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1.  Developing an adherence support intervention for patients on antiretroviral therapy in the context of the recent IDU-driven HIV/AIDS epidemic in Estonia 
AIDS care  2013;25(7):863-873.
There is limited data on and experience with interventions for antiretroviral therapy (ART) adherence support for patients on ART in Eastern Europe. We sought to identify a feasible adherence support intervention for delivery amongst HIV-positive adults receiving care in Estonia, where the HIV/AIDS epidemic has been mainly concentrated among injection drug users. Our application of intervention mapping strategies used existing literature, formative research and multidisciplinary team input to produce a brief clinic-based intervention entitled the Situated Optimal Adherence Intervention Estonia (sOAI Estonia) which uses both Next-Step Counseling and Information-Motivation-Behavioral Skills Model approach to facilitate integration of ART into the context and demands of daily life. We present the intervention development process, the resulting sOAI Estonia approach, and describe a randomized controlled trial which is underway to evaluate the intervention (results due in spring 2013).
doi:10.1080/09540121.2013.764393
PMCID: PMC3651786  PMID: 23391132
ART; HAART; adherence; intervention
2.  Interruption or deferral of antiretroviral therapy reduces markers of bone turnover compared with continuous therapy: the SMART Body Composition Substudy 
Bone mineral density (BMD) declines significantly in HIV patients on antiretroviral therapy (ART). We compared the effects of intermittent versus continuous ART on markers of bone turnover in the Body Composition substudy of the Strategies for Management of AntiRetroviral Therapy (SMART) trial and determined whether early changes in markers predicted subsequent change in BMD. For 202 participants (median age 44 years, 17% female, 74% on ART) randomised to continuous or intermittent ART, plasma markers of inflammation and bone turnover were evaluated at baseline, months 4 and 12; BMD at the spine (dual X-ray absorptiometry [DXA] and computed tomography) and hip (DXA) was evaluated annually. Compared to the continuous ART group, mean bone-specific alkaline phosphatase (bALP), osteocalcin, procollagen type 1 N-terminal propeptide (P1NP), N-terminal cross-linking telopeptide of type 1 collagen (NTX), and C-terminal cross-linking telopeptide of type 1 collagen (βCTX) decreased significantly in the intermittent ART group, whereas RANKL and the RANKL:osteoprotegerin (OPG) ratio increased (all p≤0.002 at month 4 and month 12). Increases in bALP, osteocalcin, P1NP, NTX, and βCTX at month 4 predicted decrease in hip BMD at month 12, while increases in RANKL and the RANKL:OPG ratio at month 4 predicted increase in hip and spine BMD at month 12. This study has shown that compared with continuous ART, interruption of ART results in a reduction in markers of bone turnover and increase in BMD at hip and spine, and that early changes in markers of bone turnover predict BMD changes at 12 months.
doi:10.1002/jbmr.1861
PMCID: PMC3657331  PMID: 23299909
HIV; bone mineral density; antiretroviral therapy; bone turnover marker
3.  Vitamin D and Insulin Resistance in Non-Diabetic Women's Interagency HIV Study Participants 
AIDS Patient Care and STDs  2013;27(6):320-325.
Abstract
We explored the relationship between vitamin D levels and insulin resistance (IR) among 1082 nondiabetic (754 HIV-infected) women enrolled in the Women's Interagency HIV study (WIHS), a large and well-established cohort of HIV infected and uninfected women in the US. Vitamin D levels 20–29 ng/mL were considered insufficient and <20 ng/mL deficient. IR was estimated using the homeostasis model assessment (HOMA) and a clinically significant cut-off ≥2.6 was used for HOMA-IR. In the unadjusted analysis, women who were vitamin D insufficient or deficient were 1.62 (95% CI: 1.01–2.61, p=0.05) and 1.70 (95% CI: 1.11–2.60, p=0.02) times more likely to have HOMA values≥2.6 compared to women with sufficient vitamin D. The association did not remain significant after adjustment for factors associated with IR. Among the 754 HIV-infected women, current PI use (OR 1.61, 95% CI: 1.13–2.28, p=0.008) remained independently associated with HOMA ≥2.6 while vitamin D insufficiency (OR 1.80, 95% CI: 0.99–3.27, p=0.05) was marginally associated with HOMA ≥2.6 after adjustment. Ethnicity, body mass index, smoking status, and hepatitis C status were independently associated with insulin resistance in HIV-infected and uninfected women. We found a marginally significant association between vitamin D insufficiency and insulin resistance among nondiabetic HIV-infected WIHS women.
doi:10.1089/apc.2012.0400
PMCID: PMC3671624  PMID: 23675750
4.  Relationship of vitamin D, HIV, HIV treatment and lipid levels in the Women’s Interagency HIV study (WIHS) of HIV-infected and un-infected women in the US 
Relationships between vitamin D, lipids, HIV infection, and HIV treatment (±ART) were investigated with Women’s Interagency HIV Study data (n=1758 middle-aged women) using multivariable regression. 63 % had vitamin D deficiency. Median 25-OH vitamin D was highest in HIV-infected +ART-treated women (17 ng/mL, p<0.001), but the same in HIV-uninfected or HIV-infected without ART (14 ng/mL). Vitamin D levels were lower if ART included efavirenz (15 vs 19 ng/mL, p<0.001). The most common lipid abnormality was high triglycerides (≥200 mg/dL) in HIV-infected +ART, (13%, vs 7% of HIV-infected without ART and 5% of HIV-uninfected (p<0.001) with a positive relationship between 25-OH-D and triglycerides (95% confidence interval 0.32 to 1.69, p<.01). No relationships between 25-OH-D and cholesterol were detected. Vitamin D deficiency is common irrespective of HIV status but influenced by HIV treatment. Similarly, vitamin D levels were positively related to triglycerides only in ART treated HIV infected, and unrelated to cholesterol.
