Initial Antiretroviral Therapy Regimen Research Articles

Estimating the Cost Due to Resistance Against Antiretroviral Therapies in Individuals with HIV: Perspective of the Kingdom of Saudi Arabia

BackgroundThe emergence of resistance to antiretroviral therapy (ART) has an impact on the cost of Human immunodeficiency virus (HIV) care. The objective of this study was to estimate the direct and indirect costs associated with the first episode of drug resistance in individuals with HIV receiving first-line ART. MethodsWe developed a cost calculator to estimate cost of drug resistance over a period of 12 months in the Kingdom of Saudi Arabia. The model inputs (estimated using expert opinion and publicly available sources) included costs associated with testing for resistance, adverse events (AEs) of a new regimen, and indirect costs. ResultsThe direct and indirect medical expenses for the year resistance developed were 6,980 Saudi Arabian riyal (SAR) and SAR 2,862, respectively. The addition of the cost of new ARTs would increase the total annual costs (between SAR 5,174 and SAR 34,265 per patient). One-way sensitivity analysis also reported significant impact of initial and switching therapies used after resistance develops on the total costs of resistance per year. ConclusionsThere is a significant cost burden associated with drug resistance, which emphasizes the need to select an appropriate initial ART regimen that has a strong genetic barrier and conduct pre-treatment resistance tests (if possible).

Discontinuation of tenofovir disoproxil fumarate from initial ART regimens because of renal adverse events: An analysis of data from four multi-country clinical trials.

Tenofovir disoproxil fumarate (TDF), a potent and commonly used antiretroviral drug, is associated with renal tubular dysfunction and renal adverse events. We evaluated the frequency of, time to, and baseline risk factors for discontinuing TDF from initial antiretroviral therapy (ART) regimens because of renal adverse events from presumed tenofovir renal toxicity. We conducted an observational cohort study as a secondary analysis of data from four clinical trials conducted mainly in low- and middle-income countries. We included ART naïve participants living with HIV who started TDF-containing ART regimens in the trials. Participants had to have estimated creatinine clearance (eCrCl) equal to or greater than 60ml/min before starting ART. The primary outcome was the first instance of discontinuing TDF because of renal adverse events attributed to tenofovir renal toxicity during the first 48 weeks after starting ART. We evaluated the cumulative incidence of discontinuing TDF and associated risk factors using Fine and Gray competing risk regression models with a backward elimination variable selection strategy. There were 2802 ART-naïve participants who started TDF-containing ART from the four clinical trials were included in the analysis. Fifty-eight percent were female, the median age was 34 years, and 87% had CD4 cell counts less than 200 cells/μl. Sixty-four participants (2.4%, 95% CI 1.7%-2.8%) discontinued TDF due to renal adverse events. Among the 64 participants, the median time to discontinue TDF was 9.4 weeks (IQR: 3.4-20.7 weeks). From multivariable Fine and Gray regression models, risk factors for discontinuing TDF were older age, CD4 cell count <200 cells/μl, presence and severity of anemia, and eCrCl <90 ml/min. The risk of discontinuing TDF because of renal adverse events was low in participants initiating TDF-containing ART with advanced HIV and normal renal function, attesting to the tolerability of TDF in ART in low- and middle-income countries.

Initial antiretroviral therapy regimen and risk of heart failure.

Heart failure risk is elevated in people with HIV (PWH). We investigated whether initial antiretroviral therapy (ART) regimens influenced heart failure risk. Cohort study. PWH who initiated an ART regimen between 2000 and 2016 were identified from three integrated healthcare systems. We evaluated heart failure risk by protease inhibitor, nonnucleoside reverse transcriptase inhibitors (NNRTI), and integrase strand transfer inhibitor (INSTI)-based ART, and comparing two common nucleotide reverse transcriptase inhibitors: tenofovir disoproxil fumarate (tenofovir) and abacavir. Follow-up for each pairwise comparison varied (i.e. 7 years for protease inhibitor vs. NNRTI; 5 years for tenofovir vs. abacavir; 2 years for INSTIs vs. PIs or NNRTIs). Hazard ratios were from working logistic marginal structural models, fitted with inverse probability weighting to adjust for demographics, and traditional cardiovascular risk factors. Thirteen thousand six hundred and thirty-four PWH were included (88% men, median 40 years of age; 34% non-Hispanic white, 24% non-Hispanic black, and 24% Hispanic). The hazard ratio (95% CI) were: 2.5 (1.5-4.3) for protease inhibitor vs. NNRTI-based ART (reference); 0.5 (0.2-1.8) for protease inhibitor vs. INSTI-based ART (reference); 0.1 (0.1-0.8) for NNRTI vs. INSTI-based ART (reference); and 1.7 (0.5-5.7) for tenofovir vs. abacavir (reference). In more complex models of cumulative incidence that accounted for possible nonproportional hazards over time, the only remaining finding was evidence of a higher risk of heart failure for protease inhibitor compared with NNRTI-based regimens (1.8 vs. 0.8%; P  = 0.002). PWH initiating protease inhibitors may be at higher risk of heart failure compared with those initiating NNRTIs. Future studies with longer follow-up with INSTI-based and other specific ART are warranted.

