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1.  Adherence to Highly Active Antiretroviral Treatment in HIV-Infected Rwandan Women 
PLoS ONE  2011;6(11):e27832.
Background
Scale-up of highly active antiretroviral treatment therapy (HAART) programs in Rwanda has been highly successful but data on adherence is limited. We examined HAART adherence in a large cohort of HIV+ Rwandan women.
Methods
The Rwanda Women's Interassociation Study Assessment (RWISA) was a prospective cohort study that assessed effectiveness and toxicity of ART. We analyzed patient data 12±3 months after HAART initiation to determine adherence rates in HIV+ women who had initiated HAART.
Results
Of the 710 HIV+ women at baseline, 490 (87.2%) initiated HAART. Of these, 6 (1.2%) died within 12 months, 15 others (3.0%) discontinued the study and 80 others (19.0%) remained in RWISA but did not have a post-HAART initiation visit that fell within the 12±3 month time points leaving 389 subjects for analysis. Of these 389, 15 women stopped their medications without being advised to do so by their doctors. Of the remaining 374 persons who reported current HAART use 354 completed the adherence assessment. All women, 354/354, reported 100% adherence to HAART at the post-HAART visit. The high self-reported level of adherence is supported by changes in laboratory measures that are influenced by HAART. The median (interquartile range) CD4 cell count measured within 6 months prior to HAART initiation was 185 (128, 253) compared to 264 (182, 380) cells/mm3 at the post-HAART visit. Similarly, the median (interquartile range) MCV within 6 months prior to HAART initiation was 88 (83, 93) fL compared to 104 (98, 110) fL at the 12±3 month visit.
Conclusion
Self-reported adherence to antiretroviral treatment 12±3 months after initiating therapy was 100% in this cohort of HIV-infected Rwandan women. Future studies should explore country-specific factors that may be contributing to high levels of adherence to HAART in this population.
doi:10.1371/journal.pone.0027832
PMCID: PMC3219684  PMID: 22114706
2.  Associations of HIV infection with insulin and glucose levels in antiretroviral-naïve Rwandan women: a cross-sectional analysis 
BMJ Open  2013;3(12):e003879.
Objectives
The purpose of these analyses was to determine the associations of HIV infection and related immune dysfunction with a glucose homeostasis in the population of antiretroviral-naïve HIV-infected and uninfected Rwandan women. We hypothesise that insulin resistance and its consequences in the developing countries may be further elevated with HIV infection itself regardless of antiretroviral therapy.
Study design
Cross-sectional analysis of a longitudinal cohort.
Setting
Community-based women's associations.
Participants
In 2005, 710 HIV-infected (HIV positive) antiretroviral naïve and 226 HIV-uninfected (HIV negative) women were enrolled in the Rwanda Women's Interassociation Study and Assessment (RWISA). Clinical and demographic parameters, CD4 count, fasting insulin and glucose levels, anthropometric measurements and Bioelectrical Impedance Analysis (BIA) were obtained. Linear models were fit to log-transformed Homeostasis Model Assessment (HOMA) with results exponentiated back to a multiplicative effect on the original scale.
Primary outcome measures
The outcome, insulin resistance, was measured by the HOMA, calculated as fasting insulin (μU/mL)×fasting glucose (mmol/L)⁄22.5.
Results
In adjusted models, HIV-positive women were less insulin resistant than HIV-negative; an HIV-positive woman tended to have 0.728 times as much (95% CI 0.681 to 0.861) HOMA than a comparable HIV-negative woman. Among the HIV-positive women, those with CD4 <200 cells/µL tended to have 0.741 times as much HOMA (95% CI 0.601 to 0.912) as did comparable women with CD4 >350 cells/µL. The older age was independently associated with a lower HOMA insulin resistance. After adjusting for body mass index, fat and fat-free mass were not independently associated with HOMA.
Conclusions
This study found that HIV infection and more advanced HIV infection (CD4 counts <200 cells/µL) were associated with greater insulin sensitivity in antiretroviral naïve African women. These findings provide baseline information for the interpretation of future studies on the effect of antiretroviral therapy on metabolic insulin sensitivity derangements in African population.
doi:10.1136/bmjopen-2013-003879
PMCID: PMC3855496  PMID: 24319275
Diabetes & Endocrinology; Epidemiology
3.  Assessment of haematological parameters in HIV-infected and uninfected Rwandan women: a cross-sectional study 
BMJ Open  2012;2(6):e001600.
Objectives
Although haematological abnormalities are common manifestations of HIV infection, few studies on haematological parameters in HIV-infected persons have been undertaken in sub-Saharan Africa. The authors assessed factors associated with haematological parameters in HIV-infected antiretroviral-naïve and HIV-uninfected Rwandan women.
Study design
Cross-sectional analysis of a longitudinal cohort.
Setting
Community-based women's associations.
Participants
710 HIV-infected (HIV+) antiretroviral-naïve and 226 HIV-uninfected (HIV−) women from the Rwanda Women's Interassociation Study Assessment. Haematological parameters categorised as (abnormal vs normal) were compared by HIV status and among HIV+ women by CD4 count category using proportions. Multivariate logistic regression models using forward selection were fit.
Results
Prevalence of anaemia (haemoglobin (Hb) <12.0 g/dl) was higher in the HIV+ group (20.5% vs 6.3%; p<0.001), and increased with lower CD4 counts: ≥350 (7.6%), 200–349 (16%) and <200 cells/mm3 (32.2%). Marked anaemia (Hb <10.0 g/dl) was found in 4.2% of HIV+ and none of the HIV− women (p<0.001), and was highest in HIV+ women with CD4 <200 cells/mm3 (8.4%). The HIV+ were more likely than HIV− women (4.2 vs 0.5%, respectively, p=0.002) to have moderate neutropenia with white blood cells <2.0×103 cells/mm3 and 8.4% of HIV+ women with CD4 <200 cells/mm3 had moderate neutropenia. In multivariate logistic regression analysis, BMI (OR 0.87/kg/m2, 95% CI 0.82 to 0.93; p<0.001), CD4 200–350 vs HIV− (OR 3.59, 95% CI 1.89 to 6.83; p<0.001) and CD4 <200 cells/mm3 vs HIV− (OR 8.09, 95% CI 4.37 to 14.97; <0.001) had large independent associations with anaemia. There were large independent associations of CD4 <200 cells/mm3 vs HIV− (OR 7.18, 95% CI 0.78 to 65.82; p=0.081) and co-trimoxazole and/or dapsone use (OR 5.69, 95% CI 0.63 to 51.45; p=0.122) with moderate neutropenia.