doi:10.1177/2325957413506748
PMCID: PMC4016117  PMID: 24668135
Vitamin D; lipids; HIV infected; HIV uninfected; 25-OH vitamin D; cholesterol; LDL-cholesterol; triglycerides; lipids; WIHS
5.  Tenofovir use and urinary biomarkers among HIV-infected women in the Women's Interagency HIV Study (WIHS) 
Background
Tenofovir has been associated with renal tubular injury. Biomarkers that signal early tubular dysfunction are needed because creatinine rise lags behind tenofovir-associated kidney dysfunction. We examined several urinary biomarkers to determine if rises accompanying tenofovir initiation preceded creatinine changes.
Methods
Three urinary biomarkers of tubular impairment- neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl- β -D-glucosaminidase (NAG), and β-2-microglobulin (β2MG)-were measured across three time points (one pre-tenofovir visit and two post tenofovir visits) in one hundred and thirty two HIV-positive women from the Women's Interagency HIV Study (WIHS). Women initiating HAART containing tenofovir were propensity score matched to women initiating HAART without tenofovir and women not on HAART.
Results
There were no differences between groups for NGAL or NAG but β2MG was 19 times more likely to be elevated among tenofovir users at the 2nd post tenofovir visit compared to non-TDF users at the pre-tenofovir visit (p<0.01). History of proteinuria was associated with elevated NGAL (p <0.01). Factors associated with elevated NAG were GFR<60 ml/min, history of proteinuria, hepatitis C (p<0.01 for all) and diabetes mellitus (p=0.05). Factors associated with increased odds of elevated β2MG were HIV RNA>100,000 copies/ml, hepatitis C, boosted protease inhibitor (PI) use, and GFR<60 ml/min (p≤0.01 for all).
Conclusions
β2MG levels are elevated in women on tenofovir indicating probable early renal dysfunction. Biomarker elevation is additionally associated with baseline chronic kidney disease, uncontrolled viremia, and boosted PI use. Future studies are needed to explore urinary biomarker thresholds in identifying treated HIV-infected individuals at risk for renal dysfunction.
doi:10.1097/QAI.0b013e31828175c9
PMCID: PMC3692572  PMID: 23254151
Tenofovir; urinary biomarkers; HIV infected women
6.  Nurse Task Shifting for Antiretroviral Treatment Services in Namibia: Implementation Research to Move Evidence into Action 
PLoS ONE  2014;9(3):e92014.
Background
Evidence from several sub-Saharan countries support nurse-initiated antiretroviral treatment as a feasible alternative to doctor-led models characteristic of early responses to the HIV epidemic. However, service delivery models shown to be effective in one country may not be readily adopted in another. This study used an implementation research approach to assist policy makers and other stakeholders to assess the acceptability and feasibility of task shifting in the Namibian context.
Methods
The Namibian Ministry of Health and Social Services implemented a Task Shifting Demonstration Project (TSDP) at 9 sites at different levels of the health system. Six months after implementation, a mixed methods evaluation was conducted. Seventy semi-structured interviews were conducted with patients, managers, doctors and nurses directly involved with the TSDP. Physician-evaluators observed and compared health service provision between doctors and nurses for 40 patients (80 observations), documenting performance in agreement with the national guidelines on 13 clinical care indicators.
Results
Doctors, nurses, and patients interviewed believed task shifting would improve access to and quality of HIV services. Doctors and nurses both reported an increase in nurses’ skills as a result of the project. Observation data showed doctors and nurses were in considerable agreement (>80%) with each other on all dimensions of HIV care and ≥90% on eight dimensions. To ensure success of national scale-up of the task shifting model, challenges involving infrastructure, on-going mentoring, and nursing scope of practice should be anticipated and addressed.
Conclusion
In combination with findings from other studies in the region, data from the TSDP provided critical and timely information to the Namibian Ministry of Health and Social Services, thus helping to move evidence into action. Small-scale implementation research projects enable stakeholders to learn by doing, and provide an opportunity to test and modify the intervention before expansion.
doi:10.1371/journal.pone.0092014
PMCID: PMC3958436  PMID: 24642894
7.  Does HIV infection promote early kidney injury in women? 
Antiviral therapy  2013;19(1):79-87.
Background
In HIV-infected women, urine concentrations of novel tubulointerstitial injury markers, interleukin-18 (IL-18) and kidney injury marker-1 (KIM-1) are associated with kidney function decline and all-cause mortality. We hypothesized that HIV-infected individuals with preserved kidney filtration function would have more extensive kidney injury, as determined by urine injury markers, compared to the uninfected controls, and that risk factors for tubulointerstitial injury would differ from risk factors for albuminuria.
Methods
In this cross-sectional study, we compared urine concentrations of IL-18, KIM-1, and ACR in 908 HIV-infected and 289 HIV-uninfected women enrolled in the Women’s Interagency HIV Study, utilizing stored urine specimens from visits between 1999 and 2000.
