Management Of Antiretroviral Therapy Research Articles

Survival Patterns of Human Immunodeficieny Virus-Tuberculosis (HIV-TB) Co-Infected Patients in Selected Counties in Kenya`

One nation with a significant burden of tuberculosis and the human immunodeficiency virus is Kenya. Coinfection with tuberculosis and the human immunodeficiency virus/acquired immunodeficiency syndrome complicates infection control and lowers survival rates. While research on HIV/TB coinfection has been done in Kenya, little is known about the patterns in people's survival with Antiretroviral Therapy (ART) and T.B. therapy, particularly regarding the country's many Counties. This study used the Kaplan-Meier function to determine the trends in patient survival for those receiving ART and T.B. treatment in Kenya. A retrospective cohort research design was employed in the investigation. Patients receiving co-therapy for T.B. and ART management who visited the medical institutions between January 1, 2015, and December 31, 2019, were included in the target population. The National AIDS & STIs Control Program (NASCOP) database (secondary data) records of all HIV-TB co-infected individuals from the chosen counties in Kenya were used to create the study's sample. The survival function was estimated using the Kaplan-Meier estimator. According to the study, the use of ART and T.B. treatment statistically affects the survival of patients co-infected with HIV and T.B. More persons with T.B. and HIV infections who received both ART and T.B. treatment survived longer than those who received only ART up to about the 750th day. The study also discovered that the mortality rates for HIV-TB patients between 2015 and 2019 differed from county to county. The study also showed that throughout five years, there were variations in the distribution of T.B. and HIV mortality among the 47 Counties. The overall number of T.B. and HIV deaths in the 47 countries was 1077 in 2015. This figure fell to 921 in 2016, 391 in 2017, 106 in 2018, and 60 in 2019. Conclusion: Starting treatment later in the course of the disease may have a bigger impact on lowering T.B./HIV-related mortality than focusing interventions in the first few months following ART initiation.

Knowledge and perceptions of primary healthcare providers towards integration of antiretroviral therapy (ART) services at departmental levels at selected health facilities Lira district, Uganda

BackgroundInvestigations conducted among healthcare providers to assess their knowledge and perceptions towards the integration of anti-retroviral therapy (ART) related services in Sub-Saharan Africa are limited. This study explored the knowledge and perceptions of primary healthcare providers towards the integration of ART management services at departmental levels in health facilities in Lira district.MethodsWe conducted a descriptive cross-sectional survey that employed qualitative methods of data collection in four selected health facilities in Lira district between January and February 2022. The study involved in-depth interviews with key informants and focus group discussions. The study population consisted exclusively of primary healthcare providers; however, those who were not full-time employees of the participating health facilities were excluded. We used thematic content analysis.ResultsA significant proportion of staff (especially those who are not directly involved in ART) still lack full knowledge of ART services integration. There was generally a positive perception, with some suggesting ART integration can minimize stigma and discrimination. The potential barriers to integration included limited knowledge and skills for providing comprehensive ART services, insufficient staffing and space, funding gaps, and inadequate drug supplies, coupled with increased workload due to enlarged clientele.ConclusionWhereas healthcare workers are generally knowledgeable about ART integration, but their knowledge was limited to partial integration. The participants had a basic understanding of ART services being provided by different health facilities. Furthermore, participants viewed integration as critical, but it should be implemented in conjunction with ART management training. Given that respondents reported a lack of infrastructure, increased workload, and understaffing, additional investments in staff recruitment, motivation through training and incentives, and other means are needed if ART integration is to be implemented.

Clonally expanded HIV-1 proviruses with 5'-leader defects can give rise to nonsuppressible residual viremia.

