HIV-infected Patients In sub-Saharan Africa Research Articles

Incidence, risk factors, and outcomes of acute kidney injury among hiv positive medical admissions at the Bamenda Regional Hospital

Background: There is a paucity of data on the burden of acute kidney injury (AKI) in hospitalized HIV-infected patients in Sub-Saharan Africa in the “test and treat” era. Objectives: To study the incidence, risk factors, and outcomes of AKI among HIV-positive medical admissions in a secondary hospital. Materials and methods: We prospectively screened adult HIV-positive patients who gave their informed consent and were admitted to the Bamenda Regional Hospital for AKI from February to June 2020. We excluded participants with Chronic Kidney Disease (CKD) Stage 5 and those with confounders of serum creatinine. On admission and after 2-7 days, we extracted a venous blood sample from each participant to evaluate serum creatinine and diagnose AKI. The participants were then followed up on until they were discharged or died. We measured the need for dialysis, access to dialysis, and renal recovery at three months for patients with AKI. The amended KDIGO 2012 criteria were used to define and classify AKI. The University of Bamenda’s institutional review board provided ethical approval. Results: A total of 206 participants (39.8% men) were enrolled, with a mean (SD) age of 45.71(13.13) years. On enrolment, 89.8% (n = 185) of the participants were on combination antiretroviral therapy (c-ART), with 81.6% (n = 151) on tenofovir-containing regimens. The WHO HIV clinical stages 3 and 4 were present in 81.5% (n = 168) of the individuals. The most common reason for hospitalization was opportunistic infections (69.8%; n = 142). AKI was found in 30.6% (n = 63) of the patients, with 58.7% (n = 37) of them being classified as KDIGO stage 3. A total of 12 (42.9%) participants out of the 28 in need, were dialyzed. AKI was independently associated with use of traditional medicines (aOR = 2.9; 95% CI 1.4-6.3; p = 0.006), WHO HIV stages 3 and 4 (aOR = 4.1; 95% CI 1.1-15.7; p = 0.038), hypotension (aOR = 3.3; 95% CI 1.4-7.8; p = 0.008) and low haemoglobin level ≤ 8.0 g/dl (aOR = 3.5; 95% CI 1.7-7.4; p = 0.001). The AKI group used to have a significantly higher mortality rate (42.9% vs. 16.1%; p < 0.001). Renal recovery was complete in 66.7% of the 30 survivors at three months, partial in 13.3%, and no recovery in 20% of the survivors. Conclusion: Despite the growing use of combination antiretroviral medication, significant immunosuppression is still common in hospitalized HIV-positive patients, increasing the risk of AKI and worsening prognosis. In this high-risk population, early detection of AKI with renal function monitoring may improve results.

Genetic factors associated with tuberculosis-related clinical outcomes in HIV-infected Black African patients: a systematic review and meta-analysis.

Aim: To evaluate the genetic factors influencing tuberculosis (TB) clinical outcomes in HIV-infected Black African patients. Materials & methods: We systematically searched and identified eligible publications from >550 databases indexed through February 2021. Results: Eighteen studies were included in the qualitative synthesis. Only two cohorts from one study were included in quantitative synthesis of which the low expression MIF-794 CATT5,6 (5/5 + 5/6 + 6/6) genotypes were not associated with TB infectivity in HIV-infected patients (OR: 1.31, 95% CI: 0.46-3.79). Other TB clinical outcomes observed in HIV/TB co-infected patients included: drug-induced liver injury, peripheral neuropathy, mortality, lung function and TB cure. Conclusion: This review finds inconclusive evidence that genetic factors are associated with TB clinical outcomes among HIV-infected patients in sub-Saharan Africa.

