in India. After 12-months ART we found self-reported estimates of adherence were not associated with HIV viral load. Individuals with < 100% adherence using pharmacy data predicted HIV viral load, and estimates combining pharmacy data and self-report were also predictive. Pharmacy adherence measures proved a feasible method to estimate adherence in India and appear more predictive of virological outcomes than self-report. Predictive adherence measures identified in this study warrant further investigation in populations receiving free ART in India to allow for identification of individuals at risk of virological failure and in need of adherence support.
doi:10.1007/s10461-013-0436-x
PMCID: PMC3674125  PMID: 23435750
HIV; adherence; antiretroviral therapy; India; virological outcomes
6.  Urinary Eicosanoid Metabolites in HIV-Infected Women with Central Obesity Switching to Raltegravir: An Analysis from the Women, Integrase, and Fat Accumulation Trial 
Mediators of Inflammation  2014;2014:803095.
Chronic inflammation is a hallmark of HIV infection. Eicosanoids reflect inflammation, oxidant stress, and vascular health and vary by sex and metabolic parameters. Raltegravir (RAL) is an HIV-1 integrase inhibitor that may have limited metabolic effects. We assessed urinary F2-isoprostanes (F2-IsoPs), prostaglandin E2 (PGE-M), prostacyclin (PGI-M), and thromboxane B2 (TxB2) in HIV-infected women switching to RAL-containing antiretroviral therapy (ART). Thirty-seven women (RAL = 17; PI/NNRTI = 20) with a median age of 43 years and BMI 32 kg/m2 completed week 24. TxB2 increased in the RAL versus PI/NNRTI arm (+0.09 versus −0.02; P = 0.06). Baseline PGI-M was lower in the RAL arm (P = 0.005); no other between-arm cross-sectional differences were observed. In the PI/NNRTI arm, 24-week visceral adipose tissue change correlated with PGI-M (rho = 0.45; P = 0.04) and TxB2 (rho = 0.44; P = 0.005) changes, with a trend seen for PGE-M (rho = 0.41; P = 0.07). In an adjusted model, age ≥ 50 years (N = 8) was associated with increased PGE-M (P = 0.04). In this randomized trial, a switch to RAL did not significantly affect urinary eicosanoids over 24 weeks. In women continuing PI/NNRTI, increased visceral adipose tissue correlated with increased PGI-M and PGE-M. Older age (≥50) was associated with increased PGE-M. Relationships between aging, adiposity, ART, and eicosanoids during HIV-infection require further study.
doi:10.1155/2014/803095
PMCID: PMC4058804  PMID: 24991090
7.  Metabolic Syndrome Predicts All-Cause Mortality in Persons with Human Immunodeficiency Virus 
AIDS Patient Care and STDs  2013;27(5):266-271.
Abstract
We examined the association between metabolic syndrome (MS) and its individual defining criteria on all-cause mortality in human immunodeficiency virus (HIV)-infected persons. We used data from 567 HIV-infected participants of the Nutrition for Healthy Living study with study visits between 9/1/2000 and 1/31/2004 and determined mortality through 12/31/2006. MS was defined using modified National Cholesterol Education Program guidelines. Cox proportional hazards for all-cause mortality were estimated for baseline MS status and for its individual defining criteria. There were 83 deaths with median follow-up of 63 months. Baseline characteristics associated with increased risk of mortality were: older age in years (univariate hazard ratio [HR] 1.04, p<0.01), current smoking (HR 1.99, p=0.02), current heroin use (HR 1.97, p=0.02), living in poverty (HR 2.0, p<0.01), higher mean HIV viral load (HR 1.81, p<0.01), and having a BMI <18 (HR 5.84, p<0.01). For MS and its criteria, only low HDL was associated with increased risk of mortality on univariate analysis (HR 1.84, p=0.01). However, metabolic syndrome (adjusted HR 2.31, p=0.02) and high triglycerides (adjusted HR 3.97, p<0.01) were significantly associated with mortality beyond 36 months follow-up. MS, low HDL, and high triglycerides are associated with an increased risk of mortality in HIV-infected individuals.
doi:10.1089/apc.2012.0402
PMCID: PMC3651687  PMID: 23651103
8.  Development of a nutrient-dense food supplement for HIV-infected women in rural Kenya using qualitative and quantitative research methods 
Public health nutrition  2012;16(4):721-729.