BackgroundAntiretroviral therapy (ART) halts HIV-1 replication, decreasing viremia to below the detection limit of clinical assays. However, some individuals experience persistent nonsuppressible viremia (NSV) originating from CD4+ T cell clones carrying infectious proviruses. Defective proviruses represent over 90% of all proviruses persisting during ART and can express viral genes, but whether they can cause NSV and complicate ART management is unknown.MethodsWe undertook an in-depth characterization of proviruses causing NSV in 4 study participants with optimal adherence and no drug resistance. We investigated the impact of the observed defects on 5'-leader RNA properties, virus infectivity, and gene expression. Integration-site specific assays were used to track these proviruses over time and among cell subsets.ResultsClones carrying proviruses with 5'-leader defects can cause persistent NSV up to approximately 103 copies/mL. These proviruses had small, often identical deletions or point mutations involving the major splicing donor (MSD) site and showed partially reduced RNA dimerization and nucleocapsid binding. Nevertheless, they were inducible and produced noninfectious virions containing viral RNA, but lacking envelope.ConclusionThese findings show that proviruses with 5'-leader defects in CD4+ T cell clones can give rise to NSV, affecting clinical care. Sequencing of the 5'-leader can help in understanding failure to completely suppress viremia.FundingOffice of the NIH Director and National Institute of Dental and Craniofacial Research, NIH; Howard Hughes Medical Institute; Johns Hopkins University Center for AIDS Research; National Institute for Allergy and Infectious Diseases (NIAID), NIH, to the PAVE, BEAT-HIV, and DARE Martin Delaney collaboratories.

Application of Invariant Analysesto Study Survival Trends of Patients onAntiretroviral Therapy (ART) and TB Treatment in Kenya

Kenya is one of the countries, globally, with a high burden of human immunodeficiency virus and tuberculosis. The co-infection between tuberculosis and human immunodeficiency virus/acquired immunodeficiency syndrome makes the management of the infection more complicated and reduces the chances of survival. The current study evaluates the trends in the survival of individuals with ART and TB management, especially in relation to various Counties in the country. The specific objective wasto establish the survival trends of patients on Antiretroviral Therapy (ART) and TB treatment in Kenya using Kaplan Meier function. The study used a retrospective cohort study design. The target population included patients on co-therapy TB and ART management who attended the health facilities between 1st January 2015 and 31st December 2019. The sample of the study was obtained from all the available HIV-TB co-infected patients’ records in National AIDS & STIs Control Program (NASCOP) database (secondary data) from the selected counties in Kenya. Kaplan Meier estimator was used in the estimation of the survival function. Analysis was done using STATA v14.2 and Bayes’ v3.0.2. The study also found that HIV-TB patients’ death rates for the period between 2015 and 2019 varied from one County to another. The study also established that the distribution of TB and HIV deaths in the 47 Counties varied across the five years. In the year 2015, the total number of TB and HIV deaths in the 47 Countries was 1077, which decreased to 921 TB and HIV deaths in 2016 before decreasing to 391 in 2017, 106 in 2018 and 60 in 2019. The study found that the main factors significantly influencing HIV-TB confections include gender, marital status, WHO clinical stage, age, weight and facility levels.

1259. Bictegravir or Dolutegravir-Containing Antiretroviral Regimens in Solid Organ Transplantation: Single-Center Experience

