Mosepele

Neurocognitive impairment among HIV-positive individuals in Botswana: a pilot study

BackgroundThe primary objective of this study was to determine the prevalence of neurocognitive impairment among HIV-positive individuals in Botswana, using the International HIV Dementia Scale (IHDS). We also compared performance on the IHDS with performance on tests of verbal learning/memory and processing speed, and investigated the association between performance on the IHDS and such variables as depression, age, level of education and CD4 count.MethodsWe conducted a cross-sectional study of 120 HIV-positive individuals randomly selected from an outpatient HIV clinic in Gaborone, Botswana. Patients provided a detailed clinical history and underwent neuropsychological testing; measures of depression, daily activities and subjective cognitive complaints were recorded.ResultsDespite the fact that 97.5% of subjects were receiving highly active antiretroviral therapy (HAART), 38% met criteria for dementia on the IHDS, and 24% were diagnosed with major depressive disorder. There was a significant association between neurocognitive impairment as measured by the IHDS and performance on the other two cognitive measures of verbal learning/memory and processing speed. Level of education significantly affected performance on all three cognitive measures, and age affected processing speed and performance on the IHDS. Depression and current CD4 count did not affect performance on any of the cognitive measures.ConclusionsThe prevalence of neurocognitive impairment in HIV-positive individuals in Botswana is higher than expected, especially since almost all of the subjects in this study were prescribed HAART. This suggests the need to reconsider the timing of introduction of antiretroviral therapy in developing countries where HAART is generally not administered until the CD4 cell count has dropped to 200/mm3 or below. The contribution of other factors should also be considered, such as poor central nervous system penetration of some antiretrovirals, drug resistance, potential neurotoxicity, and co-morbidities. Memory impairment and poor judgment may be underlying causes for behaviours that contribute to the spread of HIV and to poor adherence. It is important to identify these neurobehavioural complications of HIV so that effective treatments can be developed.

Depression among HIV-positive individuals in Botswana: a behavioral surveillance.

This study examined incidence of depression in HIV-positive individuals in Botswana. One hundred and twenty HIV-positive individuals were administered a measure of daily activities and two measures of depression. Twenty four to 38% were diagnosed with depression, suicidal ideation ranged from 9 to 12%, with a positive correlation between scores on the two depression measures. Depression was associated with greater impairment in activities of daily living, especially the ability to take medication. These instruments can diagnose depression in persons living with HIV in developing countries, which will help to target those at risk for poor adherence, and will enable better allocation of limited resources.

Bartonella infection in immunocompromised hosts: immunology of vascular infection and vasoproliferation.

Most infections by genus Bartonella in immunocompromised patients are caused by B. henselae and B. quintana. Unlike immunocompetent hosts who usually develop milder diseases such as cat scratch disease and trench fever, immunocompromised patients, including those living with HIV/AIDS and posttransplant patients, are more likely to develop different and severe life-threatening disease. This paper will discuss Bartonellas manifestations in immunosuppressed patients and will examine Bartonellas interaction with the immune system including its mechanisms of establishing infection and immune escape. Gaps in current understanding of the immunology of Bartonella infection in immunocompromised hosts will be highlighted.

Neurobehavioral Effects in HIV-Positive Individuals Receiving Highly Active Antiretroviral Therapy (HAART) in Gaborone, Botswana

Objective To explore the prevalence and features of HIV-associated neurocognitive disorders (HANDS) in Botswana, a sub-Saharan country at the center of the HIV epidemic. Design and Methods A cross sectional study of 60 HIV-positive individuals, all receiving highly active antiretroviral therapy (HAART), and 80 demographically matched HIV-seronegative control subjects. We administered a comprehensive neuropsychological test battery and structured psychiatric interview. The lowest 10th percentile of results achieved by control subjects was used to define the lower limit of normal performance on cognitive measures. Subjects who scored abnormal on three or more measures were classified as cognitively impaired. To determine the clinical significance of any cognitive impairment, we assessed medication adherence, employment, and independence in activities of daily living (ADL). Results HIV+ subjects were impaired for all cognitive-motor ability areas compared with matched, uninfected control subjects. Thirty seven percent of HIV+ patients met criteria for cognitive impairment. Conclusion These findings indicate that neurocognitive impairment is likely to be an important feature of HIV infection in resource-limited countries; underscoring the need to develop effective treatments for subjects with, or at risk of developing, cognitive impairment.

Vitamin D status in HIV-infected patients with and without tuberculosis: a pilot study.

