"No One Needs to be Forced": Qualitative Insights on Competing Priorities between Antiretroviral Therapy and Reproductive Health Planning during the Dolutegravir Rollout.

Potential associations between periconception dolutegravir (DTG) exposure and neural tube defects (NTDs) reported in 2018 caused shifting international and national antiretroviral treatment (ART) guidelines. They sometimes required women to use contraception prior to initiating DTG. To better understand the tensions between ART and family planning (FP) choices, and explore the decision-making processes of women living with HIV (WLHIV) and their healthcare providers (HCPs) employed, we conducted interviews with WLHIV exposed to DTG and their providers in western Kenya from July 2019 to August 2020. For the interviews with WLHIV, we sampled women at varying ages who either continued using DTG, switched to a different ART, or became pregnant while using DTG. We utilized inductive coding and thematic analysis. We conducted 44 interviews with WLHIV and 10 with providers. We found four dominant themes: (1) a range of attitudes about birth defects, (2) nuanced knowledge of DTG and its potential risk of birth defects, (3) significant tensions at the intersection of DTG and FP use with varying priorities amongst WLHIV and their providers for navigating the tensions, and (4) WLHIV desiring autonomy, and provider support for this, in such decision-making. Variations in beliefs were noted between WLHIV and HCPs. WLHIV highlighted the impact of community and social beliefs when discussing their attitudes while HCPs generally reported more medicalized views towards DTG utilization, potential adverse outcomes, and FP selection. Decisions pertaining to ART and FP selection are complex, and HIV treatment guidelines need to better support women's agency and reproductive health justice.

Impacts of the COVID-19 pandemic on access to HIV and reproductive health care among women living with HIV (WLHIV) in Western Kenya: A mixed methods analysis.

Introduction: The COVID-19 pandemic has impacted access to health services. Our objective was to understand the pandemic's impact on access to HIV, pregnancy, and family planning (FP) care among women living with HIV (WLHIV). Methods: Data were collected after June 2020, when questions about the pandemic were added to two ongoing mixed methods studies using telephone surveys and in-depth interviews among WLHIV in western Kenya. The Chaguo Langu (CL) study includes primarily non-pregnant WLHIV receiving HIV care at 55 facilities supported by AMPATH and the Opt4Mamas study includes pregnant WLHIV receiving antenatal care at five facilities supported by FACES. Our outcomes were self-reported increased difficulty refilling medication, accessing care, and managing FP during the pandemic. We summarized descriptive data and utilized multivariable logistic regression to evaluate predictors of difficulty refilling medication and accessing care. We qualitatively analyzed the interviews using inductive coding with thematic analysis. Results: We analyzed 1,402 surveys and 15 in-depth interviews. Many (32%) CL participants reported greater difficulty refilling medications and a minority (14%) reported greater difficulty accessing HIV care during the pandemic. Most (99%) Opt4Mamas participants reported no difficulty refilling medications or accessing HIV/pregnancy care. Among the CL participants, older women were less likely (aOR = 0.95, 95% CI: 0.92-0.98) and women with more children were more likely (aOR = 1.13, 95% CI: 1.00-1.28) to report difficulty refilling medications. Only 2% of CL participants reported greater difficulty managing FP and most (95%) reported no change in likelihood of using FP or desire to get pregnant. Qualitative analysis revealed three major themes: (1) adverse organizational/economic implications of the pandemic, (2) increased importance of pregnancy prevention during the pandemic, and (3) fear of contracting COVID-19. Discussion: The two unique participant groups included in our study encountered overlapping problems during the COVID-19 epidemic. Access to HIV services and antiretrovirals was interrupted for a large proportion of non-pregnant WLHIV in western Kenya, but access to pregnancy/family planning care was less affected in our cohort. Innovative solutions are needed to ensure HIV and reproductive health outcomes do not worsen during the ongoing pandemic.

Contraceptive implant use duration is not associated with breakthrough pregnancy among women living with HIV and using efavirenz: a retrospective, longitudinal analysis.

