HIV infection in adult Ugandans with new-onset type 2 diabetes: exploring its influence on the anthropometric and metabolic profile.

OBJECTIVE: HIV infection increases the risk of type 2 diabetes and may influence its phenotypic profile. In this study, we aimed to compare the anthropometric and metabolic characteristics of HIV-infected and uninfected adult Ugandans with new-onset type 2 diabetes to evaluate the influence of HIV infection on specific surrogate markers of adiposity, insulin resistance, and pancreatic beta-cell function. METHODS: We consecutively recruited 500 HIV-infected and uninfected adult Ugandans with new-onset type 2 diabetes (diagnosed in < 3 months) from seven tertiary hospitals over a 20-month period and compared their anthropometric and metabolic characteristics to identify any significant differences. RESULTS: Of the 500 participants with new-onset type 2 diabetes, 59 (11.8%) had a self-reported history of HIV infection. Compared with HIV-uninfected participants with type 2 diabetes, participants with HIV infection and type 2 diabetes had a lower median (IQR) hip circumference (97.8 [91.0-106.0] cm vs. 104.0 [96.0-112.0], p = 0.002) and visceral fat level (8 [6-11] vs. 10 [7-12], p < 0.001) assessed using bioimpedance analysis. No statistically significant difference was noted with the markers of pancreatic beta-cell function (fasting, 30-minute, and 120-minute C-peptide concentrations, oral insulinogenic index, and homeostatic model assessment 2-beta cell function) and insulin resistance (homeostatic model assessment 2-insulin resistance) between both groups. CONCLUSION: In our study population, HIV infection was not associated with increased adiposity, pancreatic beta-cell function, and insulin resistance. Large prospective studies are needed to investigate the effect of HIV on the pathogenesis of type 2 diabetes in adult Ugandans.

Patient experiences of switching from Efavirenz- to Dolutegravir-based antiretroviral therapy: a qualitative study in Uganda.

BACKGROUND: In 2019, the World Health Organisation (WHO) recommended Dolutegravir (DTG) as the preferred first-line antiretroviral treatment (ART) for all persons with HIV. ART regimen switches may affect HIV treatment adherence. We sought to describe patient experiences switching from EFV to DTG-based ART in Kampala, Uganda. METHODS: Between July and September 2019, we purposively sampled adults living with HIV who had switched to DTG at the Infectious Diseases Institute HIV clinic. We conducted in-depth interviews with adults who switched to DTG, to explore their preparation to switch and experiences on DTG. Interviews were audio-recorded, transcribed and analysed thematically using Atlas ti version 8 software. RESULTS: We interviewed 25 adults: 18 (72%) were women, and the median age was 35 years (interquartile range [IQR] 30-40). Median length on ART before switching to DTG was 67 months (IQR 51-125). Duration on DTG after switching was 16 months (IQR 10-18). Participants reported accepting provider recommendations to switch to DTG mainly because they anticipated that swallowing a smaller pill once a day would be more convenient. While most participants initially felt uncertain about drug switching, their providers offer of frequent appointments and a toll-free number to call in the event of side effects allayed their anxiety. At the same time, participants said they felt rushed to switch to the new ART regimen considering that they had been on their previous regimen(s) for several years and the switch to DTG happened during a routine visit when they had expected their regular prescription. Some participants felt unprepared for new adverse events associated with DTG and for the abrupt change in treatment schedule. Most participants said they needed additional support from their health providers before and after switching to DTG. CONCLUSION AND RECOMMENDATIONS: Adults living with HIV stable on an EFV-based regimen but were switched to DTG in a program-wide policy change found the duration between counselling and drug switching inadequate. DTG was nonetheless largely preferred because of the small pill size, once daily dosing, and absence of EFV-like side effects. Community-engaged research is needed to devise acceptable ways to prepare participants for switching ART at scale.

Prevalence, Clinical Features, and Predictors of Adrenal Insufficiency in Adults With Tuberculosis or HIV: A Systematic Review and Meta-analysis.

