By use of an automated polymerase chain reaction test of plasma and a qualitative polymerase chain reaction assay on polymorphonuclear leukocytes, we identified a subgroup of hematopoietic cell transplant recipients who were able to control cytomegalovirus infection early after hematopoietic cell transplantation without antiviral therapy. Thirty-one percent of patients had cytomegalovirus DNA detected by qualitative polymerase chain reaction assay but had no cytomegalovirus DNA detected by the automated test; this group maintained a lower peak cytomegalovirus load, compared with the group of patients who had cytomegalovirus DNA detected by both tests (P =.03), suggesting a greater degree of functional immune reconstitution.
Chronic kidney disease (CKD) is common in HIV; CKD is associated with mortality. Urinary markers of tubular injury have been associated with future kidney disease risk, but associations with mortality are unknown.
We evaluated the association of urinary interleukin-18(IL-18), liver fatty acid binding protein(L-FABP), kidney injury molecule-1(KIM-1), neutrophil gelatinase-associated lipocalin(NGAL), albumin-to-creatinine ratio(ACR) with 10-year, all-cause death in 908 HIV-infected women. Kidney function was estimated using cystatin C (eGFRcys).
There were 201 deaths during 9,269 person-years of follow-up. After demographic adjustment, compared to the lowest tertile, highest tertiles of IL-18 (HR 2.54,95%CI 1.75–3.68), KIM-1 (2.04,1.44–2.89), NGAL(1.50,1.05–2.14), and ACR(1.63,1.13–2.36) were associated with higher mortality. After multivariable adjustment including eGFRcys, only the highest tertiles of IL-18, (1.88,1.29–2.74) and ACR (1.46,1.01–2.12) remained independently associated with mortality. Findings with KIM-1 were borderline (1.41, 0.99–2.02). We found a J-shaped association between L-FABP and mortality. Compared to persons in the lowest tertile, HR for middle tertile of L-FABP was 0.67 (0.46–0.98) after adjustment. Findings were stronger when IL-18, ACR and L-FABP were simultaneously included in models.
Among HIV-infected women, some urinary markers of tubular injury are associated with mortality risk, independently of eGFRcys and ACR. These markers represent potential tools to identify early kidney injury in persons with HIV.
HIV; IL-18; KIM-1; L-FABP; NGAL; urinary biomarkers
Examine changes in, and factors associated with changing body mass index (BMI) in women following highly active antiretroviral therapy (HAART) initiation.
1177 HIV-infected Women's Interagency HIV Study participants who contributed 10,754 years of follow-up following HAART initiation were studied. Changes in median BMI up to 15 years following HAART initiation, and the highest and lowest BMI reached following HAART initiation were summarized by pre-HAART BMI category (<18.5 [underweight], 18.5–<25.0 [normal weight], 25.0–<30.0 [overweight], 30.0–<40.0 [obese], and ≥ 40.0 [morbidly obese]). Multivariate mixed effects ordinal logistic regression estimated the degree of association of each exposure of interest with post-HAART BMI.
Before HAART, 39% percent of women had normal BMI, 31% were overweight, 23% were obese, and 5% were morbidly obese. Following HAART initiation, median BMI change (per 5 years) was 0.21 kg/m2 (90% confidence interval [CI]: −1.33, 0.42) for those with normal pre-HAART BMI, 0.39 kg/m2 (90% CI: 0.15,0.66) for overweight, 0.31 kg/m2 (90% CI: −1.18,0.67) for obese, and −0.36kg/m2 for morbidly obese women. After initiating HAART, 40% with normal pre-HAART BMI became overweight at some point; of those overweight, 46% remained overweight and 47% became obese; 71% of obese women remained obese and 27% became morbidly obese. Each year of nucleoside analog reverse transcriptase inhibitor use was associated with a 3% decreased odds of reaching a higher BMI category (OR 0.97, 95% CI: 0.95, 0.99), while each year of protease inhibitor or non-nucleoside analog reverse transcriptase inhibitor use were associated with a 6% (OR 1.06, 95% CI: 1.04, 1.08) and 5%(OR 1.05, 95% CI: 1.01, 1.08) increased odds of having a higher BMI category, respectively.