Abstract Background Solid organ transplantation (SOT) is the definitive treatment for end-organ failure in HIV-positive recipients. Bictegravir (BIC) or dolutegravir (DTG) based antiretroviral therapy (ART) is the preferred ART due to high efficacy, excellent tolerability and minimal drug interactions, yet there is a paucity of data on these second generation integrase inhibitors (INSTIs) in SOT. We report the Memorial Transplant Institute’s experience using second generation INSTI-containing ART with or without emtricitabine/tenofovir alafenamide (FTC/TAF) in persons with HIV. Table 1.Demographics and clinical features of 16 patients with HIV undergoing solid organ transplantation (SOT).3TC: lamivudine; AA: African American; BIC: bictegravir; DTG: dolutegravir; F: female; FTC: emtricitabine; H: Hispanic/Latino/a/x; IN: integrase; M: male; NH: Non-Hispanic/Latino/a/x; PR: protease; RPV: rilpivirine; RT: reverse transcriptase; SOT: solid organ transplantation; TAF: tenofovir alafenamide; W: whiteTable 2.Clinical course of 8 patients with HIV after solid organ transplantation (SOT).3TC: lamivudine; ABC: abacavir; ART: antiretroviral therapy; ATV: atazanavir; BIC: bictegravir; c: cobicistat; DTG: dolutegravir; DRV: darunavir; eFGR: estimated glomerular filtration rate; ETR: etravirine; FTC: emtricitabine; r: ritonavir; RAL: raltegravir; RPV: rilpivirine; RTV: ritonavir; SOT: solid organ transplantation; TAF: tenofovir alafenamide Methods This single-center observational study compiles data from medical records of all persons with HIV undergoing SOT seen by the Division of Infectious Disease from January 2017 through April 2022. We report clinical information and ART management of SOT candidates and recipients in our center. Results Sixteen patients met inclusion criteria: 8 SOT candidates (7 kidney, 1 heart) and 8 SOT recipients (all kidney). Demographics are presented in Table 1. Patients were 63% male with a mean age of 55 years, CD4 323 cells/mm3, and living with HIV for 16 years. ART regimens were BIC/FTC/TAF (50%), DTG/rilpivirine (RPV) (19%), DTG + FTC/TAF (19%) and RPV/FTC/TAF + DTG (6%), and DTG/lamivudine (6%). All pharmacokinetic enhancers were discontinued to avoid drug interactions with anti-rejection medications. Last on-treatment HIV RNA was < 200 copies/mL for 100% of patients. The clinical course of 8 post-renal transplant recipients is presented in Table 2. The most common post-SOT regimen was BIC/FTC/TAF. Post-SOT patients maintained HIV RNA < 200 copies/mL. No ART-related adverse effects were documented. Two allograft- or life-threatening infections and one episode of acute antibody rejection was reported. Expectedly, serum creatinine decreased and estimated glomerular filtration rate increased post-renal transplant. Conclusion We provide additional insight into the use of BIC- and DTG-containing ART with or without FTC/TAF in the peri-SOT period. Our growing experience suggests second generation INSTI-containing ART regimens with or without FTC/TAF are effective and well tolerated following kidney transplantation. Additional research on the use of second generation INSTIs in the SOT patient population is needed. Disclosures All Authors: No reported disclosures.

Involvement, Perception, and Understanding as Determinants for Patient-Physician Relationship and Their Association with Adherence: A Questionnaire Survey among People Living with HIV and Antiretroviral Therapy in Austria.

Background: The relationship between patients and healthcare professionals (physicians) is the cornerstone of successful long-term antiretroviral therapy for people living with human immunodeficiency virus (HIV). Purpose: This study aimed to investigate the connection between involvement, perception, and understanding as the basis for the patient–physician relationship and drug adherence, measured as the probability of non-adherence. Methods: In an online survey, people with HIV were asked about their relationship with their physicians and the extent to which they felt involved in treatment-related decisions. A statistical analysis was conducted to determine whether a better patient–physician relationship was associated with higher adherence to therapy. This was performed by univariate group comparison (Mann–Whitney-U, Fishers Exact Test) and logistic regression. Results: A total of 303 persons living with HIV participated in the survey, and 257 patients were included in the analysis. Overall, 27.6% were classified as non-adherent and self-reporting based on whether an antiretroviral therapy (ART) was taken in the past or how often the ART was interrupted. This proportion was significantly higher among patients aged 50–74 years (39.7%) and those with a longer therapy duration (9–15 years: 46.6%; from 15 years on: 55.8%). Therapy-non-adherent patients showed significantly lower scores in the relationship aspects understanding (2.68 vs. 3.03), participation (2.63 vs. 3.07), and perception (3.00 vs. 3.24) compared to adherent patients. Logistic regression analysis confirms that higher scores for understanding, involvement, and perception are strongly associated with a reduction in the risk of becoming non-adherent. This was true for all examined regression models, regardless of whether they were adjusted for the length of therapy and socio-demographic characteristics. Conclusion: The results reinforce the need for awareness among health care professionals (HCP) regarding understanding, involvement, and perception as important aspects to improve the quality of the patient–physician relationship for high adherence levels with maximized non-adherence in ART management by PLWH.