Transcriptomic biomarker pathways associated with death in HIV-infected patients with cryptococcal meningitis

BackgroundCryptococcal meningitis (CM) is a major cause of death in HIV-infected patients in sub-Saharan Africa. Many CM patients experience cryptococcosis-associated immune reconstitution inflammatory syndrome (C-IRIS), which is often fatal. We sought to identify transcriptomic biomarker pathways in peripheral blood that are associated with or predict the development of death or fatal C-IRIS among patients with CM who were enrolled in the Cryptococcal Optimal ART Timing Trial.MethodsWe assessed peripheral blood gene expression using next-generation RNA sequencing in 4 groups of patients with CM: (1) no C-IRIS or Death; (2) C-IRIS survivors; (3) fatal C-IRIS; (4) Death without C-IRIS. Gene expression was assessed at the time of ART initiation, at 1, 4, and 8 weeks on ART, and at the time of C-IRIS events.ResultsWe identified 12 inflammatory and stress response pathways, including interferon type 1 signaling, that were upregulated at the time of ART initiation in patients with future fatal C-IRIS, as compared with survivors. The upregulation of transcripts involved in innate immunity (inflammasome, Toll-like receptor signaling), was observed at the time of fatal or nonfatal C-IRIS events. At the time of fatal C-IRIS events, numerous transcripts within fMLP, Rho family GTPases, HMGB1, and other acute phase response signaling pathways were upregulated, which reflects the severity of inflammation and systemic oxidative stress. Patients who died without recognized C-IRIS also had increased expression of pathways associated with oxidative stress and tissue damage.ConclusionsOur results showed that overactivated innate immunity, involving Toll-like receptor/inflammasome pathways, and inflammation-induced oxidative stress, are associated with fatal outcomes. The results of this study provide insight into the molecular drivers of death and fatal C-IRIS to inform future diagnostic test development or guide targeted treatments.

Cost-effectiveness analysis of flucytosine as induction therapy in the treatment of cryptococcal meningitis in HIV-infected adults in South Africa

BackgroundCryptococcal meningitis in HIV-infected patients in sub-Saharan Africa accounts for three-quarters of the global cases and 135,000 deaths per annum. Current treatment includes the use of fluconazole and amphotericin B. Recent evidence has shown that the synergistic use of flucytosine improves efficacy and reduces toxicity, however affordability and availability has hampered access to flucytosine in many countries. This study investigated the evidence and cost implications of introducing flucytosine as induction therapy for cryptococcal meningitis in HIV-infected adults in South Africa.MethodsA decision analytic cost-effectiveness and cost impact model was developed based on survival estimates from the ACTA trial and local costs for flucytosine as induction therapy in HIV-infected adults with cryptococcal meningitis in a public sector setting in South Africa. The model considered five treatment arms: (a) standard of care; 2-week course amphotericin B/fluconazole (2wk AmBd/Flu), (b) 2-week course amphotericin B/flucytosine (2wk AmBd/5FC), (c) short course; 1-week course amphotericin B/flucytosine (1wk AmBd/5FC) (d) oral course; 2-week oral fluconazole/flucytosine (oral) and e) 1-week course amphotericin B/fluconazole (1wk AmBd/Flu). A sensitivity analysis was conducted on key variables.ResultsThe highest total treatment costs are in the 2-week AmBd/5FC arm followed by the 2-week oral regimen, the 1-week AmBd/5FC, then standard of care with the lowest cost in the 1-week AmBd/Flu arm. Compared to the lowest cost option the 1-week flucytosine course is most cost-effective at USD119/QALY. The cost impact analysis shows that the 1-week flucytosine course has an incremental cost of just over USD293 per patient per year compared to what is currently spent on standard of care. Sensitivity analyses suggest that the model is most sensitive to life expectancy and hospital costs, particularly infusion costs and length of stay.ConclusionsThe addition of flucytosine as induction therapy for the treatment of cryptococcal meningitis in patients infected with HIV is cost-effective when it is used as a 1-week AmBd/5FC regimen. Savings could be achieved with early discharge of patients as well as a reduction in the price of flucytosine.

