Dolutegravir (DTG) monotherapy results in virologic failure and the development of DTG resistance. Here, we evaluated virologic outcomes of patients switched to DTG functional mono- or dual therapy with a non-cytosine nucleoside analog (NA).This retrospective, single center study included treatment-experienced patients switched to regimens containing ≥ 2 antiretrovirals between 8/13/13–11/22/14 who were later found to be on DTG functional mono- or dual therapy with a non-cytosine NA based on historical genotypes. Eligible patients were either suppressed or viremic at baseline and had ≥ 2 HIV-1 RNA measurements at least 4 weeks apart following switch. Demographics, laboratory values and clinical parameters were extracted from the charts of all eligible patients during study treatment until 12/31/2018 and were summarized using descriptive statistics. The primary endpoint was the proportion of patients with HIV-1 RNA < 50 copies/mL following switch.Of 70 patients switched to DTG functional mono- or dual therapy, 39 were eligible; 19 (49%) were on DTG functional monotherapy and 20 (51%) were on DTG functional dual therapy with a non-cytosine NA. Historical genotypes indicated that all had an M184V/I, and 23 (59%) had an M184V/I and ≥ 1 additional NA mutation. The median duration of follow-up on study treatment was 50 weeks (range 12–244). Following switch, 32/39 (82%) patients achieved or maintained an HIV-1 RNA < 50 copies/mL and 7 (18%) had persistent HIV-1 RNA ≥ 50 copies/mL. Five viremic patients were found to be on functional dual therapy with DTG plus a non-cytosine NA and 2 were on DTG functional monotherapy. Five of these patients had post-switch genotypes ordered as a part of routine clinical care and there was no evidence of treatment-emergent resistance. Five were switched to a different DTG-containing regimen and achieved HIV-1 RNA < 50 copies/mL, 1 was switched to a non-DTG containing regimen and achieved HIV-1 RNA < 50 copies/mL and 1 was lost-to-follow up at week 36.In this real-world cohort, the majority of whom had virus with the M184V/I and ≥ 1 additional NA mutation, switching to DTG functional mono-or dual therapy with a non-cytosine NA resulted in persistent HIV-1 RNA ≥ 50 copies/mL in 18%. None with post-switch genotypes developed treatment-emergent resistance. Phase 3 clinical trials have demonstrated the efficacy of 2-drug dolutegravir (DTG) containing regimens (DCRs) in both treatment-naïve and -experienced adults. In the GEMINI 1&2 studies conducted in treatment-naïve adults, DTG/lamivudine (3TC) was found to be non-inferior to DTG plus tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) with 82% on DTG/3TC versus 84% on DTG plus TDF/FTC achieving virologic suppression through Week 144 [In the SWORD 1&2 studies conducted among treatment-experienced, virologically suppressed adults on a stable regimen consisting of two NRTIs and a third agent, switching to DTG/rilpivirine (RPV) was non-inferior to remaining on baseline regimen through Week 52 with VF observed in < 1% switching to DTG/RPV versus < 1% remaining on baseline regimen . At WeekOther clinical trials of stably suppressed patients switched to DTG monotherapy revealed that a high proportion of VFs developed DTG resistance –7. This This is particularly relevant in LMICs where 50% of patients do not have access to routine viral load monitoring and genotypic resistance tests in the setting of VF . Prior rHere, we present virologic outcomes of patients switched to DCRs with ≥ 2 ARV drugs who were subsequently found to be on DTG functional mono-or dual therapy with a non-cytosine nucleoside analog (NA).This was a retrospective study to describe virologic outcomes of patients switched to DTG functional mono- or dual therapy with a non-cytosine NA. Eligible patients included all patients living with HIV (PLWH) seen at the Orlando Immunology Center between 8/13/13–11/22/14 switched to once-daily DCRs with ≥ 2 ARV drugs whose historical genotypes predicted that DTG alone or in combination with a non-cytosine NA were the only fully active ARV drugs in the regimen. Historical genotypes were discovered and reviewed during a routine clinic audit conducted in December of 2014, and due to the retrospective nature of the study, it is unknown whether they were available or assessed prior to switch. Historical genotypes included assays utilizing Sanger sequencing of protease (PR), reverse transcriptase (RT) and integrase and were performed 1–9 years (median 7) prior to switch. The Stanford HIV drug resistance database (HIVdb) algorithm was used to interpret drug resistance mutations from historical genotypes and make predictions about the activity of ARV drugs in the regimen . ARV druDemographics, laboratory values and clinical parameters were extracted from the charts of eligible patients during DCR treatment until 12/31/2018. Descriptions