Although overweight and obesity are highly prevalent in this large cohort of HIV-infected, minority women, HAART use was associated with only a modest increase in BMI over time.
Obesity; Body mass index; HIV; Women; HAART; Women's interagency HIV study
Inflammation and its resolution are central to vascular injury and repair. Maresins comprise a new family of bioactive lipid mediators synthesized from docosahexaenoic acid, an ω-3 polyunsaturated fatty acid. They have been found to exert anti-inflammatory and pro-resolving responses in macrophages, neutrophils and bronchial epithelial cells and impart beneficial actions in murine models of peritonitis and colitis. We investigated the impact of maresin-1 (MaR1) on tumor necrosis factor alpha (TNF-α) induced inflammatory responses in human vascular endothelial (EC) and smooth muscle cells (VSMC).
Primary cultures of human saphenous vein EC and VSMC were employed. We tested the naturally occurring MaR1 as modulator of TNF-α effects, with examination of monocyte adhesion, oxidant stress, and intracellular inflammatory signaling pathways.
MaR1 attenuated TNF-α induced monocyte adhesion and reactive oxygen species (ROS) generation in both EC and VSMC, associated with down-regulated expression (cell surface) of the adhesion molecule E-selectin (in EC) and NADPH-oxidases (NOX4, NOX1, NOX2). MaR1 attenuated TNF-α induced release of pro-inflammatory mediators by EC and VSMC. MaR1 caused an attenuation of TNF-α induced NF-κB activation in both cell types associated with inhibition of I-κ Kinase (IKK) phosphorylation, IκB-α degradation and nuclear translocation of the NF- κB p65 subunit. MaR1 also caused a time-dependent increase in intracellular cyclic AMP (cAMP) in both naive and TNF-α stimulated VSMC and EC.
MaR1 has broad anti-inflammatory actions on EC and VSMC, which may be partly mediated through up-regulation of cAMP and down-regulation of the transcription factor NF-κB. The results suggest that the pro-resolving lipid mediator MaR1 exerts homeostatic actions on vascular cells that counteract pro-inflammatory signals. These findings may have direct relevance for acute and chronic states of vascular inflammation.
Little information exists on the technical assistance needs of local indigenous organizations charged with managing HIV care and treatment programs funded by the US President’s Emergency Plan for AIDS Relief (PEPFAR). This paper describes the methods used to adapt the Primary Care Assessment Tool (PCAT) framework, which has successfully strengthened HIV primary care services in the US, into one that could strengthen the capacity of local partners to deliver priority health programs in resource-constrained settings by identifying their specific technical assistance needs.
Qualitative methods and inductive reasoning approaches were used to conceptualize and adapt the new Clinical Assessment for Systems Strengthening (ClASS) framework. Stakeholder interviews, comparisons of existing assessment tools, and a pilot test helped determine the overall ClASS framework for use in low-resource settings. The framework was further refined one year post-ClASS implementation.
Stakeholder interviews, assessment of existing tools, a pilot process and the one-year post- implementation assessment informed the adaptation of the ClASS framework for assessing and strengthening technical and managerial capacities of health programs at three levels: international partner, local indigenous partner, and local partner treatment facility. The PCAT focus on organizational strengths and systems strengthening was retained and implemented in the ClASS framework and approach. A modular format was chosen to allow the use of administrative, fiscal and clinical modules in any combination and to insert new modules as needed by programs. The pilot led to refined pre-visit planning, informed review team composition, increased visit duration, and restructured modules. A web-based toolkit was developed to capture three years of experiential learning; this kit can also be used for independent implementation of the ClASS framework.
A systematic adaptation process has produced a qualitative framework that can inform implementation strategies in support of country led HIV care and treatment programs. The framework, as a well-received iterative process focused on technical assistance, may have broader utility in other global programs.
