Antiretroviral Therapy Regimen Change Research Articles

Self-reported musculoskeletal disorders and associated factors among HIV/AIDS patients following ART at University of Gondar Comprehensive Specialized Hospital, Gondar, Ethiopia, 2021: Aa cross-sectional study design

BackgroundMusculoskeletal disorders is an inflammatory, degenerative diseases and disorders that cause pain and functional impairments. Musculoskeletal disorders are common and the major global health concern among people with human immunodeficiency virus/acquired immunodeficiency syndrome which causes physical disability. Despite, it is a recognized health problem among human immunodeficiency virus-positive patients, there is a lack of data on musculoskeletal disorders among patients following anti-retroviral therapy in sub-Saharan Africa, particularly Ethiopia. Therefore, the main aim of the study was to assess the prevalence and associated factors of musculoskeletal disorders among adult human immunodeficiency virus-positive patients following anti-retroviral therapy.MethodAn institutional-based cross-sectional study was conducted from September 1st to October 1st, 2021 at University of Gondar Comprehensive Specialized Hospital, Gondar, Ethiopia. The data was collected through an interview-administered questionnaire and patient medical record review of 324 participants. Binary logistic regression was used to identify associated risk factors of musculoskeletal disorders. The strength of the association was detected by the adjusted odds ratio and P-value.ResultThe annual prevalence of musculoskeletal disorders among participants was 158 (48.5%) with [95% CI: 43%, 54%], opportunistic infection [AOR, 10.43; 95% CI = 2.76–42.25], type of ART medication used, CD4-count [AOR, 0.13; 95% CI 0.03–0.85], and change in anti-retroviral therapy regimen change [AOR, 8.14; 95%CI 2.06–32.09] were significantly associated with musculoskeletal disorders.ConclusionThe prevalence of musculoskeletal disorders was moderate. Recent CD4 count, opportunistic infection, antiretroviral therapy regime at initiation, and anti-retroviral therapy regime change were significantly associated with musculoskeletal disorder. A multidisciplinary approach is required for preventing and treating musculoskeletal disorders among human immunodeficiency virus-positive patients following anti-retroviral therapy.

Assessment of Disease Burden and Immunization Rates for Vaccine-Preventable Diseases in People Living with HIV: The Korea HIV/AIDS Cohort Study.

Prophylactic immunization is important for human immunodeficiency virus (HIV)-infected patients; however, there are insufficient data on the burden of vaccine-preventable diseases (VPDs), vaccination rates, and factors influencing vaccination. The incidence and prevalence of VPDs in HIV-infected patients between 2006 and 2017 were estimated using the Korean HIV/acquired immune deficiency syndrome (AIDS) cohort database. In addition, we evaluated the vaccination rates and influencing factors for vaccination in HIV-infected patients through multilevel analysis of clinico-epidemiological factors, immune status, and psychological status. A questionnaire survey was conducted among experts to determine whether they recommend vaccination for HIV-infected patients. The incidence rates of hepatitis B virus (HBV) infection, herpes zoster, and anogenital warts were 1.74, 7.38, and 10.85 per 1,000 person-years, respectively. The prevalence of HBV infection and anogenital warts at enrollment was 4.8% and 8.6%, respectively, which increased to 5.3% and 12.0%, respectively, by 2017. In HIV-infected patients, HBV (21.7% in 2008, 56.3% in 2013, and 75.4% in 2017) and pneumococcal vaccination rates (3.0% in 2015, 7.6% in 2016, and 9.6% in 2017) increased annually, whereas the influenza vaccination rate remained similar by season (32.7 - 35.6%). In the multilevel analysis, peak HIV viral load (≥50 copies/mL: odds ratio [OR] = 0.64, 95% confidence interval [CI]: 0.44 - 0.93; reference, <50 copies/mL) was an influencing factor for pneumococcal vaccination, while nadir CD4 T-cell counts (200 - 350 cells/mm3: OR = 0.54, 95% CI: 0.38 - 0.76; <200 cells/mm3: OR = 0.89, 95% CI: 0.62 - 1.28; reference, ≥350 cells/mm3) was an influencing factor for HBV vaccination. Influenza vaccination was associated with male sex (OR = 1.94) and the number of antiretroviral therapy (ART) regimen change (OR = 1.16), but was not significantly associated with HIV viral load or CD4 T-cell counts. Most experts responded that they administer hepatitis A virus, HBV, pneumococcal, and influenza vaccines routinely, but not human papillomavirus (12.9%) or herpes zoster vaccines (27.1%). The burden of vaccine-preventable diseases was quite high in HIV-infected patients. Nadir CD4 T-cell counts, peak HIV viral loads, and the number of ART regimen change are significant factors related to vaccination. Considering the low vaccination rates for VPDs, there was a discordance between experts' opinions and real clinical practice in the medical field.