Effects of Hepatitis B Virus Co-Infection and Antiretroviral Therapy on Disease Progression among HIV Patients Treated at the Buea Regional Hospital, Southwest Region, Cameroon: A Case-Control Study

In the era of “test and treat”, when AIDS-defining events have been drastically reduced, chronic liver disease associated with viral hepatitis and antiretroviral therapy (ART) remains an important cause of non-AIDS morbidity and mortality among HIV-infected patients. Compared to the general population, HIV-infected patients are about 10-times at risk of hepatitis B virus infection. Additionally, several antiretroviral regimens are hepatotoxic. Therefore, effective monitoring and management of ART and HBV co-infection are essential to ending the AIDS epidemic and eliminating viral hepatitis by 2030. This was a hospital-based, matched (age and sex) case-control study. HIV patients (case patients) on ART for at least six months and “healthy” controls aged 18 years and older were enrolled. Blood samples were collected for immuno-hematologic indices and transaminases measurements. Data were presented as counts, percentages, median (IQR) and means (SD), and a p-value 1.5) and mild (0.6 - 1.5) liver fibrosis based on the APRI score was 0.5% and 8%, respectively. Significant fibrosis (>3.25) was 0.9%, while 18.4% had inconclusive fibrosis (1.45 - 3.25) based on the FIB-4 score. HIV/HBV co-infected patients had a higher occurrence of liver fibrosis (APRI: 0.5% vs FIB-4: 0.9%). Co-infections with HBV increase the risk of liver-related morbidity in HIV patients. Therefore, screening for serological markers of chronic HBV infection and hepatic transaminase levels in HIV patients remains crucial in the continuum of care.

Do I Have HIV or Not? Lack of RNA Detection and the Case for Sensitive DNA Testing.

We present a case of a 20-year-old male who had ambiguous HIV test results after entering new provider care and whose status was later complicated by undetectable viral RNA off antiretroviral therapy (ART). Verifying HIV infection status may occasionally require sensitive DNA testing that might need to be considered in diagnostic guidelines to resolve diagnosis and ensure appropriate ART management.

A pragmatic approach to managing antiretroviral therapy-experienced patients diagnosed with HIV-associated cryptococcal meningitis: impact of antiretroviral therapy adherence and duration.

Cryptococcal meningitis accounts for 15% of all HIV-related deaths [1]. The overall number of cryptococcal meningitis cases has remained relatively stable in many low-to-middle income countries (LMICs) despite increasing roll-out of antiretroviral therapy (ART). Increasing numbers of patients are at risk of developing cryptococcal meningitis following ART failure or discontinuation, offsetting declines in those presenting for the first time with advanced HIV [2–4]. Over half of patients diagnosed with cryptococcal meningitis in recent studies in sub-Saharan Africa are ART-experienced (i.e. currently receiving or previously received ART) [5,6]. Although there is robust evidence from prospective randomized trials that ART initiation should be delayed until 4–6 weeks after starting antifungal therapy in ART-naive cryptococcal meningitis patients [7,8], the approach to ART management among ART-experienced cryptococcal meningitis patients lacks adequate evidence, with a paucity of published data.

Diverse Human Immunodeficiency Virus-1 Drug Resistance Profiles at Screening for ACTG A5288: A Study of People Experiencing Virologic Failure on Second-line Antiretroviral Therapy in Resource-limited Settings.

Human immunodeficiency virus (HIV) drug resistance profiles are needed to optimize individual patient management and to develop treatment guidelines. Resistance profiles are not well defined among individuals on failing second-line antiretroviral therapy (ART) in low- and middle-income countries (LMIC). Resistance genotypes were performed during screening for enrollment into a trial of third-line ART (AIDS Clinical Trials Group protocol 5288). Prior exposure to both nucleoside reverse transcriptase inhibitors (NRTIs) and non-NRTIs and confirmed virologic failure on a protease inhibitor-containing regimen were required. Associations of drug resistance with sex, age, treatment history, plasma HIV RNA, nadir CD4+T-cell count, HIV subtype, and country were investigated. Plasma HIV genotypes were analyzed for 653 screened candidates; most had resistance (508 of 653; 78%) to 1 or more drugs. Genotypes from 133 (20%) showed resistance to at least 1 drug in a drug class, from 206 (32%) showed resistance to at least 1 drug in 2 drug classes, and from 169 (26%) showed resistance to at least 1 drug in all 3 commonly available drug classes. Susceptibility to at least 1 second-line regimen was preserved in 59%, as were susceptibility to etravirine (78%) and darunavir/ritonavir (97%). Susceptibility to a second-line regimen was significantly higher among women, younger individuals, those with higher nadir CD4+ T-cell counts, and those who had received lopinavir/ritonavir, but was lower among prior nevirapine recipients. Highly divergent HIV drug resistance profiles were observed among candidates screened for third-line ART in LMIC, ranging from no resistance to resistance to 3 drug classes. These findings underscore the need for access to resistance testing and newer antiretrovirals for the optimal management of third-line ART in LMIC.

