Steady State Bioequivalence of Generic and Innovator Formulations of Stavudine, Lamivudine, and Nevirapine in HIV-Infected Ugandan Adults

Generic antiretroviral therapy is the mainstay of HIV treatment in resource-limited settings, yet there is little evidence confirming the bioequivalence of generic and brand name formulations. We compared the steady-state pharmacokinetics of lamivudine, stavudine and nevirapine in HIV-infected subjects who were receiving a generic formulation (Triomune®) or the corresponding brand formulations (Epivir®, Zerit®, and Viramune®)., 1.1 (0.95–1.31). The generic formulation was not statistically bioequivalent to the brand formulations during steady state, although exposures were comparable. A mixed random effects model identified about 50% intersubject variability in the pharmacokinetic parameters.These findings provide support for the use of Triomune in resource-limited settings, although identification of the sources of intersubject variability in these populations is critical

Adherence to self-administered tuberculosis treatment in a high HIV-prevalence setting: a cross-sectional survey in Homa Bay, Kenya.

Good adherence to treatment is crucial to control tuberculosis (TB). Efficiency and feasibility of directly observed therapy (DOT) under routine program conditions have been questioned. As an alternative, Médecins sans Frontières introduced self-administered therapy (SAT) in several TB programs. We aimed to measure adherence to TB treatment among patients receiving TB chemotherapy with fixed dose combination (FDC) under SAT at the Homa Bay district hospital (Kenya). A second objective was to compare the adherence agreement between different assessment tools

Not All Missed Doses Are the Same: Sustained NNRTI Treatment Interruptions Predict HIV Rebound at Low-to-Moderate Adherence Levels

Background: While the relationship between average adherence to HIV potent antiretroviral therapy is well defined, the relationship between patterns of adherence within adherence strata has not been investigated. We examined medication event monitoring system (MEMS) defined adherence patterns and their relation to subsequent virologic rebound. Methods and Results: We selected subjects with at least 3-months of previous virologic suppression on a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen from two prospective cohorts in France and North America. We assessed the risk of virologic rebound, defined as HIV RNA of >400 copies/mL according to several MEMS adherence measurements. Seventy two subjects were studied, five of them experienced virologic rebound. Subjects with and without virologic rebound had similar baseline characteristics including treatment durations, regimen (efavirenz vs nevirapine), and dosing schedule. Each 10% increase in average adherence decreased the risk of virologic rebound (OR = 0.56; 95% confidence interval (CI) [0.37, 0.81], P<0.002). Each additional consecutive day off therapy for the longest treatment interruption (OR = 1.34; 95%CI [1.15, 1.68], P<0.0001) and each additional treatment interruption for more than 2 days (OR = 1.38; 95%CI [1.13, 1.77], P<0.002) increased the risk of virologic rebound. In those with low-to-moderate adherence (i.e. <80%), treatment interruption duration (16.2 days versus 6.1 days in the control group, P<0.02), but not average adherence (53.1% vs 55.9%, respectively, P = 0.65) was significantly associated with virologic rebound. Conclusions: Sustained treatment interruption may pose a greater risk of virologic rebound on NNRTI therapy than the same number of interspersed missed doses at low-to-moderate adherence

Measuring adherence to antiretroviral treatment in resource-poor settings: The clinical validity of key indicators

<p>Abstract</p> <p>Background</p> <p>Access to antiretroviral therapy has dramatically expanded in Africa in recent years, but there are no validated approaches to measure treatment adherence in these settings.</p> <p>Methods</p> <p>In 16 health facilities, we observed a retrospective cohort of patients initiating antiretroviral therapy. We constructed eight indicators of adherence and visit attendance during the first 18 months of treatment from data in clinic and pharmacy records and attendance logs. We measured the correlation among these measures and assessed how well each predicted changes in weight and CD4 count.</p> <p>Results</p> <p>We followed 488 patients; 63.5% had 100% coverage of medicines during follow-up; 2.7% experienced a 30-day gap in treatment; 72.6% self-reported perfect adherence in all clinic visits; and 19.9% missed multiple clinic visits. After six months of treatment, mean weight gain was 3.9 kg and mean increase in CD4 count was 138.1 cells/mm3.</p> <p>Dispensing-based adherence, self-reported adherence, and consistent visit attendance were highly correlated. The first two types of adherence measure predicted gains in weight and CD4 count; consistent visit attendance was associated only with weight gain.</p> <p>Conclusions</p> <p>This study demonstrates that routine data in African health facilities can be used to monitor antiretroviral adherence at the patient and system level.</p