Background: Despite the high frequency of adrenal insufficiency (AI) in patients with tuberculosis or HIV, its diagnosis is often missed or delayed resulting in increased mortality. This systematic review and meta-analysis aimed to document the prevalence, significant clinical features, and predictors of AI in adult patients with tuberculosis or HIV. Methods: We systematically searched databases (Medline, Embase, CINAHL, Cochrane Library, and Africa Journal Online) for published studies on AI in adult patients with tuberculosis or HIV. The pooled prevalence of AI was determined by a random-effect model meta-analysis. A narrative review was used to describe the significant clinical features and predictors of AI in adult patients with tuberculosis or HIV. Results: A total of 46 studies involving 4044 adults were included: 1599 with tuberculosis and 2445 with HIV. The pooled prevalence of AI was 33% (95% CI, 22%-45%; I2 = 97.7%, P < .001) in participants with tuberculosis and 28% (95% CI, 18%-38%; I2 = 98.9%, P < .001) in those with HIV. Presentation with multidrug-resistant tuberculosis, abdominal pain, salt craving, myalgia, increased severity and duration of tuberculosis disease, and the absence of nausea predicted AI in participants with tuberculosis in 4 studies. Cytomegalovirus antigenemia positivity, rifampicin therapy, and eosinophilia >3% predicted AI in participants with HIV in 2 studies. Conclusions: AI is relatively common in adults with tuberculosis or HIV. Its timely screening, diagnosis, and management in patients with these 2 conditions should be encouraged to avert mortality.

Two-drug regimens for the treatment of HIV in Africa.

Two-drug regimens for the treatment of HIV are increasingly available. The oral regimen of dolutegravir plus lamivudine is recommended as a preferred option in multiple national guidelines but is not currently included in WHO HIV treatment guidelines nor widely used in Africa. Long-acting injectable cabotegravir and rilpivirine is being rolled out in the USA, Europe, and Australia but its use in sub-Saharan Africa is currently restricted to clinical trials. Given the increasing life expectancy, rising prevalence of non-communicable diseases, and resulting polypharmacy among people living with HIV, there are potential advantages to the use of two-drug regimens, particularly in African women, adolescents, and older adults. This Viewpoint reviews existing evidence and highlights the risks, benefits, and key knowledge gaps for the use of two-drug regimens in settings using the public health approach in Africa. We suggest that a two-drug regimen of dolutegravir and lamivudine can be safely used as a switch option for virologically suppressed individuals in settings using the public health approach once chronic hepatitis B has been excluded. Individuals with HIV who are switched to two-drug regimens should receive a full course of hepatitis B vaccinations. More efficacy data is needed to support dolutegravir plus lamivudine combination in the test and treat approach, and long-acting cabotegravir and rilpivirine in the public health system in sub-Saharan Africa.

Comparison of different cardiovascular risk tools used in HIV patient cohorts in sub-Saharan Africa; do we need to include laboratory tests?

INTRODUCTION: Cardiovascular disease (CVD) is the leading cause of death globally, representing 31% of all global deaths. HIV and long term anti-retroviral therapy (ART) are risk factors for development of CVD in populations of people living with HIV (PLHIV). CVD risk assessment tools are currently being applied to SSA populations, but there are questions about accuracy as well as implementation challenges of these tools in lower resource setting populations. We aimed to assess the level of agreement between the various cardiovascular screening tools (Data collection on Adverse effects of anti-HIV Drugs (D:A:D), Framingham risk score, WHO risk score and The Atherosclerotic Cardiovascular Disease Score) when applied to an HIV ART experienced population in Sub-Saharan Africa. METHODS: This study was undertaken in an Anti-Retroviral Long Term (ALT) Cohort of 1000 PLHIV in care who have been on ART for at least 10 years in urban Uganda. A systematic review was undertaken to find the most frequently used screening tools from SSA PLHIV populations; these were applied to the ALT cohort. Levels of agreement between the resulting scores (those including lipids and non-lipids based, as well as HIV-specific and non-HIV specific) as applied to our cohort were compared. Prevalence Bias Adjusted Kappa was used to evaluate agreement between tools. RESULTS: Overall, PLHIV in ALT cohort had a median score of 1.1-1.4% risk of a CVD event over 5 years and 1.7-2.5% risk of a CVD event over 10 years. There was no statistical difference in the risk scores obtained for this population when comparing the different tools, including comparisons of those with lipids and non-lipids, and HIV specific vs non-HIV specific. CONCLUSION: The various tools yielded similar results, but those not including lipids are more feasible to apply in our setting. Long-term cohorts of PLHIV in SSA should in future provide longitudinal data to evaluate existing CVD risk prediction tools for these populations. Inclusion of HIV and ART history factors to existing scoring systems may improve accuracy without adding the expense and technical difficulty of lipid testing.

An Interactive Voice Response Software to Improve the Quality of Life of People Living With HIV in Uganda: Randomized Controlled Trial.