Objective
Formative research to facilitate the development, packaging and delivery of a culturally acceptable nutrition intervention for HIV-infected women in rural Kenya for an intervention trial.
Design
Focus group discussion on three areas: (i) ingredients and form of the nutrition intervention, (ii) packaging and delivery and (iii) monitoring of adherence. Two single-blind taste tests with eleven different porridge formulations of various combinations of maize flour, soyabeans, peanuts, sorghum, mung beans, dried fish, raisins and dried whole milk. Follow-up acceptability focus group discussion was also conducted.
Setting
Voi, Kenya, community based.
Subjects
Focus group discussion and two taste tests (twenty-one women aged 16–55 years). Follow-up acceptability focus group discussion (four women enrolled in intervention trial).
Results
The preferred porridge for taste consisted of maize, soyabeans and peanuts. For animal protein, dried whole milk and dried fish were used. Although the women disliked the taste of dried fish, it was acceptable if added in small undetectable quantities. Sugar over lime was favoured for taste. Women believed they could consume at least two cups of porridge per day without displacing their usual meals. The optimal delivery interval was believed to be every two weeks in individual serving packages. Women who had been consuming porridge for several weeks felt the taste was acceptable for long-term consumption.
Conclusions
This formative research resulted in the development, packaging and delivery of a nutrient-dense food supplement using local ingredients to meet the dietary needs of the population and acceptable for daily consumption by women in Kenya for evaluation in an intervention trial.
doi:10.1017/S1368980012004156
PMCID: PMC3984962  PMID: 22974548
HIV; Africa; Kenya; Nutrition therapy
9.  Comparison of standard PCR/cloning to single genome sequencing for analysis of HIV-1 populations 
Journal of virological methods  2010;168(0):114-120.
To compare standard PCR/cloning and single genome sequencing (SGS) in their ability to reflect actual intra-patient polymorphism of HIV-1 populations, a total of 530 HIV-1 pro-pol sequences obtained by both sequencing techniques from a set of 17 ART naïve patient specimens was analyzed. For each specimen, 12 and 15 sequences, on average, were characterized by the two techniques. Using phylogenetic analysis, tests for panmixia and entropy, and Bland-Altman plots, no difference in population structure or genetic diversity was shown in 14 of the 17 subjects. Evidence of sampling bias by the presence of subsets of identical sequences was found by either method. Overall, the study shows that neither method was more biased than the other, and providing that an adequate number of PCR templates is analyzed, and that the bulk sequencing captures the diversity of the viral population, either method is likely to provide a similar measure of population diversity.
doi:10.1016/j.jviromet.2010.04.030
PMCID: PMC3949620  PMID: 20451557
HIV; Single genome sequencing (SGS); pro-pol diversity; cloning and sequencing; treatment naïve
10.  Drug Use and Other Risk Factors Related to Lower Body Mass Index among HIV-Infected Individuals 
Drug and alcohol dependence  2008;95(0):10.1016/j.drugalcdep.2007.12.004.
Malnutrition is associated with morbidity and mortality in HIV infected individuals. Little research has been conducted to identify the roles that clinical, illicit drug use and socioeconomic characteristics play in the nutritional status of HIV-infected patients. This cross-sectional analysis included 562 HIV-infected participants enrolled in the Nutrition for Healthy Living study conducted in Boston, MA and Providence, RI. The relationship between body mass index (BMI) and several covariates (type of drug use, demographic, and clinical characteristics) were examined using linear regression.
Overall, drug users had a lower BMI than non-drug users. The BMI of cocaine users was 1.4 kg/m2 less than that of patients who did not use any drugs, after adjusting for other covariates (p= 0.02). The BMI of participants who were over the age of 55 years was 2.0 kg/m2 less than that of patients under the age of 35, and BMI increased by 0.3 kg/m2 with each 100 cells/mm3 increase in CD4 count. HAART use, adherence to HAART, energy intake, AIDS status, hepatitis B and hepatitis C co-infections, cigarette smoking and depression were not associated with BMI in the final model.
