Strongyloides hyperinfection in an HIV-positive kidney transplant recipient: a case report.

BACKGROUND: Strongyloidiasis is caused by the helminth Strongyloides stercoralis and is well-recognised amongst transplant recipients. Serious complications, including Strongyloides hyperinfection which is a syndrome of accelerated autoinfection, or disseminated disease, can occur post-transplantation, resulting in significant morbidity and mortality. Here we present the first published case we are aware of, describing post-transplant Strongyloides hyperinfection in an HIV-positive kidney transplant patient. We discuss the diagnostic challenges and the role of pre-transplant screening. CASE PRESENTATION: A 58-year-old African-American male, originally from the Caribbean, received a deceased donor kidney transplant for presumed focal segmental glomerulosclerosis. He was known to be HIV-positive, with a stable CD4 count, and an undetectable viral load. Five months post-transplant, he developed gastrointestinal symptoms and weight loss. He had a normal eosinophil count (0.1-0.2 × 109/L), negative serum cytomegalovirus DNA, and negative blood and stool cultures. His Strongyloides serology remained negative throughout. A diagnosis of Strongyloides hyperinfection was made by the histological examination of his duodenum and lung, which identified the parasites. He completed his course of treatment with Ivermectin but exhibited profound deconditioning and required a period of total parenteral nutrition. He was subsequently discharged after a prolonged hospital admission of 54 days. CONCLUSIONS: This case highlights the challenges in diagnosing Strongyloides infection and the need to maintain a high index of clinical suspicion. Non-invasive techniques for the diagnosis of Strongyloides may be insufficient. Routine pre-transplant serological strongyloidiasis screening is now performed at our centre.

Auditory, video head impulse test and vestibular evoked myogenic potentials findings in adults with human immunodeficiency virus.

OBJECTIVES: Even though there is an association between hearing loss and human immunodeficiency virus (HIV), particularly in low- and middle-income countries, further research is needed to investigate the nature of such hearing loss. Likewise, despite documented vestibular alterations in people with HIV, the true occurrence, presentation, and nature of these manifestations are yet to be established. Advances in technology for vestibular testing has allowed for objective site-of-lesion tests such as the video head impulse test (vHIT), cervical vestibular evoked myogenic potentials (cVEMPs) and ocular vestibular evoked myogenic potential (oVEMPs). The current study aimed to compare and describe auditory, vHIT, cVEMPs and oVEMPs findings in adults with and without HIV. METHODS: The current study included an HIV positive group (n = 30) and an HIV negative group (n = 30) who underwent an auditory assessment (tympanometry and pure tone audiometry) and objective vestibular assessments. RESULTS: The occurrence of hearing loss was 53.3% in the HIV positive group compared to 33.3% in the HIV negative group. A higher occurrence of vestibular involvement was documented in the HIV positive group (73.3%) compared to 13.3% in the HIV negative group. CONCLUSION: Auditory assessment and objective measures of vestibular end-organ function (vHIT and VEMPs) can be useful to detect sub-clinical alterations. The equipment is mobile and can be performed in any health care setting such as infectious disease clinics for surveillance and monitoring purposes.

Monocyte-macrophage activation is associated with nonalcoholic fatty liver disease and liver fibrosis in HIV monoinfection independently of the gut microbiome and bacterial translocation.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is common among people living with HIV. There are limited data available on the pathophysiology of NAFLD and the development of fibrosis in this population. OBJECTIVES: The aim of this study was to investigate the association of bacterial translocation, adipose tissue dysfunction, monocyte activation and gut dysbiosis in patients with HIV monoinfection and NAFLD. METHODS: Cases with biopsy-proven NAFLD and HIV monoinfection were age and sex-matched to HIV-positive and HIV-negative controls. Markers of bacterial translocation [lipopolysaccharide-binding protein (LBP), bacterial DNA and lipopolysaccharide (LPS)], adipose tissue dysfunction (leptin, adiponectin) and monocyte activation (sCD14 and sCD163) were measured by ELISA. Hepatic patterns of macrophage activation were explored with immunohistochemistry. 16 s rRNA sequencing was performed with stool. RESULTS: Thirty-three cases were included (≥F2 fibrosis n = 16), matched to HIV-positive (n = 29) and HIV-negative (n = 17) controls. Cases with NAFLD were more obese (BMI 31.0 ±â€Š4.4 vs. 24.1 ±â€Š2.8 kg/m, P < 0.001) and had significantly increased levels of sCD14, sCD163 and higher leptin to adiponectin ratio vs. HIV-positive controls. Cases with ≥F2 verses < F2 fibrosis had increased sCD14 (1.4 ±â€Š0.4 vs. 1.1 ±â€Š0.3 µg/ml, P = 0.023) and sCD163 (1.0 ±â€Š0.3 vs. 0.8 ±â€Š0.3 µg/ml, P = 0.060), which correlated with waist circumference (sCD14 P = 0.022, sCD163 P = 0.011). Immunohistochemistry showed increased hepatic portal macrophage clusters in patients with fibrosis. No markers of bacterial translocation or changes to the microbiome were associated with NAFLD or fibrosis. CONCLUSION: NAFLD fibrosis stage in HIV monoinfected patients is associated with monocyte activation in the context of obesity, which may be independent of bacterial translocation and gut microbiome.