Associations of modern initial antiretroviral therapy regimens with all-cause mortality in people living with HIV in resource-limited settings: a retrospective multicenter cohort study in China

Despite the proven virological advantages, there remains some controversy regarding whether first-line integrase strand transfer inhibitors (INSTIs)-based antiretroviral therapy (ART) contributes to reducing mortality of people living with HIV (PLHIV) in clinical practice. Here we report a retrospective study comparing all-cause mortality among PLHIV in China who were on different initial ART regimens (nevirapine, efavirenz, dolutegravir, lopinavir, and others [including darunavir, raltegravie, elvitegravir and rilpivirine]) between 2017 and 2019. A total of 41,018 individuals were included across China, representing 21.3% of newly reported HIV/AIDS cases collectively in the country during this period. Only the differences in all-cause mortality of PLHIV between the efavirenz group and the nevirapine group, the dolutegravir group and the nevirapine group, and the lopinavir group and the nevirapine group, were observed in China. After stratifying the cause of mortality, we found that the differences in mortality between initial ART regimens were mainly observed in AIDS-related mortality.

Neuropsychiatric Adverse Events Following Antiretroviral Therapy in People Living with HIV: A Real-World Study of Dynamic Trends and Risk Factors in Hangzhou, China.

Neuropsychiatric adverse events (NPAEs) occur frequently in people living with human immunodeficiency virus (PLWH) receiving antiretroviral therapy (ART). This study aimed to assess the dynamic trends and risk factors of NPAEs among PLWH in Hangzhou taking efavirenz (EFV)- or dolutegravir (DTG)- or elvitegravir (EVG)-based regimens. A total of 287 ART-naive PLWH were included in this study, EFV (400mg)- (n = 122), EFV (600mg)- (n = 37), DTG- (n = 73), EVG-based (n = 47) and other ART regimens (n = 8) as the initial ART regimen were administered for 12 months. All data were collected at five time points within a 12-month follow-up. The Pittsburgh Sleep Quality Index and Hospital Anxiety and Depression Scale were used to evaluate sleep disorders and anxiety and depression symptoms, respectively. The dynamic trends and potential risk factors of NPAEs were investigated using a generalized linear mixed model. Mean age was 29.4 (SD: 7.5) years with 97.2% males. After 12 months of ART, the prevalence of sleep disorders and anxiety decreased significantly, although only a slight improvement was observed for depression. In addition, there was a significant positive correlation between sleep disorders, anxiety, and depression. The risk factors for NPAEs differed slightly depending on the choice of ART regimen, but the seven factors most commonly associated with NPAEs were age, sex, marital status, education level, smoking status, body mass index, and WHO clinical stage. Treatment-induced changes in CD4-positive T-cell count and virological suppression did not depend on the particular choice of ART regimen. The prevalence of sleep disorders and anxiety changed significantly over time on ART and the risks of these disorders were associated with seven common clinical anddemographic factors.

Changes of Viral Load, Drug Resistance, and CD4 Cell Count in HIV-1-Infected Patients Receiving Antiretroviral Therapy in Hebei Province, China, 2003-2019.

In this study, a total of 462 samples of whole blood were collected from 36 patients enrolled. During the entire course of antiretroviral therapy (ART) from 2003 to 2019, both the CD4 cell count and viral load (VL) of study patients were examined annually, and an HIV-1 genotypic drug resistance (DR) assay was carried out using an in-house method when the HIV-1 VL was >1,000 copies/mL. The results indicated that 13 (36.1%) experienced treatment failure and 23 (63.9%) experienced treatment success among 36 patients. The proportion of patients with effective treatment after the adjustment of ART regimens was significantly higher than before adjustment (χ2 = 33.796, p < .001). Furthermore, the frequencies of HIV-1 DR mutations before adjustment were higher than those after adjustment (t = 3.345, p = .002). In particular, among 23 patients with effective treatment after adjustment, the means ± standard deviations of the VLs and CD4 cell counts before adjustment were 3.85 ± 0.65 log RNA copies/mL and 226.83 ± 106.06 cells/mm3, respectively, compared with 2.19 ± 0.58 log RNA copies/mL and 367.68 ± 174.62 cells/mm3, respectively, after adjustment. Obviously, there were statistically significant differences in the changes in VL (t = 8.728, p < .001) and CD4 cell count (t = -4.476, p < .001) before and after adjustment. Therefore, patients who received updated ART regimens containing LPV/r and TDF after adjustment achieved better therapeutic effects compared with patients who received initial ART regimens harboring D4T/AZT or NVP. This suggests that future research is needed to initiate the surveillance of DR, VLs, and CD4 cell counts immediately after HIV diagnosis, and dynamic changes in these indicators so as to optimize ART effects.