Conclusions
Anaemia was more common than neutropenia or thrombocytopenia in the HIV-infected Rwandan women. Future comparisons of haematological parameters in HIV-infected patients before and after antiretroviral therapy initiation are warranted.
doi:10.1136/bmjopen-2012-001600
PMCID: PMC3533001  PMID: 23169875
4.  Improvement in Posttraumatic Stress Disorder in Postconflict Rwandan Women 
Journal of Women's Health  2011;20(9):1325-1332.
Abstract
Background
Depression and posttraumatic stress disorder (PTSD) are common in developing and postconflict countries. The purpose of this study is to examine longitudinal changes in PTSD in HIV-infected and uninfected Rwandan women who experienced the 1994 genocide.
Methods
Five hundred thirty-five HIV-positive and 163 HIV-negative Rwandan women in an observational cohort study were followed for 18 months. Data on PTSD symptoms were collected longitudinally by the Harvard Trauma Questionnaire (HTQ) and analyzed in relationship to demographics, HIV status, antiretroviral treatment (ART), and depression. PTSD was defined as a score on the HTQ of ≥2.
Results
There was a continuing reduction in HTQ scores at each follow-up visit. The prevalence of PTSD symptoms changed significantly, with 61% of the cohort having PTSD at baseline vs. 24% after 18 months. Women with higher HTQ score were most likely to have improvement in PTSD symptoms (p<0.0001). Higher rate of baseline depressive symptoms (p<0.0001) was associated with less improvement in PTSD symptoms. HIV infection and ART were not found to be consistently related to PTSD improvement.
Conclusions
HIV care settings can become an important venue for the identification and treatment of psychiatric problems affecting women with HIV in postconflict and developing countries. Providing opportunities for women with PTSD symptoms to share their history of trauma to trained counselors and addressing depression, poverty, and ongoing violence may contribute to reducing symptoms.
doi:10.1089/jwh.2010.2404
PMCID: PMC3168969  PMID: 21732802
5.  Prevalence and Predictors of Posttraumatic Stress Disorder and Depression in HIV-Infected and At-Risk Rwandan Women 
Journal of Women's Health  2009;18(11):1783-1791.
Abstract
Objective
During the 1994 Rwandan genocide, rape was used as a weapon of war to transmit HIV. This study measures trauma experiences of Rwandan women and identifies predictors associated with posttraumatic stress disorder (PTSD) and depressive symptoms.
Methods
The Rwandan Women's Interassociation Study and Assessment (RWISA) is a prospective observational cohort study designed to assess effectiveness and toxicity of antiretroviral therapy in HIV-infected Rwandan women. In 2005, a Rwandan-adapted Harvard Trauma Questionnaire (HTQ) and the Center for Epidemiologic Studies Depression Scale (CES-D) were used to assess genocide trauma events and prevalence of PTSD (HTQ mean >2) and depressive symptoms (CES-D ≥ 16) for 850 women (658 HIV-positive and 192 HIV-negative).
Results
PTSD was common in HIV-positive (58%) and HIV-negative women (66%) (p = 0.05). Women with HIV had a higher prevalence of depressive symptoms than HIV-negative women (81% vs. 65%, p < 0.0001). Independent predictors for increased PTSD were experiencing more genocide-related trauma events and having more depressive symptoms. Independent predictors for increased depressive symptoms were making <$18 a month, HIV infection (and, among HIV-positive women, having lower CD4 cell counts), a history of genocidal rape, and having more PTSD symptoms.
Conclusions
The prevalence of PTSD and depressive symptoms is high in women in the RWISA cohort. Four of five HIV-infected women had depressive symptoms, with highest rates among women with CD4 cell counts <200. In addition to treatment with antiretroviral therapy, economic empowerment and identification and treatment of depression and PTSD may reduce morbidity and mortality among women in postconflict countries.
doi:10.1089/jwh.2009.1367
PMCID: PMC2828188  PMID: 19951212
6.  Association of Serum Albumin with Markers of Nutritional Status among HIV-Infected and Uninfected Rwandan Women 
PLoS ONE  2012;7(4):e35079.
Introduction
The objectives of this study are to address if and how albumin can be used as an indication of malnutrition in HIV infected and uninfected Africans.
Methods
In 2005, 710 HIV-infected and 226 HIV-uninfected women enrolled in a cohort study. Clinical/demographic parameters, CD4 count, albumin, liver transaminases; anthropometric measurements and Bioelectrical Impedance Analysis (BIA) were performed. Malnutrition outcomes were defined as body mass index (BMI), Fat-free mass index (FFMI) and Fat mass index (FMI). Separate linear predictive models including albumin were fit to these outcomes in HIV negative and HIV positive women by CD4 strata (CD4>350,200–350 and <200 cells/µl).
Results
In unadjusted models for each outcome in HIV-negative and HIV positive women with CD4>350 cells/µl, serum albumin was not significantly associated with BMI, FFMI or FMI. Albumin was significantly associated with all three outcomes (p<0.05) in HIV+ women with CD4 200–350 cells/µl, and highly significant in HIV+ women with CD4<200 cells/µl (P<0.001). In multivariable linear regression, albumin remained associated with FFMI in women with CD4 count<200 cells/µl (p<0.01) but not in HIV+ women with CD4>200.