Serum creatinine and estimated glomerular filtration rates in HIV positive and negative adults in Ethiopia.

BACKGROUND: Glomerular filtration rate estimating equations using serum creatinine are not validated in most African settings. We compared serum creatinine and estimated glomerular filtration rate (eGFR) in HIV positive and negative adults and assessed the performance of eGFR equations ((Cockcroft and Gault (CG), Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)) compared to 24-hour creatinine clearance in HIV positive adults. METHODS: Data were collected on demographic, anthropometric, body composition, clinical parameters and serum creatinine in HIV positive and negative adults. 24-hour urine was collected from some of the HIV positive adults who volunteered. Bias was calculated as mean difference between 24-hr creatinine clearance and eGFR (eGFR- 24 hour creatinine clearance) and the accuracy of each eGFR equation was calculated as the percentage of estimates within 30% of creatinine clearance. RESULTS: A total of 340 HIV positive and 100 HIV negative adults were included in this study. Creatinine clearance was determined for 46 of HIV positive adults. Serum creatinine increased with increasing age, weight, height, body surface area, fat free mass and grip strength in both HIV positive and negative adults (P<0.05). No difference was observed in eGFR between HIV positive and HIV negative adults. For all eGFR equations, the correlation between eGFR and 24-hr creatinine clearance was 0.45-0.53 and the accuracy within 30% of 24-hr creatinine clearance was 24-46%. Removing ethnic coefficient reduced the bias and improved accuracy of the CKD-EPI and the MDRD estimates. CONCLUSION: Ethiopian HIV positive adults in the present study had good kidney function at the initiation of antiretroviral treatment. However, all eGFR equations overestimated 24-hr creatinine clearance in the study population. Creatinine based eGFR equations that accounts for low muscle mass and body surface area are needed.

Differential Impacts of HIV status on short-term fertility desires among couples in Rakai, Uganda.

BACKGROUND: Fertility desires of female and male partners in current relationships are often correlated. We examined the influence of HIV seropositive status of female and male partners on short-term fertility desires in Rakai, Uganda, a setting with high fertility and HIV infection rates. METHODS: Participants were couples (15-49 years old) enrolled in the Rakai Community Cohort Study, from 2011 to 2013 (n = 2,291). Cohen's kappa coefficient was used to measure the correlation of female and male partners' short-term fertility desires (measured as 'wanting a child in the next 12 months'), in both total sample and stratified serostatus groups. HIV serostatus and additional characteristics of female and male partners were included in Poisson regression models to estimate the rate ratios (RR) for each partner's short-term fertility desires. Individual and partner characteristics included HIV status, partner HIV status, age in years, partner age in years, educational attainment, number of living children, community of residence, and socioeconomic status (SES). RESULTS: Short-term fertility desires among female and male partners were moderately associated (Kappa = 0.37, p-value<0.001). The association was weakest among female sero-positive and male sero-negative couples (Kappa = 0.29, p-value<0.001). When adjusting for parity and other covariates in the model, women's short-term fertility desires were significantly associated with their positive sero-status regardless of male partners' sero-status (adjRR = 1.58, p<0.001 for F+M-; adjRR = 1.33, p = 0.001 for F+M+; in comparison with F-M-). Men's short-term fertility desires were significantly associated with their positive sero-status, in addition to their female partners' positive sero-status (adjRR = 1.23 with p-value = 0.022 for F-M+; adjRR = 1.42 with p-value<0.001 for F+M-; adjRR = 1.26 with p-value<0.001 for F+M+; in comparison with F-M-). When the differential effect of parity was included in the model, similar associations remained for both female and male partners when the number of living children was small, but largely reduced when the number of living children was large (3 or more). CONCLUSION: Female and male partners in couple dyads demonstrated moderate agreements about short-term fertility desires. The HIV seropositive status of female partners was most strongly associated with short-term fertility desires of both genders, and this association was even stronger for women who had few or no living children.