BACKGROUND: Following the successful scale-up of antiretroviral therapy (ART), the focus is now on ensuring good quality of life (QoL) and sustained viral suppression in people living with HIV. The access to mobile technology in the most burdened countries is increasing rapidly, and therefore, mobile health (mHealth) technologies could be leveraged to improve QoL in people living with HIV. However, data on the impact of mHealth tools on the QoL in people living with HIV are limited to the evaluation of SMS text messaging; these are infeasible in high-illiteracy settings. OBJECTIVE: The primary and secondary outcomes were to determine the impact of interactive voice response (IVR) technology on Medical Outcomes Study HIV QoL scores and viral suppression at 12 months, respectively. METHODS: Within the Call for Life study, ART-experienced and ART-naïve people living with HIV commencing ART were randomized (1:1 ratio) to the control (no IVR support) or intervention arm (daily adherence and pre-appointment reminders, health information tips, and option to report symptoms). The software evaluated was Call for Life Uganda, an IVR technology that is based on the Mobile Technology for Community Health open-source software. Eligibility criteria for participation included access to a phone, fluency in local languages, and provision of consent. The differences in differences (DIDs) were computed, adjusting for baseline HIV RNA and CD4. RESULTS: Overall, 600 participants (413 female, 68.8%) were enrolled and followed-up for 12 months. In the intervention arm of 300 participants, 298 (99.3%) opted for IVR and 2 (0.7%) chose SMS text messaging as the mode of receiving reminders and health tips. At 12 months, there was no overall difference in the QoL between the intervention and control arms (DID=0.0; P=.99) or HIV RNA (DID=0.01; P=.94). At 12 months, 124 of the 256 (48.4%) active participants had picked up at least 50% of the calls. In the active intervention participants, high users (received >75% of reminders) had overall higher QoL compared to low users (received <25% of reminders) (92.2 versus 87.8, P=.02). Similarly, high users also had higher QoL scores in the mental health domain (93.1 versus 86.8, P=.008) and better appointment keeping. Similarly, participants with moderate use (51%-75%) had better viral suppression at 12 months (80/94, 85% versus 11/19, 58%, P=.006). CONCLUSIONS: Overall, there was high uptake and acceptability of the IVR tool. While we found no overall difference in the QoL and viral suppression between study arms, people living with HIV with higher usage of the tool showed greater improvements in QoL, viral suppression, and appointment keeping. With the declining resources available to HIV programs and the increasing number of people living with HIV accessing ART, IVR technology could be used to support patient care. The tool may be helpful in situations where physical consultations are infeasible, including the current COVID epidemic. TRIAL REGISTRATION: ClinicalTrials.gov NCT02953080; https://clinicaltrials.gov/ct2/show/NCT02953080.

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.

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. We describe the choices made by women, as well as determine the factors associated with women's choices to switch off dolutegravir. METHODS: A clinic response plan was developed in the first week following the alert and clinic staff were trained on safety guidance. All women aged < 55 years taking dolutegravir were identified from the clinic database and contacted by phone for earlier appointments. Non-menopausal and non-surgically sterilized women were referred for urine pregnancy testing and evaluation of pregnancy intentions in the following 12 months and effective family planning was offered. We describe the coverage of women who received the communication as well as the fidelity to the outlined plan from 21 May to 12 September, 2018. We used modified a Poisson regression analysis to determine factors associated with switching off dolutegravir. RESULTS: Of all active patients in the clinic, 9% (690/7963) were identified as female aged < 55 years taking dolutegravir. Ninety-five percent (656/690) were reviewed by September 2018 and informed of the safety alert, implying a high level of uptake. Fidelity to standard operating procedures was also high at 72%. Twenty-two percent (146/656) of patients were menopausal or surgically sterilized. Five hundred and ten women were of reproductive potential with a median age (interquartile range) of 37 years (30-42 years). Five percent (23/510) were human chorionic gonadotrophin positive and all initial ultrasound reports revealed no deformities. Twenty-one percent (108/510) had intentions to conceive and opted to stop taking dolutegravir with 90% (97/108) switching to efavirenz. Seventy-nine percent (402/510) opted to remain taking dolutegravir. However, only 40% (160/402) chose effective contraceptive methods and 60% (242/402) opted for condoms only/no contraceptive method. CONCLUSIONS: A rapid well-coordinated response ensured prompt communication of the dolutegravir safety warning. The process developed by the clinic can act as a model for response during drug safety alerts. Women made informed decisions with most opting to remain taking dolutegravir; however, effective contraception uptake was low.