Discussion
While serum albumin is widely used to indicate nutritional status it did not consistently predict malnutrition outcomes in HIV- women or HIV+ women with higher CD4. This result suggests that albumin may measure end stage disease as well as malnutrition and should not be used as a proxy for nutritional status without further study of its association with validated measures.
doi:10.1371/journal.pone.0035079
PMCID: PMC3331977  PMID: 22532840
7.  Maternal Nutritional Status Predicts Adverse Birth Outcomes among HIV-Infected Rural Ugandan Women Receiving Combination Antiretroviral Therapy 
PLoS ONE  2012;7(8):e41934.
Objective
Maternal nutritional status is an important predictor of birth outcomes, yet little is known about the nutritional status of HIV-infected pregnant women treated with combination antiretroviral therapy (cART). We therefore examined the relationship between maternal BMI at study enrollment, gestational weight gain (GWG), and hemoglobin concentration (Hb) among 166 women initiating cART in rural Uganda.
Design
Prospective cohort.
Methods
HIV-infected, ART-naïve pregnant women were enrolled between 12 and 28 weeks gestation and treated with a protease inhibitor or non-nucleoside reverse transcriptase inhibitor-based combination regimen. Nutritional status was assessed monthly. Neonatal anthropometry was examined at birth. Outcomes were evaluated using multivariate analysis.
Results
Mean GWG was 0.17 kg/week, 14.6% of women experienced weight loss during pregnancy, and 44.9% were anemic. Adverse fetal outcomes included low birth weight (LBW) (19.6%), preterm delivery (17.7%), fetal death (3.9%), stunting (21.1%), small-for-gestational age (15.1%), and head-sparing growth restriction (26%). No infants were HIV-infected. Gaining <0.1 kg/week was associated with LBW, preterm delivery, and a composite adverse obstetric/fetal outcome. Maternal weight at 7 months gestation predicted LBW. For each g/dL higher mean Hb, the odds of small-for-gestational age decreased by 52%.
Conclusions
In our cohort of HIV-infected women initiating cART during pregnancy, grossly inadequate GWG was common. Infants whose mothers gained <0.1 kg/week were at increased risk for LBW, preterm delivery, and composite adverse birth outcomes. cART by itself may not be sufficient for decreasing the burden of adverse birth outcomes among HIV-infected women.
Trial Registration
Clinicaltrials.gov NCT00993031
doi:10.1371/journal.pone.0041934
PMCID: PMC3413694  PMID: 22879899
8.  Effect of Formula Feeding and Breastfeeding on Child Growth, Infant Mortality, and HIV Transmission in Children Born to HIV-Infected Pregnant Women Who Received Triple Antiretroviral Therapy in a Resource-Limited Setting: Data from an HIV Cohort Study in India 
ISRN Pediatrics  2012;2012:763591.
We describe a programme for the prevention of mother-to-child transmission (PMTCT) of HIV that provided universal antiretroviral therapy (ART) to all pregnant women regardless of the CD4 lymphocyte count and formula feeding for children with high risk of HIV transmission through breastfeeding in a district of India. The overall rate of HIV transmission was 3.7%. Although breastfeeding added a 3.1% additional risk of HIV acquisition, formula-fed infants had significantly higher risk of death compared to breastfed infants. The cumulative 12-month mortality was 9.6% for formula-fed infants versus 0.68% for breastfed infants. Anthropometric markers (weight, length/height, weight for length/height, body mass index, head circumference, mid-upper arm circumference, triceps skinfold, and subscapular skinfold) showed that formula-fed infants experience severe malnutrition during the first two months of life. We did not observe any death after rapid weaning at 5-6 months in breastfed infants. The higher-free-of HIV survival in breastfed infants and the low rate of HIV transmission found in this study support the implementation of PMTCT programmes with universal ART to all HIV-infected pregnant women and breastfeeding in order to reduce HIV transmission without increasing infant mortality in developing countries.
doi:10.5402/2012/763591
PMCID: PMC3371722  PMID: 22701801
9.  Frequent Detection of HPV before and after Initiation of Antiretroviral Therapy among HIV/HSV-2 Co-Infected Women in Uganda 
PLoS ONE  2013;8(1):e55383.
Objectives
Most data on HPV and antiretroviral therapy (ART) come from high-resource countries with infrequent sampling for HPV pre- and post-ART initiation. Therefore, we examined the frequency of cervical HPV DNA detection among HIV/HSV-2 co-infected women followed monthly for 6 months both before and after initiation of ART in Rakai, Uganda.
Methods
Linear Array was used to detect 37 HPV genotypes in self-collected cervicovaginal swabs from 96 women who initiated ART. Random-effects log-binomial regression was used to compare the prevalence of HPV detection in the pre- and post-ART periods and determine other potential risk factors, including CD4 counts and HIV viral load.
Results
Nearly all women had detectable HPV in the 6 months preceding ART initiation (92%) and the cumulative prevalence remained high following initiation of therapy (90%). We found no effect of ART on monthly HPV DNA detection (prevalence ratio: 1.0; 95% confidence interval: 0.96, 1.08), regardless of immune reconstitution or HIV viral suppression. Older age and higher pre-ART CD4 counts were associated with a significantly lower risk of HPV DNA detection.
Conclusions
ART did not impact HPV detection within 6 months of therapy initiation, highlighting the importance of continued and consistent screening, even after ART-initiation and immune reconstitution.
doi:10.1371/journal.pone.0055383
PMCID: PMC3558485  PMID: 23383171
10.  Adherence to Antiretroviral Therapy and Its Effect on Survival of HIV-Infected Individuals in Jharkhand, India 
PLoS ONE  2013;8(6):e66860.
Introduction
Research in India has extensively examined the factors associated with non-adherence to antiretroviral therapy (ART) with limited focus on examining the relationship between adherence to ART regimen and survival status of HIV infected patients. This study examines the effect of optimal adherence to ART on survival status of HIV infected patients attending ART centers in Jharkhand, India.
