Effect of high-dose multivitamin supplements on alanine aminotransferase elevations among adults living with HIV on antiretroviral therapy in Tanzania.

Background: HIV infection can cause malabsorption and rapid utilization of nutrients. A randomized trial of multivitamin supplementation among people living with HIV/AIDS (PLWHA) initiating antiretroviral therapy (ART) in Tanzania was stopped early due to increased alanine aminotransferase (ALT) concentrations in the multiple recommended dietary allowances (RDA) multivitamin group. We conducted detailed analysis to assess the effect of multivitamins on ALT elevations and evaluate whether subgroups of PLWHA have greater hepatotoxicity risks associated with the use of high-dose multivitamins.

HIV viral suppression in the era of dolutegravir use: Findings from a national survey in Tanzania.

Background: Tanzania has made significant progress in improving access to HIV care and treatment. However, virologic suppression among people living with HIV (PLHIV) has not been fully realized. In March 2019, Tanzania introduced a World Health Organization (WHO)-recommended dolutegravir-based regimen as the default first-line regimen.

CYP2B6 and ABCB1 genotypes predict methadone plasma exposure among patients on maintenance therapy against opioid addictions in Tanzania.

Aims: Methadone maintenance therapy (MMT) exhibits significant variability in pharmacokinetics and clinical response, partly due to genetic variations. However, data from sub-Saharan African populations are lacking. We examined plasma methadone variability and pharmacogenetic influences among opioid-addicted Tanzanian patients.

Gentamicin concentration and acute kidney injury in term neonates treated for neonatal sepsis with gentamicin and ampicillin-cloxacillin combination.

Gentamicin is widely used to treat neonatal infections caused by both Gram-negative and Gram-positive bacteria, and the WHO recommends its use while monitoring serum creatinine and gentamicin concentrations to avoid drug-induced nephrotoxicity and ototoxicity. Yet in some resource-limited settings, the drug is used without monitoring. A population pharmacokinetics study involving term neonates with neonatal infection admitted to a neonatal unit.

Molecular epidemiology of pregnancy using omics data: advances, success stories, and challenges.

Multi-omics approaches have been successfully applied to investigate pregnancy and health outcomes at a molecular and genetic level in several studies. As omics technologies advance, research areas are open to study further. Here we discuss overall trends and examples of successfully using omics technologies and techniques (e.

Concomitant squamous cell carcinoma of the bladder and renal tuberculosis: A case report from northern Tanzania.

Concomitant squamous cell carcinoma (SCC) and renal tuberculosis (TB) are a rare presentation. It is associated with poor prognosis and poses a challenge in the management. To the best of our knowledge, we present a challenging first document case of locally advanced SCC of the bladder with coactive renal tuberculosis.

Polypharmacy and health related quality of life among older adults on antiretroviral therapy in a tertiary hospital in Tanzania: a hospital-based cross-sectional study.

Background: Human immunodeficiency virus (HIV) chronicity in the midst of old age multiplies the risk for chronic non communicable diseases. The old are predisposed to drug-drug interactions, overlapping toxicities and impairment of the quality of life (QoL) due to age-related physiological changes. We investigated polypharmacy, QoL and associated factors among older HIV-infected adults at Muhimbili National hospitals in Dar es Salaam Tanzania.

HIV virologic response, patterns of drug resistance mutations and correlates among adolescents and young adults: A cross-sectional study in Tanzania.

Background: The emergence of HIV drug resistance mutations (DRMs) is of significant threat to achieving viral suppression (VS) in the quest to achieve global elimination targets. We hereby report virologic outcomes and patterns of acquired DRMs and its associated factors among adolescents and young adults (AYA) from a broader HIV drug resistance surveillance conducted in Tanzania.

Methods: Data of AYA was extracted from a cross-sectional study conducted in 36 selected facilities using a two-stage cluster sampling design.

Emerging integrase strand transfer inhibitor drug resistance mutations among children and adults on ART in Tanzania: findings from a national representative HIV drug resistance survey.

Background: Despite the scale-up of ART and the rollout in Tanzania of dolutegravir, an integrase strand transfer inhibitor (INSTI), treatment success has not been fully realized. HIV drug resistance (HIVDR), including dolutegravir resistance, could be implicated in the notable suboptimal viral load (VL) suppression among HIV patients.

Objectives: To determine the prevalence and patterns of acquired drug resistance mutations (DRMs) among children and adults in Tanzania.

Factors influencing receipt of an antibiotic prescription among insured patients in Tanzania: a cross-sectional study.

Objectives: There are limited data on factors influencing antibiotic prescription among insured patients. We assessed for correlates of an antibiotic prescription among insured patients.

Design: A cross-sectional study.

The prevalence and pattern of antibiotic prescription among insured patients in Dar es Salaam Tanzania.