of adherence were summarized based on clinician documentation in the medical record. “Post-switch” genotypes obtained as a part of routine clinical care included genotypic assays utilizing both Sanger and Next-Generation Sequencing (NGS) of PR, RT, and integrase. Similarly, the HIVdb algorithm was used to interpret post-switch genotype results and predict whether any treatment-emergent drug resistance was present . The priDuring the study period, 559 treatment-experienced patients were switched to a DCR consisting of ≥ 2 ARV drugs. Based on available historical genotypes, 70/559 11%) were found to be on DTG functional mono-or dual therapy with a non-cytosine NA, however only 39/70 (56%) were eligible and had complete follow-up data (≥ two HIV-1 RNA measurements at least 4 weeks apart following switch) to be included in the study  of patients was 53 (40–74) years, 28 (72%) had baseline HIV-1 RNA < 50 copies/mL, and 11 (28%) had baseline HIV-1 RNA ≥ 50 copies/mL  patients achieved or maintained an HIV-1 RNA < 50 copies/mL, and 7 (18%) patients experienced persistent HIV-1 RNA ≥ 50 copies/mL. The median duration (range) of follow-up was 50 weeks (12–244). Eighty-nine percent (17/19) of patients treated with functional DTG monotherapy had HIV-1 RNA < 50 copies/mL compared to 75% (15/20) of those treated with functional dual therapy with DTG and a non-cytosine NA (7 on DTG/TDF and 8 on DTG/ABC)  had an HIV-1 RNA ≥ 50 copies/mL at baseline whereas 25/32 (78%) had an HIV-1 RNA < 50 copies/mL at baseline. All of these patients had a baseline M184V/I and 21/32 (66%) had ≥ 1 additional NRTI mutation. Twelve (37.5%) were switched from a dual NRTI plus boosted PI, 6 (19%) were switched from a dual NRTI + RAL, 4 (12.5%) were switched from a dual NRTI + NNRTI, 1 (3%) was switched from TDF/FTC/EVG/c, 1 (3%) was switched from DRV/r plus RAL and 8 (25%) were switched from ARV regimens containing ≥ 3 ARV drug classes. Medical records review revealed that “100% adherence” was documented on the study DCR for all 32 patients. After the study period ended, 7 patients on functional DTG dual therapy with a non-cytosine NA continued the study DCR, 2 patients on functional DTG dual therapy discontinued the study DCR but switched to a different DCR and 6 patients on functional DTG dual therapy discontinued the study DCR and switched to a regimen that did not contain DTG. Of those on functional DTG monotherapy, 10 continued the study DCR after the study period ended, 3 discontinued the study DCR but switched to a different DCR and 4 discontinued the study DCR and switched to a regimen that did not contain DTG. All patients who discontinued the study DCR (15/32) were virally suppressed (HIV-1 RNA < 50 copies/mL) at the time of switch and reasons for switch included resistance noted on historical genotypes in 12/15 and side effects in 3/15 .Of those with persistent HIV-1 RNA ≥ 50 copies/mL during the study, 2 were on DTG functional monotherapy, and 5 were on functional dual therapy (2 on DTG/TDF and 3 on DTG/ABC)  on DTG-based functional mono-or dual therapy achieved or maintained virologic suppression. All 32 suppressed patients had “100% adherence” documented throughout the study period and cumulatively these data suggest that the primary reason for persistent viremia in the patients discussed above was likely non-adherence. This is also supported by the fact that 4/5 non-adherent, persistently viremic patients had baseline HIV-1 RNA ≥ 50 copies/mL which likely indicates a history of non-adherence prior to study entry.Post-switch genotypes were only available for the 5 non-adherent patients with persistent viremia, and 4 of these were obtained on DTG. We observed no treatment-emergent NRTI or INSTI resistance, and 3/5 patients subsequently went on to achieve HIV-1 RNA < 50 copies/mL on a different DCR after discontinuation of the study regimen. One patient achieved HIV-1 RNA < 50 copies/mL on a non-DCR and the other was lost to follow up Table . Though Two persistently viremic patients were documented as 100% adherent, both were on functional dual therapy; one was on DTG/TDF and the other was on DTG/ABC. Both had baseline M184V/I without additional NRTI mutations. In the patient on DTG/ABC, the reduction in ABC susceptibility conferred by the M184V/I may have contributed to persistent viremia. However, in the other on DTG/TDF, this mutation is expected to increase TDF susceptibility and does not fully explain the inability to maintain virologic suppression. Baseline mutations may have contributed to persistent viremia in these cases; however, it is unknown how accurate their documented adherence patterns were and whether non-adherence may have also played a role.In 32/39 patients on DTG-based functional mono-and dual therapy, HIV-1 RNA < 50 copies/mL was achieved and maintained throughout the study period. All patients