Results
After multivariate-adjusted linear regression analysis, mean urine concentrations were higher in HIV-infected individuals by 38% for IL-18 (p<0.0001), 12% for KIM-1 (p=0.081), and 47% for ACR (p<0.0001). Higher HIV RNA level (15% per 10-fold increase, p<0.0001), lower CD4 count (8% per doubling, p=0.0025), HCV infection (30%, p=0.00018), and lower HDL (5% per 10 mg/dL, p=0.0024) were each associated with higher IL-18 concentrations. In contrast, hypertension (81%, p<0.0001) and diabetes (47%, p=0.018) were among the strongest predictors of higher ACR, though HIV RNA level (15% per 10-fold increase, p=0.0004) was also associated with higher ACR.
Conclusions
HIV-infected women had more extensive tubulointerstitial and glomerular injury than uninfected women, but the associated factors differed among the urine biomarkers. Combinations of urinary biomarkers should be investigated to further characterize early kidney injury in HIV-infected women.
doi:10.3851/IMP2677
PMCID: PMC3933452  PMID: 23970313
8.  Hemoglobin E Syndromes: Emerging Diagnostic Challenge in North India 
Hemoglobin E (HbE) is one of the world’s most common and important mutations. HbE disorders may be found in heterozygous (AE), homozygous (EE) and compound heterozygous state. It is important to distinguish HbE disorders diagnostically because of marked differences in clinical course among different genotypes. To find out whether RBC indices as obtained from automated cell counter can provide a clue to the diagnosis of HbE disease. This study was carried out in the Department of Clinical Pathology, PGIMER, Dr. Ram Manohar Lohia Hospital, New Delhi. It included antenatal pregnant females brought for routine check-up as well as referred patients suspected of having hemoglobinopathies. High Performance liquid chromatography was used as a confirmatory test for identification of hemoglobinopathy. Total 20 cases of subtype homozygous HbE (3), HbE trait (12) and Eβ-thalassemia (5) were identified. Statistical analysis was done to find out correlation between levels of HBA2, HBF with RBC indices. (a) There was negative correlation between HbA2/E peak values and RBC indices (Mean corpuscular volume (MCV) and Mean corpuscular hemoglobin) among all the three groups taken together. (b) There was positive correlation between HbA2/E and Red cell distribution width (RDW). (c) There was positive correlation between HbF values with MCV. The finding of positive correlation between HbA2/E and RDW may help in differentiating βthal (RDW normal) from HbE/βthal. In a patient with microcytic hypochromic blood picture and increased RDW, diagnosis of HbE/βthal should also be considered along with the more common Iron deficiency anemia. Thus, new insights into the knowledge of these diseases are important because they impart diagnostic challenges to all the experts involved in the treatment of anemic patients.
doi:10.1007/s12288-011-0140-9
PMCID: PMC3572259  PMID: 24426328
Hemoglobinopathy; HPLC; RBC indices; Hemoglobin E; Thallasemia
9.  Comparisons of creatinine and cystatin C for detection of kidney disease and prediction of all-cause mortality in HIV-infected women 
AIDS (London, England)  2013;27(14):2291-2299.
Background
Cystatin C could improve chronic kidney disease (CKD) classification in HIV-infected women relative to serum creatinine.
Design
Retrospective cohort analysis.
Methods
Cystatin C and creatinine were measured from specimens taken and stored during the 1999–2000 exam among 908 HIV-infected participants in the Women’s Interagency HIV study (WIHS). Mean follow-up was 10.2 years. The associations of baseline categories (<60, 60–90, and >90 mL/min/1.73m2) of creatinine eGFR (eGFRcr), cystatin C eGFR (eGFRcys), and combined creatinine-cystatin C eGFR (eGFRcr-cys) with all-cause mortality were evaluated using multivariable Cox regression. The net reclassification index (NRI) was calculated to evaluate the effect of cystatin C on reclassification of CKD staging.
Results
The prevalence of CKD (eGFR<60) at baseline was higher with eGFRcys (10.1%) compared to eGFRcr (6.7%, p=0.0006) and eGFRcr-cys (7.5%, p=0.011). Relative to eGFR >90, the eGFR <60 category by eGFRcys (Adjusted HR: 2.56; 95% CI: 1.63, 4.02), eGFRcr-cys (3.11; 1.94–5.00), and eGFRcr (2.34; 1.44–3.79) was associated with increased mortality risk. However, the eGFR 60–90 category was associated with increased mortality risk for eGFRcys (1.80; 1.28–2.53) and eGFRcr-cys (1.91; 1.38–2.66) but not eGFRcr (1.20; 0.85–1.67). The overall NRI for mortality was 26% when reclassifying from eGFRcr to eGFRcys (p<0.001) and was 20% when reclassifying from eGFRcr to eGFRcr-cys (p<0.001).
Conclusion
Cystatin C detected a higher prevalence of CKD relative to creatinine and improves CKD staging relative to creatinine by reclassifying individuals at the highest mortality risk to lower eGFR categories.
doi:10.1097/QAD.0b013e328362e874
PMCID: PMC3919542  PMID: 23669156
Creatinine; Cystatin C; Glomerular Filtration Rate; HIV; Mortality; Kidney; Women
10.  Improving the quality of health information: a qualitative assessment of data management and reporting systems in Botswana 
Background
Ensuring that data collected through national health information systems are of sufficient quality for meaningful interpretation is a challenge in many resource-limited countries. An assessment was conducted to identify strengths and weaknesses of the health data management and reporting systems that capture and transfer routine monitoring and evaluation (M&E) data in Botswana.