In conclusion, BMI was lower in drug users than non-drug users, and was lowest in cocaine users. BMI was also directly associated with CD4 count and inversely related to age more than 55 years old. HIV infected cocaine users may be at higher risk of developing malnutrition, suggesting the need for anticipatory nutritional support.
doi:10.1016/j.drugalcdep.2007.12.004
PMCID: PMC3837518  PMID: 18243579
drug users; cocaine users; BMI; HIV; CD4 count
11.  HIV-1 Sero-Prevalence and Awareness of Mother-to-Child Transmission Issues Among Women Seeking Antenatal Care in Tamil Nadu, India 
Background
Despite increasing availability of HIV-1 testing, education, and methods to prevent transmission, Indian women and their children remain at risk of acquiring HIV. We assessed the sero-prevalence and awareness about HIV among pregnant women presenting to a private tertiary care hospital in South India.
Methods
Sero-prevalence was determined via enzyme-linked immunosorbent assay (ELISA) testing, and questionnaires were analyzed using chi-square statistics and odds ratios to look for factors associated with HIV positivity.
Results
A total of 7956 women who presented for antenatal care were interviewed. Fifty-one women of the 7235 women who underwent HIV testing (0.7%) were found to be HIV positive. Awareness of mother-to-child transmission (MTCT) of HIV (64%), HIV transmission through breast milk (42%), and prevention of MTCT (13%) was low.
Conclusions
There is a need to educate South Indian women about HIV to give them information and the means to protect themselves and their unborn children from acquiring HIV.
doi:10.1177/1545109710371132
PMCID: PMC3652013  PMID: 20530464
HIV; sero-prevalence; awareness; pregnancy; antenatal; India
12.  Knowledge of HIV Transmission and Associated Factors among HIV-Positive and HIV-Negative Patients in Rural Kenya 
Summary
Knowledge of HIV transmission is a prerequisite to practicing safer behaviors to prevent HIV infections and may be expected to vary by region because of cultural and socioeconomic determinants. A cross-sectional study was conducted in rural Kenya using a standardized questionnaire assessing HIV transmission knowledge, socio-demographic and other characteristics. Participants were recruited from the voluntary counseling and testing clinic and the general hospital population of Moi District Hospital. “High” HIV transmission knowledge scorers (≥ 81%) (Mean score) were compared with “low” scorers (<81%). Bivariate and multivariate logistic regression analyses were performed to examine factors associated with HIV transmission knowledge. Of 214 participants, 70 (33%) were HIV-positive, 104 (49%) were HIV-negative, and 40 (19%) did not know. Factors associated with low knowledge in multivariate analyses were lower education (OR 2.36, CI 1.03–5.46), lower household money on healthcare (OR 2.03, CI 1.28–3.21), higher clinic transportation costs (OR 3.14, CI 1.20–9.82), sex without a condom (OR 2.18, CI 1.12–4.26), positive HIV status vs. negative (OR 2.50, CI 1.22–5.26) and positive HIV status vs. unknown (OR 3.57, CI 1.33–9.09). Mean HIV transmission knowledge score was relatively high; however, a large proportion of patients demonstrated low knowledge. Identifying individuals at risk for low knowledge will support targeted HIV education and prevention programs.
doi:10.4172/2155-6113.1000170
PMCID: PMC3595060  PMID: 23495369
13.  Medication Possession Ratio Associated with Short-Term Virologic Response in Individuals Initiating Antiretroviral Therapy in Namibia 
PLoS ONE  2013;8(2):e56307.
The visual-analogue scale (VAS), Likert item (rating scale), pills identification test (PIT), and medication possession ratio (MPR) provide estimates of antiretroviral therapy (ART) adherence which correlate with HIV viral suppression. These simple adherence measures are inexpensive and easy to administer; however, require validation and adjustment prior to implementation. The objective of this study was to define the optimal adherence assessment measure in Namibia to identify patients at risk for sub-optimal adherence and poor virologic response 6 months after ART initiation. We conducted a cross-sectional survey in HIV-infected adults receiving ART for 6–12 months prior to the adherence assessment. Adherence measures included 30-day VAS, 30-day Likert item, self-reported treatment interruptions, PIT, and MPR. Association of adherence measures with 6-month HIV-1 RNA level was assessed using two thresholds (1000 copies/mL and 5000 copies/mL). Adherence was assessed in 236 patients, mean age 37.3 years, 54% female. Mean adherence was 98.1% by 30-day VAS, 84.7% by 30-day Likert item, 97.0% by self-reported treatment interruptions, 90.6% by PIT, and 98.8% by MPR. Agreement between adherence measures was poor using kappa statistic. 76% had HIV-1 RNA <1000 copies/ml, and 88% had HIV-1 RNA <5000 copies/ml. MPR (continuous) was associated with viral suppression <5000 copies/ml (p = 0.036). MPR <75% was associated with virologic failure at ≥5000 copies/ml with OR 3.89 (1.24, 12.21), p = 0.013. Adherence was high with all measures. Only MPR, was associated with short-term virologic response, suggesting its cross-culturally utility for early identification of patients at high risk for virologic failure.