received DCRs with ≥ 2 ARV drugs, and though baseline resistance testing predicted either functional mono- or dual therapy, we acknowledge the possibility of partial activity from other ARV drugs deemed not fully active. This may explain the high virologic response rates observed in our study and the lack of treatment emergent INSTI resistance in those with persistent viremia due to “protection” of DTG by these partially active agents.10 of 4.2 copies/mL were randomized to switch to an optimized dual NRTI backbone plus lopinavir/r versus DTG [+ T-cell count of < 200 cells/mm3 and 82% had a baseline M184V/I mutation plus ≥ 1 additional NRTI RAM. At Week 48, virologic suppression was observed in 84% treated with a DTG-based regimen versus 70%% treated with a lopinavir (LPV)/r-based regimen, and treatment-related adverse events occurred in 16% treated with DTG versus 38% treated with LPV/r [Overall, these results deepen our knowledge about the efficacy of DTG when used in combination with 0–1 fully active ARV drugs. Given the increased global use of DTG in settings where resistance testing and complete ARV drug histories may be inaccessible, these data provide reassurance that most patients on DTG-based functional mono-or dual therapy will achieve virologic efficacy. This is especially relevant in LMICs where DTG is being used in second- and third-line ARV regimens to treat those failing first line NNRTI-based regimens. In July of 2018, the World Health Organization (WHO) published updated HIV treatment guidelines which recommended DTG in combination with an optimized NRTI backbone as a preferred option for PLWH in whom non-DTG based regimens were failing . This gursus DTG . At baseth LPV/r . Subgrouth LPV/r . In DAWNth LPV/r .+ T-cell count was 542 cells/mm3 which may be significantly higher than CD4+ T-cell counts among failing patients in LMICs, all patients in our cohort had Clade B HIV-1 virus whereas different HIV subtypes are more common globally and our study predominantly consisted of Caucasian men whereas international populations may contain greater numbers of women and individuals of Black or African descent. However, in both our study and the DAWNING trial, high adherence was reported among patients achieving virologic efficacy on DTG-based functional mono-or-dual therapy [Our data reveals similar efficacy of DTG-based regimens in the setting of functional mono-or dual therapy which may be common in LMICs among patients failing a first-line regimen given the lack of access to resistance testing outside of a randomized clinical trial . However therapy  and overIn our cohort, virologic suppression was observed among 82% of patients, all of whom had a historical M184V/I mutation and in the DAWNING study, 84% of those in the DTG arm achieved virologic suppression despite 71% of these patients having a baseline M184V/I. To date, several studies have evaluated the efficacy of DTG/3TC in the setting of pre-existing NRTI resistance including among those with an M184V/I mutation. A subgroup analysis of the TANGO study demonstrated no impact of archived NRTI resistance on virologic outcomes through Week 48 with 4/4 patients found to have an archived M184V/I mutation achieving virologic suppression . SimilarAmong our study participants, 72% were suppressed at baseline prior to DCR switch however due to the retrospective nature of the analysis and implementation of a different electronic medical record (EMR) prior to study start, we were unable to accurately calculate duration of viral suppression for patients in our cohort. This has important implications as prior data has demonstrated that duration of viral suppression is associated with lower VF rates in patients with both previous treatment failure and HIV drug resistance –26. The Limitations of this study include a small sample size, the retrospective nature of the analysis, the lack of control group, possible inaccuracy of documented information, and that data are from a single center in the Southeastern United states. Our cohort also predominantly consisted of Caucasian men which limits generalizability to other populations living with HIV and implementation of the current electronic medical record (EMR) version occurred in January of 2013, hence some data prior to this date were not readily available. Though historical genotype results had been scanned in for all patients, we did not have access to many other historical laboratory values which limited our ability to describe certain characteristics that may have impacted interpretation of our study results.Despite these limitations, this is the first report of virologic outcomes of patients treated with DTG-based functional mono-and-dual therapy from a US cohort and provides valuable insight into the efficacy and barrier to resistance of DTG-based treatment strategies with fewer ARV drugs.


