Second-Line Switch to Dolutegravir for Treatment of HIV Infection.

BACKGROUND: Data to inform the switch from a ritonavir-boosted protease inhibitor (PI) to dolutegravir in patients living with human immunodeficiency virus (HIV) infection who do not have genotype information and who have viral suppression with second-line therapy containing a ritonavir-boosted PI have been limited. METHODS: In a prospective, multicenter, open-label trial conducted at four sites in Kenya, we randomly assigned, in a 1:1 ratio, previously treated patients without genotype information who had viral suppression while receiving treatment containing a ritonavir-boosted PI to either switch to dolutegravir or continue the current regimen. The primary end point was a plasma HIV type 1 RNA level of at least 50 copies per milliliter at week 48, assessed on the basis of the Food and Drug Administration snapshot algorithm. The noninferiority margin for the between-group difference in the percentage of participants who met the primary end point was 4 percentage points. Safety up to week 48 was assessed. RESULTS: A total of 795 participants were enrolled, with 398 assigned to switch to dolutegravir and 397 assigned to continue taking their ritonavir-boosted PI; 791 participants (397 in the dolutegravir group and 394 in the ritonavir-boosted PI group) were included in the intention-to-treat exposed population. At week 48, a total of 20 participants (5.0%) in the dolutegravir group and 20 (5.1%) in the ritonavir-boosted PI group met the primary end point (difference, -0.04 percentage points; 95% confidence interval, -3.1 to 3.0), a result that met the criterion for noninferiority. No mutations conferring resistance to dolutegravir or the ritonavir-boosted PI were detected at the time of treatment failure. The incidence of treatment-related grade 3 or 4 adverse events was similar in the dolutegravir group and the ritonavir-boosted PI group (5.7% and 6.9%, respectively). CONCLUSIONS: In previously treated patients with viral suppression for whom there were no data regarding the presence of drug-resistance mutations, dolutegravir treatment was noninferior to a regimen containing a ritonavir-boosted PI when the patients were switched from a ritonavir-boosted PI-based regimen. (Funded by ViiV Healthcare; 2SD ClinicalTrials.gov number, NCT04229290.).

High rates of kidney impairment among older people (≥ 60 years) living with HIV on first-line antiretroviral therapy at screening for a clinical trial in Kenya.

BACKGROUND: There is a paucity of data on kidney impairment among older people living with HIV (PLWH). We evaluated kidney function among PLWH age ≥ 60 years on first-line antiretroviral (ARV) therapy during screening for a clinical trial in Kenya. METHODS: The bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) Elderly Study is an open-label, randomized, active-controlled, non-inferiority trial conducted at two sites in Kenya. Potential participants were screened for study entry if they were at least 60 years old, had been on ARVs for at least 24 weeks and had no history of treatment failure. At screening, participants had samples collected for serum creatinine and estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration 2021 equation. RESULTS: Between January and April 2022, 714 participants were screened and had creatinine measured. All participants were black, 54.1% were female and the median age was 64 years (range 60 to 87 years). Most participants (666 [93.3%]) were on tenofovir disoproxil fumarate-containing regimens, 711 (99.6%) were on dolutegravir-containing regimens, and only 2 (0.3%) were on a regimen with a ritonavir-boosted protease inhibitor. Most participants (686 [96.6%]) were virally suppressed. Treatment for comorbidities was common, with 175 (24.5%) on treatment for hypertension and 39 (5.5%) on treatment for diabetes mellitus. The median eGFR was 64.7 mL/min/1.73m2, and 289 (40.5%) participants had an eGFR < 60 mL/min/1.73m2. In multivariate analysis, factors associated with lower eGFR were female gender (p<0.001), being on treatment for hypertension (p<0.001) and nadir CD4 count < 50 cells/µL (p = 0.008). CONCLUSIONS: Our study identified high rates of impaired kidney function among elderly PLHW in Kenya, which highlights the importance of routine assessment of kidney function and the need to address modifiable risk factors, use of appropriate ARVs, and management of kidney disease in this population.