doi:10.1371/journal.pone.0056307
PMCID: PMC3585291  PMID: 23509605
14.  Antimicrobial Prescribing in the U.S. for Adult Acute Pharyngitis in Relation to Treatment Guidelines 
i. Rationale, aims and objectives
American College of Physicians (ACP) published guidelines for the diagnosis and treatment of acute pharyngitis in adults in 2001. The objective of this study is to characterize antibiotic prescribing patterns in the United States for acute pharyngitis and evaluate concordance with the 2001 ACP pharyngitis treatment guidelines
ii. Methods
Patients aged ≥18 years identified with acute pharyngitis via (ICD-9 CM) diagnosis codes were identified from data collected annually (1996-2006) by the National Center for Health Statistics (NCHS) and Centers for Disease Control and Prevention (CDC) from the National Ambulatory Medical Care Survey (NAMCS) and the National Hospital Ambulatory Medical Care Survey (NHAMCS). Total US office visits for acute pharyngitis were estimated. Logistic regression was performed to determine whether antibiotic prescribing was associated with the publishing of the ACP guidelines.
iii. Results
3,791 office visits met study criteria. We extrapolated 78.0 million visits for acute pharyngitis from 1996-2006. Antibiotics were prescribed in 62.6% of cases and 7.5% of cases received ACP-recommended antibiotics. There was a significant decrease in the rate of antibiotic prescriptions from 66.5% to 59.1% after publication of ACP guidelines. Univariate analysis showed that antibiotic prescribing decreased by 27%, OR=0.73 (0.55-0.95), p=0.021. Multivariate analyses confirmed this finding, OR=0.72 (0.56-0.94), p=0.014. The prescribing of ACP-recommended antibiotics did not significantly change, 8.5% to 6.6% p=0.519.
iv. Conclusions
Publishing of ACP guidelines for the diagnosis and treatment of pharyngitis was associated with a decrease in the overall prescribing of antibiotics but not the prescribing of ACP-recommended antibiotics.
doi:10.1111/j.1365-2753.2010.01495.x
PMCID: PMC2978269  PMID: 20586844
guidelines; infectious disease; pharmacoepidemiology; physician behavior; health education
15.  Malnutrition in a population of HIV-positive and HIV-negative drug users living in Chennai, South India 
Drug and alcohol dependence  2011;118(1):73-77.
Background
Malnutrition is a strong predictor of poor outcomes in people living with HIV (PLHIV). Drug users are at increased risk of malnutrition regardless of whether or not they are infected with HIV. Little data exists on the nutritional status of drug users (with or without HIV infection) in India.
Methods
We describe and compare the nutrition and metabolic status of 107 HIV-positive and 193 HIV-negative male clients of a community-based drop-in center for injection drug users in Chennai, India. Measures of nutrition and metabolic status include body composition, dietary intake, food insecurity, and serum lipid levels.
Results
We found poor overall nutritional status in both the HIV-positive and HIV-negative clients, with HIV-positive men faring worse on some parameters. Both groups had extremely low percent body fat, but levels in HIV-positive participants were significantly lower (6.5% vs. 7.9%, p=.01). HIV-positive men also had significantly lower total caloric and fat intakes compared to HIV-negative men. A considerable proportion (70%) of both HIV-positive and HIV-negative drug users were food insecure. HDL cholesterol levels were significantly lower and below normal range in the HIV-positive compared to HIV-negative men.