Immediate initiation of antiretroviral therapy (ART) for all people living with HIV has important health benefits but implications for the economic aspects of patients' lives are still largely unknown. This stepped-wedge cluster-randomized controlled trial aimed to determine the causal impact of immediate ART initiation on patients’ healthcare expenditures in Eswatini. Fourteen healthcare facilities were randomly assigned to transition at one of seven time points from the standard of care (ART eligibility below a CD4 count threshold) to the immediate ART for all intervention (EAAA). 2261 patients living with HIV were interviewed over the study period to capture their past-year out-of-pocket healthcare expenditures. In mixed-effects regression models, we found a 49% decrease  in past-year total healthcare expenditures in the EAAA group compared to the standard of care, and a 98%  decrease in spending on private and traditional healthcare. Despite a higher frequency of HIV care visits for newly initiated ART patients, immediate ART initiation appears to have lowered patients’ healthcare expenditures because they sought less care from alternative healthcare providers. This study adds an important economic argument to the World Health Organization’s recommendation to abolish CD4-count-based eligibility thresholds for ART.The online version contains supplementary material available at 10.1007/s10461-021-03241-9. Since 2015, the World Health Organization (WHO) consolidated guidelines on the use of antiretroviral drugs endorse immediate ART initiation  for all adults, adolescents, and children living with HIV, irrespective of their CD4 cell count or disease stage .While recent epidemiological evidence points to substantial health benefits associated with immediate ART initiation, –6 its imGiven this important economic burden on patients living with HIV and that patients’ out-of-pocket healthcare expenditures are a major source of health system financing,  the impaTo answer this question, we conducted a stepped-wedge cluster-randomized controlled trial of the “Early Access to ART for All” (EAAA) programme in Eswatini. Eswatini faces the world’s highest HIV prevalence . Women aThe trial  and thisThe study was carried out in the Hhohho Region of Eswatini (known as “Swaziland” until April 2018), located in the North-Western part of the country. Study sites were 14 government-managed health facilities with varying volumes of patients . At the study’s outset, all health facilities were providing comprehensive HIV care and treatment according to the national adult HIV treatment guidelines.The study was conducted over the course of three years and used a stepped-wedge randomized trial design across fourteen government-managed health facilities. Prior to randomization, health facilities were grouped into seven pairs according to geographic proximity and catchment size. Six pairs of health facilities were cluster-randomized into one of seven sequences. Each facility pair thus transitioned sequentially from the standard of care (control condition) to "Early Access to ART for All" (EAAA) (treatment condition) over the course of three years, namely from September 2014 to August 2017  who were aged 18 years or older were eligible with the exception of pregnant or breastfeeding women and those unable to give informed written consent due to cognitive impairment. For each facility, data collection days were randomly selected. The timing of data collection visits thus determined whether patients were interviewed during the standard of care phase or after roll-out of the EAAA intervention in their respective clinic. In each facility, patients were approached during their clinic visits and asked to participate in patient exit interviews. The study team was instructed to recruit the next patient entering (rather than exiting) the consultation room so as to avoid an over-representation of patients who spend more time with clinicians . Prior tThe sample size for patient exit interviews was determined by funding and feasibility constraints. To determine the statistical power of our analyses (after data collection was completed), we conducted simulation-based power calculations in R using the “SWSamp” package . The simThe primary outcome for this economic evaluation were the total private healthcare expenditures in the 12 months preceding the interview. These were composed of hospitalization co-payments and out-of-pocket expenditures for travel, food, communication, and potential childcare costs, reported for any clinic visit or hospital stay in the past 12 months. Total costs further included past-month expenses for treatment and care associated with the utilization of public sector ART clinics, private clinics, and traditional healers. These costs were summed and multiplied by 12 to compute total past-year healthcare expenditures. Lastly, we captured costs incurred for the clinic visit on the day of the interview, also inquiring whether any income losses occurred due to missing work on the day of the clinic visit. Reported out-of-pocket costs for the current visit were also added to the total past-year count of healthcare expenditures. All expenditures were based on patients’ self-reports and noted down in Lilangeni (SZL). In the results section, expenditure estimates are translated into USD. Conversions are based on the currency exchange rate averaged over the three-year study period from September 2014 to September 2017. The questionnaire is provided in supplementary file VIII.We estimated the intent-to-treat (ITT) effect based on the exposure status of the health facility at the point in time at which the patient was interviewed  pre-ART patients, (b) initiating ART patients, and (c) patients on ART. Subsequently, we determined the observed healthcare expenditures for patients in both study arms based on the self-reported frequency of clinic visits and costs of the pre-ART or ART care visit on the day of the interview. Second, we investigated whether possible changes in a patient’s health status due to EAAA may be responsible for differences in private healthcare expenditures between the study groups by comparing the overall health status between participants interviewed in the control versus the intervention phase. While medical records were not assessed, health status was captured via respondents’ self-reports based on a single question asking about their “overall health during the past two weeks”, with response options ranging from "very good" to "very poor" on a five-point Likert scale. Third, we examined whether EAAA may have led to changes in care-seeking from healthcare providers other than public ART services by analyzing possible differences in usage of private and traditional healthcare services between participants in the control and