Evaluation of a health system intervention to improve virological management in an antiretroviral programme at a municipal clinic in central Durban.

BackgroundWith the largest antiretroviral therapy (ART) programme globally, demand for effective HIV management is increasing in South Africa. While viral load (VL) testing is conducted, VL follow-up and management are sub-optimal.ObjectivesThe objective of this study was to address gaps in the VL cascade to improve VL testing and management.MethodsAntiretroviral therapy records were sampled for an in-depth review. The study team then reviewed individual records, focusing on ART management, virological suppression and retention. Multifaceted interventions focused on virological control, including a clinical summary chart for ART care; streamlining laboratory results receipt and management; monitoring VL suppression, flagging virological failure and missed visits for follow-up; down-referral of stable patients eligible for the chronic club system; and training of personnel and patients.ResultsPre-intervention, 78% (94/120) of eligible patients had VL tests, versus 92% (145/158) post-intervention (p = 0.0009). Pre-intervention, 59% (71/120) of patients accessed their VL results, versus 86% (136/158) post-intervention (p < 0.0001). Post-intervention, 73% (19/26) of patients eligible for ART change were appropriately managed, versus 11% (4/36) pre-intervention (p < 0.0001). Only 27% had no regimen changes (7/26) post-intervention, versus 81% (29/36) pre-intervention (p < 0.0001).ConclusionService delivery was streamlined to facilitate HIV services by focusing on VL test monitoring, protocol training and accessibility of results, thereby improving clinical management.

The Role of the Clinical Pharmacist in the Management of People Living with HIV in the Modern Antiretroviral Era

As the HIV epidemic has evolved, so too has the role of the clinical pharmacist (CP) in the management of people living with HIV (PLWH). The modern antiretroviral therapy (ART) era has resulted in PLWH living normal life spans with resulting increased comorbidities. CPs have long been a part of the multidisciplinary management of ART. However, with the changing demographics of PLWH and health-care system dynamics, CPs have had the opportunity to expand their role. This includes involvement in managing increasing comorbidities with expanding and more complicated medication regimens, drug interaction monitoring, and optimizing transitions of care, all while recognizing and addressing barriers to successful HIV and hepatitis C virus (HCV) treatment. In addition, with the expansion of HIV prevention and pre-exposure prophylaxis (PrEP) services, CPs have the opportunity to be involved in HIV prevention. This study summarizes the literature evaluating the impact of CPs in the management of PLWH in the era of modern ART. We conducted a literature search to identify studies that assessed the CP role in HIV clinical practice since 2006. The identified studies were grouped into two categories. The first was HIV related outcomes, including interventions on regimen selection, adherence, regimen optimization, and management of treatment failure. The second group of studies pertained to aging and vulnerable populations, including management of comorbidities, transitions of care, medication-assisted treatment, hepatitis C, and HIV screening and PrEP. We concluded that the evidence supports the expanding role of CPs to positively impact a variety of aspects related to the care of PLWH.

Factors associated with first-line antiretroviral treatment failure in adult HIV-positive patients: a case-control study from Ethiopia