INTRODUCTION: Contraceptive implants containing etonogestrel and levonorgestrel have emerged as popular contraceptive options among women in areas of high HIV burden in sub-Saharan Africa. However, recent pharmacokinetic data have shown drug-drug interactions between implants and efavirenz-containing antiretroviral therapy (ART), reducing the effectiveness of the implants. Here, we evaluated pregnancy incidence in 6-month intervals following implant initiation among women using efavirenz and contraceptive implants to assess whether the risk of breakthrough pregnancy is higher after specific periods of implant use. METHODS: We used data from a retrospective longitudinal analysis of women living with HIV ages 18-45 years in western Kenya who attended HIV-care facilities between 2011 and 2015. We used Cox proportional hazard models to compute hazard ratios (HRs) for breakthrough pregnancy by implant type and ART regimen. Depending on the model, we adjusted for socio-demographic and clinical factors, programme, site and interaction between calendar time and ART regimen. We utilized inverse probability weights (IPWs) to account for three sampling phases (electronic medical record [EMR], chart review and phone interview) and calculated overall parameter estimates. RESULTS: Women contributed 14,768 woman-years from the largest sampling phase (EMR). The median age was 31 years. Women used etonogestrel implants for 26-69% of the time and levonorgestrel implants for 7-31% of the time, depending on the sampling phase. Women used efavirenz, nevirapine or no ART for 27-33%, 40-46% and 15-26% of follow-ups, respectively. When combining sampling phases, there was little evidence to suggest that the relative hazard of pregnancy among efavirenz-containing ART users relative to nevirapine-containing ART changed with length of time on implants: IPW-adjusted HR of 3.1 (CI: [1.5; 6.4]) at 12 months, 3.4 (CI: [1.8; 6.3]) at 24 months, 3.8 (CI: [1.9; 7.7]) at 36 months and 4.2 (CI: [1.6; 11.1]) at 48 months (interaction p-value = 0.88). Similarly, no significant change in HRs over time was found when comparing women not using ART to nevirapine-containing ART users (interaction p-value = 0.49). CONCLUSIONS: We did not find evidence to suggest implants being more fallible from drug-drug interactions with efavirenz at later time intervals of implant use. Thus, we would not recommend shortening the duration of implant use or replacing implants sooner when concomitantly used with efavirenz.

Preferences for Multipurpose Technology and Non-oral Methods of Antiretroviral Therapy Among Women Living With HIV in Western Kenya: A Survey Study.

Introduction: Understanding interests in and preferences for multipurpose technology (MPT) for the co-administration of contraception and antiretroviral therapy (ART) and alternative, non-oral ART methods among women living with HIV (WLHIV) is vital to successful implementation of future treatment options, such as long-acting injectable ART. Methods: Between May 2016 and March 2017 we conducted a cross-sectional telephone survey of 1,132 WLHIV of reproductive potential with prior experience using intermediate- or long-acting contraceptive methods in western Kenya. We present descriptive statistics and multinomial logistic regression to evaluate predictors of interest in specific MPT and non-oral ART methods. Results: Two-thirds (67%) reported interest in MPT, with the most common reason for interest being ease of using a single medication for both purposes of HIV treatment and pregnancy prevention (26%). Main reasons for lack of interest in MPT were need to stop/not use contraception while continuing ART (21%) and risk of side effects (16%). Important characteristics of MPT were effectiveness for pregnancy prevention (26%) and HIV treatment (24%) and less than daily dosing (19%). Important characteristics of non-oral ART methods were less than daily dosing (47%), saving time accessing ART (16%), and effectiveness of HIV treatment (15%). The leading preferred methods for both MPT and non-oral ART were injectables (50 and 54%) and implants (32 and 31%). Prior use of a contraceptive implant or injectable predicted interest in similar methods for both MPT and non-oral ART methods, while this relationship did not appear to vary between younger vs. older WLHIV. Discussion: Most WLHIV in western Kenya are interested in MPT for HIV treatment and contraception. Prior exposure to contraceptive implants or injectables appears to predict interest in similar methods of MPT and non-oral ART. Developers of MPT and non-oral ART methods should strongly consider WLHIV's preferences, including their changing reproductive desires.

Pregnancies among women living with HIV using contraceptives and antiretroviral therapy in western Kenya: a retrospective, cohort study.