intervention phase.Fourteen healthcare facilities (“clusters”) were enrolled into the trial and 2261 participants were interviewed over the duration of the study. The mean number of participants approached at each time step varied from three participants to 91.5 participants, with a mean of 20.5 participants per facility and sequence  and the mean age was 38.4 years  and 0.83 USD (IQR: 0.38 to 2.12 USD)  in their total past-year healthcare expenditures relative to the standard of care group  versus 3.96 USD (95% CI 3.44–4.47 USD) under EAAA and the standard of care, respectively, based on the distribution of ART-initiating to pre-ART and ART patients in each study phase . When additionally using the self-reported past-month frequency of ART visit attendance to take into account that some patients miss visits and that this non-attendance varies by patient type , we estimate that patients incur a mean yearly healthcare expenditure of 3.42 USD (95% CI 3.00–3.84 USD) and 2.84 USD (95% CI 2.50–3.17 USD) under EAAA and the standard of care, respectively. Once all patients living with HIV in EAAA have been on ART for at least 6 months, the corresponding yearly expenditure would only be 3.37 USD (95% CI 2.95–3.78 USD) under EAAA. These projections are thus at odds with out empirically observed results, which reveal higher yearly healthcare costs in the standard of care group.We did not find evidence of significant differences in illness levels between both groups , which could explain differences in healthcare expenditures between study arms.Patient-borne expenditures on care-seeking from private doctors and traditional/faith healers were significantly lower in the EAAA than in the standard of care group. The relative effect size varied from 94 to 98% lower healthcare expenditures in the EAAA intervention group relative to the standard of care group, depending on the regression model used  declares financial risk protection as one of the key dimensions of universal health coverage. Out-of-pocket healthcare expenditures are considered as catastrophic according to two alternative SDG thresholds: 10% and 25% of total household consumption . Using h workers , mobile  workers , 41 as wWhile this paper focused on the effect of EAAA on patients’ health expenditures, universal test-and-treat programs may have substantial welfare benefits in addition to reducing health expenditures. As reported in separate manuscripts , 43 we dThis study has several limitations. First, this study was only able to assess the impact of EAAA on patients’ healthcare expenditures over a relatively short time horizon. Second, all pre-ART patients were initiated on ART as a facility transitioned to EAAA. The distribution of ART-initiating to more “established” ART patients is, therefore, likely higher in this study than it would be after several years of EAAA implementation. Given that ART-initiating patients had higher healthcare expenditures than did those who were on ART for at least six months, the observed absolute expenditure level in the EAAA arm in this analysis is likely higher than expenditures would be after several years of EAAA implementation. It is, thus, likely that the difference between expenditures under EAAA compared to the standard of care would have been higher if our study had continued for a longer time. Third, other than patients’ self-reported health status, the study did not collect any medical data such as CD4 count levels or viral loads in this sample, largely for reasons of confidentiality. It was therefore not possible to conduct heterogeneity analyses to test whether healthcare expenditures were particularly high among standard of care group participants with potential opportunistic infections and CD4 counts close to (but above) the treatment cutoffs. Fourth, since our recruitment strategy excluded pregnant and breastfeeding women, we were unable to assess whether early access to ART reduced mother-to-child HIV transmission and the economic benefits to women and their households of averting vertical transmission. However, the rate of vertical HIV transmission in a national sample of 18–24-month-old children in Eswatini was below 5%  suggestiImmediate ART initiation for all patients living with HIV has the potential to reduce HIV incidence and decrease HIV-related mortality and morbidity. This study adds important new evidence to this body of literature by revealing additional economic benefits. Specifically, immediate ART for all in Eswatini decreased patients’ healthcare expenditures, most likely by reducing care-seeking from traditional and private healthcare providers. Along with recent encouraging findings on the benefit for HIV incidence , this stSupplementary file1 (DOCX 570 kb)Below is the link to the electronic supplementary material.


Integrase inhibitors (INIs)-based antiretroviral therapies (ART) are more recommended than efavirenz (EFV)-based ART for people living with HIV/AIDS (PLWHA). Yet, the advantage of integrase inhibitors in treating TB/HIV coinfection is uncertain. Therefore, the objective of this systematic review is to evaluate the effects and safety of INIs- versus EFV-based ART in TB/HIV coinfection, and demonstrate the feasibility of the regimens.+ cell counts change from baseline, adherence and safety.Four electronic databases were systematically searched through September 2020. Fixed-effects models were used to calculate pooled effect size for all outcomes. The primary outcomes were virologic suppression and bacteriology suppression for INIs- versus EFV-based ART. Secondary outcomes included CD4+ cell counts increase between the two groups was 14.23 cells/μl (95% CI 0− 6.40 to 34.86). With regard to safety , and death), INIs-based regimen was broadly similar to EFV-based regimens. The analytical results in all sub-analyses of raltegravir- (RAL) and dolutegravir (DTG) -based ART were valid.Three trials (including 672 TB/HIV patients) were eligible. ART combining INIs and EFV had similar effects for all outcomes, with none of the point estimates argued against the INIs-based ART on TB/HIV patients. Compared to EFV-based ART as the reference group, the RR was 0.94 (95% CI 0.85 to 1.05) for virologic suppression, 1.00 (95% CI 0.95 to 1.05) for bacteriology suppression, 0.98 (95% CI 0.95 to 1.01) for adherence. The mean difference in CD4This meta-analysis demonstrates similar efficacy and safety of INIs-based ART compared with EFV-based ART. This finding supports INIs-based ART as a first-line treatment in TB/HIV patients. The conclusions presented here still await further validation owing to insufficient data.The online version contains supplementary material available at 10.1186/s12981-021-00348-w. Tuberculosis (TB) is the most common opportunistic infection in people living with HIV/AIDS (PLWHA) and has