Comparative Clinical Outcomes With Scale-up of Dolutegravir as First-Line Antiretroviral Therapy in Ukraine.

BACKGROUND: Achievement of the UNAIDS 95-95-95 targets requires ARV regimens that are easy to use, well-tolerated, and cost-effective. Dolutegravir (DTG)-based regimens are efficacious and less costly than other common first-line regimens. This study assessed real-world effectiveness of DTG regimens in treatment-naive people living with HIV in Ukraine. METHODS: We extracted data from the national Medical Information System on all adult patients who initiated antiretroviral therapy (ART) with DTG, lopinavir/ritonavir, or efavirenz (EFV) between October 2017 and June 2018, at 23 large clinics in 12 regions of Ukraine. Viral suppression at 12 ± 3 months and retention at 12 months after treatment initiation were the outcomes of interest. RESULTS: Of total 1057 patients, 721 had a viral load test within the window of interest, and 652 (90%) had viral load of ≤ 200 copies/mL. The proportion with suppression was lower in the EFV group [aOR = 0.4 (95% confidence interval: 0.2 to 0.8)] and not different in the LPV group [aOR = 1.6 (0.5 to 4.9)] compared with the DTG group. A 24-month or longer gap between diagnosis and treatment was associated with lower odds of suppression [aOR = 0.4 (0.2 to 0.8)]. Treatment retention was 90% (957/1057), with no significant difference by regimen group. History of injecting drug use was associated with decreased retention [aOR = 0.5 (0.3 to 0.8)]. CONCLUSIONS: DTG-based regimens were comparable with LPV and more effective than EFV in achieving viral suppression among ART-naive patients in a multisite cohort in Ukraine. Treatment retention was equally high in all 3 groups. This evidence from Ukraine supports the ART Optimization Initiative as a strategy to improve efficiency of the ART program without negatively affecting patient clinical outcomes.

Disparities in Dolutegravir Uptake Affecting Females of Reproductive Age With HIV in Low- and Middle-Income Countries After Initial Concerns About Teratogenicity : An Observational Study.

BACKGROUND: The transition to dolutegravir-containing antiretroviral therapy (ART) in low- and middle-income countries (LMICs) was complicated by an initial safety signal in May 2018 suggesting that exposure to dolutegravir at conception was possibly associated with infant neural tube defects. On the basis of additional evidence, in July 2019, the World Health Organization recommended dolutegravir for all adults and adolescents living with HIV. OBJECTIVE: To describe dolutegravir uptake and disparities by sex and age group in LMICs. DESIGN: Observational cohort study. SETTING: 87 sites that began using dolutegravir in 11 LMICs in the Asia-Pacific; Caribbean, Central and South America network for HIV epidemiology (CCASAnet); and sub-Saharan African regions of the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium. PATIENTS: 134 672 patients aged 16 years or older who received HIV care from January 2017 through March 2020. MEASUREMENTS: Sex, age group, and dolutegravir uptake (that is, newly initiating ART with dolutegravir or switching to dolutegravir from another regimen). RESULTS: Differences in dolutegravir uptake among females of reproductive age (16 to 49 years) emerged after the safety signal. By the end of follow-up, the cumulative incidence of dolutegravir uptake among females 16 to 49 years old was 29.4% (95% CI, 29.0% to 29.7%) compared with 57.7% (CI, 57.2% to 58.3%) among males 16 to 49 years old. This disparity was greater in countries that began implementing dolutegravir before the safety signal and initially had highly restrictive policies versus countries with a later rollout. Dolutegravir uptake was similar among females and males aged 50 years or older. LIMITATION: Follow-up was limited to 6 to 8 months after international guidelines recommended expanding access to dolutegravir. CONCLUSION: Substantial disparities in dolutegravir uptake affecting females of reproductive age through early 2020 are documented. Although this disparity was anticipated because of country-level restrictions on access, the results highlight its extent and initial persistence. PRIMARY FUNDING SOURCE: National Institutes of Health.