BACKGROUND: Preventing unintended pregnancies is paramount for women living with HIV (WLHIV). Previous studies have suggested that efavirenz-containing antiretroviral therapy (ART) reduces contraceptive effectiveness of implants, but there are uncertainties regarding the quality of the electronic medical record (EMR) data used in these prior studies. METHODS: We conducted a retrospective, cohort study of EMR data from 2011 to 2015 among WLHIV of reproductive age accessing HIV care in public facilities in western Kenya. We validated a large subsample of records with manual chart review and telephone interviews. We estimated adjusted incidence rate ratios (aIRRs) with Poisson regression accounting for the validation sampling using inverse probability weighting and generalized raking. RESULTS: A total of 85,324 women contributed a total of 170,845 women-years (w-y) of observation time; a subset of 5080 women had their charts reviewed, and 1285 underwent interviews. Among implant users, the aIRR of pregnancy for efavirenz- vs. nevirapine-containing ART was 1.9 (95% CI 1.6, 2.4) using EMR data only and 3.2 (95% CI 1.8, 5.7) when additionally using both chart review and interview validated data. Among efavirenz users, the aIRR of pregnancy for depomedroxyprogesterone acetate (DMPA) vs. implant use was 1.8 (95% CI 1.5, 2.1) in EMR only and 2.4 (95% CI 1.0, 6.1) using validated data. CONCLUSION: Pregnancy rates are higher when contraceptive implants are concomitantly used with efavirenz-containing ART, though rates were similar to leading alternative contraceptive methods such as DMPA. Our data provides policymakers, program staff, and WLHIV greater confidence in guiding their decision-making around contraceptive and ART options. Our novel, 3-phase validation sampling provides an innovative tool for using routine EMR data to improve the robustness of data quality.

Increasing body mass index or weight does not appear to influence the association between efavirenz-based antiretroviral therapy and implant effectiveness among HIV-positive women in western Kenya.

OBJECTIVE: Our objective was to evaluate if increasing body mass index (BMI) or weight influences the association between efavirenz-based antiretroviral therapy (ART) and implant effectiveness. STUDY DESIGN: We conducted a secondary cohort analysis of HIV-positive women aged 15 to 45 years enrolled in HIV care in western Kenya using an implant from January 2011 to December 2015. Implant use, ART regimen and weight were documented at each clinic visit and height at enrollment. We categorized BMI as underweight, normal weight, overweight or obese, and weight as <70 kg or ≥70 kg. Our primary outcome was incident pregnancy diagnosed clinically. We used crude and adjusted Poisson models with robust standard errors to account for covariates and repeated observations to estimate adjusted incident rate ratios (aIRRs). RESULTS: In this analysis, 12,960 women contributed a total of 11,285 woman-years of observation time while using an implant, with a median of 6.6 months. The aIRRs comparing efavirenz- to nevirapine-based ART groups did not increase as BMI increased; the aIRRs were 2.0 (1.1-3.6) for underweight, 1.9 (1.5-2.5) for normal, 3.1 (1.6-6.0) for overweight and 2.1 (0.6-6.9) for obese women. The aIRRs comparing efavirenz- to nevirapine-based ART groups did not increase as weight increased; the aIRRs were 2.0 (1.6-2.6) for weight <70 kg and 2.1 (1.0-4.5) for weight ≥70 kg. CONCLUSION: Higher BMI or weight did not appear to modify the relationship between efavirenz use and implant effectiveness. IMPLICATIONS: Programs should not recommend differential counseling for women with higher BMI or weight who concomitantly use implants and efavirenz.

Leveraging peer-based support to facilitate HIV care in Kenya.

Rakhi Karwa and colleagues discuss a program in which peer navigators support care for people with HIV at a Kenyan hospital.

Targeted Spontaneous Reporting: Assessing Opportunities to Conduct Routine Pharmacovigilance for Antiretroviral Treatment on an International Scale.

INTRODUCTION: Targeted spontaneous reporting (TSR) is a pharmacovigilance method that can enhance reporting of adverse drug reactions related to antiretroviral therapy (ART). Minimal data exist on the needs or capacity of facilities to conduct TSR. OBJECTIVES: Using data from the International epidemiologic Databases to Evaluate AIDS (IeDEA) Consortium, the present study had two objectives: (1) to develop a list of facility characteristics that could constitute key assets in the conduct of TSR; (2) to use this list as a starting point to describe the existing capacity of IeDEA-participating facilities to conduct pharmacovigilance through TSR. METHODS: We generated our facility characteristics list using an iterative approach, through a review of relevant World Health Organization (WHO) and Uppsala Monitoring Centre documents focused on pharmacovigilance activities related to HIV and ART and consultation with expert stakeholders. IeDEA facility data were drawn from a 2009/2010 IeDEA site assessment that included reported characteristics of adult and pediatric HIV care programs, including outreach, staffing, laboratory capacity, adverse event monitoring, and non-HIV care. RESULTS: A total of 137 facilities were included: East Africa (43); Asia-Pacific (28); West Africa (21); Southern Africa (19); Central Africa (12); Caribbean, Central, and South America (7); and North America (7). Key facility characteristics were grouped as follows: outcome ascertainment and follow-up; laboratory monitoring; documentation-sources and management of data; and human resources. Facility characteristics ranged by facility and region. The majority of facilities reported that patients were assigned a unique identification number (n = 114; 83.2 %) and most sites recorded adverse drug reactions (n = 101; 73.7 %), while 82 facilities (59.9 %) reported having an electronic database on site. CONCLUSION: We found minimal information is available about facility characteristics that may contribute to pharmacovigilance activities. Our findings, therefore, are a first step that can potentially assist implementers and facility staff to identify opportunities and leverage their existing capacities to incorporate TSR into their routine clinical programs.