Time to First Line Antiretroviral Therapy Adverse Drug Reaction and its Predictors Among Adult HIV/AIDS Patients on Treatment in Eastern Ethiopia.

Background: Even though determining the time to anti-retroviral therapy (ART) adverse drug reaction and its predictors is a crucial step to overcome the negative consequences of the adverse drug reaction, there is limited information regarding the time to ART adverse drug reaction and its predictors. Therefore, this study aimed to determine the time to first ART adverse drug reaction and its predictors among adult HIV/AIDS patients on first-line antiretroviral therapy in West Hararghe Zone, Eastern Ethiopia. Methods: An institution-based retrospective cohort study was conducted on 561 HIV/AIDS patients on first-line ART from September 2013–January 2019 at public hospitals in West Hararghe Zone, Eastern Ethiopia. Data were collected using checklists and document reviews, entered using Epi Info and analyzed in R software. A Cox proportional hazard model was fitted to identify predictors of the time to first ART adverse drug reaction. Model adequacy was checked using Cox Snell residuals. An adjusted hazard ratio with its confidence interval was used to show the presence and strength of association at a 95% confidence level. Result: Most (90.74%) ART adverse drug reactions occurred within 1 year of initiation of ART. Overall, 54 patients developed ART adverse drug reactions with an incidence density of 3.5/100 persons-years of observations (95% CI: 2.7–4.6). The initial ART regimen (TDF, 3TC, EFV) [AHR = 0.3, 95% CI 0.1–0.7], fair adherence [AHR = 8.8, 95% CI 3.3–23.2], poor adherence [AHR = 7.8, 95% CI 3.1–19.5], moderate body mass index (BMI) at the baseline [AHR = 4.4, 95% CI 1.8–11.0], severe body mass index [AHR = 2.8, 95% CI 1.1–6.8], World Health Organization (WHO) stage II [AHR = 3.7, 95% CI 1.2–11.3] and WHO stage IV [AHR = 6.3, 95% CI 2.0–19.8] were significant predictors of the time to ART adverse drug reactions. Conclusion: In conclusion, most of the ART adverse drug reactions occurred within 1 year of initiation of ART. The initial ART regimen (TDF, 3TC, EFV), adherence, HIV/AIDS stage, and BMI were risk factors for the time to ART adverse drug reaction. The incidence of the antiretroviral therapy adverse reaction was relatively low with early onset. Close monitoring of clients in clinical stage II and above is required and continuous assessment for improving the detection and management of adverse drug reactions is recommended. Patients with poor adherence need to get continuous counseling to improve their adherence status.

Treatment Outcomes of HIV Infected Children After Initiation of Antiretroviral Therapy in Southwest China: An Observational Cohort Study.

BackgroundThe number of HIV infected children receiving antiviral treatment in Guangxi is increasing. Understanding factors and trends of mortality and attrition in HIV-infected children under antiretroviral therapy (ART) was an urgent need to improve treatment outcomes. This study aimed to estimate mortality and attrition rates and identify factors that were associated with mortality and attrition after ART initiation among children with HIV in Guangxi, China between 2004 and 2018.MethodsCohort study data were extracted from the National Free Antiretroviral Treatment Program (NFATP) database, which has standard guidelines for core treatment indicators and other data at all HIV/AIDS treatment facilities in Guangxi. A total of 901 HIV-infected children who have started ART were included in the study. The study collected the following data: age, gender, WHO clinic stages before ART, CD4 cell count before ART, Cotrimoxazole prophylaxis (CTX) use before ART, initial ART regimen, malnutrition before ART, abnormal liver function before ART, abnormal kidney function before ART, severe anemia before ART, and the time lag between an HIV diagnosis and ART initiation.ResultsHIV-infected children under ART had a mortality rate of 0.87 per 100 person-years [95% Confidence Interval (CI) 0.63–1.11], and an attrition rate of 3.02 per 100 person-years (95% CI 2.57–3.47). Mortality was lower among children with a CD4 count between 200 and 500 copies/ml [Adjusted Hazard Ratio (AHR) 0.22, 95% CI 0.09–0.55], and CD4 count ≥500 copies/ml (AHR 0.10, 95% CI 0.03–0.29); but higher among children with late ART initiation at 1–3 months (AHR 2.30, 95% CI 1.07–4.94), and at ≥3 months (AHR 2.22, 95% CI 1.04–4.74). Attrition was lower among children with a CD4 count ≥500 copies/ml (AHR 0.62, 95% CI 0.41–0.95), but higher among children with late ART initiation at 1–3 months (AHR 1.55, 95% CI 1.05–2.30).ConclusionSupportive programs are needed to educate children's families and parents on early ART, link HIV-infected children to care and retain them in care among other programs that treat and manage the medical conditions of HIV-infected children before ART initiation.