significant regional differences, especially in resource-limited countries. TB is also one of the main causes of death of PLWHA , 2. HIV + cell counts and high HIV viral loads. TB/HIV patients require co-treatment for both diseases, in particular for the TB [People with TB/HIV co-infection typically present with low CD4r the TB . During r the TB . Among tRifampicin (RIF), the standard TB treatment regimen of four chemical drugs, remains the first choice, irrespective of the patient’s HIV status . AlthougIntegrase inhibitors (INIs), mainly include raltegravir (RAL) and dolutegravir (DTG), exhibit good efficacy and safety, and are superior to PIs in terms of durability . Since tThe study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines .PubMed, Medline, Embase, and Cochrane Library until 17 September 2020 were systematically searched. Studies were limited to the English language. Using the following keywords: ‘tuberculosis’, ‘raltegravir’, ‘dolutegravir’, and ‘integrase inhibitor’. We used the names of two available INIs drugs as keywords, as both drugs are the primarily recommended drugs.RCTs that compared ART in INIs- with EFV-based, in TB/HIV patients with treatment-naïve, and evaluated at least one outcome of effectiveness and/or safety. The INIs included DTG and RAL, while EFV-based ART was the preferred therapeutic regimen. All patients received a standard tuberculosis treatment regimen with isoniazid, rifampicin, pyrazinamide, and ethambutol for the first 2 months, followed by isoniazid and rifampicin for the subsequent 4 months. Rifampicin was given at a dose of 10 mg per kg per day. In case of extrapulmonary TB, the duration of the maintenance regimen was extended. Antiretroviral treatment was started after 2–8 weeks of TB treatment.We ignored results with a follow-up length shorter than 48 weeks (e.g. 24 weeks), which was not sufficient for evaluating clinically significant outcomes for intervention. The timeframe was applied in the previous systematic reviews on HIV treatment . If the After removal of duplicates, all studies identified in the search were screened by title and abstract by two independent reviewers (YS and ZD), then full-texts were reviewed to determine eligibility. All the incongruity was resolved by group discussion or a third reviewer (CQ).+ cell counts, viral load); and (3) result at the end of the study.Data extracted included: (1) research characteristics ; (2) patient demographics  and baseline characteristics , drug-related AEs, discontinuation for drugs, grade 3–4 AEs, IRIS (grade 3–4), and death during the 48 weeks.+ cell counts) in this systematic review, for efficient merging, the median and interquartile range (IQR) were converted into mean and standard deviation (SD) [EFV-based ART was used as the reference group in the meta-analysis. For continuous outcomes  , 36. A d2 statistic. To account for the heterogeneity across the studies, the fixed-effect model was used to combine the effect estimate from included studies.Statistical heterogeneity among the studies was measured by the Cochrane Q test and IThe possibility of publication bias estimated by funnel plots was not performed, because the number of studies included in the meta-analysis was fewer than 10. In such a case, the funnel plots could yield misleading results and therefore were not recommended.All data analyses were performed with Review Manager 5.4 .The flow chart summarized the detailed retrieval steps Fig. . We initThe main features of the included studies are summarized in Additional file + cell counts from baseline to Week 48 was 201.2 cells/μl for the INIs group and 184.3 cells/μl for the EFV group [mean difference 14.23 cells/μl (95% CI -6.40 to 34.86), Fig. None of the INIs-based group was significantly less than any of the EFV-based group on any of the efficacy outcomes assessed Table . As showThe occurrence of all AEs was similar in patients between the two groups Table . CompareSince publication bias was hard to detect when the number of studies was small, publication bias was not examined.This meta-analysis pooled data from 3 trials, showing that in TB/HIV patients, the effects of INIs-based ART was non-inferior to EFV-based ART. Two primary efficacy outcomes (virologic and bacteriology suppression) were effectively controlled. Prespecified subgroup analyses suggested that these results were robust in DTG- and RAL-containing ART. Two rospective cohort studies , 44 were+ recovery compared with EFV. INIs had the trend of increasing in CD4+ cell counts  when compared with EFV was observed in the present study, but there was no statistically significant difference. This finding was similar to the outcomes in cohort studies [We also had several key secondary findings. First, as PLWHA without infection TB , INIs ha studies . However studies . More da studies . This mi studies . Besides studies  showed RSince more combinations of anti-TB and antiretroviral drugs are being used, the drug toxicity in TB/HIV patients could be of concern. The incidences of AEs in both groups were high, and the main adverse events were serious (grade 3–4). Unexpectedly, the drug-related adverse events were relatively rare. INIs-based ART can achieve fast decrease of the HIV viral load, which gives high expectations regarding immune activation or inflammation recovery. But there is also concern that the drugs may lead to an increased rate of IRIS . ActuallMultiple systematic reviews –52 showeThis meta-analysis had a few limitations. Firstly, the number of included studies was very small. We were unable to perform certain subgroup analyses such as the race, since the results have not reported in individual studies. It restricts the generalizability of these results but not their validity. Secondly, patients with ART-experienced were not included in the analysis due to the insufficient study data. We were unable to assess the efficacy in TB/HIV patients who were switched  from an EFV to an INIs regimen. Finally, we could not rule out the possibility of publication bias due to the small number of studies.In this meta-analysis, the effects of INIs-based ART are equivalent to EFV-based ART in treatment-naïve of TB/HIV patients. Our finding supports recommending INIs-based ART as first-line treatment in TB/HIV patients, especially under the current guidelines. We hypothesize that INIs-based ART may be more favorable than EFV-based ART, according to the evidence from studies of PLWHA without TB infection. After these ongoing studies  are compAdditional file 1: Table S1. Main characteristic of included studies.Additional file 2: Fig S1. Risk of bias graph: Quality assessment about each risk of bias item.Additional file 3: Fig S2. Risk of bias summary: Judgment of the risk of bias for each included study with Cochrane quality assessment tool.