They are likely to be there: using a family-centered index testing approach to identify children living with HIV in Kenya.

In Kenya, only half of children with a parent living with HIV have been tested for HIV. The effectiveness of family-centered index testing to identify children (0-14 years) living with HIV was examined. A retrospective record review was conducted among adult index patients newly enrolled in HIV care between May and July 2015; family testing, results, and linkage to treatment outcomes were followed through May 2016 at 60 high-volume clinics in Kenya. Chi square test compared yield (percentage of HIV tests positive) among children tested through family-centered index testing, outpatient and inpatient testing. Review of 1937 index client charts led to 3005 eligible children identified for testing. Of 2848 (94.8%) children tested through family-centered index testing, 127 (4.5%) had HIV diagnosed, 100 (78.7%) were linked to care, and 85 of those eligible (91.4%) initiated antiretroviral therapy (ART).Family testing resulted in higher yield compared to inpatient (1.8%, p < 0.001) or outpatient testing (1.6%, p < 0.001). The absolute number of children living with HIV identified was highest with outpatient testing. The relative contribution of testing approach to total children identified with HIV was outpatient testing (69%), family testing (26%), and inpatient testing (5%). The family testing approach demonstrated promise in achieving the first two "90s" (identification and ART initiation) of the 90-90-90 targets for children, with additional effort required to improve linkage from testing to treatment.

Differentiated HIV care in sub-Saharan Africa: a scoping review to inform antiretroviral therapy provision for stable HIV-infected individuals in Kenya.

Many gaps in care exist for provision of antiretroviral therapy (ART) in sub-Saharan Africa. Differentiated HIV care tailors provision of ART for patients based on their level of acuity, providing alternatives for where, by whom, and how often care occurs. We conducted a scoping review to assess novel differentiated care models for ART provision for stable HIV-infected adults in sub-Saharan Africa, and how these models can be used to guide differentiated care implementation in Kenya. A systematic search was conducted using PubMed, Embase, Web of Science, Popline, Cochrane Library, and African Index Medicus between January 2006 and January 2017. Grey literature searches and handsearching were also used. We included articles that quantitatively assessed the health, acceptability, and cost-effectiveness of differentiated HIV care. Two reviewers independently performed article screening, data extraction and determination of inclusion for analysis. We included 40 publications involving over 240,000 participants spanning nine countries in sub-Saharan Africa - 54.4% evaluated clinical outcomes, 23.5% evaluated acceptability outcomes, and 22.1% evaluated cost outcomes. Differentiated care models included: facility fast-track drug refills and appointment spacing, facility or community-based ART groups, community ART distribution points or home-based care, and task-shifting or decentralization of care. Studies suggest that these approaches had similar outcomes in viral load suppression and retention in care and were acceptable alternatives to standard HIV care. No clear results could be inferred for studies investigating task shifting and those reporting cost-effectiveness outcomes. Kenya has started to scale up differentiated care models, but further evaluation, quality improvement and research studies should be performed as different models are rolled out.

Bridging the Gap in Implementation Science: Evaluating a Capacity-Building Program in Data Management, Analysis, Utilization, and Dissemination in Low- and Middle-Income Countries.

Building capacity in implementation science within health programs is dependent on training in theory and practice of epidemiology, statistics, and research in addition to high self-efficacy toward application of training. This article describes a training program providing technical assistance to more than 300 health facilities in Kenya and Tanzania, its evaluation results, and its ability to improve participants' knowledge, competencies, and self-efficacy on data management, analysis, and dissemination among health care professionals. Two months prior to the training, participants (n = 98) were emailed a pre-course survey including 19 questions using a Likert-type response for planning the content of the workshop. Six to 12 weeks after the training, a post-course survey was emailed to all participants. Five different trainings were conducted indicating 5 participant cohorts. The questions posed involved course satisfaction, course impact on knowledge and skills, and self-efficacy in data analysis and utilization. Post-course survey results revealed that the participants had confidence in data analysis, which was significantly different from the pre-test results (0.05 α). Qualitative commentary complemented the findings of the impact of the workshop. Four manuscripts and 13 abstracts have been submitted post training. Results suggest that a short-term training program can achieve immediate gains in data and research self-efficacy among health care professionals. Although increasing self-efficacy is a necessary first step in developing skills, educators should engage in continuing education for sustainable dissemination practices. There is an urgent need to determine the current infrastructure to promote scientific dissemination. This will assist countries to produce better evidence to support their programs, policies, and overall health programs.