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.

Virologic outcomes among adults with HIV using integrase inhibitor-based antiretroviral therapy.

Integrase strand transfer inhibitor (InSTI)-based regimens have been recommended as first-line antiretroviral therapy (ART) for adults with HIV. But data on long-term effects of InSTI-based regimens on virologic outcomes remain limited. Here we examined whether InSTI improved long-term virologic outcomes compared with efavirenz (EFV). We included adults from the North American AIDS Cohort Collaboration on Research and Design who initiated their first ART regimen containing either InSTI or EFV between 2009 and 2016. We estimated differences in the proportion virologically suppressed up to 7 years of follow-up in observational intention-to-treat and per-protocol analyses. Of 15 318 participants, 5519 (36%) initiated an InSTI-based regimen and 9799 (64%) initiated the EFV-based regimen. In observational intention-to-treat analysis, 81.3% of patients in the InSTI group and 67.3% in the EFV group experienced virologic suppression at 3 months after ART initiation, corresponding to a difference of 14.0% (95% CI 12.4-15.6). At 1 year after ART initiation, the proportion virologically suppressed was 89.5% in the InSTI group and 90.2% in the EFV group, corresponding to a difference of -0.7% (95% CI -2.1 to 0.8). At 7 years, the proportion virologically suppressed was 94.5% in the InSTI group and 92.5% in the EFV group, corresponding to a difference of 2.0% (95% CI -7.3 to 11.3). The observational per-protocol results were similar to intention-to-treat analyses. Although InSTI-based initial ART regimens had more rapid virologic response than EFV-based regimens, the long-term virologic effect was similar. Our findings may inform guidelines regarding preferred initial regimens for HIV treatment.

Trends and factors associated with modification or discontinuation of the initial antiretroviral regimen during the first year of treatment in the Turkish HIV-TR Cohort, 2011\u20132017

BackgroundThere is limited evidence on the modification or stopping of antiretroviral therapy (ART) regimens, including novel antiretroviral drugs. The aim of this study was to evaluate the discontinuation of first ART before and after the availability of better tolerated and less complex regimens by comparing the frequency, reasons and associations with patient characteristics.MethodsA total of 3019 ART-naive patients registered in the HIV-TR cohort who started ART between Jan 2011 and Feb 2017 were studied. Only the first modification within the first year of treatment for each patient was included in the analyses. Reasons were classified as listed in the coded form in the web-based database. Cumulative incidences were analysed using competing risk function and factors associated with discontinuation of the ART regimen were examined using Cox proportional hazards models and Fine-Gray competing risk regression models.ResultsThe initial ART regimen was discontinued in 351 out of 3019 eligible patients (11.6%) within the first year. The main reason for discontinuation was intolerance/toxicity (45.0%), followed by treatment simplification (9.7%), patient willingness (7.4%), poor compliance (7.1%), prevention of future toxicities (6.0%), virologic failure (5.4%), and provider preference (5.4%). Non-nucleoside reverse transcriptase inhibitor (NNRTI)-based (aHR = 4.4, [95% CI 3.0–6.4]; p < 0.0001) or protease inhibitor (PI)-based regimens (aHR = 4.3, [95% CI 3.1–6.0]; p < 0.0001) relative to integrase strand transfer inhibitor (InSTI)-based regimens were significantly associated with ART discontinuation. ART initiated at a later period (2015-Feb 2017) (aHR = 0.6, [95% CI 0.4–0.9]; p < 0.0001) was less likely to be discontinued. A lower rate of treatment discontinuation for intolerance/toxicity was observed with InSTI-based regimens (2.0%) than with NNRTI- (6.6%) and PI-based regimens (7.5%) (p < 0.001). The percentage of patients who achieved HIV RNA < 200 copies/mL within 12 months of ART initiation was 91% in the ART discontinued group vs. 94% in the continued group (p > 0.05).ConclusionART discontinuation due to intolerance/toxicity and virologic failure decreased over time. InSTI-based regimens were less likely to be discontinued than PI- and NNRTI-based ART.

Brief Report: Weight Gain Following ART Initiation in ART-Naïve People Living With HIV in the Current Treatment Era.