Methods
This was a descriptive, qualitative assessment. In-depth interviews were conducted at the national (n = 27), district (n = 31), and facility/community (n = 71) levels to assess i) M&E structures, functions, and capabilities; ii) indicator definitions and reporting guidelines; iii) data collection forms and tools; iv) data management processes; and v) links with the national reporting system. A framework analysis was conducted using ATLAS.ti v6.1.
Results
Health programs generally had standardized data collection and reporting tools and defined personnel for M&E responsibilities at the national and district levels. Best practices unique to individual health programs were identified and included a variety of relatively low-resource initiatives such as attention to staffing patterns, making health data more accessible for evidence-based decision-making, developing a single source of information related to indicator definitions, data collection tools, and management processes, and utilization of supportive supervision visits to districts and facilities. Weakness included limited ownership of M&E-related duties within facilities, a lack of tertiary training programs to build M&E skills, few standard practices related to confidentiality and document storage, limited dissemination of indicator definitions, and limited functionality of electronic data management systems.
Conclusions
Addressing fundamental M&E system issues, further standardization of M&E practices, and increasing health services management responsiveness to time-sensitive information are critical to sustain progress related to health service delivery in Botswana. In addition to high-resource initiatives, such as investments in electronic medical record systems and tertiary training programs, there are a variety of low-resource initiatives, such as regular data quality checks, that can strengthen national health information systems. Applying best practices that are effective within one health program to data management and reporting systems of other programs is a practical approach for strengthening health informatics and improving data quality.
doi:10.1186/1478-4505-12-7
PMCID: PMC3910237  PMID: 24479822
Data quality; Health information system; Monitoring and evaluation
11.  Vitamin D insufficiency may impair CD4 recovery among Women’s Interagency HIV Study participants with advanced disease on HAART 
AIDS (London, England)  2013;27(4):573-578.
Background
Recent studies in HIV-infected men report an association between low vitamin D (25OH-D) and CD4 recovery on HAART. We sought to test this relationship in the Women’s Interagency HIV Study (WIHS).
Methods
We examined 204 HIV-infected women with advanced disease, who started HAART after enrollment in the WIHS. We measured vitamin D (25OH-D) levels about 6 months prior to HAART initiation. The relationship between CD4 recovery (defined as increases of ≥50, 100, and 200 cells at 6, 12, and 24 months) and exposure variables was examined using logistic regression models at 6, 12 and 24 months post-HAART initiation in unadjusted and adjusted analyses, and using multivariable longitudinal Generalized Estimating Equations (GEE). Vitamin D insufficiency was defined as 25OH-D levels at least 30 ng/ml.
Results
The majority were non-Hispanic black (60%) and had insufficient vitamin D levels (89%). In adjusted analyses, at 24 months after HAART, insufficient vitamin D level (OR 0.20, 95% CI 0.05–0.83) was associated with decreased odds of CD4 recovery. The undetectable viral load (OR 11.38, 95% CI 4.31–30.05) was associated with CD4 recovery. The multivariable GEE model found that average immune reconstitution attenuated significantly (P <0.01) over time among those with insufficient vitamin D levels compared with those with sufficient vitamin D levels.
Conclusion
Vitamin D insufficiency is associated with diminished late CD4 recovery after HAART initiation among US women living with advanced HIV. The mechanism of this association on late CD4 recovery may be late vitamin D-associated production of naive CD4 cells during immune reconstitution.
doi:10.1097/QAD.0b013e32835b9ba1
PMCID: PMC3902982  PMID: 23095316
antiretroviral therapy; HIV; immune reconstitution; vitamin D; women
12.  Urinary Markers of Kidney Injury and Kidney Function Decline in HIV-Infected Women 
Objective
HIV-infected persons have substantially higher risk of kidney failure than persons without HIV, but serum creatinine levels are insensitive for detecting declining kidney function. We hypothesized that urine markers of kidney injury would be associated with declining kidney function among HIV-infected women.
Methods
In the Women's Interagency HIV Study (WIHS), we measured concentrations of albumin-to-creatinine ratio (ACR), interleukin-18 (IL-18), kidney injury marker-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) from stored urine among 908 HIV-infected and 289 uninfected participants. Primary analyses used cystatin C based estimated glomerular filtration rate (CKD-EPI eGFRcys) as the outcome, measured at baseline and two follow-up visits over eight years; secondary analyses used creatinine (CKD-EPI eGFRcr). Each urine biomarker was categorized into tertiles, and kidney decline was modeled with both continuous and dichotomized outcomes.
Results
Compared with the lowest tertiles, the highest tertiles of ACR (−0.15ml/min/1.73m2, p<0.0001), IL-18 (−0.09ml/min/1.73m2, p<0.0001) and KIM-1 (−0.06ml/min/1.73m2, p<0.001) were independently associated with faster eGFRcys decline after multivariate adjustment including all three biomarkers among HIV-infected women. Among these biomarkers, only IL-18 was associated with each dichotomized eGFRcys outcome: ≥3% (Relative Risk 1.40; 95%CI 1.04-1.89); ≥5% (1.88; 1.30-2.71); and ≥10% (2.16; 1.20-3.88) for the highest versus lowest tertile. In alternative models using eGFRcr, the high tertile of KIM-1 had independent associations with 5% (1.71; 1.25-2.33) and 10% (1.78; 1.07-2.96) decline, and the high IL-18 tertile with 10% decline (1.97; 1.00-3.87).