Building capacity in implementation science research training at the University of Nairobi.

BACKGROUND: Health care systems in sub-Saharan Africa, and globally, grapple with the problem of closing the gap between evidence-based health interventions and actual practice in health service settings. It is essential for health care systems, especially in low-resource settings, to increase capacity to implement evidence-based practices, by training professionals in implementation science. With support from the Medical Education Partnership Initiative, the University of Nairobi has developed a training program to build local capacity for implementation science. METHODS: This paper describes how the University of Nairobi leveraged resources from the Medical Education Partnership to develop an institutional program that provides training and mentoring in implementation science, builds relationships between researchers and implementers, and identifies local research priorities for implementation science. RESULTS: The curriculum content includes core material in implementation science theory, methods, and experiences. The program adopts a team mentoring and supervision approach, in which fellows are matched with mentors at the University of Nairobi and partnering institutions: University of Washington, Seattle, and University of Maryland, Baltimore. A survey of program participants showed a high degree satisfaction with most aspects of the program, including the content, duration, and attachment sites. A key strength of the fellowship program is the partnership approach, which leverages innovative use of information technology to offer diverse perspectives, and a team model for mentorship and supervision. CONCLUSIONS: As health care systems and training institutions seek new approaches to increase capacity in implementation science, the University of Nairobi Implementation Science Fellowship program can be a model for health educators and administrators who wish to develop their program and curricula.

Integration of HIV Care with Primary Health Care Services: Effect on Patient Satisfaction and Stigma in Rural Kenya.

HIV departments within Kenyan health facilities are usually better staffed and equipped than departments offering non-HIV services. Integration of HIV services into primary care may address this issue of skewed resource allocation. Between 2008 and 2010, we piloted a system of integrating HIV services into primary care in rural Kenya. Before integration, we conducted a survey among returning adults ≥18-year old attending the HIV clinic. We then integrated HIV and primary care services. Three and twelve months after integration, we administered the same questionnaires to a sample of returning adults attending the integrated clinic. Changes in patient responses were assessed using truncated linear regression and logistic regression. At 12 months after integration, respondents were more likely to be satisfied with reception services (adjusted odds ratio, aOR 2.71, 95% CI 1.32-5.56), HIV education (aOR 3.28, 95% CI 1.92-6.83), and wait time (aOR 1.97 95% CI 1.03-3.76). Men's comfort with receiving care at an integrated clinic did not change (aOR = 0.46 95% CI 0.06-3.86). Women were more likely to express discomfort after integration (aOR 3.37 95% CI 1.33-8.52). Integration of HIV services into primary care services was associated with significant increases in patient satisfaction in certain domains, with no negative effect on satisfaction.

Predictors of outcome in routine care for Cryptococcal meningitis in Western Kenya: lessons for HIV outpatient care in resource-limited settings.