Exclusive breastfeeding and associated factors among HIV positive mothers in Northern Ethiopia.

BACKGROUND: It is estimated that sub-optimal feeding, especially non-exclusive breastfeeding in the first 6months of life, results in 1.4million deaths and 10% of disease burden in children younger than five years. Worldwide, it is estimated that only 34.8% of infants are exclusively breastfed for the first 6months of life, the majority receiving some other food or fluid in the early months. Besides, the Ethiopian demographic and health survey (2016) stated that the median duration of exclusive breastfeeding in Tigray region was 3.8 months which is shorter than the recommended duration. The main purpose of this study was to determine the magnitude of exclusive breastfeeding practice and associated factors among HIV positive mothers in public hospitals of Tigray region, Northern Ethiopia. METHODS: A facility based cross-sectional study was conducted from July 9 to October 11, 2016, in public hospitals of Tigray region. Data was collected by using structured questionnaire using face-to-face interview among 304 eligible women through a systematic sampling technique. Data was analyzed using SPSS version 20.0. Binary and multiple variable logistic regressions ("odds ratio") analyses were calculated with 95% CI and p value ≤ 0.05 as significance were used. RESULT: Two hundred seventy (88.8%) of mothers practiced exclusive breastfeeding for the first six months of life. Infant feeding counseling during antenatal care of last pregnancy [AOR = 6.9, 95% CI; 2.63, 17.99], knowledge on exclusive breastfeeding (AOR = 5.5, 95% CI; (2.12, 14.02] and attitude towards exclusive breastfeeding [AOR = 7.9; 95% CI; 2.96, 21.21] had significant association with exclusive breastfeeding practice. CONCLUSIONS: A high proportion of mothers practiced exclusive breastfeeding for the first six months of life. Infant feeding counseling, knowledge and attitude towards exclusive breastfeeding practice were the predictors of exclusive breastfeeding among HIV positive mothers. Strengthening infant feeding counseling during antenatal care and improving mothers' knowledge and attitude on exclusive breastfeeding is essential.

Placental Structure in Preterm Birth Among HIV-Positive Versus HIV-Negative Women in Kenya.

BACKGROUND: Preterm birth (PTB) is a major cause of infant morbidity and mortality in developing countries. Recent data suggest that in addition to Human Immunodeficiency Virus (HIV) infection, use of antiretroviral therapy (ART) increases the risk of PTB. As the mechanisms remain unexplored, we conducted this study to determine whether HIV and ART were associated with placental changes that could contribute to PTB. SETTING: We collected and evaluated placentas from 38 HIV-positive women on ART and 43 HIV-negative women who had preterm deliveries in Nairobi, Kenya. METHODS: Anatomical features of the placentas were examined at gross and microscopic levels. Cases were matched for gestational age and compared by the investigators who were blinded to maternal HIV serostatus. RESULTS: Among preterm placentas, HIV infection was significantly associated with thrombosis (P = 0.001), infarction (P = 0.032), anomalies in cord insertion (P = 0.02), gross evidence of membrane infection (P = 0.043), and reduced placental thickness (P = 0.010). Overall, preterm placentas in both groups were associated with immature villi, syncytial knotting, villitis, and deciduitis. Features of HIV-positive versus HIV-negative placentas included significant fibrinoid deposition with villus degeneration, syncytiotrophoblast delamination, red blood cell adhesion, hypervascularity, and reduction in both surface area and perimeter of the terminal villi. CONCLUSIONS: These results imply that HIV infection and/or ART are associated with morphological changes in preterm placentas that contribute to delivery before 37 weeks. Hypervascularity suggests that the observed pathologies may be attributable, in part, to hypoxia. Further research to explore potential mechanisms will help elucidate the pathways that are involved perhaps pointing to interventions for decreasing the risk of prematurity among HIV-positive women.