Magnitude and predictors of first-line antiretroviral therapy regimen change among HIV infected adults: A retrospective cross sectional study

BackgroundRegimen change remains a significant challenge towards the achievement of human immunodeficiency virus (HIV) treatment success. In developing countries where limited treatment options are available, strategies are required to ensure the sustainability and durability of the starting regimens. Nevertheless, information regarding the rate and predictors of regimen change is limited in these settings. ObjectiveThis study was undertaken to determine the prevalence and predictors of changes in ART regimens among patients initiating highly active antiretroviral therapy (HAART) at XX. Materials and methodsAn institutional based retrospective cross-sectional study was conducted among adult naïve HIV patients who had initiated HAART at XX between 2010. Data were extracted by reviewing their medical charts using a pretested structured check-list. The Kaplan–Meier survival analyses were used to describe the probability of ARV regimen changes while Cox proportional hazard regression models were employed to identify the predictors of ARV regimen modifications. Data were analyzed using SPSS version 21 software, and statistical significant was deemed at p < 0.05. ResultsA total of 770 patients were enrolled in this study of these 165 (21.43%) had their ART regimen modified at least once. Drug toxicity was the main reason for regimen change followed by TB comorbidity, and treatment failure. Positive baseline TB symptoms (aHR = 1.63, p = 0.037), and Zidovudine based regimen (aHR = 1.76, p = 0.011) as compared to Stavudine based regimen were at higher risk of ART modification. Conversely, urban residence, baseline World Health organization (WHO) stage 2 as compared to WHO stage 1, baseline CD4 count ≥301 as compared to CD4 count ≤200 were at lower risk of ART modification. ConclusionThe rate of initial HAART regimen change was found to be high. Thus, less toxic and better tolerated HIV treatment options should be available and used more frequently. Moreover, early detection and initiation of ART by the government is highly demanded to maximize the benefit and reduce risk of ART modifications.

Determinants and reasons for switching anti-retroviral regimen among HIV-infected youth in a large township of South Africa (2002–2019)

BackgroundThere are limited data exploring antiretroviral therapy (ART) changes and time to change among South Africa young people living with HIV/AIDS.ObjectiveWe describe the time to first drug switch, which includes ART regimen change (three drug switch) and substitutions (single drug switch). We describe common reasons for ART switch among young people aged 10 to 24 years in South Africa.MethodsWe conducted a retrospective cohort study at a primary health care clinic in Cape Town, South Africa, providing ART to HIV-infected adolescents and adults since 2002. Those aged 10 to 24 years at ART initiation, who accessed care clinic between September 2002 and April 2019. Data was retrieved from electronic information systems: ART regimens, ART changes, dates for initiation or stop of each drug/regimen, laboratory results (viral loads, haemoglobin, liver enzyme results, and creatinine to support the reason for ART switch. From written records, we abstracted reason for single drug switch or regimen change, as well as socio demographic and clinical data. We fitted cox regression models to determine factors associated with ART switch (Having a change in one or more drugs in ART combination) and the rate of occurrence.ResultsOf 2601 adolescents included, 605 (24.9%) adolescents switched ART over 5090.5 person years at risk (PYAR), a rate of 11.9 /100PYAR. Median follow-up time was 4.4 (± 3.2) years. At multivariable analysis, the older age group was protective of the risk of ART switch: adjusted Hazard Ratio [aHR] 0.78, 95% CI 0.62–0.98, transfer status [transferred out 1.42 [1.11–1.82]. The hazard of ART switch increased with more severe HIV-disease at ART start, as observed by increasing WHO clinical stage or reduced CD4 count at baseline. The primary reasons for ART switch were side effects (20.0%), virological failure (17.9%) and formulation switch (27.8%). Others reasons included pregnancy, Hepatitis B, tuberculosis and psychosis.ConclusionART switches are frequent and occur at a consistent rate across 7.5 years from initiation. The main reasons for ART switch were virological failure and drug side effects.

Incidence and predictors of initial antiretroviral therapy regimen change among children in public health facilities of Bahir Dar City, Northwest Ethiopia, 2021: multicenter retrospective follow-up study

BackgroundThe inconsistent use of antiretroviral therapy can lead to the risk of cross-resistance between drugs. This reduces subsequent antiretroviral drug options. The burden of initial antiretroviral therapy ranges from 11.3% in South Africa to 71.8% in Malaysia. There is evidence that it is important to maintain children’s initial antiretroviral therapy regimens. However, the incidence and predictive factors of initial antiretroviral therapy regimen changes in the research context are still unknown in the study setting. So, the study was aimed to assess incidence and predictors of initial antiretroviral therapy regimen changes among children in public health facilities of Bahir Dar city.MethodsA retrospective follow-up study was conducted in 485 children who received antiretroviral therapy between January 1, 2011 and December 30, 2020. These children were selected using simple random sampling techniques. The data were entered by Epi data 3.1 and the analysis was completed by STATA 14.0. The missing data was treated with multiple imputation method. The data were also summarized by median or mean, interquartile range or standard deviation, proportion and frequency. The survival time was determined using the Kaplan Meier curve. The Cox Proportional Hazard model was fitted to identify predictors of initial antiretroviral therapy regimen change. The global and Shoenfeld graphical proportional hazard tests were checked. Any statistical test was considered significant at P-value < 0.05. Finally, the data were presented in the form of tables, graphics and text.ResultAmong the 459 study participants, 315 of them underwent initial regimen changes during the study accumulation period. The shortest and longest follow up time of the study were 1 month and 118 months, respectively. The overall incidence rate of initial regimen change was 1.85, 95% CI (1.66–2.07) per 100 person-month observation and the median follow up time of 49 (IQR 45, 53) months. The independent predictors of initial regimen changes were poor adherence (AHR = 1.49, 95%CI [1.16, 1.92]), NVP based regimen (AHR = 1.45, 95%CI [1.15, 1.84]) comparing to EFV based regimen, LPVr based regimen (AHR = 0.22, 95%CI: (0.07, 0.70)) comparing to EFV based regimen, history of tuberculosis (AHR = 1.59, 95%CI [1.14, 2.23]) and being male (AHR = 1.28, 95%CI [1.02, 1.60]).Conclusions and recommendationsIn this study, the incidence of initial regimen change was high. The risk of initial regimen change would be increased by being male, poor adherence, having history of tuberculosis and NVP based initial regimen. Therefore, strengthening the health care providers’ adherence counseling capability, strengthening tuberculosis screening and prevention strategies and care of initial regimen type choice needs attention in the HIV/AIDS care and treatment programs.