BackgroundTreatment failure has become a significant challenge in patients taking antiretroviral therapy (ART). The aim of the present study was to identify risk factors for first-line ART failure among patients attending clinical follow-up.MethodsA 1:2 matched case-control study (by age, sex, and treatment duration since initiated on ART) was conducted from June 2015 to July 2017 on adult patients (aged ≥15 years) who were on ART for at least 6 months. Cases were selected from patients who were switched to second-line ART after first-line ART failure (viral load ≥1000 copies/mL). Controls were randomly selected from patients on first-line ART with viral load < 50 copies/mL. Data were collected using an interview questionnaire, reviewing chart and electronic health records and laboratory tests. Multivariate logistic regression analysis was performed to identify risk factors for treatment failure.ResultsOf the 273 patients who participated in this study, 55% were males. Ninety-one cases were compared with 182 controls. The median age of participants was 40 years and the median duration of treatment since initiated on ART was 69 months. Independent risk factors associated with first-line antiretroviral treatment failure were discontinuation of ART (adjusted odds ratio (AOR) = 9.8, 95% confidence interval (CI): 4.0–23.8), baseline CD4 lymphocyte count ≤50 cells/mm3 (AOR = 3.8, 95% CI: 1.5–9.6) and persistent diarrhea (AOR = 4.4, 95% CI: 1.5–13.2). The risk of ART failure was high and comparable whether the duration of ART discontinuation was greater or less than 1 month (crude odds ratio (COR) = 6.3 and 8. 5 respectively, p-value < 0.001). Frequent eating of a diet containing wheat or barley (AOR = 2.3, 95% CI: 0.9–5.4) showed a trend to be a risk factor for first-line ART failure (p-value = 0.064).ConclusionsOur findings underscore the importance of avoiding ART discontinuation of any duration, early initiation of ART and diarrhea management to prevent first-line ART failure.

Nursing Practice to Support People Living With HIV With Antiretroviral Therapy Adherence: A Qualitative Study.

Antiretroviral therapy (ART) management is a core competency for nursing practice in HIV as documented in best practice guidelines. Nurse-led interventions are effective in fostering ART adherence in people living with HIV (PLWH). However, these evidence-based interventions and professional expectations pertaining to these guidelines do not reflect current practice, nor do they expose the challenges faced by nurses. We conducted a qualitative exploratory study with nurses to explore their professional practices in the context of ART adherence. Sixteen nurses participated in data collection: nine in a focus group and seven in individual interviews. We identified four themes: building a therapeutic relationship with PLWH as a foundation of HIV nursing care; nursing activities to support PLWH with ART adherence; challenges faced by nurses providing ART-related care; and resource mobilization supporting nursing practice development in ART management and HIV care. Aspects of HIV nursing practice need to be strengthened to enhance best practice care, such as managing powerlessness in the context of ART nonadherence.

Nationwide Estimates of Viral Load Suppression and Acquired HIV Drug Resistance in Cameroon

BackgroundPopulation-based studies to estimate viral load (VL) suppression and rate of acquired HIV drug resistance (ADR) are essential in sub-Saharan Africa. We conducted the first nationally representative study estimating VL suppression and ADR in Cameroon. MethodsEligible participants were patients on antiretroviral therapy (ART) for 12 to 24 months (ART 12–24) or 48 to 60 months (ART 48–60). ART 12–24 participants were recruited from 24 randomly selected clinics in both urban and rural regions. ART 48–60 participants were recruited from 7 urban clinics. Recruitment occurred from February to August 2015. Dried blood spots (DBSs) and plasma specimens were collected and tested for HIV-1 RNA level and presence of drug resistance mutations (DRM) when VL ≥1000 copies/ml. ResultsOverall, 1064 ART 12–24 and 388 ART 48–60 participants were recruited. Viral suppression in the ART 12–24 group was 72.1% (95% CI: 66.3–77.2) overall, 75.0% (65.2–82.7) in urban sites, and 67.7% (58.3–75.8) in rural sites. In the ART 48–60 group, viral suppression was 67.7% (55.8–77.7). Overall, HIV drug resistance (HIVDR) was 17.7% (15.1–20.6) and 28.3% (17.4–42.5) in the ART 12–24 and ART 48–60 groups, respectively. However, among patients with VL ≥1000 copies/ml, HIVDR was identified in 63.3% (52.0–73.3) of ART 12–24 patients, and in 87.7% (67.4–96.1) of ART 48–60 patients. ConclusionsResults of this first nationwide study indicate alarming levels of virological failure and ADR in Cameroon. Better ART management is urgently needed and should focus on improving ART adherence, availability of VL monitoring, and more timely switches to second-line ART.