Addressing social issues in a universal HIV test and treat intervention trial (ANRS 12249 TasP) in South Africa: methods for appraisal

Background: The Universal HIV Test and Treat (UTT) strategy represents a challenge for science, but is also a challenge for individuals and societies. Are repeated offers of provider-initiated HIV testing and immediate antiretroviral therapy (ART) socially-acceptable and can these become normalized over time? Can UTT be implemented without potentially adding to individual and community stigma, or threatening individual rights? What are the social, cultural and economic implications of UTT for households and communities? And can UTT be implemented within capacity constraints and other threats to the overall provision of HIV services? The answers to these research questions will be critical for routine implementation of UTT strategies. Methods/design: A social science research programme is nested within the ANRS 12249 Treatment-as-Prevention (TasP) cluster-randomised trial in rural South Africa. The programme aims to inform understanding of the (i) social, economic and environmental factors affecting uptake of services at each step of the continuum of HIV prevention, treatment and care and (ii) the causal impacts of the TasP intervention package on social and economic factors at the individual, household, community and health system level. We describe a multidisciplinary, multi-level, mixed-method research protocol that includes individual, household, community and clinic surveys, and combines quantitative and qualitative methods. Discussion: The UTT strategy is changing the overall approach to HIV prevention, treatment and care, and substantial social consequences may be anticipated, such as changes in social representations of HIV transmission, prevention, HIV testing and ART use, as well as changes in individual perceptions and behaviours in terms of uptake and frequency of HIV testing and ART initiation at high CD4. Triangulation of social science studies within the ANRS 12249 TasP trial will provide comprehensive insights into the acceptability and feasibility of the TasP intervention package at individual, community, patient and health system level, to complement the trial's clinical and epidemiological outcomes. It will also increase understanding of the causal impacts of UTT on social and economic outcomes, which will be critical for the long-term sustainability and routine UTT implementation. Trial registration: Clinicaltrials.gov: NCT01509508; South African Trial Register: DOH-27-0512-3974

Measuring adherence to antiretroviral treatment in resource-poor settings: The feasibility of collecting routine data for key indicators

<p>Abstract</p> <p>Background</p> <p>An East African survey showed that among the few health facilities that measured adherence to antiretroviral therapy, practices and definitions varied widely. We evaluated the feasibility of collecting routine data to standardize adherence measurement using a draft set of indicators.</p> <p>Methods</p> <p>Targeting 20 facilities each in Ethiopia, Kenya, Rwanda, and Uganda, in each facility we interviewed up to 30 patients, examined 100 patient records, and interviewed staff.</p> <p>Results</p> <p>In 78 facilities, we interviewed a total of 1,631 patients and reviewed 8,282 records. Difficulties in retrieving records prevented data collection in two facilities. Overall, 94.2% of patients reported perfect adherence; dispensed medicine covered 91.1% of days in a six month retrospective period; 13.7% of patients had a gap of more than 30 days in their dispensed medication; 75.8% of patients attended clinic on or before the date of their next appointment; and 87.1% of patients attended within 3 days.</p> <p>In each of the four countries, the facility-specific median indicators ranged from: 97%-100% for perfect self-reported adherence, 90%-95% of days covered by dispensed medicines, 2%-19% of patients with treatment gaps of 30 days or more, and 72%-91% of appointments attended on time. Individual facilities varied considerably.</p> <p>The percentages of days covered by dispensed medicine, patients with more than 95% of days covered, and patients with a gap of 30 days or more were all significantly correlated with the percentages of patients who attended their appointments on time, within 3 days, or within 30 days of their appointment. Self reported recent adherence in exit interviews was significantly correlated only with the percentage of patients who attended within 3 days of their appointment.</p> <p>Conclusions</p> <p>Field tests showed that data to measure adherence can be collected systematically from health facilities in resource-poor settings. The clinical validity of these indicators is assessed in a companion article. Most patients and facilities showed high levels of adherence; however, poor levels of performance in some facilities provide a target for quality improvement efforts.</p