Tuberculosis (TB) is a leading cause of death in human immunodeficiency virus (HIV)-infected individuals. Efforts to reduce the burden of TB include isoniazid prophylactic therapy (IPT) for latent TB infection (LTBI).1 However, IPT confers a risk of hepatotoxicity and requires at least six months of therapy.2 Therefore, additional strategies to reduce the burden of active TB are needed. Vitamin D supplementation may decrease the progression of LTBI to active TB. Primarily, in vitro studies demonstrate that 1,25-dihydroxyvitamin D (1,25[OH]2D) enhances macrophage function, thereby augmenting immunologic control of mycobacteria.3 The benefit of vitamin D supplementation is suggested by the observation of increased rates of clearance of TB from sputum in HIV-uninfected individuals.4 Vitamin D, however, may have detrimental effects in HIV-infected patients. In vitro, vitamin D depresses cell mediated immune function, 5 which could hasten progression of LTBI to active disease. This may limit vitamin D supplementation as an adjunct for TB control. Given vitamin D’s conflicting mechanisms of action on the immune system, we conducted a study in Botswana, an area of high TB and HIV prevalence,6 to determine if there was evidence for differences in 25-hydroxyvitamin D (25-OHD) levels in HIV-infected individuals with and without active TB. We hypothesized that 25-OHD levels would be significantly lower in HIV-infected individuals with active TB as compared to those without active TB.

Depression in HIV-positive women in Gaborone Botswana.

This cross-sectional study measured prevalence of depression and suicide ideation in 62 randomly selected HIV-positive (HIV+) women in Botswana, a resource-limited country at the center of the HIV/AIDS epidemic. They were administered two screening measures of depression, an inventory of activities of daily living (ADL), and subjective questionnaire of cognitive functioning. Results show that the two screening measures are useful for detecting depression in women infected with HIV in resource-limited countries. Diagnosis of depression is of great importance, not only clinically, but also to ensure judicious allocation of scarce medical resources in the regions worst affected by the HIV epidemic.

CYP2B6 genotypes and early efavirenz-based HIV treatment outcomes in Botswana

Objectives: To determine the association between cytochrome p450 2B6 genotypes and efavirenz-based HIV treatment outcomes. Design: Observational cohort study of HIV-infected adults initiating efavirenz-based regimens in Botswana. Methods: The primary endpoint was a composite of death or loss to care or HIV RNA more than 25 copies/ml at 6 months. CYP2B6 516G>T and 983T>C genotyping was done with Taqman Open Array platform. Adverse experiences were measured by using the Subject Experience Questionnaire. Metabolism alleles were included in logistic regression models of the composite endpoint. Results: A total of 801 individuals included 406 (51%) men, median age 37 years, median baseline CD4+ cell count 195 cells/&mgr;l, and plasma HIV RNA 4.9 log10 copies/ml. 288 (36%) reached the endpoint, including 34 (4%) deaths, 151 (19%) lost to care, 11 (1%) lost to the study, but alive and in care, and 92 (11%) with plasma HIV RNA more than 25 copies/ml. Metabolism variant alleles were common with 396 (49%) intermediate and 192 (24%) slow metabolizers. There were no statistically significant associations between metabolism and treatment endpoints. However, slower metabolism was associated with fewer adverse experiences. Conclusion: Slow metabolism alleles were associated with lower efavirenz clearance but not any of the treatment endpoints. Slow efavirenz metabolism did not exacerbate central nervous system toxicity. These results should allay concern that slow efavirenz metabolism adversely impacts individuals in sub-Saharan African settings in which these alleles are common.

Presentation and mortality of patients hospitalised with acute heart failure in Botswana

