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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. METHODS: We conducted a cross-sectional survey from April 2019 to July 2019 in five government health facilities in central Uganda, where dolutegravir-based regimens were offered as the preferred first-line antiretroviral treatment. We randomly selected 359 non-pregnant women aged 15–49 years taking dolutegravir-based regimens and interviewed them using semi-structured interviewer-administered questionnaires. We collected data on demographics, contraceptive use, individual, social, and health system factors. We described patients' characteristics using descriptive statistics and assessed factors associated with contraceptive uptake using a modified Poisson regression model. RESULTS: A total of 359 women were included in the study. The mean age was 37 years (standard deviation = 6.8) and overall contraceptive uptake was 38.4%. The most utilized method was injectable method at 58.4% followed by condoms (15%), intrauterine device (10.7%), pills (6.4%), implants (5.4%), and sterilization (0.7%). Predictors for contraceptive uptake were parity of 3–4 children (Adjusted Prevalence Ratio (APR) = 1.48, 95% confidence interval (CI): 1.14, 1.92) in reference to those with 1–2 children. There was reduced contraceptive uptake in women of the age range 40–49 years (APR = 0.45, CI: 0.21–0.94) compared to those aged 15–24 years. Unemployed women were less likely to use contraceptives (APR: 0.6, CI: 0.42- 0.94) than the formally employed. Contraceptive uptake was lower among women who did not discuss family planning with their partners (APR = 0.39, CI: 0.29–0.52) than those who discussed ...

The COVID-19 pandemic exposed frontline healthcare workers (HCWs) to mental health problems and various challenges that impacted their job satisfaction. We explored the job satisfaction and psychosocial/mental well-being of COVID-19 frontline HCWs in Uganda. This was a mixed-methods study conducted at Mulago National Referral Hospital (MNRH), Entebbe Regional Referral Hospital (ERRH), and Uganda Virus Research Institute (UVRI). A pre-tested self-administered questionnaire and Four Focus Group Discussions (FGDs) were used for data collection. A five-point Likert scale was used for the quantitative data to measure mental well-being and job satisfaction. Bloom's cut-off was used to categorize participants' job satisfaction and mental well-being into good (≥80%), moderate (60% - <80%), and poor (<60%). FGDs were audio-recorded, transcribed, and analyzed thematically using NVivo version 12 software. 218 participants participated in the quantitative survey and 24 of them further participated in the FGDs. 51.4% ( n = 112) were males, aged 18 to 39 years (77.5%, n = 169) and 50.9% ( n = 111) were at MNRH. Overall, 54%, 28%, and 18% of the participants reported moderate, good, and poor job satisfaction respectively. Satisfaction with salary (2.6 ± 1.2) and compensation (risk) allowances (2.4 ± 1.3) was particularly low. Furthermore, 35%, 33%, and 32% of the participants reported moderate, good, and poor mental well-being respectively. Anxiety, burnout, stigma, and discrimination contributed to poor psychosocial/mental well-being. Less than half of the frontline HCWs reported good job satisfaction and psychosocial/mental well-being. There is a need for prioritization of the psychosocial well-being of frontline HCWs, in addition to improvement of remuneration systems.

IntroductionSub‐dermal hormone implants, such as levonorgestrel (LNG), are a safe and desirable form of long‐acting contraception, but their use among HIV‐positive women on antiretroviral therapy (ART) may be compromised given the potential for a cytochrome P450 3A‐mediated drug–drug interaction. Our study aimed to characterize the pharmacokinetics of LNG released from a sub‐dermal implant over six months in HIV‐positive Ugandan women on nevirapine (NVP)‐ or efavirenz (EFV)‐based ART.Material and MethodsThis non‐randomized, parallel group study compared LNG pharmacokinetics between HIV‐positive Ugandan women not yet eligible for ART (control group, n=18) and those on stable NVP‐ (n=20) or EFV‐ (n=20) based ART. The two‐rod (75 mg/rod) LNG sub‐dermal implant was inserted at study enrolment. LNG sampling was obtained pre‐implant and at weeks 1, 4, 12 and 24 post‐insertion. LNG concentrations were analyzed using a validated LC‐MS/MS method, with an assay calibration range of 50–1500 pg/mL. Safety monitoring, including a pregnancy test, was conducted at each study visit.ResultsAt enrolment, participants had a mean age of 31 years; CD4+ cell counts were similar between the control, NVP and EFV groups (758, 645 and 568 cells/mm3, respectively; p=0.09); all women in the NVP and EFV groups had an undetectable HIV‐RNA. Women in the control group had a higher baseline body weight (73 kg) compared to those in the NVP (63 kg; p=0.03) or EFV groups (60 kg; p<0.01). By linear regression, weight was a significant predictor of LNG concentrations (1 kg increase in weight=5 pg/mL decrease in LNG, p=0.03). LNG concentrations are reported in the table.ConclusionsOver a 24‐week period, LNG concentrations were 40–54% lower in women on EFV‐based ART, despite their having a significantly lower body weight, compared to those not on ART. In women on NVP‐based ART, LNG concentrations were 32–39% higher than those observed in the control group, a difference partially explained by body weight. These data confirm a significant drug interaction occurs between the LNG implant and EFV, adding to growing concern for reduced contraceptive efficacy with their combined use. In contrast, these data support use of the LNG implant with NVP‐based ART.