Evaluate differences in weight change by regimen among people living with HIV (PLWH) initiating antiretroviral therapy (ART) in the current era. Between 2012 and 2019, 3232 ART-naïve PLWH initiated ≥3-drug ART regimens in 8 Centers for AIDS Research Network of Integrated Clinical Systems sites. We estimated weight change by regimen for 11 regimens in the immediate (first 6 months) and extended (all follow-up on initial regimen) periods using linear mixed models adjusted for time on regimen, interaction between time and regimen, age, sex, race/ethnicity, hepatitis B/C coinfection, nadir CD4, smoking, diabetes, antipsychotic medication, and site. We included more recently approved regimens [eg, with tenofovir alafenamide fumarate (TAF)] only in the immediate period analyses to ensure comparable follow-up time. Mean follow-up was 1.9 years on initial ART regimen. In comparison to efavirenz/tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC), initiating bictegravir/TAF/FTC {3.9 kg [95% confidence interval (CI): 2.2 to 5.5]} and dolutegravir/TAF/FTC [4.4 kg (95% CI: 2.1 to 6.6)] were associated with the greatest weight gain in the immediate period, followed by darunavir/TDF/FTC [3.7 kg (95% CI: 2.1 to 5.2)] and dolutegravir/TDF/FTC [2.6 kg (95% CI: 1.3 to 3.9)]. In the extended period, compared with efavirenz/TDF/FTC, initiating darunavir/TDF/FTC was associated with a 1.0 kg (95% CI: 0.5 to 1.5) per 6-months greater weight gain, whereas dolutegravir/abacavir/FTC was associated with a 0.6-kg (95% CI: 0.3 to 0.9) and dolutegravir/TDF/FTC was associated with a 0.6-kg (95% CI: 0.1 to 1.1) per 6-months greater gain. Weight gain on dolutegravir/abacavir/FTC and darunavir/TDF/FTC was significantly greater than that for several integrase inhibitor-based regimens. There is heterogeneity between regimens in weight gain following ART initiation among previously ART-naïve PLWH; we observed greater gain among PLWH taking newer integrase strand transfer inhibitors (DTG, BIC) and DRV-based regimens.

Clinical Effectiveness of Integrase Strand Transfer Inhibitor-Based Antiretroviral Regimens Among Adults With Human Immunodeficiency Virus: A Collaboration of Cohort Studies in the United States and Canada.

Integrase strand transfer inhibitor (InSTI)-based regimens are now recommended as first-line antiretroviral therapy (ART) for adults with human immunodeficiency virus, but evidence on long-term clinical effectiveness of InSTI-based regimens remains limited. We examined whether InSTI-based regimens improved longer-term clinical outcomes. We included participants from clinical cohorts in the North American AIDS Cohort Collaboration on Research and Design who initiated their first ART regimen, containing either InSTI (ie, raltegravir, dolutegravir, and elvitegravir-cobicistat) or efavirenz (EFV) as an active comparator, between 2009 and 2016. We estimated observational analogs of 6-year intention-to-treat and per-protocol risks, risk differences (RDs), and hazard ratios (HRs) for the composite outcome of AIDS, acute myocardial infarction, stroke, end-stage renal disease, end-stage liver disease, or death. Of 15 993 participants, 5824 (36%) initiated an InSTI-based and 10 169 (64%) initiated an EFV-based regimen. During the 6-year follow-up, 440 in the InSTI group and 1097 in the EFV group incurred the composite outcome. The estimated 6-year intention-to-treat risks were 14.6% and 14.3% for the InSTI and EFV groups, respectively, corresponding to a RD of 0.3% (95% confidence interval, -2.7% to 3.3%) and a HR of 1.08 (.97-1.19); the estimated 6-year per-protocol risks were 12.2% for the InSTI group and 11.9% for the EFV group, corresponding to a RD of 0.3% (-3.0% to 3.7%) and a HR of 1.09 (.96-1.25). InSTI- and EFV-based initial ART regimens had similar 6-year composite clinical outcomes. The risk of adverse clinical outcomes remains substantial even when initiating modern ART.

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.

Association of Male Sex and Obesity With Residual Plasma Human Immunodeficiency Virus 1 Viremia in Persons on Long-Term Antiretroviral Therapy.

Although adipose tissue has been proposed to harbor part of the human immunodeficiency virus 1 (HIV-1) reservoir, the influence of host characteristics, including sex and body mass index (BMI), on measures of HIV-1 persistence during antiretroviral therapy (ART) are incompletely understood. We evaluated age, sex, BMI, waist circumference, years on ART, pre-ART HIV-1 RNA, pre-ART CD4+ T-cell count, and initial ART regimen with measures of HIV-1 persistence in blood (residual viremia, cellular HIV-1 DNA and RNA) in a cohort of 295 individuals with well-documented long-term virologic suppression (HIV-1 RNA <50 copies/mL) on ART (AIDS Clinical Trials Group study A5321). Men were more likely than women to have detectable plasma HIV-1 RNA by single-copy assay (52% vs 29%; P = .003), and the proportion of participants with detectable residual viremia increased in a stepwise fashion by BMI category (normal weight or underweight, 38%; overweight, 50%; and obese, 55%). ART regimen type was not associated with measures of HIV-1 persistence after controlling for ART duration. Sex and obesity are independently associated with residual viremia in people on long-term ART. Additional studies to confirm these relationships and to define the mechanisms by which sex and obesity affect HIV-1 persistence are needed to inform HIV-1 cure strategies.