Materials and Methods
Data from a cohort of 239 HIV infected individuals who were initiated ART in 2007 were compiled from medical records retrospectively for 36 months. Socio-demographic characteristics, CD4 T cell count, presence of opportunistic infections at the time of ART initiation and ART regimen intake and survival status was collected periodically. Optimal adherence was assessed using pill count methods; patients who took <95% of the specified regimens were identified as non-adherent. Cox-proportional hazard model was used to determine the relative hazards of mortality.
Results
More than three-fourths of the patients were male, on an average 34 year old and median CD4 T cell count was 118 cells/cmm at the time of ART registration. About 57% of the patients registered for ART were found to be adherent to ART. A total of 104 patients died in 358.5 patient-years of observation resulting in a mortality rate of 29 per 100 patient-years (95% confidence interval (CI): 23.9–35.2) and median survival time of 6.5 months (CI: 2.7–10.9). The mortality rate was higher among patients who were non-adherent to ART (64.5, CI: 50.5–82.4) than who were adherent (15.4, CI: 11.3–21.0). The risk of mortality was fourfold higher among individuals who were non-adherent to ART than who were adherent (Adjusted hazard ratio: 3.9, CI: 2.6–6.0).
Conclusion
Adherence to ART is associated with a higher chance of survival of HIV infected patients, ascertaining the need for interventions to improve the ART adherence and early initiation of ART.
doi:10.1371/journal.pone.0066860
PMCID: PMC3688964  PMID: 23825577
11.  Living Situation Affects Adherence to Combination Antiretroviral Therapy in HIV-Infected Adolescents in Rwanda: A Qualitative Study 
PLoS ONE  2013;8(4):e60073.
Introduction
Adherence to combination antiretroviral therapy (cART) is vital for HIV-infected adolescents for survival and quality of life. However, this age group faces many challenges to remain adherent. We used multiple data sources (role-play, focus group discussions (FGD), and in-depth interviews (IDI)) to better understand adherence barriers for Rwandan adolescents. Forty-two HIV positive adolescents (ages 12–21) and a selection of their primary caregivers were interviewed. All were perinatally-infected and received (cART) for ≥12 months. Topics discussed during FGDs and IDIs included learning HIV status, disclosure and stigma, care and treatment issues, cART adherence barriers.
Results
Median age was 17 years, 45% female, 45% orphaned, and 48% in boarding schools. We identified three overarching but inter-related themes that appeared to influence adherence. Stigma, perceived and experienced, and inadvertent disclosure of HIV status hampered adolescents from obtaining and taking their drugs, attending clinic visits, carrying their cARTs with them in public. The second major theme was the need for better support, in particular for adolescents with different living situations, (orphanages, foster-care, and boarding schools). Lack of privacy to keep and take medication came out as major barrier for adolescents living in congested households, as well the institutionalization of boarding schools where privacy is almost non-existent. The third important theme was the desire to be ‘normal’ and not be recognized as an HIV-infected individual, and to have a normal life not perturbed by taking a regimen of medications or being forced to disclose where others would treat them differently.
Conclusions
We propose better management of HIV-infected adolescents integrated into boarding school, orphanages, and foster care; training of school-faculty on how to support students and allow them privacy for taking their medications. To provide better care and support, HIV programs should stimulate caregivers of HIV-infected adolescents to join them for their clinic visits.
doi:10.1371/journal.pone.0060073
PMCID: PMC3616046  PMID: 23573232
12.  Effect of age on immunological response in the first year of antiretroviral therapy in HIV-1-infected adults in West Africa 
AIDS (London, England)  2012;26(8):951-957.
Objective
To assess the effect of aging on the immunological response to antiretroviral therapy (ART) in the West African context.
Methods
The change in CD4 T-cell count was analysed according to age at the time of ART initiation among HIV-infected patients enrolled in the International epidemiological Database to Evaluate AIDS (IeDEA) Collaboration in the West African region. CD4 gain over 12 months of ART was estimated using linear mixed models. Models were adjusted for baseline CD4 cell count, sex, baseline clinical stage, calendar period and ART regimen.
Results
The total number of patients included was 24 107, contributing for 50 893 measures of CD4 cell count in the first year of ART. The baseline median CD4 cell count was 144 cells/μl [interquartile range (IQR) 61–235]; median CD4 cell count reached 310 cells/μl (IQR 204–443) after 1 year of ART. The median age at treatment initiation was 36.3 years (10th–90th percentiles=26.5–50.1). In adjusted analysis, the mean CD4 gain was significantly higher in younger patients (P < 0.0001). At 12 months, patients below 30 years recovered an additional 22 cells/μl on average [95% confidence interval (CI) 2–43] compared to patients at least 50 years.
Conclusion
Among HIV-infected adults in West Africa, the immunological response after 12 months of ART was significantly poorer in elderly patients. As the population of treated patients is likely to get older, the impact of this age effect on immunological response to ART may increase over time.
doi:10.1097/QAD.0b013e3283528ad4
PMCID: PMC3704338  PMID: 22382142
age; antiretroviral treatment; HIV/AIDS; immunological response; linear mixed models; West Africa
13.  Regional Anthropometry Changes in Antiretroviral-Naïve Persons Initiating a Zidovudine-Containing Regimen in Mbarara, Uganda 
Abstract
Lipodystrophy is commonly reported in Africa after antiretroviral therapy (ART) is initiated, but few studies have objectively measured changes in body composition. Body composition was determined in 76 HIV-infected participants from Mbarara, Uganda after starting a thymidine-analog regimen, and annual change was determined using repeated measures analysis. We measured skinfolds (tricep, thigh, subscapular, and abdomen), circumferences (arm, hip, thigh, waist), and total lean and fat mass (using bioelectric impedance analysis). A cross-sectional sample of 49 HIV-uninfected participants was studied for comparison. At baseline, most body composition measures were lower in HIV-infected than uninfected participants, but waist circumference was similar. After 12 months on ART, there was little difference in body composition measures between HIV-infected and uninfected participants; median waist circumference appeared higher in HIV-infected participants (79 vs. 75 cm; p = 0.090). Among HIV-infected participants, increases were observed in total lean and fat mass, circumference, and skinfold measures; only the increase in tricep skinfold did not reach statistical significance (+1.05 mm; 95% confidence interval: −0.24, 2.34; p = 0.11). Regional anthropometry in peripheral and central body sites increased over 12 months after ART initiation in HIV-infected persons from southwestern Uganda, suggesting a restoration to health. Gains in the tricep skinfold, a reliable marker of subcutaneous fat, appeared blunted, which could indicate an inhibitory effect of zidovudine on peripheral subcutaneous fat recovery.