IntroductionThere is limited data available on exposure to anti‐tuberculosis (TB) drugs in this region. Peloquin has described reference ranges [1] however some studies have demonstrated that patients actually achieve concentrations below these ranges [2]. There is limited data about exposure to anti‐TB drugs in the HIV/TB co‐infected population in Sub‐Saharan Africa. Our objective is to describe the concentration of anti‐TB drug levels in a well characterized prospective cohort of adult patients starting treatment for pulmonary TB.MethodsThis study is an ongoing study carried out in the TB/HIV integrated clinic at the Infectious Diseases Institute in Kampala, Uganda. Sputum culture and microscopy was done for all patients. We performed pharmacokinetic blood sampling of anti‐TB drugs for 1 hour, 2 hours and 4 hours post dose at 2 weeks, 8 weeks and 24 weeks after initiation of anti‐TB treatment using ultraviolet high‐performance liquid chromatography (UV‐HPLC). We described the maximum concentration (Cmax) of isoniazid (H), rifampicin (R), ethambutol (E) and pyrazinamide (Z) and compare them with the values observed by Peloquin et al. referenced in other studies.ResultsWe started 113 HIV infected adults on a fixed dose combination of HREZ. The median age of our population was 33 years, of which 52% were male with a median BMI of 19 kg/m2 and a median CD4 cell count of 142 cells/µL. In 90% of the participants, the diagnosis of TB was based on microscopy and or cultures. The boxplot graph shows the median Cmax and IQR of H and R.Levels of H were found to be below the reference ranges (3–6 µg/mL) in 54/77(70.1%), 38/59(64.4%) and 15/24(62.5%) participants at weeks 2, 8 and 24. Rif levels were also found to be below the reference ranges (8–24 µg/mL) in 41/66(62.1%), 26/48(54.2%) and 8/10(8%) participants at weeks 2, 8 and 24, respectively. The mean Cmax of E and Z were within the reference range at week 2 and 8; mean Cmax of 3.2±SD2.1 µg/mL and 4.0±SD3.1 µg/mL for E and 41.6±SD13.1 µg/mL and 42.6±SD16.4 µg/mL for Z.ConclusionWe observed lower concentrations of isoniazid and rifampicin in our study population of HIV/TB co‐infected patients. The implications of these findings are not yet clear. We therefore need to correlate our findings with the response to TB treatment.

Following the 2013–2016 Ebola virus outbreak in West Africa, numerous groups advocated for the importance of executing clinical trials in outbreak settings. The difficulties associated with obtaining reliable data to support regulatory approval of investigational vaccines and therapeutics during that outbreak were a disappointment on a research and product development level, as well as on a humanitarian level. In response to lessons learned from the outbreak, the United States Department of Defense established a multi-institute project called the Joint Mobile Emerging Disease Intervention Clinical Capability (JMEDICC). JMEDICC's primary objective is to establish the technical capability in western Uganda to execute clinical trials during outbreaks of high-consequence pathogens such as the Ebola virus. A critical component of clinical trial execution is the establishment of laboratory operations. Technical, logistical, and political challenges complicate laboratory operations, and these challenges have been mitigated by JMEDICC to enable readiness for laboratory outbreak response operations.