Urinary clusterin and glutathione-s-transferase levels in HIV positive normotensive and preeclamptic pregnancies.

OBJECTIVE: To determine the level and effect of urinary clusterin (CLU) and glutathione-s-transferase (GST) proteins in normotensive and preeclamptic pregnant women with HIV infection. METHODS: The urine concentration of CLU and GST in normotensive (n = 38) and preeclamptic pregnant (n = 38) women stratified by HIV status were estimated using the Bio-Plex® ProTM immunoassay. RESULTS: Across the group, a significant down-regulation of CLU (p = 0.039) with a reduced trend in GST was shown in HIV positive preeclampsia. CONCLUSION: HIV infection affects the activity of urinary CLU protein in HIV positive preeclampsia. However, the cytoprotective role of these proteins neutralizes the oxidative radicals associated with preeclampsia development through complement response in HIV infection.

Beyond HIV-serodiscordance: Partnership communication dynamics that affect engagement in safer conception care.

INTRODUCTION: We explored acceptability and feasibility of safer conception methods among HIV-affected couples in Uganda. METHODS: We recruited HIV-positive men and women on antiretroviral therapy (ART) ('index') from the Uganda Antiretroviral Rural Treatment Outcomes cohort who reported an HIV-negative or unknown-serostatus partner ('partner'), HIV-serostatus disclosure to partner, and personal or partner desire for a child within two years. We conducted in-depth interviews with 40 individuals from 20 couples, using a narrative approach with tailored images to assess acceptability of five safer conception strategies: ART for the infected partner, pre-exposure prophylaxis (PrEP) for the uninfected partner, condomless sex timed to peak fertility, manual insemination, and male circumcision. Translated and transcribed data were analyzed using thematic analysis. RESULTS: 11/20 index participants were women, median age of 32.5 years, median of 2 living children, and 80% had HIV-RNA <400 copies/mL. Awareness of HIV prevention strategies beyond condoms and abstinence was limited and precluded opportunity to explore or validly assess acceptability or feasibility of safer conception methods. Four key partnership communication challenges emerged as primary barriers to engagement in safer conception care, including: (1) HIV-serostatus disclosure: Although disclosure was an inclusion criterion, partners commonly reported not knowing the index partner's HIV status. Similarly, the partner's HIV-serostatus, as reported by the index, was frequently inaccurate. (2) Childbearing intention: Many couples had divergent childbearing intentions and made incorrect assumptions about their partner's desires. (3) HIV risk perception: Participants had disparate understandings of HIV transmission and disagreed on the acceptable level of HIV risk to meet reproductive goals. (4) Partnership commitment: Participants revealed significant discord in perceptions of partnership commitment. All four types of partnership miscommunication introduced constraints to autonomous reproductive decision-making, particularly for women. Such miscommunication was common, as only 2 of 20 partnerships in our sample were mutually-disclosed with agreement across all four communication themes. CONCLUSIONS: Enthusiasm for safer conception programming is growing. Our findings highlight the importance of addressing gendered partnership communication regarding HIV disclosure, reproductive goals, acceptable HIV risk, and commitment, alongside technical safer conception advice. Failing to consider partnership dynamics across these domains risks limiting reach, uptake, adherence to, and retention in safer conception programming.

Effects of sex and HIV serostatus on spatial navigational learning and memory among cocaine users.

Spatial learning and memory are critically dependent on the integrity of hippocampal systems. Functional MRI and neuropathological studies show that hippocampal circuitry is prominently affected among HIV-seropositive individuals, but potential spatial learning and memory deficits have not been studied in detail in this population. We investigated the independent and interactive effects of sex and HIV serostatus on performance of a spatial learning and memory task in a sample of 181 individuals with a history of cocaine dependence. We found that men showed faster times to completion on immediate recall trials compared with women and that delayed recall was significantly poorer among HIV-infected compared with HIV-uninfected participants. Additionally, a sex × serostatus effect was found on the total number of completed learning trials. Specifically, HIV-infected men successfully completed more learning trials compared with HIV-infected women. Results are discussed in the context of recent reports of sex and HIV serostatus effects on episodic memory performance.