Adherence Support Workers: A Way to Address Human Resource Constraints in Antiretroviral Treatment Programs in the Public Health Setting in Zambia

BACKGROUND: In order to address staff shortages and improve adherence counseling for people on antiretroviral therapy (ART), the Zambia Prevention, Care and Treatment Partnership (ZPCT) developed an innovative strategy of training community volunteers to provide adherence support at the health facility and community levels. The objective of this study was to assess the effectiveness of these 'adherence support workers' (ASWs) in adherence counseling, treatment retention and addressing inadequate human resources at health facilities.METHODOLOGY/PRINCIPAL FINDINGS: The study used quantitative and qualitative research techniques at five selected ART sites in four provinces in Zambia. Five hundred patients on ART were interviewed using a structured questionnaire to compare the quality of adherence counseling before and after the ASW scheme was introduced at the selected sites and between ASWs and HCWs after the introduction of ASWs. In addition, 3,903 and 4,972 electronic records of all new patients accessing antiretroviral therapy for the time period of 12 months before and 12 months after the introduction of ASWs respectively, were analyzed to assess loss to follow-up rates. Two focus group discussions with ASWs and health care workers (HCWs) were conducted in each clinic. Key informant interviews in the ART clinics were also conducted. There was a marked shift of workload from HCWs to ASWs without any compromise in the quality of counseling. Quality of adherence counseling by ASWs was comparable to HCWs after their introduction. The findings suggest that the deployment of ASWs helped reduce waiting times for adherence counseling. Loss to follow-up rates of new clients declined from 15% to 0% after the deployment of ASWs.CONCLUSION: Adherence counseling tasks can be shifted to lay cadres like ASWs without compromising the quality of counseling. Follow-up of clients by ASWs within the community is necessary to improve retention of clients on ART

Correcting for Mortality Among Patients Lost to Follow Up on Antiretroviral Therapy in South Africa: A Cohort Analysis

Loss to follow-up (LTF) challenges the reporting of antiretroviral treatment (ART) programmes, since it encompasses patients alive but lost to programme and deaths misclassified as LTF. We describe LTF before and after correction for mortality in a primary care ART programme with linkages to the national vital registration system

Relationship between CD4 count and quality of life over time among HIV patients in Uganda: A cohort study

© 2015 Mwesigire et al. Background: Immunological markers (CD4 count) are used in developing countries to decide on initiation of antiretroviral therapy and monitor HIV/AIDS disease progression. HIV is an incurable chronic illness, making quality of life paramount. The direct relationship between quality of life and CD4 count is unclear. The purpose of this study is to determine the relationship between change in CD4 count and quality of life measures in a Ugandan cohort of people living with HIV. Methods: We prospectively assessed quality of life among 1274 HIV patients attending an HIV clinic within a national referral hospital over a period of 6months. Quality of life was measured using an objective measure, the Medical Outcomes Study HIV health survey summarized as Physical Health Score and Mental Health Score and a subjective measure, the Global Person Generated Index. Generalized estimating equations were used to analyze the data. The primary predictor variable was change in CD4 count, and the outcome was quality of life scores. We controlled for sociodemographic characteristics, clinical factors and behavioral factors. Twenty in-depth interviews were conducted to assess patient perception of quality of life and factors influencing quality of life. Results: Of the 1274 patients enrolled 1159 had CD4 count at baseline and six months and 586 (51%) received antiretroviral therapy. There was no association found between change in CD4 count and quality of life scores at univariate and multivariate analysis among the study participants whether on or not on antiretroviral therapy. Participants perceived quality of life as happiness and well-being, influenced by economic status, psychosocial factors, and health status. Conclusions: Clinicians and policy makers cannot rely on change in immunological markers to predict quality of life in this era of initiating antiretroviral therapy among relatively healthy patients. In addition to monitoring immunological markers, socioeconomic and psychosocial factors should be underscored in management of HIV patients