In-hospital mortality of HIV-positive patients with acute kidney injury a decade after the roll-out of anti-retroviral therapy in Cape Town, South Africa

Background: Acute kidney injury (AKI) in HIV-infected patients in sub-Saharan Africa is a common cause of hospitalisation and is associated with high morbidity and mortality. There is a paucity of comparative data regarding the outcomes of AKI in those patients with and without HIV infection from the African continent. Methods: This was a single-centre retrospective study of all consecutive adult patients with AKI referred to the renal unit at Tygerberg Hospital for the period January 2015 to December 2016. The diagnosis of AKI required evidence of the following: a recent normal serum creatinine and/or normal kidney sizes on ultrasound examination and/or granular casts on urine microscopy. Kaplan–Meier curves and logistic regression were used to assess survival and identify factors predicting mortality. Results: We identified a total of 291 patients with AKI of whom 116 (40%) were HIV positive. HIV-positive patients had a mortality rate of 34.5% vs. 29.1% in the HIV-negative patients (P = 0.34). At hospital admission, HIV-positive patients had a higher admission serum creatinine (551 μmol/L vs. 190 μmol/L, P < 0.01). Of those who died, the HIV-positive patients were younger (41 vs. 52 years, P < 0.01), predominantly Black (87.5% vs. 23.5%, P < 0.01) and were mostly admitted to medical wards (92.5% vs. 41.2%, P < 0.01). There was no difference in mortality related to the use of renal replacement therapy (P = 0.50). Logistic regression identified mixed ancestry (OR 2.47, P = 0.02), HIV infection (OR 2.69, P < 0.01) and surgical ward admission (OR 2.05, P = 0.03) as predictors of death. Conclusions: In-hospital mortality of AKI was high, and HIV infection was associated with a greater risk of death. This may be the result of late presentation of both the AKI as well as the HIV infection.

Factors associated with desired fertility among HIV-positive women and men attending two urban clinics in Lilongwe, Malawi.

As access to antiretroviral therapy increases, more HIV-infected patients in sub-Saharan Africa may desire fertility. We conducted a cross-sectional study of reproductive health knowledge, attitudes and practices to identify factors associated with desired fertility among women and men receiving care at two large public HIV clinics in Lilongwe, Malawi. Research assistants administered questionnaires to participants. We performed descriptive, bivariable and multivariable analysis of factors related to desired fertility and of factors related to contraceptive non-use among participants who did not desire fertility. One-third of participants desired future children. Having a partner who desired fertility and having lower parity were associated with desiring children among both genders. For women, believing that pregnancy was unhealthy was associated with decreased fertility desire. Fifty-five percent of women and 69% of men who did not want children in the future reported using contraception at last intercourse. Increasing age, lower parity, and making the decision to use contraception herself were associated with contraceptive non-use among women who did not desire fertility. Having discussed family planning with his partner was associated with contraceptive use among men who did not desire fertility. Knowledge of these factors can guide reproductive health counseling and service provision.

Insulin resistance and associated factors among HIV-infected patients in sub-Saharan Africa: a cross sectional study from Cameroon

Introduction: little is known on the magnitude and correlates of insulin resistance in HIV-infected people in Africa. We determined the prevalence of insulin resistance and investigated associated factors in HIV-infected adult Cameroonians. Methods: we conducted a cross-sectional studyat the Yaounde Central Hospital, Cameroon; during which we enrolled HIV-infected people aged 30 to 74 years with no previous history of cardiovascular disease. The homeostatic model assessment of insulin resistance (HOMA-IR) index served to assess insulin sensitivity with insulin resistance defined by values of 2.1 or higher. Results: we included 452 patients (20% men). Their mean age was 44.4 ± 9.8 years and 88.5% of them were on antiretroviral therapy (93.3% on first line regimen including Zidovudine, lamivudine and Efavirenz/Nevirapine). Of all participants, 28.5% were overweight, 19.5% had obesity and 2.0% had diabetes. The prevalence of insulin resistance was 47.3% without any difference between patients on ART and those ART-naive (48.5% vs. 38.5%; p = 0.480). Obesity was the only factor independently associated with insulin resistance (adjusted odds ratio: 2.28; 95% confidence interval: 1.10-4.72). Conclusion: insulin resistance is present in nearly half of HIV-infected patients in Cameroon despite a low prevalence rate of diabetes, and is associated with obesity.