Profile of 26 HIV Seropositive individuals with Cerebral Venous Thrombosis.

BACKGROUND: HIV infection has been found to be prothrombotic condition. However, venous thromboembolism associated with HIV is restricted to peripheral vasculature with few reports of cerebral venous thrombosis (CVT). OBJECTIVE: To examine the clinical manifestations of CVT among HIV seropositive individuals and explore the possible etiological factors. METHODS AND RESULTS: It is a prospective study of 26 (M:F-18:8) patients of CVT associated with HIV seropositive status. Their age and duration of illness was 33.8±6.8years and 11.3±8.5days respectively. Headache and vomiting was the most common symptom followed by seizures. Drowsiness with GCS (Glasgow coma score) ranging from 9-14 was present in two-thirds of the patients. Serum homocysteine was elevated in 70% of patients. Vitamin B12 was low in 12.5% and insufficient levels in 25%. 88.5% of the patients recovered completely to GCS 15/15 in 2-7days during follow up; 11.5% patients expired during the acute state. CONCLUSION: This study represents the largest series of CVT in HIV seropositive individuals. There is increased risk of thrombosis due to elevated homocysteine and low Vitamin B12. They have better sensorium inspite of extensive radiological involvement.

Role of intestinal dysfunction in the nutritional compromise seen in human immunodeficiency virus-infected adults in rural India.

Human immunodeficiency virus (HIV) disease progression is often marked by significant weight loss with or without chronic diarrhoea. We studied the extent of intestinal dysfunction using a D-xylose absorption test and association with nutritional compromise as measured by body mass index (BMI) and serum antioxidants levels in HIV-infected individuals through a cross-sectional survey of 45 ART naïve, HIV-positive and 45, age-socioeconomic status matched negative controls in a rural population in India. More than 40% of HIV-positive and HIV-negative participants had intestinal dysfunction (42.2% vs. 44.4%). However an increasing gradient of low D-xylose absorption was noted with decreasing CD4 counts (32%, 50% and 58.3% among those with >350, 200-350 and <200 cells/mm3, respectively). Multivariate analysis revealed a significant association between intestinal dysfunction and low BMI (P = 0.03) independent of HIV infection and calorie intake per day (P = 0.02). Weight loss in HIV-infected individuals should be investigated for intestinal dysfunction especially in low resource settings.

Adaptive working memory training improved brain function in human immunodeficiency virus-seropositive patients.

OBJECTIVE: We aimed to evaluate the effectiveness of an adaptive working memory (WM) training (WMT) program, the corresponding neural correlates, and LMX1A-rs4657412 polymorphism on the adaptive WMT, in human immunodeficiency virus (HIV) participants compared to seronegative (SN) controls. METHODS: A total of 201 of 206 qualified participants completed baseline assessments before randomization to 25 sessions of adaptive WMT or nonadaptive WMT. A total of 74 of 76 (34 HIV, 42 SN) completed adaptive WMT and all 40 completed nonadaptive WMT (20 HIV, 20 SN) and were assessed after 1 month, and 55 adaptive WMT participants were also assessed after 6 months. Nontrained near-transfer WM tests (Digit-Span, Spatial-Span), self-reported executive functioning, and functional magnetic resonance images during 1-back and 2-back tasks were performed at baseline and each follow-up visit, and LMX1A-rs4657412 was genotyped in all participants. RESULTS: Although HIV participants had slightly lower cognitive performance and start index than SN at baseline, both groups improved on improvement index (>30%; false discovery rate [FDR] corrected p < 0.0008) and nontrained WM tests after adaptive WMT (FDR corrected, p ≤ 0.001), but not after nonadaptive WMT (training by training type corrected, p = 0.01 to p = 0.05) 1 month later. HIV participants (especially LMX1A-G carriers) also had poorer self-reported executive functioning than SN, but both groups reported improvements after adaptive WMT (Global: training FDR corrected, p = 0.004), and only HIV participants improved after nonadaptive WMT. HIV participants also had greater frontal activation than SN at baseline, but brain activation decreased in both groups at 1 and 6 months after adaptive WMT (FDR corrected, p < 0.0001), with normalization of brain activation in HIV participants, especially the LMX1A-AA carriers (LMX1A genotype by HIV status, cluster-corrected-p < 0.0001). INTERPRETATION: Adaptive WMT, but not nonadaptive WMT, improved WM performance in both SN and HIV participants, and the accompanied decreased or normalized brain activation suggest improved neural efficiency, especially in HIV-LMX1A-AA carriers who might have greater dopaminergic reserve. These findings suggest that adaptive WMT may be an effective adjunctive therapy for WM deficits in HIV participants. ANN NEUROL 2017;81:17-34.