HIV; Health system strengthening; PEPFAR; Technical assistance; ART; Sustainability; Capacity building
Engaging in partnerships is a strategic means of achieving objectives common to each partner. The Post Graduate Diploma in Public Health Management (PGDPHM) partners in consultation with the government and aims to strengthen the public health managerial capacity. This case study examines the PGDPHM program conducted jointly by the Public Health Foundation of India and the Government of Madhya Pradesh (GoMP) at the State Institute of Health Management and Communication, Gwalior, which is the apex training and research institute of the state government for health professionals. This is an example of collaborative partnership between an academic institution and the Department of Public Health and Family Welfare, GoMP. PGDPHM is a 1-year, fully residential course with a strong component of field-based project work, and aims to bridge the gap in public health managerial capacity of the health system through training of health professionals. The program is uniquely designed in the context of the National Rural Health Mission and uses a multidisciplinary approach with a focus on inter-professional education. The curriculum is competency driven and health systems connected and the pedagogy uses a problem-solving approach with multidisciplinary faculty from different programs and practice backgrounds that bring rich field experience to the classroom. This case study presents the successful example of the interface between academia and the health system and of common goals achieved through this partnership for building capacity of health professionals in the state of Madhya Pradesh over the past 3 years.
public health management; capacity building; partnership; Madhya Pradesh; NRHM; academics; health system
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).
ART; HAART; adherence; intervention
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.
HIV; bone mineral density; antiretroviral therapy; bone turnover marker
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.
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.
Vitamin D; lipids; HIV infected; HIV uninfected; 25-OH vitamin D; cholesterol; LDL-cholesterol; triglycerides; lipids; WIHS
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.
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.
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).
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.
Tenofovir; urinary biomarkers; HIV infected women
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.
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.
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.
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.
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.
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.
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.
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.
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.
Hemoglobinopathy; HPLC; RBC indices; Hemoglobin E; Thallasemia
Cystatin C could improve chronic kidney disease (CKD) classification in HIV-infected women relative to serum creatinine.
Retrospective cohort analysis.
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.
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).
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.
Creatinine; Cystatin C; Glomerular Filtration Rate; HIV; Mortality; Kidney; Women
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.
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.
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.
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.
Data quality; Health information system; Monitoring and evaluation
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).
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.
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.
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.
antiretroviral therapy; HIV; immune reconstitution; vitamin D; women
A young female was admitted in medical emergency room with fever, tachycardia and breathing difficulty. A provisional diagnosis of septicemia was made and empirical antibiotics were started. The patient required intubation and assisted ventilation. The patient recovered within 72 hours completely except bilateral mid-dilated fixed pupils. Atropine was not administered in the hospital. All blood investigations and infection screening tests were negative. After detailed history, examination and discussions, atropine poisoning was suspected which could explain all the signs and symptoms of the patient. This highlights the examination of pupillary reflexes in emergency room and meticulous clinical examination.
Atropine poisoning; Differential diagnosis of septicemia
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.
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.
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).
Among HIV-infected women in the WIHS cohort, novel urine markers of kidney injury detect risk for subsequent declines in kidney function.
HIV; KIM-1; NGAL; IL-18; albumin-to-creatinine ratio; cystatin C; kidney injury
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.
This article examines the role of ClASS in building capacity of LPs that can endure and adapt to changing financial and policy environments.
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.
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.
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.
local partner; capacity building; participatory assessment; technical assistance; HIV/AIDS; program transition
To understand how regional body composition affects bone mineral density (BMD) in HIV-infected and uninfected women.
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.
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).
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.
Body composition; fat redistribution; bone mineral density; HIV; women
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.
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.
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.
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.
Diabetes mellitus; HIV; Women; Hemoglobin A1C
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.
acidic phospholipids; DnaA protein; chromosomal replication; Escherichia coli
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.
(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.
Anemia; art; clinicoimmunologic stage; human immunodeficiency virus
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.
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.
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.)
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.
osteopenia; osteoporosis; bone mineral density; HIV; women