Conclusions
The high levels of food insecurity and poor nutritional status in this population, regardless of HIV status, indicates critical need for intervention. Improving nutritional status in those who are infected with HIV prior to initiation of antiretroviral treatment may help patients to reap the full benefits of therapy.
doi:10.1016/j.drugalcdep.2011.02.020
PMCID: PMC3130882  PMID: 21420798
Nutritional status; injection drug users; India; HIV-infection
16.  Repeated assessments of food security predict CD4 change in the setting of antiretroviral therapy 
Food insecurity is highly prevalent in HIV-infected populations, and analyses utilizing multiple assessments of food security to predict CD4 change are lacking. 592 patients with ≥ 4 food security assessments were followed prospectively. In the final model, for patients using antiretroviral therapy, increases in CD4 counts were on average 99.5 cells less for individuals with at least one episode of food insecurity compared to those consistently food secure (P < 0.001). Other sociodemographic factors were not predictive. Repeated assessments of food security are potent predictors of treatment response notwithstanding antiretroviral therapy use. Potential mechanisms for this association are proposed.
doi:10.1097/QAI.0b013e318227f8dd
PMCID: PMC3159819  PMID: 21694604
Food security; Immunological response; Antiretroviral therapy
17.  A Randomized Trial of Raltegravir Replacement for Protease Inhibitor or Non-Nucleoside Reverse Transcriptase Inhibitor in HIV-Infected Women with Lipohypertrophy 
AIDS Patient Care and STDs  2012;26(9):532-540.
Abstract
Lipohypertrophy in HIV-infected patients is associated with metabolic abnormalities. Raltegravir (RAL) is not known to induce fat changes or severe metabolic perturbations. HIV-infected women with central adiposity and HIV-1 RNA less than 50 copies per milliliter on non-nucleoside reverse transcriptase inhibitor (NNRTI)- or protease inhibitor (PI)-based antiretroviral therapy (ART) continued their nucleoside reverse transcriptase inhibitor (NRTI) backbone and were randomized to switch to open label RAL immediately or after 24 weeks. The primary end point was 24-week between-group change in computed tomography (CT)-quantified visceral adipose tissue (AT) volume. Fasting lipids, glucose, C-reactive protein (CRP), anthropometric measurements, and patient-reported quality of life assessments were also measured. Thirty-six subjects provided 80% power to detect a 10% between-group difference in visceral AT over 24 weeks. Thirty-seven of 39 enrolled subjects completed week 24. At entry, subjects were 75% black or Hispanic, and on 62% PI-based and 38% NNRTI-based regimens. The median age was 43 years, CD4 count 558 cells per microliter, and body mass index (BMI) 32 kg/m2. After 24 weeks, no statistically significant changes in visceral or subcutaneous AT, anthropometrics, BMI, glucose, or CRP were observed. In subjects receiving RAL, significant improvements in total and LDL cholesterol (p=0.04), self-reported belly size (p=0.02) and composite body size (p=0.02) were observed. Body size changes correlated well with percent visceral AT change. No RAL-related adverse events occurred. Compared to continued PI or NNRTI, switch to RAL was associated with statistically significant 24-week improvements in total and LDL cholesterol but not AT volumes. Additional insights into AT and metabolic changes in women on RAL will be provided by 48-week follow-up of the immediate-switch arm.
doi:10.1089/apc.2012.0135
PMCID: PMC3426192  PMID: 22823027
18.  Pharmacy Adherence Measures to Assess Adherence to Antiretroviral Therapy: Review of the Literature and Implications for Treatment Monitoring 
Prescription or pill-based methods for estimating adherence to antiretroviral therapy (ART), pharmacy adherence measures (PAMs), are objective estimates calculated from routinely collected pharmacy data. We conducted a literature review to evaluate PAMs, including their association with virological and other clinical outcomes, their efficacy compared with other adherence measures, and factors to consider when selecting a PAM to monitor adherence. PAMs were classified into 3 categories: medication possession ratio (MPR), pill count (PC), and pill pick-up (PPU). Data exist to recommend PAMs over self-reported adherence. PAMs consistently predicted patient outcomes, but additional studies are needed to determine the most predictive PAM parameters. Current evidence suggests that shorter duration of adherence assessment (≤6 months) and use of PAMs to predict future outcomes may be less accurate. PAMs which incorporate the number of days for which ART was prescribed without the counting of remnant pills, are reasonable minimum-resource methods to assess adherence to ART.
doi:10.1093/cid/ciq167
PMCID: PMC3060901  PMID: 21245156
19.  Markers of Atherosclerosis and Inflammation and Mortality in Patients with HIV Infection 
Atherosclerosis  2010;214(2):468-473.