Lymphocyte CD4+ cell count, strength improvements, heart rate and body composition of HIV-positive patients during a 3-month strength training program.

BACKGROUND: There is a lack of information regarding the positive effects of different types of physical training on HIV-positive patient immune function, body composition and physical fitness. The goal of this study was two-fold: 1) to determine the effects of a three-month progressive strength training program on lymphocyte CD4+ cell counts in HIV-positive patients; and 2) to measure strength improvements, body composition and cardiovascular alterations in HIV-positive patients after a strength training program. METHODS: Sixteen HIV-positive male subjects participated in a strength-training program. CD4+ cell count, heart rate body composition and strength measurements were acquired at rest two days before and two days after the program. RESULTS: The average CD4+ cell count was increased (%=23%, P=0.0005), and all strength tests also showed improvement (%=95%, P=0,0001). Patient resting heart rate decreased (%=9%, P=0.0042), as did the skinfold sum (%=16%, P=0.002). Limb circumference sum and body weight did not change. CONCLUSIONS: Considering that a decrease in CD4+ cell count, muscle mass and overall physical fitness are expected results of HIV infection, the strength training protocol described here is an effective and safe way to improve immune function, body composition and cardiovascular fitness in HIV-positive patients. The results provided an important evidence for the effectiveness of a 3-month progressive resistance exercise training program at increasing immune function and physical fitness, strongly recommending its inclusion in the standardized treatment plan of HIV-positive patients.

Pulmonary effects of immediate versus deferred antiretroviral therapy in HIV-positive individuals: a nested substudy within the multicentre, international, randomised, controlled Strategic Timing of Antiretroviral Treatment (START) trial.

BACKGROUND: Observational data have been conflicted regarding the potential role of HIV antiretroviral therapy (ART) as a causative factor for, or protective factor against, COPD. We therefore aimed to investigate the effect of immediate versus deferred ART on decline in lung function in HIV-positive individuals. METHODS: We did a nested substudy within the randomised, controlled Strategic Timing of Antiretroviral Treatment (START) trial at 80 sites in multiple settings in 20 high-income and low-to-middle-income countries. Participants were HIV-1 infected individuals aged at least 25 years, naive to ART, with CD4 T-cell counts of more than 500 per µL, not receiving treatment for asthma, and without recent respiratory infections (baseline COPD was not an exclusion criterion). Participants were randomly assigned to receive ART (an approved drug combination derived from US Department of Health and Human Services guidelines) either immediately, or deferred until CD4 T-cell counts decreased to 350 per µL or AIDS developed. The randomisation was determined by participation in the parent START study, and was not specific to the substudy. Because of the nature of our study, site investigators and participants were not masked to the treatment group assignment; however, the assessors who reviewed the outcomes were masked to the treatment group. The primary outcome was the annual rate of decline in lung function, expressed as the FEV1 slope in mL/year; spirometry was done annually during follow-up for up to 5 years. We analysed data on an intention-to-treat basis, and planned separate analyses in smokers and non-smokers because of the known effects of smoking on FEV1 decline. The substudy was registered at ClinicalTrials.gov number NCT01797367. FINDINGS: Between March 11, 2010, and Aug 23, 2013, we enrolled 1026 participants to our substudy, who were then randomly assigned to either immediate (n=518) or deferred (n=508) ART. Median baseline characteristics included age 36 years (IQR 30-44), CD4 T-cell count 648 per µL (583-767), and HIV plasma viral load 4·2 log10 copies per mL (3·5-4·7). 29% were female and 28% were current smokers. Median follow-up time was 2·0 years (IQR 1·9-3·0). We noted no differences in FEV1 slopes between the immediate and deferred ART groups either in smokers (difference of -3·3 mL/year, 95% CI -38·8 to 32·2; p=0·86) or in non-smokers (difference of -5·6 mL/year, -29·4 to 18·3; p=0·65) or in pooled analyses adjusted for smoking status at each study visit (difference of -5·2 mL/year, -25·1 to 14·6; p=0·61). INTERPRETATION: The timing of ART initiation has no major short-term effect on rate of lung function decline in HIV-positive individuals who are naive to ART, with CD4 T-cell counts of more than 500 per µL. In light of updated WHO recommendations that all HIV-positive individuals should be treated with ART, regardless of their CD4 T-cell count, our results suggest an absence of significant pulmonary harm with such an approach. FUNDING: US National Heart Lung and Blood Institute, US National Institute of Allergy and Infectious Diseases, Division of AIDS, Agence Nationale de Recherches sur le SIDA et les Hipatites Virales (France), Australian National Health and Medical Research Council, Danish National Research Foundation, European AIDS Treatment Network, German Ministry of Education and Research, UK Medical Research Council and National Institute for Health Research, and US Veterans Health Administration Office of Research and Development.