We assessed the prevalence and factors related to the time to antiretroviral (ART) initiation among persons who entered HIV care and subsequently started ART in Croatia from 2005 to 2014. Included were patients ≥ 18 years, the follow-up ended on Dec/31/2017. 628 patients were included into the study 91.9% were men; median age was 36.1 (Q1–Q3: 29.6–43.8) years. Rapid (within 7 days of diagnosis) ART initiation was observed in 21.8% patients, 49.8% initiated ART within 30 days, 21.7% and 28.5% had intermediate (31 days–1 year) and late initiation (> 1 year), respectively. Of 608 patients that achieved an undetectable viral load, 94% had a plasma HIV-1 RNA < 50 copies/ml at last measurement after a median follow-up of 5.2 years. On quantile regression analysis, calendar year of entry into care, and markers of more advanced HIV disease  were significantly associated with earlier ART initiation. Early ART was not related to a gap in care afterwards at all quantiles. In conclusion, a significant proportion of patients started ART early in Croatia in 2005–2014. Early ART initiation led to durable viral load suppression and was not associated with a subsequent gap in care. The landmark START trial2 in conjunction with other randomized trials3 and observational studies5 led to a policy change in 2015 by recommending ART for all patients regardless of the CD4 cell count6. Another WHO update in 2017 recommended rapid initiation (within 7 days of diagnosis) of ART to indicated, willing patients7. These guidelines also raised concerns over the elimination of the series of standard counseling sessions preceding ART due to a possibility of resulting physical or psychological harm and potential non-adherence7. The 2020 European AIDS Clinical Society guidelines also mention the importance of rapid ART initiation but emphasizes patient understanding and readiness to begin, as do current U.S. Department of Health and Human Services recommendations9.Guidelines concerning antiretroviral therapy (ART) initiation have evolved over the past decade. While there was a consensus that ART should be started as soon as possible in patients with clinical AIDS, a CD4 cell count threshold for ART initiation has been debated since the introduction of modern ART in 1996. In 2010 WHO recommended ART for patients with a CD4 cell count beneath 350 cells/µL10. This policy is linked to faster viral suppression for people living with HIV (PLWH) which also means that the risk of onward transmission can be greatly reduced10. Another consideration in rapid ART is the feasibility of implementation. Retrospective evaluation of rapid-start ART in community settings at risk for loss to follow-up, comorbidities, and other vulnerabilities show that implementation is possible and successful in these instances12. Even in the setting of high HIV prevalence communities experiencing a variety of health care challenges, the goal of reducing time to ART initiation from diagnosis is achievable11. However, a recent study from the French Dat’AIDS cohort examining patients diagnosed with HIV between 2010 and 2015 reported that a longer time between first encounter and first ART prescription was associated with a better 1-year retention and higher viral load suppression at 6 months13.Several low- and middle-income countries have introduced rapid ART initiation as a means to address the challenge of follow-up loss and late patient presentation to careIn the era before universal ART, data on the timing of ART initiation from a patient’s documented HIV infection or first clinical visit was generally not highlighted and seldom reported. The aim of our study was to examine the timeliness of ART initiation among persons who entered HIV care in Croatia from 2005 to 2014. We sought to identify factors associated with differences in timing of ART.3 at inclusion into care ART initiation within 30 days of HIV diagnosis was observed in 40 (16.4%), it was more frequent in the period 2012 to 2014  compared to the period 2005 to 2011 . Median time from confirmed HIV test to first clinical visit was 7 (Q1–Q3: 2–15) days; this integration into care was within 7 days in 339 (54.0%) and within 1-month in 540 (86.0%) patients.A total of 628 patients were included into the study with a total of 4333.0 years of follow-up, of which 3684.9 (85%) years of follow-up were after ART initiation. The median follow-up time per person was 6.7 (Q1–Q3: 4.3–9.5) years and the median time on ART was 5.4 (Q1–Q3: 3.5–8.2) years. The main characteristics of our study population are presented in Table The median time