Outcomes After Second-Line Antiretroviral Therapy in Children Living With HIV in Latin America.

Little is known about the long-term outcomes of children living with HIV in Latin America. Few studies have examined antiretroviral therapy (ART) regimen switches in the years after the introduction of ART in this population. This study aimed to assess clinical outcomes among children who started second-line ART in the Caribbean, Central and South America network for HIV epidemiology. Children (<18 years old) with HIV who switched to second-line ART at sites within Caribbean, Central and South America network for HIV epidemiology were included. The cumulative incidence and relative hazards of virologic failure while on second-line ART, loss to follow-up, additional major ART regimen changes, and all-cause mortality were evaluated using competing risks methods and Cox models. A total of 672 children starting second-line ART were included. Three years after starting second-line ART, the cumulative incidence of death was 0.10 [95% confidence interval (CI) 0.08 to 0.13], loss to follow-up was 0.14 (95% CI: 0.11 to 0.17), and major regimen change was 0.19 (95% CI: 0.15 to 0.22). Of those changing regimens, 35% were due to failure and 11% due to toxicities/side effects. Among the 312 children with viral load data, the cumulative incidence of virologic failure at 3 years was 0.62 (95% CI: 0.56 to 0.68); time to virologic failure and regimen change were uncorrelated (rank correlation -0.001; 95% CI -0.18 to 0.17). Poor outcomes after starting second-line ART in Latin America were common. The high incidence of virologic failure and its poor correlation with changing regimens was particularly worrisome. Additional efforts are needed to ensure children receive optimal ART regimens.

Incidence and Predictors of Initial Antiretroviral Therapy Regimen Change Among HIV-Infected Adults Receiving Antiretroviral Therapy at Arba Minch General Hospital, Southern Ethiopia.

BackgroundThe effectiveness of the initial antiretroviral therapy regimen is the key to treatment success. However, regimen change affects this treatment success. Yet, evidence on the incidence and predictors of regimen change is scarce. Therefore, the aim of this study was to assess the incidence and predictors of initial antiretroviral therapy regimen change among HIV-infected adults receiving antiretroviral therapy.MethodsAn institutional-based retrospective cohort study was conducted. Data were collected from patients’ charts selected by simple random sampling. Data entered into EpiData version 4.43 and analyzed by STATA version 13. The life table was used to estimate cumulative survival. Kaplan–Meir curve and Log-rank test were used to compare the survival experience of explanatory variables. Cox proportional hazard model was used to identify predictors.ResultsFive hundred and eight patients were followed for 871.87 person-years of observation with the median follow-up period of 16.12 months. The incidence rate of initial ART regimen change was 11.36 (95% CI: 9.32–13.83) per 100 person-year and the median survival time is 54 months. Not disclosing HIV status (adjusted hazard ratio (AHR) = 5.41, 95% CI = 2.38–12.27), co-medication with ART (AHR = 4.64, 95% CI = 1.43–15.10), occurrence of side effect on initial regimen (AHR = 7.32, 95% CI = 4.43–12.10), baseline CD4 count <200 cells/mm3 (AHR = 2.18, 95% CI = 1.37–3.47), ambulatory/bedridden baseline functional status (AHR = 3.55, 95% CI = 2.30–5.48) were significant predictors of initial regimen change.ConclusionThe incidence rate of initial ART regimen change was found to be low. HIV disclosure status, co-medication with ART, the occurrence of side effects on an initial regimen, low baseline CD4 count, ambulatory and bedridden baseline functional status were found to be predictors.

Magnitude and causes of first-line antiretroviral therapy regimen changes among HIV patients in Ethiopia: a systematic review and meta-analysis