Neurocognitive Function and Neuroimaging Markers in Virologically Suppressed HIV-positive Patients Randomized to Ritonavir-boosted Protease Inhibitor Monotherapy or Standard Combination ART: A Cross-sectional Substudy From the PIVOT Trial.

BACKGROUND: To determine whether treatment with ritonavir-boosted protease inhibitor (PI) monotherapy is associated with detrimental effects on neurocognitive function or brain imaging markers compared to standard antiretroviral therapy (ART). METHODS: Neuropsychological assessment and brain magnetic resonance imaging were performed at the last study visit in a subset of participants randomized to PI monotherapy (PI-mono group) or ongoing triple ART (OT group) in the PIVOT trial. We calculated a global z-score (NPZ-7) from the average of the individual test z-scores and the proportion of participants with symptomatic neurocognitive impairment (score >1 standard deviation below normative means in ≥2 cognitive domains and neurocognitive symptoms). In a subgroup, white matter hyperintensities, bicaudate index, global cortical (GCA) and medial temporal lobe atrophy scores and single voxel (basal ganglia) N-acetylaspartate (NAA)/Choline, NAA/Creatine and myo-inositol/Creatine ratios were measured. RESULTS: 146 participants (75 PI-mono) had neurocognitive testing (median time after randomization 3.8 years), of whom 78 were imaged. We found no difference between arms in NPZ-7 score (median -0.4 (interquartile range [IQR] = -0.7; 0.1) vs -0.3 (IQR = -0.7; 0.3) for the PI-mono and OT groups respectively, P = .28), the proportion with symptomatic neurocognitive impairment (13% and 18% in the PI-mono and OT groups respectively; P = .41), or any of the neuroimaging variables (P > .05). Symptomatic neurocognitive impairment was associated with higher GCA score (OR = 6.2 per additional score; 95% confidence interval, 1.7-22.3 P = .005) but no other imaging variables. CONCLUSIONS: Based on a comprehensive neuropsychological assessment and brain imaging, PI monotherapy does not increase the risk of neurocognitive impairment in stable human immunodeficiency virus-positive patients.

Incidence and risk factors for postpartum hemorrhage in Uganda.