Choice of initial antiretroviral drugs and treatment outcomes among HIV-infected patients in sub-Saharan Africa: systematic review and meta-analysis of observational studies

BackgroundThe effectiveness of antiretroviral therapy (ART) depends on the choice of regimens during initiation. Most evidences from developed countries indicated that there is difference between efavirenz (EFV) and nevirapine (NVP). However, the evidences are limited in resource poor countries particularly in Africa. Thus, this systematic review and meta-analysis was carried out to summarize reported long-term treatment outcomes among people on first line therapy in sub-Saharan Africa.MethodsObservational studies that reported odds ratio, relative risk, hazard ratio, or standardized incidence ratio to compare risk of treatment failure among HIV/AIDS patients who initiated ART with EFV versus NVP were systematically searched. Searches were conducted using the MEDLINE database within PubMed, Google Scholar, HINARI, and Research Gates between 2007 and 2016. Information was extracted using standardized form. Pooled risk ratios (RR) and 95% confidence intervals (CI) were calculated using random-effect, generic inverse variance method.ResultA total of 6394 articles were identified, of which, 29 were eligible for review and abstraction in sub-Saharan Africa. Seventeen articles were used for the meta-analysis. Of a total of 121,092 independent study participants, 76,719 (63.36%) were females. Of these, 40,480 (33.43%) initiated with NVP containing regimen. Two studies did not report the median CD4 cell counts at initiation. Patients who have low CD4 cell counts initiated with EFV containing regimen. The pooled effect size indicated that treatment failure was reduced by 15%, 0.85 (95%CI: 0.75–0.98), and non-nucleoside reverse transcriptase inhibitor (NNRTI) switch was reduced by 43%, 0.57 (95%CI: 0.37–0.89).ConclusionThe risk of treatment failure and NNRTI switch were lower in patients who initiated with EFV than NVP-containing regimen. The review suggests that initiation of patients with EFV-containing regimen will reduce treatment failure and NNRTI switch.

Improved Retention With 6-Month Clinic Return Intervals for Stable Human Immunodeficiency Virus-Infected Patients in Zambia.

Extending appointment intervals for stable HIV-infected patients in sub-Saharan Africa can reduce patient opportunity costs and decongest overcrowded facilities. We analyzed a cohort of stable HIV-infected adults (on treatment with CD4 >200 cells/μL for more than 6 months) who presented for clinic visits in Lusaka, Zambia. We used multilevel, mixed-effects logistic regression adjusting for patient characteristics, including prior retention, to assess the association between scheduled appointment intervals and subsequent missed visits (>14 days late to next visit), gaps in medication (>14 days late to next pharmacy refill), and loss to follow-up (LTFU; >90 days late to next visit). A total of 62084 patients (66.6% female, median age 38, median CD4 438 cells/μL) made 501281 visits while stable on antiretroviral therapy. Most visits were scheduled around 1-month (25.0% clinical, 44.4% pharmacy) or 3-month intervals (49.8% clinical, 35.2% pharmacy), with fewer patients scheduled at 6-month intervals (10.3% clinical, 0.4% pharmacy). After adjustment and compared to patients scheduled to return in 1 month, patients with six-month clinic return intervals were the least likely to miss visits (adjusted odds ratio [aOR], 0.20; 95% confidence interval [CI], 0.17-0.24); miss medication pickups (aOR, 0.47; 95% CI 0.39-0.57), and become LTFU prior to the next visit (aOR, 0.41; 95% CI, 0.31-0.54). Six-month clinic return intervals were associated with decreased lateness, gaps in medication, and LTFU in stable HIV-infected patients and may represent a promising strategy to reduce patient burdens and decongest clinics.