Meeting the Needs of Underserved Patients in Western Kenya by Creating the Next Generation of Global Health Pharmacists.

Objective. To describe a novel training model used to create a sustainable public health-focused pharmacy residency based in Kenya and to describe the outcomes of this training program on underserved populations. Design. The postgraduate year 2 residency was designed to expose trainees to the unique public health facets of inpatient, outpatient, and community-based care delivery in low and middle-income countries. Public health areas of focus included supply chain management, reproductive health, pediatrics, HIV, chronic disease management, and teaching. Assessment. The outcomes of the residency were assessed based on the number of new clinical programs developed by residents, articles and abstracts written by residents, and resident participation in grant writing. To date, six residents from the United States and eight Kenyan residents have completed the residency. Eleven sustainable patient care services have been implemented as a result of the residency program. Conclusion. This pharmacy residency training model developed accomplished pharmacists in public health pharmacy, with each residency class expanding funding and clinical programming, contributing to curriculum development, and creating jobs.

The Revolving Fund Pharmacy Model: backing up the Ministry of Health supply chain in western Kenya.

OBJECTIVES: A pressing challenge in low and middle-income countries (LMIC) is inadequate access to essential medicines, especially for chronic diseases. The Revolving Fund Pharmacy (RFP) model is an initiative to provide high-quality medications consistently to patients, using revenues generated from the sale of medications to sustainably resupply medications. This article describes the utilization of RFPs developed by the Academic Model Providing Access to Healthcare (AMPATH) with the aim of stimulating the implementation of similar models elsewhere to ensure sustainable access to quality and affordable medications in similar LMIC settings. METHODS: The service evaluation of three pilot RFPs started between April 2011 and January 2012 in select government facilities is described. The evaluation assessed cross-sectional availability of essential medicines before and after implementation of the RFPs, number of patient encounters and the impact of community awareness activities. FINDINGS: Availability of essential medicines in the three pilot RFPs increased from 40%, 36% and <10% to 90%, 94% and 91% respectively. After the first year of operation, the pilot RFPs had a total of 33 714 patient encounters. As of February 2014, almost 3 years after starting up the first RFP, the RFPs had a total of 115 991 patient encounters. In the Eldoret RFP, community awareness activities led to a 51% increase in sales. CONCLUSIONS: With proper oversight and stakeholder involvement, this model is a potential solution to improve availability of essential medicines in LMICs. These pilots exemplify the feasibility of implementing and scaling up this model in other locations.

The oncology pharmacy in cancer care delivery in a resource-constrained setting in western Kenya.

The movement to deliver cancer care in resource-limited settings is gaining momentum, with particular emphasis on the creation of cost-effective, rational algorithms utilizing affordable chemotherapeutics to treat curable disease. The delivery of cancer care in resource-replete settings is a concerted effort by a team of multidisciplinary care providers. The oncology pharmacy, which is now considered integral to cancer care in resourced medical practice, developed over the last several decades in an effort to limit healthcare provider exposure to workplace hazards and to limit risk to patients. In developing cancer care services in resource-constrained settings, creation of oncology pharmacies can help to both mitigate the risks to practitioners and patients, and also limit the costs of cancer care and the environmental impact of chemotherapeutics. This article describes the experience and lessons learned in establishing a chemotherapy pharmacy in western Kenya.

Prevalence of potential drug-drug interactions involving antiretroviral drugs in a large Kenyan cohort.