Objective
HIV-infected patients are at increased risk for cardiovascular disease, which may be mediated in part by inflammation. Surrogate marker studies suggest an increased prevalence of vascular abnormalities in HIV infection. We examined the association of all-cause mortality in HIV-infected patients with carotid artery intima-media thickness (cIMT) and high-sensitivity C-reactive protein (hsCRP).
Design and Methods
Baseline risk factors, cIMT and hsCRP were prospectively measured in 327 HIV-infected participants. Follow-up time with median of 3.1 years was calculated from baseline to death or censored dated 7/31/07. Cox Proportional Hazards models were used to study risk factors associated with mortality.
Results
Thirty eight (11.6 %) of participants have died since study enrollment. CIMT was significantly higher in those who died and decedents were significantly more likely to have cIMT above the 75th percentile. Those who died had higher hsCRP than those alive and more had hsCRP values above 3 mg/L. CD4 count was lower and log10 viral load was higher in decedents, but antiretroviral regimens were similar in both groups. CIMT and hsCRP levels were significantly associated with mortality (HR=2.74, 95% CI 1.26 to 5.97, p=0.01; HR=2.38, 95% CI 1.15 to 4.9, p=0.02).
Conclusions
Our study demonstrated a strong association of carotid IMT and hsCRP with all-cause death in this HIV-infected population despite being similar with respect to exposure to antiretroviral medications. Together these surrogate markers may be indices of chronic inflammation and unfavorable outcomes in HIV-positive patients.
doi:10.1016/j.atherosclerosis.2010.11.013
PMCID: PMC3034311  PMID: 21130995
20.  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
21.  Poverty, Hunger, Education, and Residential Status Impact Survival in HIV 
AIDS and behavior  2011;15(7):1503-1511.
Despite combination antiretroviral therapy (ART), HIV infected people have higher mortality than non-infected. Lower socioeconomic status (SES) predicts higher mortality in many chronic illnesses but data in people with HIV is limited. We evaluated 878 HIV infected individuals followed from 1995 to 2005. Cox proportional hazards for all-cause mortality were estimated for SES measures and other factors. Mixed effects analyses examined how SES impacts factors predicting death. The 200 who died were older, had lower CD4 counts, and higher viral loads (VL). Age, transmission category, education, albumin, CD4 counts, VL, hunger, and poverty predicted death in univariate analyses; age, CD4 counts, albumin, VL, and poverty in the multivariable model. Mixed models showed associations between (1) CD4 counts with education and hunger; (2) albumin with education, homelessness, and poverty; and (3) VL with education and hunger. SES contributes to mortality in HIV infected persons directly and indirectly, and should be a target of health policy in this population.
doi:10.1007/s10461-010-9759-z
PMCID: PMC3010417  PMID: 20632079
HIV; Socioeconomic status; Mortality
22.  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
23.  Circulating Nef Induces Dyslipidemia in SIV-Infected Macaques by Suppressing Cholesterol Efflux 
The Journal of infectious diseases  2010;202(4):614-623.
HIV infection and subsequent antiretroviral therapy have been associated with an increased incidence of dyslipidemia and cardiovascular disease and has been shown to suppress cholesterol efflux from virus-infected macrophages by inducing Nef-dependent downregulation of ABCA1. The SIV/macaque model was used to examine consequences and mechanisms involved. SIV infection drove a significant remodeling of high-density lipoprotein profiles suggesting systemic inhibition of the ABCA1-dependent reverse cholesterol transport pathway. The ABCA1 cholesterol transporter was significantly down regulated in the livers of the SIV-infected macaques and the viral protein Nef could be detected in the liver as well as in plasma of infected animals. Extracellular myristoylated HIV Nef inhibited cholesterol efflux from macrophages and hepatocytes. Moreover, sera from SIV-infected macaques also suppressed cholesterol efflux in a Nef-dependent fashion. These results indicate that SIV infection is a significant contributor to primary dyslipidemia, likely through the ability of Nef to suppress ABCA1-dependent reverse cholesterol transport.
doi:10.1086/654817
PMCID: PMC2932757  PMID: 20617930
HIV; SIV; ABCA1; Nef; atherosclerosis
24.  Predictors of Weight Change in Male HIV-Positive Injection Drug Users Initiating Antiretroviral Therapy in Hanoi, Vietnam 
AIDS Research and Treatment  2011;2011:890308.