Conclusions
Among HIV-infected women in the WIHS cohort, novel urine markers of kidney injury detect risk for subsequent declines in kidney function.
doi:10.1097/QAI.0b013e3182737706
PMCID: PMC3509242  PMID: 23023103
HIV; KIM-1; NGAL; IL-18; albumin-to-creatinine ratio; cystatin C; kidney injury
13.  Building sustainable organizational capacity to deliver HIV programs in resource-constrained settings: stakeholder perspectives 
Global Health Action  2013;6:10.3402/gha.v6i0.22571.
Background
In 2008, the US government mandated that HIV/AIDS care and treatment programs funded by the US President's Emergency Plan for AIDS Relief (PEPFAR) should shift from US-based international partners (IPs) to registered locally owned organizations (local partners, or LPs). The US Health Resources and Services Administration (HRSA) developed the Clinical Assessment for Systems Strengthening (ClASS) framework for technical assistance in resource-constrained settings. The ClASS framework involves all stakeholders in the identification of LPs’ strengths and needs for technical assistance.
Objective
This article examines the role of ClASS in building capacity of LPs that can endure and adapt to changing financial and policy environments.
Design
All stakeholders (n=68) in Kenya, Zambia, and Nigeria who had participated in the ClASS from LPs and IPs, the US Centers for Disease Control and Prevention (CDC), and, in Nigeria, HIV/AIDS treatment facilities (TFs) were interviewed individually or in groups (n=42) using an open-ended interview guide. Thematic analysis revealed stakeholder perspectives on ClASS-initiated changes and their sustainability.
Results
Local organizations were motivated to make changes in internal operations with the ClASS approach, PEPFAR's competitive funding climate, organizational goals, and desired patient health outcomes. Local organizations drew on internal resources and, if needed, technical assistance from IPs. Reportedly, ClASS-initiated changes and remedial action plans made LPs more competitive for PEPFAR funding. LPs also attributed their successful funding applications to their preexisting systems and reputation. Bureaucracy, complex and competing tasks, and staff attrition impeded progress toward the desired changes. Although CDC continues to provide technical assistance through IPs, declining PEPFAR funds threaten the consolidation of gains, smooth program transition, and continuity of treatment services.
Conclusions
The well-timed adaptation and implementation of ClASS successfully engaged stakeholders who committed their own resources toward strengthening organizational capacity. The sustainability of built capacity depends on continued investment in leadership, staff retention, and quality improvement.
doi:10.3402/gha.v6i0.22571
PMCID: PMC3864159  PMID: 24331715
local partner; capacity building; participatory assessment; technical assistance; HIV/AIDS; program transition
14.  Association of Regional Body Composition with Bone Mineral Density in HIV-infected and Uninfected Women: Women's Interagency HIV Study 
Objective
To understand how regional body composition affects bone mineral density (BMD) in HIV-infected and uninfected women.
Methods
Dual energy X-ray absorptiometry was used to measure regional lean and fat mass and BMD at lumbar spine (LS), total hip (TH), and femoral neck (FN) in 318 HIV-infected and 122 HIV-uninfected Women's Interagency HIV Study participants at baseline and 2 and 5 years later. Total lean and fat mass were measured using bioimpedance analysis. Multivariate marginal linear regression models assessed the association of HIV status and body composition on BMD change.
Results
Compared to HIV-uninfected women, HIV-infected women were older (44 vs. 37 yrs), more likely to be HCV-infected (32% vs. 14%), and post-menopausal (26% vs. 3%), and had lower baseline total fat mass, trunk fat and leg fat. In multivariate models, increased total lean mass was independently associated with increased BMD at LS, TH and FN and total fat mass was associated with increased BMD at TH and FN (all p<0.05). When total fat was replaced in multivariate models with trunk fat and leg fat, increased trunk fat (and not leg fat) was associated with increased TH and FN BMD (p<0.001).
Conclusions
Total fat and lean mass are strong, independent predictors of TH and FN BMD, and lean mass was associated with greater LS BMD. Regardless of HIV status, greater trunk fat (and not leg fat) was associated with increased TH and FN BMD, suggesting that weight bearing fat may be a more important predictor of BMD in the hip.
doi:10.1097/QAI.0b013e31826cba6c
PMCID: PMC3494812  PMID: 22895436
Body composition; fat redistribution; bone mineral density; HIV; women
15.  Association of HIV infection with Incident Diabetes Mellitus: Impact of using Hemoglobin A1C as a Criterion for Diabetes 
Background
Data regarding the association between HIV and DM are conflicting, with little known regarding the impact of including hemoglobin A1C (A1C) as a criterion for DM.
Methods
Pooled logistic regression was used to quantify the association between HIV and DM in 1501 HIV-infected and 550 HIV-uninfected participants from the Women’s Interagency HIV Study. Incident DM was defined using three DM definitions: (I) fasting glucose (FG) ≥126mg/dl, anti-DM medication, or reporting DM diagnosis (with confirmation by FG≥126mg/dl or anti-DM medication); (II) confirmation with a second FG≥126mg/dl; and (III) addition of A1C≥6.5% confirmed by FG≥126mg/dl or anti-DM medication.