Summary Introduction: Heart failure is a common cause of hospitalisation and therefore contributes to in-hospital outcomes such as mortality. In this study we describe patient characteristics and outcomes of acute heart failure (AHF) in Botswana. Methods: Socio-demographic, clinical and laboratory data were collected from 193 consecutive patients admitted with AHF at Princess Marina Hospital in Gaborone between February 2014 and February 2015. The length of hospital stay and 30-, 90- and 180-day in-hospital mortality rates were assessed. Results: The mean age was 54 ± 17.1 years, and 53.9% of the patients were male. All patients were symptomatic (77.5% in NYHA functional class III or IV) and the majority (64.8%) presented with significant left ventricular dysfunction. The most common concomitant medical conditions were hypertension (54.9%), human immuno-deficiency virus (HIV) (33.9%), anaemia (23.3%) and prior diabetes mellitus (15.5%). Moderate to severe renal dysfunction was detected in 60 (31.1%) patients. Peripartum cardiomyopathy was one of the important causes of heart failure in female patients. The most commonly used treatment included furosemide (86%), beta-blockers (72.1%), angiotensin converting enzyme inhibitors (67.4%), spironolactone (59.9%), digoxin (22.1%), angiotensin receptor blockers (5.8%), nitrates (4.7%) and hydralazine (1.7%). The median length of stay was nine days, and the in-hospital mortality rate was 10.9%. Thirty-, 90- and 180-day case fatality rates were 14.7, 25.8 and 30.8%, respectively. Mortality at 180 days was significantly associated with increasing age, lower haemoglobin level, lower glomerular filtration rate, hyponatraemia, higher N-terminal pro-brain natriuretic peptide levels, and prolonged hospital stay. Conclusions: AHF is a major public health problem in Botswana, with high in-hospital and post-discharge mortality rates and prolonged hospital stays. Late and symptomatic presentation is common, and the most common aetiologies are preventable and/or treatable co-morbidities, including hypertension, diabetes mellitus, renal failure and HIV.

Cholesterol Screening and Statin Prescription is Low Among HIV-Infected Patients on Protease-Inhibitor Regimens in Botswana

Background: Little is known about the use of statin for cardiovascular disease (CVD) risk reduction among HIV-infected patients on protease inhibitors (PI`s) in sub-Saharan Africa (SSA). Objective: Cholesterol screening and statin use were retrospectively assessed among HIV-infected participants on PI`s between 2008 and 2012 at a large urban HIV clinic in Botswana. Methods: Proportion of participants screened per year was calculated and statin indication was assessed using atherosclerosis CVD (ASCVD) and Framingham risk (FRS) scores as of the year 2012 guidelines. Results: Cholesterol screening ranged between 19% and 30% per year (2008-2011) but increased to 80% after study enrollment. The rate of hypercholesterolemia (> 5.0 mmol/L) was 31% in 2012. Fewer than 1% participants were on statin therapy but 14.3% and 9.4% had statins indicated by ASCVD and FRS respectively. Conclusion: The high proportion of participants indicated for, but not prescribed statins highlights a substantial gap in the care to reduce CVD risk among these patients.

Cardiovascular disease risk prediction by the American College of Cardiology (ACC)/American Heart Association (AHA) Atherosclerotic Cardiovascular Disease (ASCVD) risk score among HIV-infected patients in sub-Saharan Africa

Objectives HIV-infected patients are at increased risk for cardiovascular disease (CVD). However, general population CVD risk prediction equations that identify HIV-infected patients at elevated risk have not been widely assessed in sub-Saharan African (SSA). Methods HIV-infected adults from 30–50 years of age with documented viral suppression were enrolled into a cross-sectional study in Gaborone, Botswana. Participants were screened for CVD risk factors. Bilateral carotid intima-media thickness (cIMT) was measured and 10-year predicted risk of cardiovascular disease was calculated using the Pooled Cohorts Equation for atherosclerotic CVD (ASCVD) and the 2008 Framingham Risk Score (FRS) (National Cholesterol Education Program III–NCEP III). ASCVD ≥7.5%, FRS ≥10%, and cIMT≥75th percentile were considered elevated risk for CVD. Agreement in classification of participants as high-risk for CVD by cIMT and FRS or ASCVD risk score was assessed using McNemar`s Test. The optimal cIMT cut off-point that matched ASCVD predicted risk of ≥7.5% was assessed using Youden’s J index. Results Among 208 HIV-infected patients (female: 55%, mean age 38 years), 78 (38%) met criteria for ASCVD calculation versus 130 (62%) who did not meet the criteria. ASCVD classified more participants as having elevated CVD risk than FRS (14.1% versus 2.6%, McNemar’s exact test p = 0.01), while also classifying similar proportion of participants as having elevated CVD like cIMT (14.1% versus 19.2%, McNemar’s exact test p = 0.34). Youden’s J calculated the optimal cut point at the 81st percentile for cIMT to correspond to an ASCVD score ≥7.5% (sensitivity = 72.7% and specificity = 88.1% with area under the curve for the receiver operating characteristic [AUC] of 0.82, 95% Mann-Whitney CI: 0.66–0.99). Conclusion While the ASCVD risk score classified more patients at elevated CVD risk than FRS, ASCVD score classified similar proportion of patients as high risk when compared with established subclinical atherosclerosis. However, potential CVD risk category misclassification by established equations such as ASCVD may still exist among HIV-infected patients; hence there is still a need for development of a CVD risk prediction equation tailored to HIV-infected patients in SSA.