BACKGROUND: Globally, postpartum haemorrhage (PPH) remains a leading cause of maternal deaths. However in many low and middle income countries, there is scarcity of information on magnitude of and risk factors for PPH (blood loss of 500 ml or more). It is important to understand the relative contributions of different risk factors for PPH. We assessed the incidence of, and risk factors for postpartum hemorrhage among rural women in Uganda. METHODS: Between March 2013 and March 2014, a prospective cohort study was conducted at six health facilities in Uganda. Women were administered a questionnaire to ascertain risk factors for postpartum hemorrhage, defined as a blood loss of 500 mls or more, and assessed using a calibrated under-buttocks drape at childbirth. We constructed two separate multivariable logistic regression models for the variables associated with PPH. Model 1 included all deliveries (vaginal and cesarean sections). Model 2 analysis was restricted to vaginal deliveries. In both models, we adjusted for clustering at facility level. RESULTS: Among the 1188 women, the overall incidence of postpartum hemorrhage was 9.0%, (95% confidence interval [CI]: 7.5-10.6%) and of severe postpartum hemorrhage (1000 mls or more) was 1.2%, (95% CI 0.6-2.0%). Most (1157 [97.4%]) women received a uterotonic after childbirth for postpartum hemorrhage prophylaxis. Risk factors for postpartum hemorrhage among all deliveries (model 1) were: cesarean section delivery (adjusted odds ratio [aOR] 7.54; 95% CI 4.11-13.81); multiple pregnancy (aOR 2.26; 95% CI 0.58-8.79); foetal macrosomia ≥4000 g (aOR 2.18; 95% CI 1.11-4.29); and HIV positive sero-status (aOR 1.93; 95% CI 1.06-3.50). Risk factors among vaginal deliveries only, were similar in direction and magnitude as in model 1, namely: multiple pregnancy, (aOR 7.66; 95% CI 1.81-32.34); macrosomia, (aOR 2.14; 95% CI1.02-4.47); and HIV positive sero-status (aOR 2.26; 95% CI 1.20-4.25). CONCLUSION: The incidence of postpartum hemorrhage was high in our setting despite use of uterotonics. The risk factors identified could be addressed by extra vigilance during labour and preparedness for PPH management in all women giving birth.

Neurobehavioral Disturbances During Acute and Early HIV Infection.

BACKGROUND AND OBJECTIVE: Acute and early human immunodeficiency virus infection (AEH) is accompanied by neuroinflammatory processes as well as impairment in neurocognitive and everyday functions, but little is known about the frequency and clinical correlates of the neurobehavioral disturbances during this period. We compared pre-seroconversion with current levels of apathy, disinhibition, and executive dysfunction; we also examined everyday function and HIV disease correlates of neuropsychiatric impairment in individuals with AEH. METHODS: In this study, 34 individuals with AEH and 39 HIV-seronegative participants completed neuromedical and neuropsychological assessments, a structured psychiatric interview, and the apathy, disinhibition, and executive dysfunction subscales of the Frontal Systems Behavioral Scale. RESULTS: Independent of any substance use and mood disorders, the AEH group had significantly higher levels of current apathy and executive dysfunction than the controls, but not greater disinhibition. Retrospective ratings of pre-seroconversion levels of apathy, disinhibition, and executive dysfunction were all higher in the AEH group than the controls. After seroconversion, the AEH cohort had increases in current apathy and executive dysfunction, but not disinhibition. In the AEH cohort, higher current global neurobehavioral dysfunction was significantly associated with lower nadir CD4 counts, slowed information processing speed, and more everyday function problems. CONCLUSIONS: These data suggest that individuals who have recently acquired HIV experienced higher-than-normal premorbid levels of neurobehavioral disturbance. Apathy and executive dysfunction are exacerbated during AEH, particularly in association with lower CD4 counts.

Affective differences in Iowa Gambling Task performance associated with sexual risk taking and substance use among HIV-positive and HIV-negative men who have sex with men.

We investigated the relationship between emotional distress and decision making in sexual risk and substance use behavior among 174 (ages 25 to 50 years, 53% black) men who have sex with men (MSM), a population at increased risk for HIV. The sample was stratified by HIV status. Measures of affective decision making, depression, anxiety, sex acts, and substance use during the past 60 days were collected at our research center. Negative binomial regression models were used to examine the relationship between age, HIV status, anxiety, depression, and IGT performance in the prediction of number of risky sex acts and substance use days. Among those without anxiety or depression, both number of risky sex acts and drug use days decreased with better performance during risky trials (i.e., last two blocks) of the IGT. For those with higher rates of anxiety, but not depression, IGT risk trial performance and risky sex acts increased concomitantly. Anxiety also interacted with IGT performance across all trials to predict substance use, such that anxiety was associated with greater substance use among those with better IGT performance. The opposite was true for those with depression, but only during risk trials. HIV-positive participants reported fewer substance use days than HIV-negative participants, but there was no difference in association between behavior and IGT performance by HIV status. Our findings suggest that anxiety may exacerbate risk-taking behavior when affective decision-making ability is intact. The relationship between affective decision making and risk taking may be sensitive to different profiles of emotional distress, as well as behavioral context. Investigations of affective decision making in sexual risk taking and substance use should examine different distress profiles separately, with implications for HIV prevention efforts.