Results
DM incidence per 100 person-years was 2.44, 1.55, and 1.70 for HIV-infected women; 1.89, 0.85, and 1.13 for HIV-uninfected women, using definition I, II, and III, respectively. After adjustment for traditional DM risk factors, HIV infection was associated with 1.23, 1.90, and 1.38-fold higher risk of incident DM, respectively; the association reached statistical significance only when confirmation with a second FG≥126mg/dl was required. Older age, obesity, and a family history of DM were each consistently and strongly associated with increased DM risk.
Conclusions
HIV infection is consistently associated with greater risk of DM. Inclusion of an elevated A1C to define DM increases the accuracy of the diagnosis and only slightly attenuates the magnitude of the association otherwise observed between HIV and DM. By contrast, a DM diagnosis made without any confirmatory criteria for FG ≥126mg/dl overestimates the incidence, while also underestimating the effects of HIV on DM risk, and should be avoided.
doi:10.1097/QAI.0b013e31826bfc32
PMCID: PMC3480977  PMID: 22878421
Diabetes mellitus; HIV; Women; Hemoglobin A1C
16.  Crosstalk between DnaA Protein, the Initiator of Escherichia coli Chromosomal Replication, and Acidic Phospholipids Present in Bacterial Membranes 
Anionic (i.e., acidic) phospholipids such as phosphotidylglycerol (PG) and cardiolipin (CL), participate in several cellular functions. Here we review intriguing in vitro and in vivo evidence that suggest emergent roles for acidic phospholipids in regulating DnaA protein-mediated initiation of Escherichia coli chromosomal replication. In vitro acidic phospholipids in a fluid bilayer promote the conversion of inactive ADP-DnaA to replicatively proficient ATP-DnaA, yet both PG and CL also can inhibit the DNA-binding activity of DnaA protein. We discuss how cellular acidic phospholipids may positively and negatively influence the initiation activity of DnaA protein to help assure chromosomal replication occurs once, but only once, per cell-cycle. Fluorescence microscopy has revealed that PG and CL exist in domains located at the cell poles and mid-cell, and several studies link membrane curvature with sub-cellular localization of various integral and peripheral membrane proteins. E. coli DnaA itself is found at the cell membrane and forms helical structures along the longitudinal axis of the cell. We propose that there is cross-talk between acidic phospholipids in the bacterial membrane and DnaA protein as a means to help control the spatial and temporal regulation of chromosomal replication in bacteria.
doi:10.3390/ijms14048517
PMCID: PMC3645759  PMID: 23595001
acidic phospholipids; DnaA protein; chromosomal replication; Escherichia coli
17.  Association of Hematological Profile of Human Immunodeficiency Virus-Positive Patients with Clinicoimmunologic Stages of the Disease 
Aim:
This work was carried out to study the hematologic profile of human immunodeficiency virus (HIV)-positive patients and its association with the clinicoimmunologic stage of the disease.
Materials and Methods:
A total of 187 patients with HIV, whether symptomatic or asymptomatic, diagnosed by enzyme-linked immunosorbent assay (ELISA) method according to the National AIDS Control Organization (NACO) guidelines were included in this study. Patients in the study population were divided into two groups: (1) Group A (antiretroviral therapy (ART) included patients receiving ART [ART-Y]) and (2) Group B included treatment naïve patients (ART-N). The patients were tested for hemoglobin (Hb), total red blood cells (RBC) count, RBC indices, reticulocyte count, packed cell volume (PCV), total lymphocyte counts(TLC), differential leukocyte counts (DLC), platelet count, and erythrocyte sedimentation rate (ESR). Cut-off values were determined as Hb < 10 g/dl, platelet count < 1.5 lakh/cumm, and TLC < 4,000/cumm. The group or categorical data were tested for statistical significance using Chi-square test and Z-test. The difference was reported as significant if P < 0.05.
Results:
(1) Anemia (predominantly normocytic normochromic) was prevalent in 40.1%, with slightly higher prevalence in those not receiving ART. It occurred with high frequency in patients with immunological (42.05%) and clinical acquired immunodeficiency disease syndrome (AIDS) (70.58%) compared with those who had an asymptomatic HIV infection with CD4 > 200/μl (28.57%). Patients on zidovudine (AZT) therapy had 34.6% anemia with increased mean corpuscular volume (MCV). (2) Thrombocytopenia was seen in 3.74% patients (higher percentage in untreated patients). (3) Leucopenia was observed in 5.88% in ART-Y (Group A) and 8.14% in ART-N (Group B) patients. (4) Pancytopenia was found in 1.6% patients.
doi:10.4103/0974-2727.115929
PMCID: PMC3758702  PMID: 24014966
Anemia; art; clinicoimmunologic stage; human immunodeficiency virus
18.  Prospective Evaluation of Bone Mineral Density among Middle-Aged HIV-Infected and Uninfected Women: Association between Methadone Use and Bone Loss 
Maturitas  2011;70(3):295-301.
Objective
We undertook a prospective study to assess the impact of HIV infection on BMD in a cohort of HIV-infected and uninfected women that included illicit drug users, and to measure the contribution of traditional risk factors as well as HIV-related factors to loss of BMD over time.
Methods
We analyzed BMD at baseline and after ≥18 months in 245 middle-aged HIV-infected and 219 uninfected women, and conducted linear regression analysis to determine factors associated with annual BMD change at the femoral neck, total hip and lumbar spine.