doi:10.1089/aid.2010.0272
PMCID: PMC3159125  PMID: 21128866
14.  HIV infection and obesity: Where did all the wasting go? 
Antiviral therapy  2012;17(7):1281-1289.
Background
The success of antiretroviral therapy (ART) has led to dramatic changes in causes of morbidity and mortality in HIV-infected individuals. As chronic diseases rates have increased in HIV+ populations, modifiable risk factors such as obesity have increased in importance. Our objective was to evaluate factors associated with weight change among patients receiving ART.
Methods
ART-naïve patients initiating therapy at the University of Alabama - Birmingham 1917 HIV/AIDS Clinic from 2000– 2008 were included. Body Mass Index (BMI) was categorized as: underweight (<18.5), normal weight (18.5–24.9), overweight (25–29.9) and obese (≥30). Linear regression models were used to evaluate overall change in BMI and factors associated with increased BMI category 24 months following ART initiation.
Results
Among 681 patients, the mean baseline BMI was 25.4 ± 6.1; 44% of patients were overweight/obese. At 24 months, 20% of patients moved from normal to overweight/obese or overweight to obese BMI categories. Greater increases in BMI were observed in patients with baseline CD4 count < 50 cells/μl (3.4 ± 4.1, P<0.01) and boosted protease inhibitor use (2.5±4.1 P=0.01), but did not account for all of the variation observed in weight change.
Conclusions
The findings that almost half of patients were overweight or obese at ART initiation, and 1 in 5 patients moved to a deleterious BMI category within 2 years of ART initiation are alarming. ART therapy provides only a modest contribution to weight gain in patients. Obesity represents a highly prevalent condition in patients with HIV infection and an important target for intervention.
doi:10.3851/IMP2348
PMCID: PMC3779137  PMID: 22951353
obesity; HIV; body mass index
15.  Longitudinal neuropsychological test performance among HIV seropositive individuals in Uganda 
Journal of neurovirology  2013;19(1):48-56.
Objective
To evaluate longitudinal neuropsychological testing performance over a 12 month period among HIV+ individuals, and to evaluate the impact of antiretroviral therapy (ART) initiation on neuropsychological test changes in Uganda.
Methods
The study examined 77 HIV+ individuals recruited from the Infectious Diseases Clinic at Makerere University, Uganda. They underwent detailed sociodemographic, medical history, immune status, functional, neurologic, and neuropsychological evaluations at baseline and 12 months later. Thirty-one individuals initiated ART (ART group) after their baseline visit, whereas 46 individuals were not placed on ART (no-ART group) during those 12 months. Paired samples t-tests were used to evaluate longitudinal changes in neuropsychological test performance for the entire sample, as well as for groups defined by ART initiation and baseline neurocognitive status.
Results
The study evaluated 77 HIV individuals (62% women, mean age=37 years, mean education=8 years, mean CD4 count=235 cells/μL). Both the ART and no-ART groups showed significant improvements in tests of verbal memory, executive functioning, motor, and psychomotor speed performance, as well as depression symptoms. The ART group had significant improvements in CD4 count over the 12 months (p<.001) whereas the no-ART group had no CD4 count improvement.
Conclusion
ART use is associated with improvements in cognitive functioning among HIV+ individuals in Uganda. However, these improvements did not appear to be higher than those seen among HIV+ individuals who did not initiate ART. Possible reasons for this include practice effects among the no-ART group as well as improvements in their mood and overall quality of life.
doi:10.1007/s13365-012-0139-5
PMCID: PMC3568232  PMID: 23315423
HIV; dementia; neurocognitive; neuropsychological assessment; Uganda
16.  Comparison of CD4 Cell Count, Viral Load, and Other Markers for the Prediction of Mortality among HIV-1–Infected Kenyan Pregnant Women 
The Journal of infectious diseases  2009;199(9):1292-1300.
Background
There are limited data regarding the relative merits of biomarkers as predictors of mortality or time to initiation of antiretroviral therapy (ART).
Methods
We evaluated the usefulness of the CD4 cell count, CD4 cell percentage (CD4%), human immunodeficiency virus type 1 (HIV-1) load, total lymphocyte count (TLC), body mass index (BMI), and hemoglobin measured at 32 weeks’ gestation as predictors of mortality in a cohort of HIV-1–infected women in Nairobi, Kenya. Sensitivity, specificity, positive predictive value (PPV), and area under the receiver operating characteristic (ROC) curve (AUC) were determined for each biomarker separately, as well as for the CD4 cell count and the HIV-1 load combined.
Results
Among 489 women with 10,150 person-months of follow-up, mortality rates at 1 and 2 years postpartum were 2.1% (95% confidence interval [CI], 0.7%–3.4%) and 5.5% (95% CI, 3.0%–8.0%), respectively. CD4 cell count and CD4% had the highest AUC value (>0.9). BMI, TLC, and hemoglobin were each associated with but poorly predictive of mortality (PPV, <7%). The HIV-1 load did not predict mortality beyond the CD4 cell count.