Assessing the level of institutionalization of donor-funded anti-retroviral therapy (ART) programs in health facilities in Uganda: implications for program sustainability

ABSTRACTBackground: In the context of declining international assistance for ART scale-up in Sub-Saharan Africa, the institutionalization of ART programs through integrating them in the organizational routines of health facilities is gaining importance as a program sustainability strategy.Objective: The aims of this study were; (i) to compare the level of institutionalization of ART programs in health facilities in Uganda and (ii) to explore reasons for variations in the degree of program institutionalization.Methods: In Phase One, we utilized Level of Institutionalization Scales developed by Goodman (1993) to measure the degree of institutionalization of ART interventions in 195 health facilities across Uganda. The 45-item questionnaire measured institutionalization based on four sub-systems (production, maintenance, supportive, managerial) theorized to make up an organization assessed against two levels of institutionalization; routines (lowest) niche saturation (highest). In Phase Two, four health facilities were purposively selected (2 with the highest and 2 with the lowest institutionalization scores) for a multiple case-study involving semi-structured interviews with ART clinic managers(n = 32), on-site observations and document review.Results: The two highest scoring health facilities had a longer HIV intervention implementation history of between 8 and 11 years. The highest scoring cases associated intervention institutionalization with sustained workforce trainings in ART management, the retention of ART-trained personnel and generating in-house ART manuals. The turnover of ART-proficient staff was identified as a barrier to intervention institutionalization in the lowest-ranked cases. Significant differences in organizational contexts were identified. The two highest-ranked health facilities were well-established, higher-tier hospitals while the lowest scoring health facilities were lower-level health facilities.Conclusions: The level of institutionalization of ART interventions appeared to be differentiated by level of care in the Ugandan health system. Interventions aimed at strengthening program institutionalization in lower-level health centers at the level of human resources for health could enhance ART scale-up sustainability.

Improving community mobilization in HIV treatment management: practical suggestions from patients in Brazil.

ABSTRACTObjectives.To describe patients’ suggestions on improving the management of antiretroviral therapy (ART) and to identify the roles that key stakeholders should play in taking responsibility for those recommendations.Methods.This research was embedded within a national cross-sectional study on patient adherence to ART and the associated factors. A subsample of the study patients were asked to offer suggestions on how to improve daily management of ART, and their answers were analyzed using a content analysis approach. The recommendations were then interpreted in terms of who should be responsible for them, and the suggestions were organized into three levels: micro (patient), meso (health care team), and macro (researchers, policymakers, family, friends, and the general public).Results.Of the 552 participants from the subsample, 60% were male, their average age was 44.1 years, and 62% were nonadherent in at least at one of three dimensions (missing doses, improper timing, or improper dosing). The categories underlying the micro level were “believing in treatment efficacy,” “being motivated,” “accepting HIV status,” and “sharing experiences with other patients.” At the meso level the suggestion categories were “more information from health care providers” and “humanization of care.” The macro level categories were “social support and actions against stigma,” “research proposals,” and “improvement of health care services.”Conclusions.Patients are influenced by the health policies, care, and support offered by health care providers, organizations, policymakers, and communities. In turn, these stakeholders develop the policies and deliver their care and support based on the responses and actions of patients. All stakeholders should work together to engage, educate, and support patients in addressing ART management.

Transitioning to Second-line Antiretroviral Therapy Among Adolescents in Copperbelt Province, Zambia: Predictors of Treatment Switching and Adherence to Second-line Regimens.

Adolescents living with HIV (ALHIV) experience less favorable antiretroviral therapy (ART) outcomes than other age groups. First-line treatment failure complicates ART management as second-line regimens can be costlier and have greater pill burdens. Understanding predictors of switching ART regimens and adherence among adolescents on second-line ART may help to prevent poor treatment outcomes. A quantitative survey was administered to 309 ALHIV attending 3 ART clinics in the Copperbelt Province, Zambia. Medical chart data, including pharmacy refill data, were abstracted. Associations between being on second-line ART and sociodemographic, psychosocial and ART adherence characteristics were tested. Cox proportional hazards models were used to estimate the effect of baseline ART variables on time to switching. Ten percent of participants were on second-line regimens. Compared with ALHIV on first-line ART, adolescents on second-line regimens were older (P = 0.02), out of school due to completion of secondary studies (P = 0.04) and on ART longer (P = 0.03). Adolescents on second-line regimens were more likely to report missing ≥48 consecutive hours of drugs in the last 3 months (P = 0.01). Multivariable analysis showed that adolescents who initiated ART with efavirenz-based regimens were more likely to switch to second-line than those put on nevirapine-based regimens (hazard ratio = 2.6; 95% confidence interval: 1.1-6.4). Greater support is needed for ALHIV who are on second-line regimens. Interventions for older adolescents that bridge the gap between school years and young adulthood would be helpful. More research is needed on why ALHIV who start on efavirenz-based regimens are more likely to switch within this population.