BackgroundAntiretroviral therapy (ART) has markedly decreased the morbidity and mortality due to HIV/AIDS. ART regimen change is a major challenge for the sustainability of human immunodeficiency virus (HIV) treatment program. This is found to be a major concern among HIV/AIDS patients in a resource-limited setting, where treatment options are limited.ObjectivesThe aim of this review is to generate the best available evidence regarding the magnitude of first-line antiretroviral therapy regimen change and the causes for regimen change among HIV patients on ART in Ethiopia.MethodsThe reviewed studies were accessed through electronic web-based search strategy from PubMed Medline, EMBASE, Hinari, Springer link and Google Scholar. Data were extracted using Microsoft Excel and exported to Stata software version 13 for analyses. The overall pooled estimation of outcomes was calculated using a random-effect model of DerSimonian–Laird method at 95% confidence level. Heterogeneity of studies was determined using I2 statistics. For the magnitude of regimen change, the presence of publication bias was evaluated using the Begg’s and Egger’s tests. The protocol of this systematic review and meta-analysis was registered in the Prospero database with reference number ID: CRD42018099742. The published methodology is available from: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=99742.ResultsA total of 22 studies published between the years 2012 and 2018 were included. Out of 22 articles, 14 articles reported the magnitude of regimen change and consisted of 13,668 HIV patients. The estimated national pooled magnitude of regimen change was 37% (95% CI: 34, 44%; Range: 15.1–63.8%) with degree of heterogeneity (I2), 98.7%; p-value < 0.001. Seventeen articles were used to identify the causes for first-line antiretroviral therapy regimen change. The major causes identified were toxicity, 58% (95% CI: 46, 69%; Range: 14.4–88.5%); TB co-morbidity, 12% (95% CI: 8, 16%; Range: 0.8–31.7%); treatment failure, 7% (95% CI: 5, 9%; Range: 0.4–24.4%); and pregnancy, 5% (95% CI: 4, 7%; Range: 0.6–11.9%).ConclusionsThe original first-line regimen was changed in one-third of HIV patients on ART in Ethiopia. Toxicity of the drugs, TB co-morbidity, treatment failure, and pregnancy were the main causes for the change of the first-line regimen among HIV patients on antiretroviral therapy.

Viral suppression among children and their caregivers living with HIV in western Kenya.

IntroductionDespite the central role of caregivers in managing HIV treatment for children living with HIV, viral suppression within caregiver–child dyads in which both members are living with HIV is not well described.MethodsWe conducted a retrospective analysis of children living with HIV <15 years of age and their caregivers living with HIV attending HIV clinics affiliated with the Academic Model Providing Access to Healthcare (AMPATH) in Kenya between 2015 and 2017. To be included in the analysis, children and caregivers must have had ≥1 viral load (VL) during the study period while receiving antiretroviral therapy (ART) for ≥6 months, and the date of the caregiver's VL must have occurred ±90 days from the date of the child's VL. The characteristics of children, caregivers and dyads were descriptively summarized. Multivariable logistic regression was used to estimate the odds of viral non‐suppression (≥ 1000 copies/mL) in children, adjusting for caregiver and child characteristics.ResultsOf 7667 children who received care at AMPATH during the study period, 1698 were linked to a caregiver living with HIV and included as caregiver–child dyads. For caregivers, 94% were mothers, median age at ART initiation 32.8 years, median CD4 count at ART initiation 164 cells/mm3 and 23% were not virally suppressed. For children, 52% were female, median age at ART initiation 4.2 years, median CD4 values at ART initiation were 15% (age < 5 years) and 396 cells/mm3 (age ≥ 5 years), and 38% were not virally suppressed. In the multivariable model, children were found more likely to not be virally suppressed if their caregivers were not suppressed compared to children with suppressed caregivers (aOR = 2.40, 95% CI: 1.86 to 3.10). Other characteristics associated with child viral non‐suppression included caregiver ART regimen change prior to the VL, caregiver receipt of a non‐NNRTI‐based regimen at the time of the VL, younger child age at ART initiation and child tuberculosis treatment at the time of the VL.ConclusionsChildren were at higher risk of viral non‐suppression if their caregivers were not virally suppressed compared to children with suppressed caregivers. A child's viral suppression status should be closely monitored if his or her caregiver is not suppressed.

Pattern of and reasons for antiretroviral therapy regimen change among adult HIV/AIDS patients at regional hospital in Eastern Ethiopia: A 10-year retrospective study

Objectives:Despite the successes of treatment with antiretroviral therapy in reducing morbidity and mortality among HIV-infected patients, long-term sustainability of the initial regimen has become challenging. Therefore, this study is aimed to address pattern of and reasons for change of antiretroviral therapy regimens among HIV/AIDS patients at Jugel Hospital, Eastern Ethiopia.Methods:A retrospective cross-sectional study was conducted to review medical records of 220 patients who had been on treatment and experienced regimen change at least once from September 2006 to August 2016. Structured data abstraction format was customized from World Health Organization guideline. Data were entered in Epi-data version 3.1, and exported to and analyzed with Statistical Package for Social Sciences version 20. Following descriptive statistics, binary logistic regression was run to determine the association between selected variables and second-time regimen change.Results:The mean age of patients was 37.6 (±8.9) years and 62.3% of them were female. Majority of the patients were presented to the hospital with World Health Organization clinical stage III (59.1%) and CD4 count below 200 cells/mm3 (68.6%). The mean duration of stay on initial regimen was found to be 3.26 (±1.92) years. The average number of initial regimen changes per year was 22 (±11.28). In two-thirds (66.36%) of the patients, their initial regimen was changed to tenofovir disproxil fumarate–based alternatives. The most-frequent reason for initial regimen change was toxicity (32.3%). Among those who experienced the regimen change for the first time, the prevalence of second-time regimen change was found to be 18.18%. Patients who had been taking tuberculosis treatment along with antiretroviral therapy were more likely to get their regimen changed for the second-time compared to those who were not infected with tuberculosis (adjusted odds ratio: 3.40; 95% confidence interval: 1.87–6.47). Besides, patients who were on zidovudine-based (adjusted odds ratio: 0.26; 95% confidence interval: 0.33–0.47) and tenofovir disoproxil fumarate–based regimens (adjusted odds ratio: 0.03; 95% confidence interval: 0.01–0.12) were less likely to get their regimen changed for the second-time compared to those who were on stavudine-based regimens.Conclusion:The majority of the patients had their treatment regimen changed because of drug-related toxicities, treatment failure, and comorbid conditions. Some regimen changes might be attributable to failure of either hospital supply system or patient-related factors which would have been prevented considering limited number of treatment options. There must be consideration of risks and benefits prior to changing a particular regimen.