Conclusions
The CD4 cell count and CD4% measured during pregnancy were both useful predictors of mortality among pregnant women. TLC, BMI, and hemoglobin had a limited predictive value, and the HIV-1 load did not predict mortality any better than did the CD4 cell count alone.
doi:10.1086/597617
PMCID: PMC2758232  PMID: 19317628
17.  Mean CD4 cell count changes in patients failing a first-line antiretroviral therapy in resource-limited settings 
BMC Infectious Diseases  2012;12:147.
Background
Changes in CD4 cell counts are poorly documented in individuals with low or moderate-level viremia while on antiretroviral treatment (ART) in resource-limited settings. We assessed the impact of on-going HIV-RNA replication on CD4 cell count slopes in patients treated with a first-line combination ART.
Method
Naïve patients on a first-line ART regimen with at least two measures of HIV-RNA available after ART initiation were included in the study. The relationships between mean CD4 cell count change and HIV-RNA at 6 and 12 months after ART initiation (M6 and M12) were assessed by linear mixed models adjusted for gender, age, clinical stage and year of starting ART.
Results
3,338 patients were included (14 cohorts, 64% female) and the group had the following characteristics: a median follow-up time of 1.6 years, a median age of 34 years, and a median CD4 cell count at ART initiation of 107 cells/μL. All patients with suppressed HIV-RNA at M12 had a continuous increase in CD4 cell count up to 18 months after treatment initiation. By contrast, any degree of HIV-RNA replication both at M6 and M12 was associated with a flat or a decreasing CD4 cell count slope. Multivariable analysis using HIV-RNA thresholds of 10,000 and 5,000 copies confirmed the significant effect of HIV-RNA on CD4 cell counts both at M6 and M12.
Conclusion
In routinely monitored patients on an NNRTI-based first-line ART, on-going low-level HIV-RNA replication was associated with a poor immune outcome in patients who had detectable levels of the virus after one year of ART.
doi:10.1186/1471-2334-12-147
PMCID: PMC3573925  PMID: 22742573
HIV-1; CD4 count; CD4 slope; HIV-RNA threshold; Resource limited settings
18.  An Optimal Body Mass Index Range Associated With Improved Immune Reconstitution Among HIV-Infected Adults Initiating Antiretroviral Therapy 
In a cohort of human immunodeficiency virus–infected adults beginning antiretroviral therapy, CD4+ lymphocyte recovery at 12 months was highest among overweight patients (body mass index, 25–30 kg/m2). Similar results were observed in the subgroups with virologic suppression and minimal weight change.
Background. Higher body mass index (BMI) was associated with slower human immunodeficiency virus (HIV) disease progression before the availability of effective antiretroviral therapy (ART), but the relationship between pretreatment BMI and CD4+ lymphocyte recovery on ART is not well described.
Methods. We conducted an observational cohort study of HIV-infected, ART-naive adults starting treatment at a clinic affiliated with Vanderbilt University in Nashville, Tennessee. We assessed the relationship between pretreatment BMI and CD4+ lymphocyte count change from baseline to 12 months in all subjects, among those with plasma HIV-1 RNA levels <400 copies/mL for ≥6 months and those with <10% change in weight during follow-up. Linear regression models were adjusted for age, sex, race, protease inhibitor usage, year of ART initiation, and baseline CD4+ lymphocyte count and HIV-1 RNA level.
Results. A total of 915 patients met inclusion criteria; 78% were male, and their median age, BMI, and CD4+ lymphocyte count were 39 years, 24 kg/m2, and 171 cells/μL, respectively. The CD4+ lymphocyte increase at 12 months was greatest among patients with a pretreatment BMI of ∼25–30 kg/m2 and diminished above and below this range (P = .03). Similar patterns were observed in the subgroup analyses. Among patients with a pretreatment CD4+ lymphocyte count <200 cells/μL, a BMI of ∼25 kg/m2 was associated with the highest odds of reaching a CD4+ lymphocyte count >350 cells/μL at 12 months (P = .05).
Conclusions. 12-month immune reconstitution on ART was highest among patients commonly classified as overweight, suggesting there may be an optimal BMI range for immune recovery on ART.
doi:10.1093/cid/cir606
PMCID: PMC3189168  PMID: 21946189
19.  First report of HIV-related oral manifestations in Mali 
Introduction
In 2004, the sudden availability of free antiretroviral therapy (ART in Mali, within the context of an already overburdened health care system created gaps in individual patient quality of care. The objective of this study was to determine the prevalence of HIV-related oral manifestations (OM) during the first month of ART therapy in a Malian health facility.
Methods
Medical records of adult patients who initiated ART regimens at the Gabriel Touré Hospital, Mali (2001 to 2008) were randomly identified. Multiple logistic regression models were used to evaluate the relationship between the presence of OM during the first month of ART and selected variables, including CD4 counts and WHO clinical staging at ART initiation.
Results
Out of 205 patients on ART (mean age 39 ± 10 years), 71.0% were females and 36.1% had no formal education. 40.6% were in WHO clinical stage III. OM prevalence during the first month of HIV care was 31.4%, being oral candidiasis the commonest lesion. 73.2% and 82.5% of the patients with OM had CD4 count < 200 cells/mm3 and were classified as WHO clinical stage III or IV. WHO clinical stage III and VI patients had 5.4-fold increased odds of having any OM (both p< 0.01) when controlling for age, ethnicity, gender, marital status, and CD4 counts.
Conclusion
OM detected in people with low CD4 count and WHO clinical stage III and IV at ART initiation suggested that they were very immune-compromised when initiating HIV care. Early identification of OM could improve the quality of care and guarantee the benefits of ART.
PMCID: PMC3283017  PMID: 22368761
Oral manifestations; HIV; CD4 count; prevalence; ART
20.  Who Starts? Factors Associated with Starting Antiretroviral Therapy among Eligible Patients in Two, Public HIV Clinics in Lilongwe, Malawi 
PLoS ONE  2012;7(11):e50871.