Insulin resistance and associated factors among HIV-infected patients in sub-Saharan Africa: a cross sectional study from Cameroon

BackgroundLittle is known on the magnitude and correlates of insulin resistance in HIV-infected people in Africa. We determined the prevalence of insulin resistance and investigated associated factors in HIV-infected adult Cameroonians.MethodsWe conducted a cross-sectional study at the Yaoundé Central Hospital, Cameroon; during which we enrolled HIV-infected people aged 30 to 74 years with no previous history of cardiovascular disease. An homeostatic model assessment of insulin resistance (HOMA-IR) like index served to assess insulin sensitivity with insulin resistance defined by values of 2.1 or higher.ResultsWe included 452 patients (20% men). Their mean age was 44.4 ± 9.8 years and 88.5% of them were on antiretroviral therapy (93.3% on first line regimen including Zidovudine, lamivudine and Efavirenz/Nevirapine). Of all participants, 28.5% were overweight, 19.5% had obesity and 2.0% had diabetes. The prevalence of insulin resistance was 47.3% without any difference between patients on ART and those ART-naïve (48.5% vs. 38.5%; p = 0.480). Obesity was the only factor independently associated with insulin resistance (adjusted odds ratio: 2.28; 95% confidence interval: 1.10–4.72).ConclusionInsulin resistance is present in nearly half of HIV-infected patients in Cameroon despite a low prevalence rate of diabetes, and is associated with obesity.

New-onset type 2 diabetes mellitus among patients receiving HIV care at Newlands Clinic, Harare, Zimbabwe: retrospective cohort analysis.

To assess the incidence and associated factors of Type 2 Diabetes Mellitus (T2DM) among people living with HIV (PLHIV) in Zimbabwe. We analysed data of all HIV-infected patients older than 16years who attended Newlands Clinic between March 1, 2004 and April 29, 2015. The clinic considers patients whose random blood sugar is higher than 11.1mmol/l and which is confirmed by a fasting blood sugar higher than 7.0mmol/l to have T2DM. T2DM is also diagnosed in symptomatic patients who have a RBS >11.0mmol/l. Risk factors for developing T2DM were identified using Cox proportional hazard models adjusted for confounding. Missing baseline BMI data were multiply imputed. Results are presented as adjusted hazard ratios (aHR) with 95% confidence intervals (95% CI). Data for 4,110 participants were included: 67.2% were women; median age was 37 (IQR: 31-43) years. Median baseline CD4 count was 197 (IQR: 95-337) cells/mm3 . The proportion of participants with hypertension at baseline was 15.5% (n=638). Over a median follow-up time of 4.7 (IQR: 2.1-7.2) years, 57 patients developed T2DM; the overall incidence rate was 2.8 (95% CI: 2.1-3.6) per 1000 person-years of follow-up. Exposure to PIs was associated with T2DM (HR: 1.80, 95% CI: 1.04-3.09). In the multivariable analysis, obesity (BMI>30kg/m2 ) (aHR=2.26, 95% CI: 1.17-4.36), age >40years (aHR=2.16, 95% CI: 1.22-3.83) and male gender, (aHR=2.13, 95% CI: 1.22-3.72) were independently associated with the risk of T2DM. HIV-related factors (baseline CD4 cell count and baseline WHO clinical stage) were not independent risk factors for developing T2DM. Although the incidence of T2DM in this HIV cohort was lower than that has been observed in others, our results show that risk factors for developing T2DM among HIV-infected people are similar to those of the general population. HIV-infected patients in sub-Saharan Africa need a comprehensive approach to care that includes better health services for prevention, early detection and treatment of chronic diseases especially among the elderly and obese.

High correlation between Framingham equations with BMI and with lipids to estimate cardiovascular risks score at baseline in HIV-infected adults in the Temprano trial, ANRS 12136 in Côte d'Ivoire.