Results
HIV-infected women had lower baseline BMD at the femoral neck and total hip compared with controls; unadjusted rates of BMD change did not differ by HIV status at any site. In multivariable analyses, we found that HIV seropositivity without protease inhibitor (PI) use was associated with BMD decline at the lumbar spine (−.009 gm/cm2 per year, p=.03.) Additional factors associated with BMD decline were: postmenopausal status, lower BMI, and methadone use at the lumbar spine; postmenopausal status and hepatitis C seropositivity at the femoral neck; and postmenopausal status, age, smoking, and lower BMI at the total hip (all p<.05). Among HIV-infected women, ≥3 years of PI use was associated with an increase in lumbar spine BMD (.013 gm/cm2 per year, p=.008.)
Conclusions
Bone loss among HIV–infected middle-aged women was modest, and possibly mitigated by PI use. Methadone use was associated with BMD decline, and should be considered when evaluating women for osteoporosis risk.
doi:10.1016/j.maturitas.2011.08.003
PMCID: PMC3189307  PMID: 21944566
osteopenia; osteoporosis; bone mineral density; HIV; women
19.  Antiproliferative Effect of Solanum nigrum on Human Leukemic Cell Lines 
Solanum nigrum is used in various traditional medical systems for antiproliferative, antiinflammatory, antiseizure and hepatoprotective activities. We have evaluated organic solvent and aqueous extracts obtained from berries of Solanum nigrum for antiproliferative activity on leukemic cell lines, Jurkat and HL-60 (Human promyelocytic leukemia cells). The cell viability after the treatment with Solanum nigrum extract was measured by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) assay. Results indicated increased cytotoxicity with increasing extract concentrations. Comparative analysis indicated that 50% inhibitory concentration value of methanol extract is the lowest on both cell lines.
doi:10.4103/0250-474X.108421
PMCID: PMC3660872  PMID: 23716874
Cytotoxicity; HL-60; Jurkat; MTT assay; Solanum nigrum
20.  Vitamin D deficiency in HIV-infected and un-infected women in the US 
Background
Vitamin D deficiency is of increasing concern in HIV-infected persons, because of its reported association with a number of negative health outcomes that are common in HIV. We undertook this study to determine the prevalence and predictors of vitamin D deficiency among a nationally representative cohort of middle-aged, ethnically diverse HIV-infected and uninfected women enrolled in the Women’s Interagency HIV study (WIHS).
Methods
Vitamin D testing was performed by Quest Diagnostics on frozen sera using the liquid chromatography/mass spectroscopy (LC-MS) method. Vitamin D deficiency was defined as 25 (OH) D ≤20 ng/ml. Comparisons of continuous and categorical characteristics among HIV-infected and HIV-uninfected women were made by Wilcoxon tests and Pearson chi-squared tests, respectively.
Results
1778 women (1268 HIV+) were studied. 63% had vitamin D deficiency (60% HIV +vs. 72% HIV−; p<0.001). Multivariable predictors of Vitamin D Deficiency were being African American (AOR 3.02), Hispanic (AOR 1.40), Body mass index (AOR 1.43), Age (AOR 0.84), HIV+ (AOR 0.76), Glomerular filtration rate <90/ml/min (AOR 0.94) and WIHS site; Los Angeles (AOR 0.66), Chicago (AOR 0.63). In the HIV+ women multivariate predictors were; undetectable HIVRNA (AOR 0.69), CD4 50–200 cells/mm3 (AOR 1.60), CD4 <50 cells/mm3 (AOR 1.94) and recent Protease Inhibitor use (AOR 0.67).
Conclusions
In this study of over 1700 women in the US, most women with or without HIV infection had low vitamin D levels and African American women had the highest rates of Vitamin D deficiency. An understanding of the role that vitamin D deficiency plays in non-AIDS related morbidities is planned for investigation in WIHS.
doi:10.1097/QAI.0b013e31821ae418
PMCID: PMC3431159  PMID: 21471818
Vitamin D; Vitamin D Deficiency; HIV infected; HIV uninfected
21.  Pharmacist counseling in a cohort of women with HIV and women at risk for HIV 
Background and methods
Achieving high adherence to antiretroviral therapy for human immunodeficiency virus (HIV) is challenging due to various system-related, medication-related, and patient-related factors. Community pharmacists can help patients resolve many medication-related issues that lead to poor adherence. The purpose of this cross-sectional survey nested within the Women’s Interagency HIV Study was to describe characteristics of women who had received pharmacist medication counseling within the previous 6 months. The secondary objective was to determine whether HIV-positive women who received pharmacist counseling had better treatment outcomes, including self-reported adherence, CD4+ cell counts, and HIV-1 viral loads.
Results
Of the 783 eligible participants in the Women’s Interagency HIV Study who completed the survey, only 30% of participants reported receiving pharmacist counseling within the last 6 months. Factors independently associated with counseling included increased age (odds ratio [OR] 1.28; 95% confidence interval [CI] 1.07–1.55), depression (OR 1.75; 95% CI 1.25–2.45), and use of multiple pharmacies (OR 1.65; 95% CI 1.15–2.37). Patients with higher educational attainment were less likely to report pharmacist counseling (OR 0.68; 95% CI 0.48–0.98), while HIV status did not play a statistically significant role. HIV-positive participants who received pharmacist counseling were more likely to have optimal adherence (OR 1.23; 95% CI 0.70–2.18) and increased CD4+ cell counts (+43 cells/mm3, 95% CI 17.7–104.3) compared with those who had not received counseling, though these estimates did not achieve statistical significance.
