Search

Summary Background Drug-drug interactions between orally administered antiretroviral therapy (ART) and hormones released from an intravaginal ring are not known. We hypothesised that ART containing either efavirenz or ritonavir-boosted atazanavir would alter plasma concentrations of vaginally administered etonogestrel and ethinylestradiol but that ART concentrations would be unchanged during use of an intravaginal ring. Methods We did a parallel, three-group, pharmacokinetic evaluation at HIV clinics in Asia (two sites), South America (five), sub-Saharan Africa (three), and the USA (11) between Dec 30, 2014, and Sept 12, 2016. We enrolled women with HIV who were either ART-naive (control group; n=25), receiving efavirenz-based ART (n=25), or receiving atazanavir–ritonavir-based ART (n=24). Women receiving ART were required to be on the same regimen for at least 30 days, with 400 copies or less per mL of plasma HIV-1 RNA; women not receiving ART had CD4 counts of 350 cells per μL or less. We excluded participants who had a bilateral oophorectomy or conditions that were contraindicated in the intravaginal ring product labelling. An intravaginal ring releasing etonogestrel and ethinylestradiol was inserted at entry (day 0). Single plasma samples for hormone concentrations were collected on days 7, 14, and 21 after intravaginal ring insertion. The primary outcome was the plasma concentration of etonogestrel and ethinylestradiol on day 21. Etonogestrel and ethinylestradiol concentrations were compared between each ART group and the control group by geometric mean ratio (GMR) with 90% CIs and Wilcoxon rank-sum test. As secondary outcomes, efavirenz or ritonavir-boosted atazanavir concentrations were assessed by 8-h intensive pharmacokinetic sampling at entry before intravaginal ring insertion and before intravaginal ring removal on day 21. Antiretroviral areas under the concentration-time curve (AUC0–8 h) were compared before and after intravaginal ring insertion by GMR (90% CI) and Wilcoxon signed-rank test. This study is registered with ClinicalTrials.gov , number NCT01903031 . Findings Between Dec 30, 2014, and Sept 12, 2016, we enrolled 84 participants in the study; ten participants were excluded from the primary hormone analysis. 74 participants met the primary endpoint: 25 in the control group, 25 in the efavirenz group, and 24 in the atazanavir group. On day 21 of intravaginal ring use, participants receiving efavirenz had 79% lower etonogestrel (GMR 0·21, 90% CI 0·16–0·28; p Interpretation Hormone exposure was significantly lower when an intravaginal ring contraceptive was combined with efavirenz-based ART. Further studies designed to examine pharmacodynamic endpoints, such as ovulation, when intravaginal ring hormones are combined with efavirenz are warranted. Funding National Institutes of Health, through the AIDS Clinical Trials Group and the International Maternal Pediatric Adolescent AIDS Clinical Trials Network, National Institute of Allergy and Infectious Diseases, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Institute of Mental Health.

Low-income and rural populations often delay seeking treatment for malaria. Delays in seeking treatment increase the likelihood of mortality and add to the cost of treatment. Delaying health care can also increase hospital admissions and add further burden to strained health systems in developing countries. Interventions that prompt early diagnosis and treatment can reduce delays and rates of hospital admission, resulting in decreased costs to the clients, the health system, and health microinsurance (HMI) schemes. Further, understanding determinants of health seeking behavior would be useful in planning malaria control strategies. Case study reports and anecdotal information obtained through interviews revealed certain benefits to the use of healthcare microinsurance. HMI users are less likely to be financially vulnerable to health crisis when the HMI system works. However, there was no scientific evidence to suggest that participation in a HMI plan made a difference in healthcare behavior. Whet...

The Centers for Medicare and Medicaid Services (CMS) have begun a major national initiative to reduce disparities in health care for the underserved through their contracts with state quality improvement organizations (QIOs). This initiative has translated into state-level projects that are, in many cases, investigating these populations to determine how best to address their health care deficiencies and improve the quality of their care. Tennessee's campaign, coordinated by the Center for Healthcare Quality (CHQ), the state's QIO, focused on the use of formative research to gain insights into diversity among the underserved in different settings across the state. Results aided the design of a series of site-appropriate interventions aimed at improving the utilization of mammography screening among Tennessee's Dual Enrolled: Medicare beneficiaries who are also enrolled in Medicare.