We examined clinical and nutritional predictors of weight change over two consecutive 6-month intervals among 99 HIV-positive male injection drug users initiating antiretroviral therapy (ART) in Hanoi, Vietnam. The average weight gain was 3.1 ± 4.8 kg in the first six months after ART and 0.8 ± 3.0 kg in the following six months. Predictors of weight change differed by interval. In the first interval, CD4 < 200 cells/μL, excellent/very good adherence to ART, bothersome nausea, and liquid supplement use were all associated with positive weight changes. Moderate to heavy alcohol use and tobacco smoking were associated with negative weight changes. In the second interval, having a CD4 count <200 cells/μL at the beginning of the interval and tobacco smoking were the only significant predictors and both were associated with negative weight changes. We identified several potential areas for interventions to promote weight gain immediately after starting ART in this population. Studies are needed to determine whether improving weight prior to, or at, ART initiation will result in improved outcomes on ART.
doi:10.1155/2011/890308
PMCID: PMC3137978  PMID: 21776380
25.  Dyslipidemia among HIV-infected Patients with Tuberculosis Taking Once-daily Nonnucleoside Reverse-Transcriptase Inhibitor–Based Antiretroviral Therapy in India 
HIV-infected patients with tuberculosis who initiate nonnucleoside reverse-transcriptase-based anti-retroviral treatment in combination with rifampicin-based antituberculosis treatment demonstrate increases in total cholesterol, low-density cholesterol, and high-density cholesterol levels but no change in blood glucose level after 1 year. Cholesterol increases were more frequent among patients receiving efavirenz.
Background. Our aim was to study the incidence and pattern of dyslipidemia among human immunodeficiency virus (HIV)–infected patients with tuberculosis (TB) who received once-daily antiretroviral therapy (ART).
Methods. Antiretroviral-naive HIV-infected patients with TB were recruited to a trial of once-daily nonnucleoside reverse-transcriptase inhibitor (NNRTI)–based ART and treated with rifampicin-based thrice-weekly antituberculosis treatment (ATT); participants were randomized to receive didanosine (250/400 mg) and lamivudine (300 mg) with either efavirenz (600 mg) or nevirapine (400 mg) once-daily after an intensive phase of ATT. Fasting triglyceride (TG) level, total cholesterol (TC) level, low-density cholesterol (LDL-c) level and high-density cholesterol (HDL-c) level were measured at baseline and at 6 and 12 months. Lipid levels at 6 and 12 months were compared with baseline values with use of repeated measures analyses. McNemar test was used to compare the proportion of patients with lipid abnormality at baseline versus at 12 months, and χ2 test was used to compare between the 2 groups.
Results. Of 168 patients (79% men; mean age, 36 years; mean weight, 42 kg; median CD4+ cell count, 93 cells/mm3), 104 received efavirenz-based ART, and 64 received nevirapine-based ART. After 6 months, TC levels increased by 49 mg/dL, LDL-c levels by 30 mg/dL, and HDL-c levels increased by 18 mg/dL (P < .001 for all). At baseline and at 12 months, TC was >200 mg/dL for 1% and 26% of patients, respectively; LDL-c level was >130 mg/dL for 3% and 23%, respectively; HDL-c level was <40 mg/dL for 91% and 23%, respectively; and blood glucose level was >110 mg/dL for 14% and 13%, respectively. TC level >200 mg/dL was more common among patients who received efavirenz than among those who received nevirapine (32% vs 16%; P = .04).
Conclusions. HIV-infected patients with TB who initiate NNRTI-based ART undergo complex changes in lipid profile, highlighting the importance of screening and treating other cardiovascular disease risk factors in this population.
doi:10.1093/cid/ciq195
PMCID: PMC3060904  PMID: 21252141

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