Background
Lighthouse Trust operates two, public, integrated HIV clinics, Lighthouse (LH) and Martin Preuss Center (MPC), in Lilongwe, Malawi. Approximately 20% of patients eligible for antiretroviral therapy (ART) do not start ART. We explore individual and geographic factors that influence whether ART-eligible patients initiate ART.
Methods
Adult patients eligible for ART between 2008–2011 were included. Analysis was stratified by clinic. Using logistic regression, we evaluated factors associated with initiating ART including gender, age, body mass index (BMI), employment, tuberculosis (TB), eligible at initial registration, WHO stage, CD4, months in pre-ART care (from initial registration to eligibility date), and patient neighborhood distance to clinic.
Results
Of 14,216 study patients, 4841 were from LH; 9285 were from MPC. At LH and MPC, respectively, median age was 34.2 and 33.8 years; median BMI was 22.0 and 20.6; and median distance was 5.6 and 4.9 Km. In multivariate models, odds of starting ART was highest among those older than 35 years and those eligible for ART based on WHO stages 3–4 vs. those in WHO stages 1–2 with CD4<250. Patients with 1–12 months in pre-ART were at least 11 times more likely to start ART than peers with less pre-ART time. At LH, living 2.5–5 Km from the clinic increased the likelihood of starting ART over patients living closer.
Conclusions
Length of the pre-ART period is the most significant predictor of starting ART among eligible patients. Better understanding of motivation for retention in pre-ART care may reduce attrition along the treatment cascade.
doi:10.1371/journal.pone.0050871
PMCID: PMC3511327  PMID: 23226413
21.  Short Communication: From Wasting to Obesity: Initial Antiretroviral Therapy and Weight Gain in HIV-Infected Persons 
Abstract
Data on weight gain and the progression to overweight/obesity in HIV-infected persons during initial combination antiretroviral therapy (cART) are limited, and comparisons to the general population are inconclusive. Weight and body mass index (BMI) changes were studied in HIV-infected adults who remained on initial cART for 12 consecutive months and in an HIV-uninfected cohort receiving care at Duke University Medical Center between 1998 and 2008. Overweight/obesity was defined as BMI ≥25 kg/m2. Variables were analyzed by Chi-square and Student's t-tests. Ninety-two HIV-infected persons (median age 38.2 years) met inclusion criteria. Weight and BMI increased during 12 months of cART (80.0 to 84.4 kg, p<0.0001; 26.4 to 27.9 kg/m2, p<0.0001; respectively). Weight gain was greater in HIV-infected females compared to males (8.6 vs. 3.6 kg, p=0.04), in persons treated with protease inhibitor (PI)-based cART compared to non-PI-based cART (9.0 vs. 2.7 kg, p=0.001), and in persons with a pretreatment CD4 count <200 cells/mm3 compared to ≥200 cells/mm3 (8.9 vs. 0.3 kg, p<0.0001). Overweight/obesity prevalence increased from 52% to 66% during 12 months of initial cART, a 27% relative increase (p=0.002). HIV-infected persons had a lower prevalence of pretreatment overweight/obesity compared to 94 age-matched control subjects (52% vs. 91%, p<0.001); however, there was no change in weight (92.7 vs. 93.0 kg, p=0.5) or overweight/obesity prevalence (91% to 92%, p>0.9) during 12 months in the control cohort. Management should anticipate excess weight gain during the first year of cART in persons who are female, have a pretreatment CD4 <200 cells/mm3, or will initiate PI-based cART.
doi:10.1089/aid.2012.0234
PMCID: PMC3581041  PMID: 23072344
22.  Changes in food insecurity, nutritional status, and physical health status after antiretroviral therapy initiation in rural Uganda 
Objective
To investigate whether time on antiretroviral treatment (ART) is associated with improvements in food security and nutritional status, and the extent to which associations are mediated by improved physical health status (PHS).
Design
The Uganda AIDS Rural Treatment Outcomes study (UARTO), a prospective cohort of HIV-infected adults newly initiating ART in Mbarara, Uganda.
Methods
Participants initiating ART underwent quarterly structured interview and blood draws. The primary explanatory variable was time on ART, constructed as a set of binary variables for each three-month period. Outcomes were food insecurity, nutritional status and PHS. We fit multiple regression models with cluster-correlated robust estimates of variance to account for within-person dependence of observations over time, and analyses were adjusted for clinical and socio-demographic characteristics.
Results
228 ART-naive participants were followed for up to 3 years, and 41% were severely food insecure at baseline. The mean food insecurity score progressively declined (test for linear trend P<0.0001), beginning with the second quarter (b=-1.6; 95% CI, -2.7 to -0.45) and ending with the final quarter (b=-6.4; 95% CI, -10.3 to -2.5). PHS and nutritional status improved in a linear fashion over study follow-up (P<0.001). Inclusion of PHS in the regression model attenuated the relationship between ART duration and food security.
Conclusions
Among HIV-infected individuals in Uganda, food insecurity decreased and nutritional status and PHS improved over time after initiation of ART. Changes in food insecurity were partially explained by improvements in PHS. These data support early initiation of ART in resource-poor settings prior to decline in functional status to prevent worsening food insecurity and its detrimental effects on HIV treatment outcomes.
doi:10.1097/QAI.0b013e318261f064
PMCID: PMC3948100  PMID: 22692093
23.  Absence of Effect of Menopause Status at Initiation of First-Line Antiretroviral Therapy on Immunologic or Virologic Responses: A Cohort Study from Rio de Janeiro, Brazil 
PLoS ONE  2014;9(2):e89299.
Objective
To compare the effectiveness of first-line combination antiretroviral therapy (cART) between premenopausal and postmenopausal women.