Efficacy and safety of abacavir/lamivudine plus rilpivirine as a first-line regimen in treatment-na\xefve HIV-1 infected adults

BackgroundThe anti-retroviral combination of abacavir/lamivudine plus rilpivirine (ABC/3TC/RPV) is not recommended by international guidelines as the first-line regimen. However, it is potent, well-tolerated, and affordable, especially in resource-limited settings. This study evaluates the efficacy and safety of ABC/3TC/RPV as an initial regimen for treatment-naïve HIV-1 infected patients.MethodsA retrospective study was conducted in the largest HIV care centre in Singapore, with data collected June 2011 to September 2017. All treatment-naïve HIV-1 infected adults prescribed ABC/3TC as part of their initial anti-retroviral therapy regimen were included. The third drug was a non-nucleoside reverse-transcriptase inhibitor (NNRTI) such as RPV or efavirenz (EFV), or boosted protease-inhibitor (PI). Patients were followed up for 48 weeks. The primary end-point was the percentage of patients achieving virologic suppression, analysed using on-treatment analysis. Secondary outcomes included CD4-count change, treatment discontinuation and treatment-related adverse events.Results170 patients were included in the study, 66 patients in the RPV group, 104 patients in the comparator group (EFV or boosted PI). 96% (n = 24) in the RPV group and 87% (n = 26) in the comparator group achieved viral suppression at 48 weeks (p = 0.28). Median (interquartile range) time to viral suppression was similar: 17 (14–24) weeks in the RPV group, and 21 (13–26) weeks in the comparator group. There were no statistically significant differences in the CD4 count between the two groups. 14% (n = 9) of patients on RPV discontinued treatment before 48 weeks, compared to 30% (n = 31) from the comparator group (p = 0.053). Of these, 23 discontinuations were due to drug adverse effects, and only 1 attributed to RPV (p < 0.01). One patient in each group had virologic failure.ConclusionRPV is effective, safe and considerably more tolerable than compared to NNRTI or boosted PI in ABC/3TC-containing regimens for treatment-naïve patients. It offers an affordable and attractive option, especially in resource-limited settings.

SOME ASPECTS OF MANAGEMENT OF HIV-INFECTED PATIENTS WITH PATHOLOGY OF DIGESTIVE SYSTEM IN CONTEXT OF FAMILY MEDICINE PRACTICE

Introduction. In the current situation of the HIV-infection epidemic, every 100-th citizen of Ukraine aged between 15 and 49 is infected with HIV. It is one of the highest rates among countries in the European Region. The issue of retaining HIV-positive patients in the medical surveillance system and support for adherence to ART treatment are becoming particularly relevant. At the same time, the comorbidity of HIV-infection with digestive system lesion is one of the main elements of pathological changes, both in the progression of HIV infection and in the occurrence of various complications leading to interruptions or failure to receive continuous antiretroviral therapy (ART). The purpose of the study is to examine the features of the digestive system lesions of HIV-infected patients and their impact on the effectiveness of antiretroviral therapy. Materials and methods. The study was conducted on randomly selected 215 HIV-infected patients in compliance with the bioethical and scientific standards, in accordance with industry standards and clinical guidelines approved by the Ministry of Health of Ukraine. Results and Discussion. Patients were divided into two comparison groups: the main group (MG) had 158 (73.5%) of HIV-infected persons with pathology of the digestive system, the controlled group (СG) had 57 (26.5%) of HIV-infected patients with no signs of gastric lesions of the gastrointestinal tract. Among the lesions of the digestive system in HIV-infected patients, hepatitis of viral and/or toxic genesis, chronic inflammatory diseases of the esophagus and gastroduodenal zone, chronic pancreatitis and cholecystitis were most often observed. In 61.4%, the pathology of the digestive tract was combined. When evaluating the efficacy of ART, no statistical difference was found between MG and CG in the frequency of the virologic response and the level of viral load at the beginning of the study and at 6 months of follow-up. However, MG patients had a worse immunologic response compared to CG, they were significantly more likely to switch the initial ART regimen, have breaks in treatment and development of adverse reactions. Patients treated for comorbid digestive system disorders had ART replacements less frequently and after 6 months of treatment they had an average level of CD4 + lymphocytes, which corresponded to the normal value. Conclusions. A significant majority of the examined patients with HIV-infection had digestive system lesions (73.5%). HIV-infected patients with digestive system pathology had more treatment interruptions, switch of ART regimens, and a worse immunological response, compared with the controlled group. Untreated diseases of the digestive system could be predictors of an increased break rate of ART, switch of treatment regimens, and decreased treatment efficacy. The introduction of an integrated, patient-oriented approach to the management of these nosologies in family medicine practice is proposed.