Interdisciplinary Care Team with Pharmacist in a Community-based HIV Clinic

BackgroundHuman immunodeficiency virus (HIV) infection presents a significant burden, especially in the Washington, DC area. Literature is limited in describing the role of pharmacists in the outpatient clinic setting to provide patient-centered pharmaceutical care for patients with HIV. ObjectiveOur study aims to describe an interdisciplinary HIV care model including a clinical pharmacist at a community-based transcultural clinic in the Washington, DC area, and to describe the role of the pharmacist as indicated by an association between non-adherence to antiretroviral therapy (ART) and an ART regimen change. MethodsUsing the electronic health record at the clinic from May 2011 through July 2013, 53 patients were identified who were referred to the clinical pharmacist. ResultsThe average age of the patients with HIV was 46.57 years in the clinic. About 28% of patients had documented non-adherence to ART and 30% of patients had one or more ART regimen changes during the study period. Medication non-adherence was a significant predictor of ART regimen change (ORadj 8.44; 95% CI 1.91–37.29). Substance use was a strong predictor of ART regimen change (ORunadj 3.47; 95% CI 1.02–11.81), but the relationship disappeared in the multivariate analysis. ConclusionsA strong association between pharmacist's evaluation of non-adherence to ART and a regimen change was demonstrated and the role of the pharmacist as the interdisciplinary team member was described. A follow-up study should be made to assess the services provided by the pharmacist on clinical, economic, and humanistic outcomes in the community-based clinical setting.

Characterizing Human Immunodeficiency Virus Antiretroviral Therapy Interruption and Resulting Disease Progression Using Population-Level Data in British Columbia, 1996-2015.

Suboptimal retention is among the biggest challenges to realize the full benefits of combination antiretroviral therapy (ART). We aimed to describe ART interruption patterns and identify determinants of disease progression while off ART in British Columbia, Canada. With population-level data on ART utilization and laboratory testing in British Columbia (1996-2015), we described the timing, frequency, and duration of ART interruptions (a gap of ≥90 days in ART dispensation records). A 4-state continuous-time Markov model was implemented to identify determinants of disease progression during individuals' first ART interruption episode. Disease progression was measured according to CD4-based state transitions (cells/μL: ≥500 to 200-499; 200-499 to <200; ≥500 to death; 200-499 to death; and <200 to death). Among individuals initiating ART, 3129 (38.6%) interrupted ART over a median 8-year follow-up (interquartile range [IQR], 4.3-13.5 years). Those interrupting ART had a median of 1 interruption (IQR, 1.0-3.0), with the first interruption occurring 12.8 (IQR, 4.0-36.1) months after ART initiation, lasting for 7.5 (IQR, 4.1-20.3) months. The proportion of individuals interrupting ART within the first year of ART initiation decreased over time; however, the absolute number of individuals interrupting ART remained high. In a multivariable analysis, age, historical plasma viral load, and ART regimen changes prior to interruption were associated with increased hazard of CD4 decline and death. Our results demonstrate that ART interruptions are common even in a high-resource setting with universal free access to human immunodeficiency virus care. Further efforts are needed to promote ART reengagement and may consider prioritizing individuals with poorer prognostic factors.

Economic Outcomes of First-Line Regimen Switching Among Stable Patients with HIV.