Conclusion
Pharmacist medication counseling rates are suboptimal in HIV-positive and at-risk women. Pharmacist counseling is an underutilized resource which may contribute to improved adherence and CD4+ counts, though prospective studies should be conducted to explore this effect further.
doi:10.2147/PPA.S30797
PMCID: PMC3393123  PMID: 22791983
human immunodeficiency virus; acquired immunodeficiency syndrome; antiretroviral therapy; community pharmacy; pharmacy practice; women’s health
23.  Fracture incidence in HIV-infected women: results from the Women’s Interagency HIV Study 
AIDS (London, England)  2010;24(17):2679-2686.
Background
The clinical importance of the association of HIV infection and antiretroviral therapy (ART) with low bone mineral density (BMD) in premenopausal women is uncertain because BMD stabilizes on established ART and fracture data are limited.
Methods
We measured time to first new fracture at any site with median follow-up of 5.4 years in 2391 (1728 HIV-infected, 663 HIV-uninfected) participants in the Women’s Interagency HIV Study (WIHS). Self-report of fracture was recorded at semiannual visits. Proportional hazard models assessed predictors of incident fracture.
Results
At baseline, HIV-infected women were older (40 ± 9 vs. 36 ± 10 years, P <0.0001), more likely to report postmenopausal status and be hepatitis C virus-infected, and weighed less than HIV-uninfected women. Among HIV-infected women, mean CD4+ cell count was 482 cells/μl; 66% were taking ART. Unadjusted incidence of fracture did not differ between HIV-infected and uninfected women (1.8 vs. 1.4/100 person-years, respectively, P = 0.18). In multivariate models, white (vs. African-American) race, hepatitis C virus infection, and higher serum creatinine, but not HIV serostatus, were statistically significant predictors of incident fracture. Among HIV-infected women, older age, white race, current cigarette use, and history of AIDS-defining illness were associated with incidence of new fracture.
Conclusion
Among predominantly premenopausal women, there was little difference in fracture incidence rates by HIV status, rather traditional risk factors were important predictors. Further research is necessary to characterize fracture risk in HIV-infected women during and after the menopausal transition.
doi:10.1097/QAD.0b013e32833f6294
PMCID: PMC3108019  PMID: 20859192
fracture; fragility fracture; HIV-infected women; premenopausal
24.  Ataxia telangiectasia: A report of two cousins and review of literature 
Ataxia telangiectasia (AT) is a rare multisystem, neurodegenerative genetic disorder. Due to its wide clinical heterogeneity, it often leads physicians to an incorrect or missed diagnosis, and insight into this rare disease is important. Here is a case report of two cousins from the same family who showed salient characteristic features of AT along with the incidental finding of co-inheritance of hemoglobin E trait. Though both of them were from the same family, they showed differences in the type of humoral immune deficiencies, laboratory findings, and their susceptibility to develop different types of malignancies. One of them developed T cell acute lymphoblastic leukemia, isolated immunoglobulin A deficiency, and normal serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19.9 (CA 19.9) levels. He expired at the age of nine years. The other, though a year older, has still got normal blood counts, normal immunoglobulin levels, and elevated serum CEA and CA 19.9 levels. Thus, insight into this disease is very important as AT patients require protection from unnecessary exposure to ionizing radiation to prevent malignancies. Diagnosis of AT allows appropriate genetic counseling for the family.
doi:10.4103/0971-5851.95145
PMCID: PMC3343250  PMID: 22563157
Ataxia telangiectasia; hemoglobin E; T cell acute lymphoblastic leukemia; humoral immunodeficiency
25.  Prospective study of bone mineral density changes in aging men with or at risk for HIV infection 
AIDS (London, England)  2010;24(15):2337-2345.
Objective
To investigate rates and predictors of change in bone mineral density (BMD) in a cohort of aging men with or at risk for HIV infection.
Design
Prospective cohort study among 230 HIV-infected and 159 HIV-uninfected men aged ≥49 years.
Methods
Longitudinal analyses of annual change in BMD at the femoral neck, total hip and lumbar spine.
Results
At baseline 46% of men had normal BMD, 42% had osteopenia, and 12% had osteoporosis. Of those men with normal BMD, 14% progressed to osteopenia and 86% continued to have normal BMD. Of the men initially with osteopenia, 12% progressed to osteoporosis, and 83% continued to have osteopenia. Osteopenia incidence per 100 person-years at risk (PYAR) was 2.6 for HIV-uninfected men and 7.2 for HIV-infected men; osteoporosis incidence was 2.2/100 PYAR among men with osteopenia, regardless of HIV status. In multivariable analysis of annual change in BMD at the femoral neck, we found a significant interaction between heroin use and AIDS diagnosis, such that the greatest bone loss occurred with both AIDS and heroin use (adjusted predicted mean annual bone loss 0.0196 gm/cm2). Hepatitis C virus seropositivity was also associated with femoral neck bone loss (p=.04). The interaction between AIDS and heroin use also was associated with bone loss at the total hip, as was current methadone use (p<.01).
Conclusions
We found an association of heroin use and AIDS with BMD change, suggesting that heroin users with AIDS may be at particular risk for bone loss.
doi:10.1097/QAD.0b013e32833d7da7
PMCID: PMC2936812  PMID: 20683316
osteopenia; osteoporosis; bone mineral density; HIV; men; aging

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