Introduction: high prevalence of antibiotic prescriptions may contribute to the problem of antibiotic resistance. Understanding the pattern of antibiotic prescriptions in a country may inform monitoring and stewardship activities, which are crucial in the fight against antibiotic resistance. We aimed to determine the prevalence and describe the pattern of antibiotic prescriptions among National Health Insurance Fund (NHIF) insured patients receiving treatment at health facilities in Ilala Municipality, Dar es Salaam, Tanzania.

Effect of aspirin on HIV disease progression among HIV-infected individuals initiating antiretroviral therapy: study protocol for a randomised controlled trial.

Introduction: An increase in cardiovascular disease (CVD) among people living with HIV infection is linked to platelet and immune activation, a phenomenon unabolished by antiretroviral (ARV) drugs alone. In small studies, aspirin (acetylsalicylic acid [ASA]) has been shown to control immune activation, increase CD4+ count, halt HIV disease progression and reduce HIV viral load (HVL). We present a protocol for a larger ongoing randomised placebo controlled trial on the effect of an addition of ASA to ARV drugs on HIV disease progression.

Impact of Population and Pharmacogenetics Variations on Efavirenz Pharmacokinetics and Immunologic Outcomes During Anti-Tuberculosis Co-Therapy: A Parallel Prospective Cohort Study in Two Sub-Sahara African Populations.

Efavirenz-based combination antiretroviral-therapy (cART) is the recommended regimen during tuberculosis (TB) therapy. In a multi-national parallel prospective-cohort study, we investigated the impact of population and pharmacogenetic variations for efavirenz pharmacokinetics, auto-induction, and immunologic outcome during antituberculosis treatment. A total of 921 treatment-naïve HIV patients with (196 Ethiopians and 231 Tanzanians) or without TB co-infection (285 Ethiopians and 209 Tanzanians) were enrolled and treated with efavirenz-based cART.

Risk Factors for Alanine Aminotransferase Elevations in a Prospective Cohort of HIV-Infected Tanzanian Adults Initiating Antiretroviral Therapy.

Introduction: Serum alanine aminotransferase (ALT) elevations are common among HIV-infected patients on combination antiretroviral therapy (cART).

Approach: We conducted a prospective cohort study of 3023 HIV-infected Tanzanian adults initiating cART. We assessed risk factors for mild/moderate ALT elevations >40 IU/L and severe ALT elevations >200 IU/L.

Adherence to combination antiretroviral therapy among orphaned children in Dar es Salaam, Tanzania.

Background: Adherence to combination antiretroviral therapy (cART) among HIV-infected children is often complicated by various factors including medication formulation, dosing frequency, drug toxicities, age and developmental stage, psychosocial and behavioural characteristics of both children and caregivers and can additionally be complicated by being an orphan.

Objectives: This study was aimed at determining the factors and the extent of their influence on cART adherence among HIV-infected orphaned children attending Care and Treatment Centres (CTCs) in Dar es Salaam, Tanzania.

Methods: A cross-sectional study was performed, which assessed adherence in HIV-positive orphaned children aged 2-14 years receiving nevirapine (NVP) based cART for at least 6 months.

Long-term efavirenz pharmacokinetics is comparable between Tanzanian HIV and HIV/Tuberculosis patients with the same CYP2B6*6 genotype.

The impact of anti-tuberculosis co-treatment on efavirenz (EFV) exposure is still uncertain as contradictory reports exist, and the relevance of CYP2B6*6 genetic polymorphism on efavirenz clearance while on-and-off anti-tuberculosis co-treatment is not well investigated. We investigated the determinants of long-term efavirenz pharmacokinetics by enrolling HIV (n = 20) and HIV/Tuberculosis (n = 36) subjects undergoing efavirenz and efavirenz/rifampicin co-treatment respectively. Pharmacokinetic samplings were done 16 weeks after initiation of efavirenz-based anti-retroviral therapy and eight weeks after completion of rifampicin-based anti-tuberculosis treatment.

Variability of efavirenz plasma concentrations among pediatric HIV patients treated with efavirenz based combination antiretroviral therapy in Dar es Salaam, Tanzania.

Background: Children are subject to varying drug pharmacokinetics which influence plasma drug levels, and hence treatment outcomes especially for drugs like efavirenz whose plasma concentrations are directly related to treatment outcomes. This study is aimed at determining plasma efavirenz concentrations among Tanzanian pediatric HIV-1 patients on efavirenz-based combination antiretroviral therapy (cART) and relating it to clinical, immunological and virologic treatment responses.

Methods: A cross sectional study involving pediatric HIV patients aged 5-15 years on efavirenz-based cART for ≥ 6 months were recruited in Dar es Salaam.