PURPOSE: Cryptococcal meningitis is a leading cause of mortality among HIV-infected individuals in sub-Saharan Africa but little is known about its treatment and outcomes in decentralised HIV outpatient settings. We assessed adherence to treatment guidelines and determined predictors of survival. DESIGN: A computerised laboratory database identified HIV-infected adults with cryptococcal meningitis at Family AIDS Care and Education Services in Nyanza Province, Kenya, between 2005-2009. Medical records were reviewed. Kaplan-Meier survival curves were generated. Bivariate and multivariate Cox proportional hazards models were used to determine associations between key clinical characteristics and survival. RESULTS: Medical records were located for 79% (71/90). Mortality was 38% (27/71) over a median follow-up period of 201 days (IQR: 10-705 days). Adherence to local guidelines for treatment of cryptococcal meningitis was 48% (34/71). Higher body mass index was associated with improved survival (HR: 0.82, 95% CI (0.68 to 0.99)) even after controlling for factors such as age, CD4 cell count, receipt of highly active anti-retroviral therapy, and treatment with any anti-fungal therapy. CONCLUSIONS: Cryptococcal meningitis diagnosed in routine HIV outpatient settings is largely treated as an outpatient and adherence to treatment guidelines is poor. Body mass index is a critical independent predictor of outcome. Additional research to determine the most effective strategies to reduce premature mortality is urgently needed.

The study of HIV and antenatal care integration in pregnancy in Kenya: design, methods, and baseline results of a cluster-randomized controlled trial.

BACKGROUND: Despite strong evidence for the effectiveness of anti-retroviral therapy for improving the health of women living with HIV and for the prevention of mother-to-child transmission (PMTCT), HIV persists as a major maternal and child health problem in sub-Saharan Africa. In most settings antenatal care (ANC) services and HIV treatment services are offered in separate clinics. Integrating these services may result in better uptake of services, reduction of the time to treatment initiation, better adherence, and reduction of stigma. METHODOLOGY/PRINCIPAL FINDINGS: A prospective cluster randomized controlled trial design was used to evaluate the effects of integrating HIV treatment into ANC clinics at government health facilities in rural Kenya. Twelve facilities were randomized to provide either fully integrated services (ANC, PMTCT, and HIV treatment services all delivered in the ANC clinic) or non-integrated services (ANC clinics provided ANC and basic PMTCT services and referred clients to a separate HIV clinic for HIV treatment). During June 2009- March 2011, 1,172 HIV-positive pregnant women were enrolled in the study. The main study outcomes are rates of maternal enrollment in HIV care and treatment, infant HIV testing uptake, and HIV-free infant survival. Baseline results revealed that the intervention and control cohorts were similar with respect to socio-demographics, male partner HIV testing, sero-discordance of the couple, obstetric history, baseline CD4 count, and WHO Stage. Challenges faced while conducting this trial at low-resource rural health facilities included frequent staff turnover, stock-outs of essential supplies, transportation challenges, and changes in national guidelines. CONCLUSIONS/SIGNIFICANCE: This is the first randomized trial of ANC and HIV service integration to be conducted in rural Africa. It is expected that the study will provide critical evidence regarding the implementation and effectiveness of this service delivery strategy, with important implications for programs striving to eliminate vertical transmission of HIV and improve maternal health. TRIAL REGISTRATION: ClinicalTrials.gov NCT00931216 http://clinicaltrials.gov/ct2/show/NCT00931216.

Family model of HIV care and treatment: a retrospective study in Kenya.

BACKGROUND: Nyanza Province, Kenya, had the highest HIV prevalence in the country at 14.9% in 2007, more than twice the national HIV prevalence of 7.1%. Only 16% of HIV-infected adults in the country accurately knew their HIV status. Targeted strategies to reach and test individuals are urgently needed to curb the HIV epidemic. The family unit is one important portal. METHODS: A family model of care was designed to build on the strengths of Kenyan families. Providers use a family information table (FIT) to guide index patients through the steps of identifying family members at HIV risk, address disclosure, facilitate family testing, and work to enrol HIV-positive members and to prevent new infections. Comprehensive family-centred clinical services are built around these steps. To assess the approach, a retrospective study of patients receiving HIV care between September 2007 and September 2009 at Lumumba Health Centre in Kisumu was conducted. A random sample of FITs was examined to assess family reach. RESULTS: Through the family model of care, for each index patient, approximately 2.5 family members at risk were identified and 1.6 family members were tested. The approach was instrumental in reaching children; 61% of family members identified and tested were children. The approach also led to identifying and enrolling a high proportion of HIV- positive partners among those tested: 71% and 89%, respectively. CONCLUSIONS: The family model of care is a feasible approach to broaden HIV case detection and service reach. The approach can be adapted for the local context and should continue to utilize index patient linkages, FIT adaption, and innovative methods to package services for families in a manner that builds on family support and enhances patient care and prevention efforts. Further efforts are needed to increase family member engagement.