Is laboratory screening prior to antiretroviral treatment useful in Johannesburg, South Africa? Baseline findings of a clinical trial

BackgroundScreening for renal, hepatic and haematological disorders complicates the initiation of current first-line antiretroviral therapy (ART). Each additional test done adds substantial costs, both through direct laboratory expenses, but also by increasing the burden on health workers and patients. Evaluating the prevalence of clinically relevant abnormalities in different population groups could guide decisions about what tests to recommend in national guidelines, or in local adaptations of these.MethodsAs part of enrolment procedures in a clinical trial, 771 HIV-positive adults, predominantly from inner-city primary health care clinics, underwent laboratory screening prior to ART. Participants had to be eligible for ART, based on the then CD4 eligibility threshold of 350 cells/μL, antiretroviral naïve and have no symptoms of peripheral neuropathy.ResultsParticipants were mostly female (57%) and a mean 34 years old. Creatinine clearance rates were almost all above 50 mL/min (99%), although 5% had microalbuminuria. Hepatitis B antigenaemia was common (8% of participants), of whom 40% had a raised AST/ALT, though only 2 had transaminase levels above 200 IU/L. Only 2% of participants had severe anaemia (haemoglobin <8 g/dl) and 1% neutropaenia (neutrophils <0.75 × 10^9/L). Costs per case detected of hepatitis B infection was USD135, but more than USD800 for a raised creatinine.ConclusionsHepatitis B continues to be a common co-infection in HIV-infected adults, and adds complexity to management of ART switches involving tenofovir. Routine renal and haematological screening prior to ART detected few abnormalities. The use of these screening tests should be assessed among patients with higher CD4 counts, who may even have fewer abnormalities. Formal evaluation of cost-effectiveness of laboratory screening prior to ART is warranted.

Plasma nevirapine concentrations predict virological and adherence failure in Kenyan HIV-1 infected patients with extensive antiretroviral treatment exposure.

Treatment failure is a key challenge in the management of HIV-1 infection. We conducted a mixed-model survey of plasma nevirapine (NVP) concentrations (cNVP) and viral load in order to examine associations with treatment and adherence outcomes among Kenyan patients on prolonged antiretroviral therapy (ART). Blood plasma was collected at 1, 4 and 24 hours post-ART dosing from 58 subjects receiving NVP-containing ART and used to determine cNVP and viral load (VL). Median duration of treatment was 42 (range, 12–156) months, and 25 (43.1%) of the patients had virologic failure (VF). cNVP was significantly lower for VF than non- VF at 1hr (mean, 2,111ng/ml vs. 3,432ng/ml, p = 0.003) and at 4hr (mean 1,625ng/ml vs. 3,999ng/ml, p = 0.001) but not at 24hr post-ART dosing. Up to 53.4%, 24.1% and 22.4% of the subjects had good, fair and poor adherence respectively. cNVP levels peaked and were > = 3μg.ml at 4 hours in a majority of patients with good adherence and those without VF. Using a threshold of 3μg/ml for optimal therapeutic nevirapine level, 74% (43/58), 65.5% (38/58) and 86% (50/58) of all patients had sub-therapeutic cNVP at 1, 4 and 24 hours respectively. cNVP at 4 hours was associated with adherence (p = 0.05) and virologic VF (p = 0.002) in a chi-square test. These mean cNVP levels differed significantly in non-parametric tests between adherence categories at 1hr (p = 0.005) and 4hrs (p = 0.01) and between ART regimen categories at 1hr (p = 0.004) and 4hrs (p<0.0001). Moreover, cNVP levels correlated inversely with VL (p< = 0.006) and positively with adherence behavior. In multivariate tests, increased early peak NVP (cNVP4) was independently predictive of lower VL (p = 0.002), while delayed high NVP peak (cNVP24) was consistent with increased VL (p = 0.033). These data strongly assert the need to integrate plasma concentrations of NVP and that of other ART drugs into routine ART management of HIV-1 patients.