Methods
ART-naïve women initiating cART between January 2000/June 2010 at the Instituto de Pesquisa Clínica Evandro Chagas Cohort were studied. Women were defined as postmenopausal after 12 consecutive months of amenorrhea. CD4 cell counts and HIV-1 RNA viral load (VL) measurements were compared between pre- and postmenopausal at 6, 12 and 24 months after cART initiation. Women who modified/discontinued a drug class or died due to an AIDS defining illness were classified as ART-failures. Variables were compared using Wilcoxon test, χ2 or Fisher’s exact test. The odds of cART effectiveness (VL<400 copies/mL and/or no need to change cART) were compared using logistic regression. Linear model was used to access relationship between CD4 change and menopause.
Results
Among 383 women, 328 (85%) were premenopausal and 55 (15%) postmenopausal. Median pre cART CD4 counts were 231 and 208 cells/mm3 (p = 0.14) in pre- and postmenopausal women, respectively. No difference in the median pre cART VL was found (both 4.8 copies/mL). Median CD4 changes were similar at 6 and 12 months. At 24 months after cART initiation, CD4 changes among postmenopausal women were significantly lower among premenopausal women (p = 0.01). When the analysis was restricted to women with VL<400 copies/mL, no statistical difference was observed. Overall, 63.7% achieved cART effectiveness at 24 months without differences between groups at 6, 12 and 24 months.
Conclusion
Menopause status at the time of first-line cART initiation does not impact CD4 cell changes at 24 months among women with a virologic response. No relationship between menopause status and virologic response was observed.
doi:10.1371/journal.pone.0089299
PMCID: PMC3930701  PMID: 24586673
24.  Daily co-trimoxazole prophylaxis in severely immunosuppressed HIV-infected adults in Africa started on combination antiretroviral therapy: an observational analysis of the DART cohort 
Lancet  2010;375(9722):1278-1286.
Summary
Background
Co-trimoxazole prophylaxis can reduce mortality from untreated HIV infection in Africa; whether benefits occur alongside combination antiretroviral therapy (ART) is unclear. We estimated the effect of prophylaxis after ART initiation in adults.
Methods
Participants in our observational analysis were from the DART randomised trial of management strategies in HIV-infected, symptomatic, previously untreated African adults starting triple-drug ART with CD4 counts lower than 200 cells per μL. Co-trimoxazole prophylaxis was not routinely used or randomly allocated, but was variably prescribed by clinicians. We estimated effects on clinical outcomes, CD4 cell count, and body-mass index (BMI) using marginal structural models to adjust for time-dependent confounding by indication. DART was registered, number ISRCTN13968779.
Findings
3179 participants contributed 14 214 years of follow-up (8128 [57%] person-years on co-trimoxazole). Time-dependent predictors of co-trimoxazole use were current CD4 cell count, haemoglobin concentration, BMI, and previous WHO stage 3 or 4 events on ART. Present prophylaxis significantly reduced mortality (odds ratio 0·65, 95% CI 0·50–0·85; p=0·001). Mortality risk reduction on ART was substantial to 12 weeks (0·41, 0·27–0·65), sustained from 12–72 weeks (0·56, 0·37–0·86), but not evident subsequently (0·96, 0·63–1·45; heterogeneity p=0·02). Variation in mortality reduction was not accounted for by time on co-trimoxazole or current CD4 cell count. Prophylaxis reduced frequency of malaria (0·74, 0·63–0·88; p=0·0005), an effect that was maintained with time, but we observed no effect on new WHO stage 4 events (0·86, 0·69–1·07; p=0·17), CD4 cell count (difference vs non-users, −3 cells per μL [−12 to 6]; p=0·50), or BMI (difference vs non-users, −0·04 kg/m2 [−0·20 to 0·13); p=0·68].
Interpretation
Our results reinforce WHO guidelines and provide strong motivation for provision of co-trimoxazole prophylaxis for at least 72 weeks for all adults starting combination ART in Africa.
Funding
UK Medical Research Council, the UK Department for International Development, the Rockefeller Foundation, GlaxoSmithKline, Gilead Sciences, Boehringer-Ingelheim, and Abbott Laboratories.
doi:10.1016/S0140-6736(10)60057-8
PMCID: PMC2858802  PMID: 20347483
25.  Early Mortality and AIDS Progression Despite High Initial Antiretroviral Therapy Adherence and Virologic Suppression in Botswana 
PLoS ONE  2011;6(6):e20010.
Background
Adverse outcomes occurring early after antiretroviral therapy (ART) initiation are common in sub-Saharan Africa, despite reports of high levels of ART adherence in this setting. We sought to determine the relationship between very early ART adherence and early adverse outcomes in HIV-infected adults in Botswana.
Methods
This prospective cohort study of 402 ART-naïve, HIV-infected adults initiating ART at a public HIV clinic in Gaborone, Botswana evaluated the relationship between suboptimal early ART adherence and HIV treatment outcomes in the initial months after ART initiation. Early adherence during the interval between initial ART dispensation and first ART refill was calculated using pill counts. In the primary analysis patients not returning to refill and those with adherence <0.95 were considered to have suboptimal early adherence. The primary outcome was death or loss to follow-up during the first 6 months of ART; a secondary composite outcome included the primary outcome plus incident opportunistic illness (OIs) and virologic failure. We also calculated the percent of early adverse outcomes theoretically attributable to suboptimal early adherence using the population attributable risk percent (PAR%).
Results
Suboptimal early adherence was independently associated with loss to follow-up and death (adjusted OR 2.3, 95% CI 1.1–4.8) and with the secondary composite outcome including incident OIs and virologic failure (adjusted OR 2.6, 95% CI 1.4–4.7). However, of those with early adverse outcomes, less than one-third had suboptimal adherence and approximately two-thirds achieved virologic suppression. The PAR% relating suboptimal early adherence and primary and secondary outcomes were 14.7% and 17.7%, respectively.
Conclusions
Suboptimal early adherence was associated with poor outcomes, but most early adverse outcomes occurred in patients with optimal early adherence. Clinical care and research efforts should focus on understanding early adverse outcomes that occur despite optimal adherence.
doi:10.1371/journal.pone.0020010
PMCID: PMC3115945  PMID: 21698283

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