Although switching of antiretroviral therapy (ART) is a valid approach for addressing treatment failure in patients with human immunodeficiency virus (HIV), ART changes among those who are well maintained on their current regimens may lead to the development of new side effects or resistance. To examine the effect of first-line regimen switching on subsequent health care utilization and cost among stable HIV patients. This was a retrospective claims data study of adult patients with HIV who initiated ART between 2007 and 2013 and had been treated with their initial regimens for at least 6 continuous months. Those with evidence of pregnancy or HIV-2 were excluded. Patients who underwent an ART change were assigned to a switcher cohort; a nonswitcher cohort was then generated by matching up to 20 nonswitchers for each switcher, with replacement. The index date was the date of the first ART change for switchers and was the claim date closest to the corresponding switcher's switch date for nonswitchers. Patient characteristics at baseline and post-index annualized health care utilization and costs were analyzed descriptively and with multivariable models. Analyses were performed in the full population and among patients designated as virologically stable (had undetectable viral ribonucleic acid [RNA] for 90 days pre-index) and virologically and clinically stable (had undetectable viral RNA and no apparent clinical reason for switching ART). The study population consisted of 6,983 individuals, which included 927 switchers (168 virologically stable; 55 virologically+clinically stable), who were matched with replacement with 18,511 nonswitcher comparators. The switcher cohort was 88.8% male (mean age 43.8 years). Mean preindex and follow-up treatment durations for switchers and nonswitchers were 1.8 years and 1.5 years, respectively; demographic characteristics, pre-index treatment duration, and follow-up duration were similar between cohorts. Significantly more nonswitchers than switchers had a first-line efavirenz-based regimen (67.2% vs. 47.8%, P < 0.001). In the virologically stable subset, follow-up annualized health care utilization for switchers versus nonswitchers, respectively, was 14.8 versus 12.3 ambulatory visits (P < 0.05), 0.8 versus 0.9 emergency department visits (P = 0.652), and 0.05 versus 0.05 inpatient hospitalizations (P = 0.915). Follow-up annualized health care costs were $37,120 for switchers versus $31,771 for nonswitchers (P < 0.05), with the difference driven largely by pharmacy costs. Multivariable-adjusted follow-up annualized health care costs were 8.9% higher among switchers versus nonswitchers (P < 0.01), and switchers also had a shorter time to subsequent ART regimen change (P < 0.001). Results were similar for the virologically+clinically stable subset. In this large, real-world population, stable patients with HIV who switched from their first-line ART regimens had significantly higher health care costs than those who did not change therapies, suggesting that ART regimen changes may be costly and should be undertaken only when clinically warranted. This work was funded by Bristol-Myers Squibb (BMS), which participated in the design of the study, interpretation of the data, revision of the manuscript, and the decision to submit the manuscript for publication. Rosenblatt is an employee and stock owner of BMS; Villasis-Keever was an employee of BMS at the time this study was conducted and is currently an employee of Janssen. Buikema is an employee and stock owner of Optum, and Seare, Bengston, Johnson, and Cao are employees of Optum, which was contracted by BMS to conduct the study. Optum contracts with pharmaceutical companies, such as Janssen, Merck, EMD Serano, GlaxoSmithKline, and Gilead, to conduct research in HIV. Optum is also a subsidiary of a health plan that has interest in managing the health and associated costs of patients with HIV. Study concept and design were contributed by Rosenblatt and Buikema, along with the other authors. Cao and Johnson took the lead in data collection, along with Buikema, Seare, and Bengston. Data interpretation was performed by Buikema, Seare, Bengston, and Villasis-Keever. The manuscript was written by Buikema and Bengston, along with Rosenblatt, Seare, Johnson and Villasis-Keever, and revised by Rosenblatt, Villasis-Keever, and Johnson, along with the other authors.

Confirmation of factors that influence antiretroviral regimen change and the subsequent patient outcomes at a Regional Hospital in rural KwaZulu-Natal.

BackgroundTreatment failure (TF) and adverse drug reactions (ADRs) are the main indications for antiretroviral therapy (ART) regimen change. Identification of factors influencing regimen change and subsequent health outcomes of patients after regimen change is essential in providing a sustainable and effective antiretroviral roll-out campaign.AimTo confirm the factors that influence antiretroviral regimen change and to evaluate patient outcomes post regimen change.MethodsA retrospective chart analysis of 269 HIV-infected non-pregnant patients (age >18 years), who underwent an antiretroviral (ARV) regimen change and were followed up for approximately one year since initiation, was undertaken at a Provincial Hospital ARV Clinic in KwaZulu-Natal, from January 2008 to December 2012.ResultsOf the 269 patients, there were 200 females (75%). Most patients were between the ages 30 and 44 (57.6%). Only five patients had coexisting tuberculosis (TB) infection (2%). The most common first-line ART regimen to be changed was stavudine (D4T)/lamivudine(3TC)/ efavirenz(EFV) n = 111(41%). The most common regimen patients were changed to was tenofovir (TDF)/3TC/EFV n = 89(33%). Stavudine was the most commonly substituted drug (35.5%). Lipodystrophy was the most common ADR (56.8%). ADR was the indication for ART regimen change in 175 patients (65%), whilst TF accounted for ART regimen change in 94 patients (35%). Immunological success (CD4 counts) was shown after regimen change (374.21 ± 243.16 vs. 456.09 ± 250.07, CI: 0.95, p < 0.001). Undetectable viral loads were measured in 172/205 (83.9%) patients post regimen change.ConclusionADRs were the main cause for antiretroviral regimen change. Stavudine was the most substituted drug with lipodystrophy being the most common side effect. Coexisting TB infection did not influence regimen change. Immunological and virological success was shown after regimen modification.

Rate of initial highly active anti-retroviral therapy regimen change and its predictors among adult HIV patients at University of Gondar Referral Hospital, Northwest Ethiopia: a retrospective follow up study.