Death and attrition among HIV–infected persons receiving initial antiretroviral treatment in Xichang, Sichuan, 2008–2018

Objective To understand the death and attrition and influencing factors among HIV–infected persons receiving initial antiretroviral therapy(ART) in Xichang City, Sichuan Province during 2008–2018. Methods Retrospective cohort research was adopted to analyze the death and attrition among HIV–infected persons receiving initial ART in Xichang City, Sichuan Province, 2008–2018. Data were collected through national AIDS comprehensive treatment and prevention system. Cox proportional hazard regression model was employed to analyze related factors of death and attrition. Results A total of 2 723 eligible HIV–infected persons were enrolled. The mortality and ART attrition rates among all patients were 1.92 deaths and 2.49 attritions per 100 person–years, respectively. The mortality and attrition rates were 10.83 and 13.89 per 100 person–years in the first year of ART. Cox regression analysis showed that the main risk factors of mortality were aged ≥ forty years ( HR =2.30, 95% CI : 1.53–3.48), males ( HR =1.94, 95% CI : 1.14–3.30), tuberculosis infection one year before ART ( HR =1.92, 95% CI : 1.01–3.65), AIDS–related disease/symptom three months before ART ( HR =2.44, 95% CI : 1.50–3.99), hepatitis B infection before ART ( HR =2.50, 95% CI : 1.32–4.71) and less than 200 cells/uL of CD4 + T lymphocyte counts ( HR =1.79, 95% CI : 1.12–2.86) at the initiation of ART. And the main risk factors of attrition were aged ≥ forty years ( HR =1.53, 95% CI : 1.07–2.18), males ( HR =5.60, 95% CI : 2.60–12.08), injection drug users ( HR =2.18, 95% CI : 1.46–3.27) and initial ART regimen EFV+3TC+TDF ( HR =2.57, 95% CI : 1.32–5.01). Conclusion The effect of antiretroviral treatment was remarkable among HIV–infected persons in Xichang City. But the mortality and ART attrition rate in the first year were high. Targeted measures should be taken and focus on reducing the attrition among injection drug users after releasing from prison, so as to improve the effect of antiretroviral treatment. 摘要： 目的 了解四川省西昌市2008－2018年初始抗病毒治疗HIV感染者死亡和脱失的情况及其影响因素。 方法 采用回顾性队列研究的方法, 从艾滋病基本防治信息系统选取2008－2018年在西昌市首次开始抗病毒治疗 (ART) 的HIV感染者, 分析抗病毒治疗者的死亡和脱失情况。采用Cox比例风险回归模型对影响抗病毒治疗HIV感染者病死率和脱失率的相关因素进行分析。 结果 共计2 723例HIV感染者进入队列, 总体病死率为1.92/100人年, 总体脱失率为2.49/100人年。在开始抗病毒治疗的第1年内病死率和脱失率分别为10.83/100人年、13.89/100人年。Cox 回归分析结果显示接受抗病毒治疗患者主要的死亡风险是年龄≥40岁 ( HR =2.30, 95% CI ：1.53~3.48) 、男性 ( HR =1.94, 95% CI ：1.14~3.30) 、ART前一年内结核感染 ( HR =1.92, 95% CI ：1.01~3.65) 、ART前三个月出现艾滋病相关疾病/症状 ( HR =2.44, 95% CI ：1.50~3.99) 、ART前乙肝感染 ( HR =2.50, 95% CI ：1.32~4.71) 、CD4+T淋巴细胞计数< 200 cells/ul ( HR =1.79, 95% CI ：1.12~2.86) 。接受抗病毒治疗患者主要的脱失风险是年龄≥40岁 ( HR =1.53, 95% CI ：1.07~2.18) 、男性 ( HR =5.60, 95% CI ：2.60~12.08) 、静脉吸毒 ( HR =2.18, 95% CI ：1.46~3.27) 、初始抗病毒治疗方案为EFV+3TC+TDF ( HR =2.57, 95% CI ：1.32~5.01) 。 结论 西昌市HIV感染者的抗病毒治疗效果显著, 但在开始治疗的第1年内病死率和脱失率较高。抗病毒治疗工作需采取针对性的措施, 重点要减少静脉吸毒人群刑满释放后的脱失, 从而提高抗病毒治疗效果。

LB9. The Effect of Initiating Integrase Inhibitor-based vs. Non-Nucleoside Reverse Transcriptase Inhibitor-based Antiretroviral Therapy on Progression to Diabetes among North American Persons in HIV Care