ContextData on cardiovascular risk (CVR) score among HIV-infected patients in sub-Saharan Africa are scarce. Our first objective was to compare the CVR score of Framingham utilizing BMI and lipids at baseline, and secondary to assess evolution of CVR score over time at Month 30 in the Temprano trial.MethodsHIV-infected adults with CD4 <800/mm3 without criteria for initiating ART were included and followed for 30 months in the Temprano trial, which assessed the benefits and risks of early antiretroviral treatment (ART) vs deferred ART. CVR score was estimated at baseline and Month-30 using Framingham equations with either BMI or lipids and classified as high (>20%), moderate (10–20%), and low risk (<10%). At baseline, we compare these two estimations utilizing the Pearson correlation test and analyze the increasing CV risk score over time by Proportional odds cumulative logit models for people attending the Month-30 (M30) visit.ResultsAmong the 2056 patients, 78% were women, median age was 35 years, and median CD4 count was 464/mm3, 6.8% were obese, 6.3% had hypertension, 7.8% were smokers (1.8% women, 26.8% men), 19% had Total Cholesterol (TC) >5mmol/L, and 1% diabetes at baseline. At baseline the concordance between the two Framingham equations was excellent (r = 0.95; p<0.0001). Among the 1700 patients who attended M30 visit and with available data, 1.3% had a high CV risk score at baseline and 3.1% at M30 visit using Framingham equation with BMI. Adjusted odds ratio (aOR) of being at a higher CV risk score at M30 visit compared to a higher CV risk score at M0 visit was 1.35 (CI 95% 1.17–1.57). Stratified by sex, the increasing CV risk score was OR 1.73 (CI 95%: 1.30–2.29) for women and OR 1.24 (CI 95%: 1.02–1.50) for men. Early ART was not associated with an increasing CV risk score (p = 0.88). Results for the 1422 patients with Framingham equation using lipids were similar.ConclusionIn a large trial evaluating early ART for HIV infection in Côte d’Ivoire, Framingham equation with BMI and lipids were highly correlated and CV risk score increases over time. Early ART was not significantly associated with this increasing CV risk score.

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

ObjectivesHIV-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).MethodsHIV-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.ResultsAmong 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).ConclusionWhile 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.

Suicidal Behavior and Associations with Quality of Life among HIV-Infected Patients in Ibadan, Nigeria.

Suicidality has rarely been studied in HIV-infected patients in sub-Saharan Africa. This study explored suicidal behavior in a clinic sample of people living with HIV, in Nigeria. Consecutive patients were interviewed using the Composite International Diagnostic Interview (CIDI-10.0) and the World Health Organization Quality of Life (WHO-QOL-HIV-BREF). Associations of suicidal behavior were explored using logistic regression models. In this sample of 828 patients (71% female, mean age 41.3 ± 10 years), prevalence of suicidal behaviors were 15.1%, 5.8%, and 3.9% for suicidal ideation, plans, and attempts, respectively. Women were more likely than men to report suicidal ideation (odds ratio 1.7; 95% confidence interval 1.05-2.64). Depression and/or anxiety disorder was associated with increased odds of all suicidal behaviors. Suicidal behavior was associated with significantly lower overall and domain scores on the WHO-QOL. Suicidal behaviors were common and significantly associated with the presence of mental disorders and lower quality of life.

Molecular types of Cryptococcus gattii/Cryptococcus neoformans species complex from clinical and environmental sources in Nairobi, Kenya.