BackgroundRegimen change is a major challenge for the sustainability of human immunodeficiency virus (HIV) treatment program. In a resource limited setting where treatment options are limited, designing strategies to increase the durability of original regimen are essential. However, information’s on rate of initial regimen change and its predictors is scarce in Ethiopia. Therefore, the purpose of this study was to assess the rate of initial highly active anti retroviral therapy (HAART) regimen change and its predictors among adult HIV patients at the University of Gondar Referral Hospital, Northwest Ethiopia.MethodsAn institutional based retrospective follow up study was conducted among 410 adult HIV patients started HAART from January 2010 to December 2014. Simple random sampling technique was used to select patient records using computer generated random number. Data were collected from patient chart using data extraction tool. The Kaplan–Meier curve was used to estimate the median duration of regimen change. Life table was used to estimate the cumulative survival for initial regimen change and log rank test to compare regimen change survival curves between the different categories of explanatory variables. Bivariate and multivariate Cox proportional hazard model were used to identify predictors of initial regimen change.ResultsThe overall incidence rate of initial regimen change was 10.11 (95 % CI 8.29, 12.6) per 100 person years (PY). Baseline WHO clinical stage III (AHR = 1.92, 95 % CI 1.12–3.35), occurrence of tuberculosis (TB) on the initial regimen (AHR = 8.33, 95 % CI 4.47–15.53), side effect on the initial regimen (AHR = 25.27, 95 % CI 15.12–42.00) and co-medication with ART (AHR = 2.5, 95 % CI 1.46–4.34) were significant predictors of initial regimen change.ConclusionsThe rate of initial HAART regimen change was found to be high. Having WHO clinical stage III, co-medication with ART, occurrence of tuberculosis and side effect on initial regimen were independent predictors of regimen change. Hence, close follow-up and screening of patient for side effect and tuberculosis is important.

Low Primary and Secondary HIV Drug-Resistance after 12 Months of Antiretroviral Therapy in Human Immune-Deficiency Virus Type 1 (HIV-1)-Infected Individuals from Kigali, Rwanda

Treatment outcomes of HIV patients receiving antiretroviral therapy (ART) in Rwanda are scarcely documented. HIV viral load (VL) and HIV drug-resistance (HIVDR) outcomes at month 12 were determined in a prospective cohort study of antiretroviral–naïve HIV patients initiating first-line therapy in Kigali. Treatment response was monitored clinically and by regular CD4 counts and targeted HIV viral load (VL) to confirm drug failure. VL measurements and HIVDR genotyping were performed retrospectively on baseline and month 12 samples. One hundred and fifty-eight participants who completed their month 12 follow-up visit had VL data available at month 12. Most of them (88%) were virologically suppressed (VL≤1000 copies/mL) but 18 had virological failure (11%), which is in the range of WHO-suggested targets for HIVDR prevention. If only CD4 criteria had been used to classify treatment response, 26% of the participants would have been misclassified as treatment failure. Pre-therapy HIVDR was documented in 4 of 109 participants (3.6%) with an HIVDR genotyping results at baseline. Eight of 12 participants (66.7%) with virological failure and HIVDR genotyping results at month 12 were found to harbor mutation(s), mostly NNRTI resistance mutations, whereas 4 patients had no HIVDR mutations. Almost half (44%) of the participants initiated ART at CD4 count ≤200cell/µl and severe CD4 depletion at baseline (<50 cells/µl) was associated with virological treatment failure (p = 0.008).Although the findings may not be generalizable to all HIV patients in Rwanda, our data suggest that first-line ART regimen changes are currently not warranted. However, the accumulation of acquired HIVDR mutations in some participants underscores the need to reinforce HIVDR prevention strategies, such as increasing the availability and appropriate use of VL testing to monitor ART response, ensuring high quality adherence counseling, and promoting earlier identification of HIV patients and enrollment into HIV care and treatment programs.

Modeling Clinical Endpoints as a Function of Time of Switch to Second‐Line ART with Incomplete Data on Switching Times

Modeling clinical endpoints as a function of change in antiretroviral therapy (ART) attempts to answer one simple but very challenging question: was the change in ART beneficial or not? We conceive a similar scientific question of interest in the current manuscript except that we are interested in modeling the time of ART regimen change rather than a comparison of two or more ART regimens. The answer to this scientific riddle is unknown and has been difficult to address clinically. Naturally, ART regimen change is left to a participant and his or her provider and so the date of change depends on participant characteristics. There exists a vast literature on how to address potential confounding and those techniques are vital to the success of the method here. A more substantial challenge is devising a systematic modeling strategy to overcome the missing time of regimen change for those participants who do not switch to second-line ART within the study period even after failing the initial ART. In this article, we adopt and apply a statistical method that was originally proposed for modeling infusion trial data, where infusion length may be informatively censored, and argue that the same strategy may be employed here. Our application of this method to therapeutic HIV/AIDS studies is new and interesting. Using data from the AIDS Clinical Trials Group (ACTG) Study A5095, we model immunological endpoints as a polynomial function of a participant's switching time to second-line ART for 182 participants who already failed the initial ART. In our analysis, we find that participants who switch early have somewhat better sustained suppression of HIV-1 RNA after virological failure than those who switch later. However, we also found that participants who switched very late, possibly censored due to the end of the study, had good HIV-1 RNA suppression, on average. We believe our scientific conclusions contribute to the relevant HIV literature and hope that the basic modeling strategy outlined here would be useful to others contemplating similar analyses with partially missing treatment length data.

