Ethical issues surrounding the implementation of long-acting injectable antiretroviral therapy in sub-Saharan Africa.

Background: This article discusses the ethical issues surrounding the integration of long-acting injectable antiretroviral therapy (LA-ART) in the programmatic management of human immunodeficiency virus (HIV). As the medical landscape evolves, implementing LA-ART introduces many ethical issues that should be considered for the success of scale-up in diverse settings.

Methods: This article examines key issues such as bioethical concerns around the rollout of LA-ART, including regulatory requirements, a person's autonomy, informed consent, privacy and confidentiality; the societal implications of providing LA-ART, including the impact on stigma and discrimination; ethics around who receives LA-ART, financial accessibility, equitable access, inclusive decision-making and cultural sensitivity; and the ethics of providing an expensive intervention, including cost-effectiveness, supply chain sustainability and resource allocation.

Clinical predictors of 3-month isoniazid rifapentine (3HP)-related adverse drug reactions (ADR) during tuberculosis preventive therapy (PAnDoRA-3HP study): an observational study protocol.

Introduction: Tuberculosis (TB) is the leading infectious cause of death globally. Despite WHO recommendations for TB preventive therapy (TPT), challenges persist, including incompletion of treatment and adverse drug reactions (ADRs). There is limited data on the 3-month isoniazid and rifapentine (3HP) pharmacokinetics, pharmacogenomics and their relation with ADRs.

Clinical pharmacology considerations and drug-drug interactions with long-acting cabotegravir and rilpivirine relevant to sub-Saharan Africa.

Long-acting injectable (LAI) cabotegravir and rilpivirine for HIV treatment and LAI cabotegravir for pre-exposure HIV prophylaxis are being rolled out in a multitude of countries worldwide. Due to the prolonged exposure, it can be challenging to undertake 'traditional' pharmacokinetic studies and current guidance is derived from their oral equivalents or physiologically based pharmacokinetic studies. This review aims to consider pharmacokinetic characteristics of cabotegravir and rilpivirine and describe anticipated drug-drug interactions (DDIs) with frequent concomitant medications in African settings.

Dolutegravir use over 48 weeks is not associated with worsening insulin resistance and pancreatic beta cell function in a cohort of HIV-infected Ugandan adults.

Background The Uganda Ministry of Health issued restrictive guidelines on the use of dolutegravir (DTG) in persons stratified to have a heightened risk of diabetes mellitus. This followed multiple reports of persons with HIV (PWH) presenting with accelerated hyperglycemia after a few weeks to months of exposure to DTG. Having demonstrated a low incidence of diabetes mellitus and improving blood glucose trajectories in a cohort of ART naïve Ugandan PWH on DTG, we sought to determine whether the observed improvement in blood glucose did not mask background compensated insulin resistance.

Prevalence of overweight and obesity and associated factors among people living with HIV attending a tertiary care clinic in Uganda.

Background: Overweight and obesity are significantly increasing among people living with HIV (PLWH), contributing to the risk of major adverse cardio-metabolic events. However, little is known on its prevalence among PLWH in sub-Saharan Africa. In this study, we report the prevalence and factors associated with overweight and obesity among PLWH in a large tertiary HIV clinic in Kampala, Uganda.

Factors associated with uptake of contraceptives among HIV positive women on dolutegravir based anti-retroviral treatment-a cross sectional survey in urban Uganda.

Background: In May 2018, following the preliminary results of a study in Botswana that reported congenital anomalies in babies born to HIV-positive women taking dolutegravir drug, the WHO issued a teratogenicity alert. However, there are scarce data on the impact of this guidance on contraceptive uptake among women taking dolutegravir. We assessed the uptake of contraceptives in HIV-positive women of reproductive age on dolutegravir regimens.

The burden of drug resistant tuberculosis in a predominantly nomadic population in Uganda: a mixed methods study.

Background: Emergence of drug resistant tuberculosis (DR-TB) has aggravated the tuberculosis (TB) public health burden worldwide and especially in low income settings. We present findings from a predominantly nomadic population in Karamoja, Uganda with a high-TB burden (3500 new cases annually) and sought to determine the prevalence, patterns, factors associated with DR-TB.

Methods: We used mixed methods of data collection.

The Potential Teratogenicity Alert for Women Conceiving on Dolutegravir-Based Regimens: An Assessment of Risk Communication by an Urban HIV Clinic in Uganda and Choices made by Women.

Unlabelled: INTRODUCTION AND OBJECTIVE: In May 2018, the World Health Organization and other regulatory authorities released a safety alert for dolutegravir related to a risk of neural tube defects among women exposed to dolutegravir at the time of conception. Models of how drug safety information can be shared effectively in the shortest time are necessary to prevent interruptions of public health programs. We sought to describe an implementation process to inform and support women already on dolutegravir-based regimens at the time of conception to make informed choices following the safety alert of a potential teratogenicity risk.

Phase I EnACT Trial of the Safety and Tolerability of a Novel Oral Formulation of Amphotericin B.

Amphotericin B deoxycholate (AMB) has substantial toxicities. A novel encochleated amphotericin B deoxycholate (cAMB) formulation has oral bioavailability, efficacy in an animal model, and minimal toxicity due to targeted drug delivery into macrophages, where intracellular fungi reside. We conducted a phase I, ascending-dose trial of cAMB administered at 1.

Erratum: Symptomatic cerebrospinal fluid HIV-1 escape in two patients on second-line antiretroviral therapy in Uganda.

[This corrects the article DOI: 10.1093/omcr/omy132.].

An observational study in an urban Ugandan clinic comparing virological outcomes of patients switched from first-line antiretroviral regimens to second-line regimens containing ritonavir-boosted atazanavir or ritonavir-boosted lopinavir.

Background: The World Health Organisation approved boosted atazanavir as a preferred second line protease inhibitor in 2010. This is as an alternative to the current boosted lopinavir. Atazanavir has a lower genetic barrier than lopinavir.

Symptomatic cerebrospinal fluid HIV-1 escape in two patients on second-line antiretroviral therapy in Uganda.

Two HIV-infected individuals on second-line atazanavir-based antiretroviral therapy presented with neuropsychiatric symptoms. Cerebrospinal fluid HIV RNA was higher than plasma HIV RNA and antiretroviral regimens' optimization led to prompt resolution of symptoms in one. Patients on second-line atazanavir-based antiretroviral therapy with documented previous treatment failure may be at risk of symptomatic cerebrospinal fluid escape.

High prevalence and long duration of nervous system and psychiatric adverse drug reactions in Ugandan patients taking efavirenz 600 mg daily.

Background: Efavirenz-related nervous system or psychiatric adverse drug reactions (ADRs) are conventionally reported to resolve soon after initiation, with incidence of dizziness at 8.5% in large clinical trials. Patients of black ethnicity are genetically at greater risk of elevated efavirenz exposure, which has been linked to nervous system toxicity.

Boosted lopinavir vs boosted atazanavir in patients failing a NNRTI first line regimen in an urban clinic in Kampala.

Introduction: In 2011 Uganda recommended boosted atazanavir (ATV/r) as the preferred PI for second line due to once daily dosing, replacing aluvia (LPV/r) (1, 2). The evidence was based on the BMS O45 trial, of LPV/r vs ATV/r was performed in a high-income setting, on patients with prior PI use and resistance testing (2, 3). There are no RCTs or observational studies comparing use of ATV/r with LPV/r in patients failing NNRTI first line antiretroviral therapy in sub-Saharan Africa (3, 4).