Cryptococcal meningitis infections cause high mortality rates among HIV-infected patients in Sub-Saharan Africa. The high incidences of cryptococcal infections may be attributed to common environmental sources which, if identified, could lead to institution of appropriate control strategies. To determine the genotypes of Cryptococcus gattii/C. neoformans- species complex from Nairobi, Kenya, 123 clinical and environmental isolates were characterised. Typing was done using orotidine monophosphate pyrophosphorylase (URA5) gene restriction fragment length polymorphism (URA5-RFLP). The majority of the isolates [105/123; 85.4%] were C. neoformans genotype (AFLPI/VNI) and 1.6% AFLP1A/VNB/VNII, whereas (13%) were C. gattii (AFLP4/VGI). This is the first report on the genotypes of C. gattii/C. neoformans species complex from clinical and environmental sources in Nairobi, Kenya and the isolation of C. gattii genotype AFLP4/VGI from the environment in Kenya.

Epidemiology of HBV infection in a cohort of Ugandan HIV-infected patients and rate and pattern of lamivudine-resistant HBV infection in patients receiving antiretroviral therapy.

Many HIV-infected patients in sub-Saharan Africa are not routinely screened for hepatitis B virus (HBV) infection and are on antiretroviral therapy (ART) regimens containing only lamivudine as anti-HBV active drug. In 2009-2011, we screened for hepatitis B surface antigen (HBsAg) in 2820 HIV-infected adults patients at the Mbarara Hospital Uganda and investigated risk factors for HBV infection. Using samples of dried plasma or blood spots, we tested for HBV viral load and HBV drug resistance mutations in all HBsAg-positive patients on ART for ≥ 12 months. In this study, 109 patients tested HBsAg positive (3.9%; 109/2820). HBsAg-positive patients were more likely to have had >4 lifetime sexual partners (p<0.01). Of the 55 HBsAg-positive patients on ART for ≥ 12 months, 53 were only on lamivudine as anti-HBV active drug and two were on tenofovir and lamivudine. HBV-DNA was detected in 30 patients (54.5%; 30/55), all on lamivudine-monotherapy. Of the 23 patients in whom HBV-DNA sequencing was successful, 17 had lamivudine-resistant HBV strains harbouring rtM204V/I mutations accompanied by secondary/compensatory mutations. Our study suggests that sexual transmission may represent a major mode of spread of HBV in southwest Uganda and confirms the importance of screening for HBV and of using ART regimens containing tenofovir in HIV/HBV co-infected patients.

Sulfamethoxazole susceptibility of Mycobacterium tuberculosis isolates from HIV-infected Ugandan adults with tuberculosis taking trimethoprim-sulfamethoxazole prophylaxis.

Additional drugs are needed for the treatment of multidrug-resistant tuberculosis (TB). Sulfamethoxazole has been shown to have in vitro activity against Mycobacterium tuberculosis; however, there is concern about resistance given the widespread use of trimethoprim-sulfamethoxazole prophylaxis among HIV-infected patients in sub-Saharan Africa. Thirty-eight of 40 Mycobacterium tuberculosis isolates (95%) from pretreatment sputum samples from Ugandan adults with pulmonary TB, including HIV-infected patients taking trimethoprim-sulfamethoxazole prophylaxis, were susceptible with MICs of ≤38.4 μg/ml.

Examining the Psychometric Properties of the Beck Depression Inventory-IiUsing an Item Response Modelling Approach in an HIV Infected Population in Kampala, Uganda

Abstract Background: Depression is prevalent among individuals living with HIV, with evidence suggesting that more than one third of people with HIV/AIDS may have mood disorders or clinically significant depressive symptoms. Sub-Saharan Africa bears the greatest burden due to HIV/AIDS. The social, economic and health impact of depression in sub-Saharan Africa is great. However, there are few scales for measuring depression that have been validated in this population. The Beck Depression Inventory (BDI-II) is one of the most widely used instruments for assessing depressive symptom severity. Although the BDI-II has been used in sub-Saharan Africa, the psychometric properties of the BDI have not been well studied in this region especially among HIV infected patients. The purpose of this analysis therefore, was to examine the psychometric properties of the BDI-II in a low income HIV-infected population using an item response modeling (IRM) approach. Methods: Data for this analysis were obtained from a survey of adult members of the Mother-To-Child-Transmission Plus Program in Kampala, Uganda. The BDI-II was administered to every study participant at enrollment. Data were analyzed using both the Classical Test Theory (CTT) approach and the Item Response Modeling (IRM) approach. Results: Mean depression score was 8.86 + 5.44. The Cronbach’s alpha was 0.79 and the reliability coefficient was 0.86. The Wright map showed a good spread of the items over the entire span of the construct of depression. Differential item functioning was observed for some items. There was evidence for validity based on instrument content, internal structure and relations to other external variables. Conclusion: In conclusion, this analysis demonstrated good psychometric properties of the BDI-II when used to screen for depression in a low income predominantly female HIV-infected population. These findings therefore support the use of the BDI-II in assessing depressive symptoms for HIV-infected patients in sub-Saharan Africa especially women.