BackgroundIntegrase strand transfer inhibitor (INSTI)-based antiretroviral therapy (ART) has been implicated in greater weight gain than other regimens among people with HIV, but there is little evidence about its role in serious clinical outcomes proximal to weight gain. We therefore examined the impact of initial ART regimen class/drug on incident diabetes mellitus (DM) in a large North American HIV cohort.MethodsTreatment-naïve adults (≥18 years) initiating INSTI-, protease inhibitor (PI)-, or non-nucleoside reverse transcriptase inhibitor (NNRTI)-based ART from January 2007 to December 2016 in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) were included. Individuals were followed until date of incident DM (HgA1c >6.5%, diabetes-specific medication, DM diagnosis along with diabetes-related medication, or random glucose measure ≥200 mg/dL), virologic failure, regimen core switch, cohort close (through December 2016), death date, or loss to follow-up (≥12 months with no contact before cohort close). Cox regression stratified by site and adjusting for age, sex, race, HIV transmission risk, year of ART initiation, and baseline weight, CD4+ cell count, and HIV-1 RNA yielded adjusted hazard ratios (HR) and 95% confidence intervals (CI) for incident DM by ART class and INSTI drug.ResultsAmong 21,516 eligible ART initiators, 10,553 (49%) started NNRTIs, 6,677 (31%) PIs, and 4,286 (20%) INSTIs, with median follow-up of 3.0, 2.4, and 1.6 years, respectively. Among INSTI initiators, 21% started dolutegravir (DTG), 28% raltegravir (RAL), and 51% elvitegravir (EVG). Overall, 669 (3%) developed DM. Patients differed by all characteristics except baseline body mass index and HIV-1 RNA. Those starting INSTIs vs. NNRTIs had increased risk of incident DM (HR = 1.22; CI: 0.95–1.57) similar in magnitude as for PI vs. NNRTI initiators (HR = 1.25; CI: 1.05–1.49) (figure). Among INSTIs, starting RAL- vs. NNRTI-based ART was associated with a 50% increased risk of DM (HR = 1.50, CI: 1.11–2.03).ConclusionInitiating ART with INSTI- or PI- vs. NNRTI-based regimens may confer increased risk of incident DM, though risk is heterogeneous among INSTIs. Further research is needed to determine whether this elevated risk can be attributed to weight gain. DisclosuresKassem Bourgi, MD, Gilead Sciences (Grant/Research Support), Joseph J. Eron, MD, Gilead Sciences (Consultant, Grant/Research Support), Janssen (Grant/Research Support), Merck (Consultant), ViiV Healthcare (Consultant, Grant/Research Support), M. John Gill, MB, ChB, MSc, Gilead (Board Member), Merck (Board Member), Viiv (Board Member), Michael Silverberg, PhD, MPH, Gilead (Grant/Research Support). Other Authors: No reported disclosures.

Choice of the initial antiretroviral treatment for HIV-positive individuals in the era of integrase inhibitors.

BackgroundWe aimed to describe the most frequently prescribed initial antiretroviral therapy (ART) regimens in recent years in HIV-positive persons in the Cohort of the Spanish HIV/AIDS Research Network (CoRIS) and to investigate factors associated with the choice of each regimen.MethodsWe analyzed initial ART regimens prescribed in adults participating in CoRIS from 2014 to 2017. Only regimens prescribed in >5% of patients were considered. We used multivariable multinomial regression to estimate Relative Risk Ratios (RRRs) for the association between sociodemographic and clinical characteristics and the choice of the initial regimen.ResultsAmong 2874 participants, abacavir(ABC)/lamivudine(3TC)/dolutegavir(DTG) was the most frequently prescribed regimen (32.1%), followed by tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC)/elvitegravir(EVG)/cobicistat(COBI) (14.9%), TDF/FTC/rilpivirine (RPV) (14.0%), tenofovir alafenamide (TAF)/FTC/EVG/COBI (13.7%), TDF/FTC+DTG (10.0%), TDF/FTC+darunavir/ritonavir or darunavir/cobicistat (bDRV) (9.8%) and TDF/FTC+raltegravir (RAL) (5.6%).Compared with ABC/3TC/DTG, starting TDF/FTC/RPV was less likely in patients with CD4<200 cells/μL and HIV-RNA>100.000 copies/mL. TDF/FTC+DTG was more frequent in those with CD4<200 cells/μL and HIV-RNA>100.000 copies/mL. TDF/FTC+RAL and TDF/FTC+bDRV were also more frequent among patients with CD4<200 cells//μL and with transmission categories other than men who have sex with men. Compared with ABC/3TC/DTG, the prescription of other initial ART regimens decreased from 2014–2015 to 2016–2017 with the exception of TDF/FTC+DTG. Differences in the choice of the initial ART regimen were observed by hospitals’ location.ConclusionsThe choice of initial ART regimens is consistent with Spanish guidelines’ recommendations, but is also clearly influenced by physician’s perception based on patient’s clinical and sociodemographic variables and by the prescribing hospital location.