Notification of HIV status disclosure and its related factors in HIV‐infected adolescents in 2009 in the Aconda program (CePReF, CHU Yopougon) in Abidjan, Côte d'Ivoire, The PRADO‐CI Study

IntroductionWe studied the frequency of documentation of disclosure of HIV status in medical charts and its correlates among HIV-infected adolescents in 2009, in Abidjan, Côte d'Ivoire.MethodsThe PRADO-CI is a cross-sectional study aimed at studying HIV-infected adolescents’ social, psychological, and behavioural difficulties and their determinants in Abidjan, Côte d'Ivoire. In this study, we present specific analyses on disclosure. All HIV-infected adolescents aged 13–21 years and followed at least once in 2009 in two urban HIV-care centres in Abidjan (Cepref and Yopougon Teaching Hospital) were enrolled in the study. Standardized data were extracted from medical records to document if there was notification of disclosure of HIV status in the medical record. Frequency of notification of HIV disclosure was estimated with its 95% confidence interval (CI) and correlates were analyzed using logistic regression.ResultsIn 2009, 229 adolescents were included: 126 (55%) males; 93% on antiretroviral therapy (ART), 61% on cotrimoxazole prophylaxis. Their median age was 15 years at the time of the study. Among the 193 patients for whom information on HIV status disclosure was documented (84%), only 63 (32.6%; 95% CI=26.0–39.3%) were informed of their status. The proportion of adolescents informed increased significantly with age: 19% for 13–15 years, 33% for 16–18 years and 86% for 19–21 years (p <0.0001). Adolescents on ART tended to be more likely to be informed of their HIV status (34.5%) than those not treated (13.3%) (p=0.11). Those on cotrimoxazole were significantly more likely to be informed (39.6%) than those not (21.9%) (p=0.01). Disclosure was significantly higher in adolescents with a history of ART regimen change (p=0.003) and in those followed in the Cepref (48.4%) compared to the Yopougon Teaching Hospital (24.8%), (p=0.001). In multivariate analyses, disclosed HIV status was significantly higher in those followed-up in the Cepref compared to the other centre: adjusted odds ratio (aOR)=3.5 (95% CI: 1.1–10.9), and among older adolescents compared to those aged 13–15 years: [16–18 years] aOR=4.2 (95% CI: 1.5–11.5) and [>18 years]: aOR=22.1 (95% CI: 5.2–93.5).ConclusionsHIV disclosure rate was low among Ivoirian HIV adolescents and was site- and age-dependent. There is a need for practical interventions to support HIV disclosure to adolescents which provides age-appropriate information about the disease.

Effects of laboratory data exchange in the care of patients with HIV

BackgroundElectronic health record (EHR) systems are often modified through the addition of new features over time. Few studies have examined the specific effects of such changes. We examined whether implementation of a bidirectional laboratory interface for order entry and data reporting within an existing ambulatory EHR would result in more prompt responses to laboratory indications for antiretroviral therapy (ART) changes or in improved communication with HIV+ patients about relevant laboratory results. MethodsWe conducted a single-arm intervention study comparing the timeliness of ART regimen changes, HIV viral load (VL) outcomes and patient-reported assessments of care before and after implementation of a laboratory data exchange interface within an existing EHR, without changing the EHR ordering or results reporting user interface. Patient data was extracted from the EHR covering the period from 1 year before to 2 years after the intervention for a cohort of 1181 patients who had received care during the baseline year. The timeliness of ART changes was represented by the days from a laboratory-result “signal” (CD4 dropping below 350 or 200 or VL increasing by a half-log or to a value over 100,000) to an ART-change “response”. Patient assessments of care were collected by interviewing 100 anonymous patients at baseline and another 125 at 2 years post-intervention. ResultsA total of 171 laboratory “signal” events were followed within 80 days by a change in ART therapy. The mean time from signal to therapy change (adjusted for clustering by patient) initially increased, from 37.7 days during the pre-intervention year to 48.2 days during the quarter immediately following activation of the lab intervention. It then declined to a mean of 31.4 days over the remaining 21 months of observation (P=0.03 for the 6-day improvement from the pre-period). A majority of patients (65%) achieved undetectable VL values by the end of the observation period; faster signal–response times were not associated with greater achievement of undetectable VL. Patients rated communication about laboratory tests more highly after implementation of the interface (91 vs. 83 on a 100-point scale, P=0.01); ratings were not higher for other aspects of care. ConclusionsAdding laboratory data exchange interfaces within existing EHRs holds promise for improving HIV care, both in the timeliness of responses to important laboratory results and in the quality of provider communication about lab tests. However, the benefits from this incremental change may be modest unless more extensive redesign of laboratory follow-up workflows is undertaken, with support from enhanced user interfaces that take advantage of the laboratory information delivered. Providers should also consider increased staffing to compensate for dips in follow-up performance during the initial post-implementation months.

Changing antiretroviral therapy in the setting of virologic relapse: Review of the current literature

Virologic relapse after initial virologic suppression remains a concern for patients on antiretroviral therapy (ART). Multiple factors may contribute to virologic relapse, including suboptimal adherence, resistance, and pharmacokinetic issues. The major guidelines for HIV care are in agreement that ART regimen change is indicated in relapse because resistance is identified, but the guidelines are not completely clear on the timing of regimen change. When relapse occurs due to resistance, patients may continue with viremia well below their set points, stable or increasing CD4+ counts, and clinical health for several years. However, delaying a switch in the treatment regimen may lead to the accumulation of resistance which compromises future treatment response. In general, a lower switch threshold is recommended for patients during relapse on first or second line regimens.