Neuropsychiatric manifestations among HIV-1 infected African patients receiving efavirenz-based cART with or without tuberculosis treatment containing rifampicin.

Purpose: Efavirenz-based combination antiretroviral therapy (cART) is associated with neuropsychiatric adverse events. We investigated the time to onset, duration, clinical implications, impact of pharmacogenetic variations, and anti-tuberculosis co-treatment on efavirenz-associated neuropsychiatric manifestations.

Methods: Prospective cohort study of cART naïve HIV patients with or without tuberculosis (HIV-TB) co-infection treated with efavirenz-based cART.

Drug resistance testing through remote genotyping and predicted treatment options in human immunodeficiency virus type 1 infected Tanzanian subjects failing first or second line antiretroviral therapy.

Introduction: Antiretroviral therapy (ART) has been successfully introduced in low-middle income countries. However an increasing rate of ART failure with resistant virus is reported. We therefore described the pattern of drug resistance mutations at antiretroviral treatment (ART) failure in a real-life Tanzanian setting using the remote genotyping procedure and thereafter predicted future treatment options using rule-based algorithm and the EuResist bioinformatics predictive engine.

SLCO1B1 Gene Variations Among Tanzanians, Ethiopians, and Europeans: Relevance for African and Worldwide Precision Medicine.

The solute carrier organic anion transporter family member 1B1 (SLCO1B1) gene encodes for a membrane-bound organic anion transporter protein involved in active cellular influx of many endogenous compounds and xenobiotics. SLCO1B1 genetic variation is associated, for example, with highly variable rifampicin exposure, thus influencing the cornerstone antituberculosis therapy, especially in sub-Saharan Africa where it is a key therapeutic modality. Yet, there is no SLCO1B1-guided pharmacogenetic dosing recommendation for rifampicin to reduce the risk of adverse events or therapy failure.

Copy number variation of Fc gamma receptor genes in HIV-infected and HIV-tuberculosis co-infected individuals in sub-Saharan Africa.

AIDS, caused by the retrovirus HIV, remains the largest cause of morbidity in sub-Saharan Africa yet almost all genetic studies have focused on cohorts from Western countries. HIV shows high co-morbidity with tuberculosis (TB), as HIV stimulates the reactivation of latent tuberculosis (TB). Recent clinical trials suggest that an effective anti-HIV response correlates with non-neutralising antibodies.

CCL3L1 copy number, HIV load, and immune reconstitution in sub-Saharan Africans.

Background: The role of copy number variation of the CCL3L1 gene, encoding MIP1α, in contributing to the host variation in susceptibility and response to HIV infection is controversial. Here we analyse a sub-Saharan African cohort from Tanzania and Ethiopia, two countries with a high prevalence of HIV-1 and a high co-morbidity of HIV with tuberculosis.

Methods: We use a form of quantitative PCR called the paralogue ratio test to determine CCL3L1 gene copy number in 1134 individuals and validate our copy number typing using array comparative genomic hybridisation and fiber-FISH.

Importance of ethnicity, CYP2B6 and ABCB1 genotype for efavirenz pharmacokinetics and treatment outcomes: a parallel-group prospective cohort study in two sub-Saharan Africa populations.

Objectives: We evaluated the importance of ethnicity and pharmacogenetic variations in determining efavirenz pharmacokinetics, auto-induction and immunological outcomes in two African populations.

Methods: ART naïve HIV patients from Ethiopia (n = 285) and Tanzania (n = 209) were prospectively enrolled in parallel to start efavirenz based HAART. CD4+ cell counts were determined at baseline, 12, 24 and 48 weeks.

β-defensin genomic copy number is associated with HIV load and immune reconstitution in sub-saharan Africans.

AIDS, caused by the retrovirus human immunodeficiency virus (HIV), is the leading cause of death of economically active people (age, 15-59 years) in sub-Saharan Africa. The host genetic variability of immune response to HIV and immune reconstitution following initiation of highly active antiretroviral therapy (HAART) is poorly understood. Here we focused on copy number variation of the β-defensin genes, which have been shown to have anti-HIV activity, and are important chemoattractants for Th17 lymphocytes via the chemokine receptor CCR6.

Liver enzyme abnormalities and associated risk factors in HIV patients on efavirenz-based HAART with or without tuberculosis co-infection in Tanzania.

Objectives: To investigate the timing, incidence, clinical presentation, pharmacokinetics and pharmacogenetic predictors for antiretroviral and anti-tuberculosis drug induced liver injury (DILI) in HIV patients with or without TB co-infection.

Methods And Findings: A total of 473 treatment naïve HIV patients (253 HIV only and 220 with HIV-TB co-infection) were enrolled prospectively. Plasma efavirenz concentration and CYP2B6*6, CYP3A5*3, *6 and *7, ABCB1 3435C/T and SLCO1B1 genotypes were determined.