Pharmacokinetics of levonorgestrel and etonogestrel contraceptive implants over 48†weeks with rilpivirine- or darunavir-based antiretroviral therapy.

BACKGROUND: Pharmacokinetic data are lacking for progestin-releasing subdermal contraceptive implants when used with either rilpivirine- or darunavir/ritonavir-based ART. OBJECTIVES: To characterize the pharmacokinetics of etonogestrel or levonorgestrel implants when administered with these ART regimens over 48 weeks. PATIENTS AND METHODS: Two separate, parallel, three-group, non-randomized, pharmacokinetic studies evaluated either etonogestrel or levonorgestrel in women receiving rilpivirine- or darunavir-based ART compared with women without HIV (control group). Participants on ART were switched to rilpivirine-based ART with a run-in period of 6 weeks or darunavir-based ART with a run-in of 2 weeks prior to implant insertion. Plasma was collected on Day 0, and 1, 4, 12, 24, 36 and 48 weeks post-insertion. Plasma progestin concentrations were compared between ART and control groups by geometric mean ratio (GMR) and 90% CI. RESULTS: At the primary endpoint of Week 24, progestin concentrations were similar between the rilpivirine and control groups [etonogestrel: 1.18 (0.99-1.37); levonorgestrel: 1.16 (0.97-1.33)]. At Week 24, progestin exposure was higher in the darunavir groups compared with the control group [etonogestrel: 2.56 (1.69-3.28); levonorgestrel: 1.89 (1.38-2.29)]. Results remained consistent through to Week 48. No differences in etonogestrel-related adverse events were observed, but both ART groups experienced more menstrual abnormalities versus the control group with levonorgestrel. CONCLUSIONS: Etonogestrel and levonorgestrel concentrations were not altered by rilpivirine-based ART. Although progestin concentrations were higher in the ART groups containing ritonavir-boosted darunavir, no implant-related serious adverse events were observed. Both progestin-releasing implants are an appropriate contraceptive option with either rilpivirine- or darunavir/ritonavir-based ART.

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. 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 family planning with their partners and women who did not receive family planning counseling (APR = 0.56, CI: 0.34-0.92) than those who received family planning counselling. CONCLUSION: We observed a low-level uptake of contraceptives, with injectables as the most used method. Family planning counseling and partner discussion on family planning were associated with contraceptive uptake among the women who used dolutegravir-based regimens. There is a need for more strategies to integrate FP services and increase male involvement in HIV care programs.

A case for routine microbial diagnostics: Results from antimicrobial susceptibility testing in post-traumatic wound infections at a Ugandan tertiary care hospital.

The global spread of antimicrobial resistance (AMR) poses an increasing challenge for clinicians in Uganda, where microbiological diagnostics are not routinely available or accessible. The aim of this study was to determine pathogen prevalence and antibiotic resistance patterns in patients with wound infections following trauma at a national referral hospital in Kampala, Uganda. In addition, the suitability of currently used empirical treatment options in this setting was evaluated. This prospective, observational study analysed antimicrobial prescriptions, culture results and antimicrobial sensitivity testing (AST) of wound swabs and blood samples from patients with clinical signs of wound infections on the trauma ward. A total of 124 patients (n = 99, 79.8% male) with a median age of 30 years (IQR 23-39) were enrolled between October 2021 and January 2022. Wound infections were classified as nosocomial in 69% of the cases. Pathogens were isolated from 122 wound swabs, yielding 238 bacterial isolates. The most prevalent pathogens were gram-negative bacteria including Escherichia coli (n = 48, 20.2%) and Acinetobacter spp. (n = 43, 18.1%). Empiric treatment consisted of ceftriaxone and gentamicin which was administered to 67.2% (n = 78) and 62.1% (n = 72) of patients, respectively. High rates of antimicrobial resistance could be demonstrated across gram-negative and gram-positive species towards the most common empiric antibiotics. Following the AST results, over 95% (n = 111) of patients required a change of treatment. Our findings demonstrate that current empiric treatment for wound infections is missing its target in hospitalized patients in Kampala. To address the growing problem of AMR in Uganda, there is a pressing need to enhance diagnostic capacity and implement structured antimicrobial stewardship programs.