Do the epidemiology, physiological mechanisms and characteristics of hepatocellular carcinoma in HIV-infected patients justify specific screening policies?

Reducing the incidence of hepatocellular carcinoma (HCC) in HIV-infected patients has become a serious problem when managing these patients. There are many explanations for this disease evolution, which notably include their longer survival under effective antiviral therapy and also the more rapid evolution of chronic liver disease. Despite recent advances in the management of hepatitis B (HBV) and hepatitis C (HCV) viral diseases, which will probably increase the number of patients achieving a virological response, HIV-infected patients with cirrhosis are still at risk of the onset of HCC. This evolution to HCC is also correlated to other comorbidities such as excessive alcohol consumption and nonalcoholic steatohepatitis (NASH). HCC thus remains a public health issue in this population. The poor prognosis and aggressiveness of HCC have been fully demonstrated, but the mechanisms underlying this aggressiveness are not yet well defined. As well as underlying mechanisms that contribute to accelerating hepatocarcinogenesis in HIV-infected patients, there are other reasons why HIV-infected patients should be considered a higher risk population. This review discusses the principal epidemiological determinants; the mechanisms of pathogenesis; and the treatment of HCC in HIV/HBV and HIV/HCV coinfected patients. It also discusses the probable need to develop a specific screening policy for HCC in this population in order to prevent the rapid development and to make them more amenable to a curative treatment.

Predictive Value of Anemia for Tuberculosis in HIV-Infected Patients in Sub-Saharan Africa

The relationship between anemia and undiagnosed tuberculosis (TB) in patients living with HIV in sub-Saharan Africa is incompletely defined. We assessed the prevalence of TB among those with HIV-related anemia and evaluated new means of rapid TB diagnosis. Blood hemoglobin levels were measured in unselected antiretroviral treatment-naive patients in Cape Town, South Africa, and anemia was classified according to World Health Organization criteria. All patients were screened for TB by testing paired sputum samples using liquid culture (reference standard), fluorescence microscopy, and Xpert MTB/RIF. Urine samples were tested for lipoarabinomannan (LAM) using the Determine TB-LAM diagnostic assay. Of 602 adults screened, 485 had complete results. Normal hemoglobin levels were found in 44.5% (n = 216) of patients, and mild, moderate, or severe anemia were present in 24.9% (n = 121), 25.4% (n = 123) and 5.2% (n = 25) of patients, respectively. Culture-confirmed pulmonary TB was diagnosed in 8.8% (19/216) of those without anemia compared with 16.5% (20/121), 26.0% (32/123), and 40.0% (10/25) among those with mild, moderate, or severe anemia, respectively (P < 0.001). Anemia was a strong independent predictor of TB. The sensitivities of diagnostic assays were much higher among those with moderate/severe anemia compared with those with no/mild anemia using sputum microscopy (42.9% vs 15.4%), urine LAM (54.8% vs 0%), sputum microscopy plus urine LAM (71.4% vs 15.4%), and sputum Xpert (73.8% vs 41.0%) (P < 0.01 for all). A very high prevalence of undiagnosed TB was found in patients with moderate or severe anemia. Such patients should be prioritized for routine microbiological investigation using rapid diagnostic assays.