Evaluating the uptake, acceptability, and effectiveness of Uliza! clinicians' HIV hotline: a telephone consultation service in Kenya.

OBJECTIVE: Many clinical sites that serve patients who are HIV positive face challenges of insufficient staffing levels and staff training and have limited access to consultation resources including specialists on site. Uliza! (Swahili for "ask") Clinicians' HIV Hotline was launched in April 2006 in Nyanza province in Kenya as a HIV telephone consultation service for healthcare providers. Hotline users called an Uliza! consultant who discussed the patients' problems and helped the caller work through a solution, as well as reinforced national guidelines. This objective of this study was to evaluate the uptake, acceptability, and effectiveness of Uliza! MATERIALS AND METHODS: Consultants completed a form with details of each call, and healthcare workers completed satisfaction surveys during site visits. All available medical records were audited to determine whether the advice given by the consultant was implemented. RESULTS: After a year of service, Uliza! responded to 296 calls. Clinical officers (64%) followed by nurses (21%) most frequently used the service. Most callers had questions regarding antiretroviral therapy (36%) or tuberculosis (18%). Thirty-six percent of all consults were pediatric questions. Ninety-four percent of users rated the service as useful. Advice given to providers was implemented and documented in the medical records in 72% of the charts audited. CONCLUSION: Healthcare providers in HIV clinics will use a telephone consultation service when easily accessible. Clinicians using Uliza! found it useful, and advice given was usually implemented. Uliza! increased access to current information for quality care in a rural and resource limited setting and has potential for scale-up to a national level.

Risk factors for pneumonia in urban-dwelling HIV-infected women: a case-control study in Nairobi, Kenya.

In sub-Saharan Africa, respiratory tract infections (RTI) are the leading cause of serious morbidity and mortality in HIV-infected persons. This study sought to investigate demographic, socioeconomic, and environmental risk factors for pneumonia in a cohort of HIV-infected women. The authors performed a nested case-control study in a cohort of HIV-1-infected adults followed in Nairobi, Kenya. Thirty-nine women who developed pneumonia during the follow-up period were selected as cases, and 66 women who did not develop pneumonia were randomly chosen to serve as control subjects. A questionnaire was administered in subjects' homes that assessed demographics, home environment, and socioeconomic status. Women were followed in the cohort for a median of 36.8 months (range, 27.3-39.3). Adjusting for length of follow-up period, factors associated with lower socioeconomic status (lower monthly spending [OR = 3.2; 95% CI, 1.2-8.4 per 10,000 Kenyan shilling decrease], having no savings [OR = 4.1; 95% CI, 1.4-11.9], less sturdy home construction material such as mud or cement walls [OR = 2.6; 95% CI, 1.1-5.9] or dirt floors [OR = 2.8; 95% CI, 1.0-7.6], and lack of a window in the home [OR = 5.5; 95% CI, 0.9-32.2]) and being widowed (OR = 4.3; 95% CI, 1.2-15.1) or single (OR = 3.3; 95% CI, 1.0-11.2) were associated with an increased risk of pneumonia. In multivariate analysis, widowed (AOR = 5.9; 95% CI, 1.3-26.3), single (AOR = 7.7; 95% CI, 1.6-36.4), and divorced (AOR = 4.5; 95% CI, 1.0-20.1) women, those without savings (AOR = 3.7; 95% CI, 1.2-11.7), and those living in more crowded and contagious conditions (AOR = 1.5; 95% CI, 1.1-2.1) remained at increased risk of pneumonia. If confirmed by prospective investigation, these findings could help identify persons and subpopulations of HIV-infected women with the greatest risk of pneumonia.