Dose optimization with population pharmacokinetics of ritonavir-boosted lopinavir for Thai people living with HIV with and without active tuberculosis

BackgroundPrior to dolutegravir availability, ritonavir-boosted lopinavir (LPV/r) was an alternative recommendation when first-line drugs could not be used. A high concentration of protease inhibitors was observed in the Thai people living with HIV (PLWH). Thus, dose reduction of LPV/r may be possible. However, the pharmacokinetics and dose optimization of LPV/r have never been investigated. This study aimed to develop a population pharmacokinetic model of LPV/r and provide dosage optimization in Thai PLWH.MethodsLPV and RTV trough concentrations from Thai PLWH were combined with intensive data. The data were analyzed by the nonlinear mixed-effects modeling approach. The influence of RTV concentration on LPV oral clearance (CL/F) was investigated.ResultsRifampicin (RIF) use increased LPV and RTV CL/F by 2.16-fold and 1.99-fold, respectively. The reduced dose of 300/75 and 200/150 mg twice daily provided a comparable percentage of patients achieving LPV target trough concentration to the standard dose for PI-naïve patients. For HIV/TB co-infected patients receiving RIF who could not tolerate the recommended dose, the reduced dose of 600/150 mg twice daily was recommended.ConclusionThe population pharmacokinetic model was developed by integrating the interaction between LPV and RTV. The reduced LPV/r dosage offers sufficient LPV exposure for Thai PLWH.     

Can we increase the cervical cancer screening interval with an HPV test for women living with HIV? Results of a cohort study from Maharashtra,India

We are reporting (a) updated incidence of cervical intraepithelial neoplasia (CIN) among women who did not have colposcopic or histopathological disease at baseline and (b) disease outcomes among women treated for CIN and their follow-up HPV status; in a cohort of women living with HIV (WHIV). The median overall follow-up was 3.5 years (IQR 2.8-4.3). The incidence of any CIN and that of CIN 2 or worse disease was 16.7 and 7.0 per 1000 person-years of observation (PYO), respectively. Compared with women who were HPV negative at baseline, women who cleared HPV infection had 23.95 times increased risk of incident CIN 2 or worse lesions (95% CI 2.40-661.07). Women with persistent HPV infection had 138.18 times increased risk of CIN 2 or worse lesions (95% CI 20.30-3300.22). Complete disease regression was observed in 65.6% of the HPV positive women with high-grade CIN and were treated with thermal ablation but HPV persistence was seen in 44.8% of those with high-grade disease. Among those who did not have any disease at baseline and were also HPV negative, about 87% (95% CI 83.79-89.48) women remained HPV negative during consecutive HPV test/s with the median interval of 3.5 years. Long-term surveillance of WHIV treated for any CIN is necessary for the prevention of cervical cancer among them. Our study provides an early indication that the currently recommended screening interval of 3 to 5 years among WHIV may be extended to at least 5 years among HPV negative women. Increasing the screening interval can be cost saving and improve scalability among WHIV to support WHO's cervical cancer elimination initiative.     

Integrated Prenatal Care for Women Living With HIV: Primary Care Outcomes in Saskatoon,Saskatchewan

Saskatchewan has the highest rate of new human immunodeficiency virus (HIV) infections in Canada. Of those newly diagnosed, 56% identify as female, 76% identify as Indigenous, and 71% report a history of intravenous drug use. These statistics are strikingly different compared with Canadian data. This brief communication describes prenatal care provided to women living with HIV at an interdisciplinary primary care clinic in Saskatchewan, demonstrating that, despite facing great barriers such as housing insecurity, substance use, and institutionalized racism, women living with HIV can have positive outcomes, including engagement in care and the prevention of perinatal HIV infection.     

Primary Care Physician Attitudes and Intentions Toward the Use of HIV Pre-exposure Prophylaxis in Adolescents in One Metropolitan Region

Purpose

Understanding the attitudes of physicians toward the use of pre-exposure prophylaxis (PrEP) for HIV prevention among youth is critical to improving access to PrEP. We examined PrEP-related attitudes among physicians who provide primary care to 13- to 21-year-old adolescents.

Pharmacokinetic,biologic and epidemiologic differences in MPA- and NET-based progestin-only injectable contraceptives relative to the potential impact on HIV acquisition in women

Access to safe and effective contraceptive choices is a reproductive right and contributes tremendously to improvements in maternal and child health. Progestin-only injectables, particularly intramuscularly injected depot medroxyprogesterone acetate (DMPA-IM), have received increased attention given findings suggesting a potential association with increased HIV risk. For women at high risk of HIV, the World Health Organization's Medical eligibility criteria for contraceptive use currently aggregate recommendations for all progestin-only injectables, including DMPA-IM, subcutaneously injected DMPA (DMPA-SC) and intramuscularly injected norethindrone/ norethisterone enanthate (NET-EN), except in the case of some drug interactions. We considered whether published data indicate differences or similarities between these injectables relevant to risk of acquiring HIV. In vitro data confirm different biological activities of these distinct progestins, including that MPA, and not NET, binds and activates the glucocorticoid receptor resulting in different biological effects relevant to immune function. Limited clinical data suggest changes in immunologic activity following DMPA-IM and NET-EN initiation, but interstudy variation and study design differences diminish ability to determine clinical relevance and the degree to which DMPA-IM and NET-EN could act differentially. The highest-quality epidemiologic studies suggest a potential 40% increase in HIV incidence in users of DMPA-IM relative to women not using hormonal contraception but no significant increase in risk in users of NET-EN. In our opinion, most of the available biologic activity and epidemiologic data indicate that DMPA and NET-EN are likely to act differently, and data remain too limited to evaluate differences between DMPA-IM and DMPA-SC.     

Gender,power and intimate relationships over the life course among Ethiopian female peer educators living with HIV

Historically, Ethiopian women have faced numerous challenges to gender equity at the individual, relational and community levels; such inequalities can lead to increased risk of HIV acquisition. Over the past two decades, some progress has been made towards changing policies and norms to reduce gender inequality. We sought to understand the ways in which marriage and other romantic/sexual relationships of a group of Ethiopian women living with HIV had been impacted by gender norms, relational power dynamics and HIV status over the life course. We conducted in-depth interviews with 19 women living with HIV who were working as peer educators at a large clinic in Addis Ababa, Ethiopia. Reflecting on their early lives, participants often described traumatic prior relationships characterised by rape, forced marriage and HIV nondisclosure. In the aftermath of being diagnosed with HIV, participants’ more recent relationships embodied a more egalitarian dynamic characterised by mutual support for HIV care engagement and open communication. Participants’ narratives illustrate encouraging examples of ways in which HIV-positive women can form and maintain equitable and satisfying personal relationships even in the context of obstacles at multiple levels.