BACKGROUND: Clinically significant drug-drug interactions (CSDIs) involving antiretrovirals are frequent and under-recognized in developed countries, but data are lacking for developing countries. METHODOLOGY AND PRINCIPAL FINDINGS: To investigate the prevalence of CSDIs between antiretrovirals and coadministered drugs, we surveyed prescriptions dispensed in a large HIV clinic in Kenya. Of 1040 consecutive patients screened, 996 were eligible for inclusion. CSDIs were defined as 'major' (capable of causing severe or permanent damage, contraindicated, avoid or not recommended by the manufacturer, or requiring dose modification) or 'moderate' (manufacturers advise caution, or close monitoring, or capable of causing clinical deterioration). A total of 334 patients (33.5%) were at risk for a CSDI, potentially lowering antiretroviral drug concentrations in 120 (12%) patients. Major interactions most frequently involved rifampicin (12.4%, mostly with efavirenz) and azoles (2.7%) whereas moderate interactions were frequently azoles (13%), steroids (11%), and antimalarials (3%). Multivariable analyses suggested that patients at risk for CSDIs had lower CD4 counts (P = 0.006) and baseline weight (P = 0.023) and WHO Stage 3 or 4 disease (P≤0.007). Risk for CSDIs was not associated with particular regimens, although only 116 (11.6%) patients were receiving WHO second line regimens. CONCLUSIONS: One in three patients receiving antiretrovirals in our programme were at risk of CSDIs. Strategies need to be urgently developed to avoid important drug interactions, to identify early markers of toxicity and to manage unavoidable interactions safely in order to reduce risk of harm, and to maximize the effectiveness of mass antiretroviral deployment in Africa.

Retrospective analysis of the efficacy of gemcitabine for previously treated AIDS-associated Kaposi's sarcoma in western Kenya.

OBJECTIVES: Evaluation of outcomes in the use of single-agent gemcitabine for the treatment of AIDS-associated Kaposi's sarcoma (KS) in a western Kenyan cancer treatment program. METHODS: Retrospective chart review of all patients with KS treated with single agent gemcitabine following failure of first-line Adriamycin, bleomycin, and vincristine (ABV). Baseline demographics were collected, and clinicians' assessments of response were utilized to fill out objective criteria for both response as well as symptom benefit assessment. RESULTS: Twenty-three patients with KS who had previously failed first-line therapy with ABV were evaluated. Following treatment, 22 of the 23 patients responded positively to treatment with stable disease or better. Of the 18 patients who had completed therapy, with a median follow-up of 5 months, 12 patients had no documented progression. CONCLUSIONS: Treatment options in the resource-constrained setting are limited, both by financial constraints as well as the need to avoid myelotoxicity, which is associated with high morbidity in this treatment setting. This work shows that gemcitabine has promising activity in KS, with both objective responses and clinical benefit observed in this care setting. Gemcitabine as a single agent merits further investigation for AIDS-associated KS.

Collaborative partnership for clinical pharmacy services in Kenya.

PURPOSE: A collaborative partnership for clinical pharmacy services in Kenya is described. SUMMARY: Purdue University School of Pharmacy and Pharmaceutical Sciences (PUSOPPS) agreed to collaborate with the United States Agency for International Development-Academic Model for Providing Access to Healthcare (USAID-AMPATH) partnership to provide pharmacy services necessary for patients infected with human immunodeficiency virus (HIV) in Kenya. In addition to assisting Kenyan collaborators, the full-time, onsite faculty member from PUSOPPS serves as a preceptor to pharmacy clerkship students from PUSOPPS and the University of Nairobi in the delivery of clinical pharmacy services in inpatient and outpatient settings. Through PUSOPPS's unique collaboration, Kenyan pharmacy technologist students and University of Nairobi pharmacy students partner with clerkship students from PUSOPPS to participate in eight-week rotations. In addition to inpatient activities, students spend one day each week at one of the rural HIV clinics or observing one of the burgeoning specialized care clinics. Students also participate in public health activities, such as providing adherence counseling for HIV-infected patients, participating in door-to-door HIV counseling and testing, and preparing educational and recreational activities for pediatric patients. PUSOPPS's sustainable involvement with this program has addressed many of the immediate pharmacy needs of providing antiretroviral therapy and medications for opportunistic infections throughout western Kenya. CONCLUSION: The collaboration between PUSOPPS and USAID-AMPATH in Eldoret, Kenya, has provided a bilateral educational exchange for Kenyan and American pharmacy students and has allowed for year-round clinical pharmacy services in both inpatient and outpatient settings.