from HIV diagnosis to ART initiation was 31 days , decreasing by 77.8% from the period 2005–2008 to 2012–2014 Table . About 2In patients entering care between 2005 and 2008, the median time from the first clinical visit to ART initiation was 1.3 months (41 days) . Patients from 2009 to 2011 had a median time from HIV diagnosis to ART initiation of 1.0 months (Q1–Q3: 0.3–16.9 months) and 0.5 months (14.5 days) from first clinical visit to ART initiation . Patients in the most recent studied time period, 2012–2014, had the earliest initiation of ART, the median time from diagnosis to ART initiation was 0.6 months (18 days)  and 0.2 months (6 days)  from the first clinical visit.The proportion of patients starting ART from the date of first clinical visit follows the pattern of the time from HIV diagnosis to ART initiation Fig. b. MedianWe estimated the time from HIV diagnosis to reaching undetectable (< 50 copies/mL) HIV-1 RNA by the Kaplan–Meier product-limit survival estimates. Overall, of 628 patients 608 (96.8%) became undetectable during follow-up. Of the 20 who did not, 15 died and 5 were lost to follow-up (LTFU). The median time to reach an undetectable viral load (VL) was 9.6 months (95% CI 7.9–10.6) for the whole study population Fig. c, timingVirological failure, defined as one or more plasma HIV-1 RNA measurement > 1000 copies/ml, was observed in 92 15.3%) of 601 patients who had a viral load test done 6-months after ART initiation  had < 50 copies of HIV-1 RNA per ml at the last viral load measurement . Of the whole study population (N = 628), 574 (91.4%) had < 50 copies of HIV-1 RNA per ml at the last viral load measurement after a median of 5.1 (Q1–Q3: 3.2–7.9) years of follow-up.In our cohort, 120 patients (19.1%) experienced at least 1 gap of > 12 months in care, 28 (4.5%) had ≥ 2 gaps and 9 (1.4%) had ≥ 3 gaps in care over their follow-up period. After the first gap 85.0% (102/120) patient had a subsequent visit. After the last gap, altogether 26 of 120 (21.7%) patients had no subsequent visit within 12 months till the end of follow-up and were considered LTFU. Of the 120 persons with a gap in care, 62 (51.7%) had a gap after and 49 (40.8%) before ART start; nine (7.5%) had both a gap before and after ART start.There was a total of 159 episodes of gaps with a median length of 579 days (Q1–Q3: 415.0–1099.0 days). There were 76 episodes (11.7 per 100 patient years of follow-up) of gap before ART initiation and 83 (2.2 per 100 patient years of follow-up) after ART initiation. The rate ratio suggests that a gap before ART initiation was 5.2 times more likely than a gap after ART initiation (95% CI 3.8–7.1).vs not MSM), age and place of residence (Zagreb vs outside of Zagreb) did not have a significant impact on time of ART initiation. MSM had a somewhat longer time to ART initiation than non-MSM but this was significant only at the 60th and 65th quantile  times later than those with < 200 CD4 cells per mm3. Also, persons with clinical AIDS started ART later in comparison to persons with CD4 count < 200/mm3, with an increasing difference from low to high quantiles, at the 75th quantile, ART was initiated 2.6 (95% CI 1.8–3.5) times later. The analysis was also adjusted for the time to integration into care, and as expected integration into care was associated with later ART initiation at all quantiles. The effect of integration into care was more pronounced at lower quantiles.Higher viral load also resulted in earlier ART initiation. At the 50th quantile an increase of one unit (log10) of viral load resulted in 46.5% (95% CI 33.2–57.2) earlier ART initiation. Among persons with no clinical AIDS, those with CD4 count ≥ 200/mmarXiv:2010.00740) showed that the percentage of MSM on ART within 180 days of diagnosis increased from 34.7% in 2008 to 84.5% in 2016 and 91.0% in 2018. The North American AIDS Cohort Collaboration on Research and Design study group recently reported that the median days from entry into care to ART prescription was 69 days in 2005, 29 days in 2012, and 6 days in 2018. In 2018, 35% of participants entering HIV care were prescribed ART the same day14. Many reports from cohorts, clinic-based or program-based sites have published trends of shorter times to ART initiation in more recent years22 particularly after 2015 when “treat all” policy was introduced by WHO6.We report on Croatian national data on time from HIV diagnosis to ART initiation for the period 2005 to 2014. The time from diagnosis to ART initiation decreased by 77.8% through the study periods and the overall median time from diagnosis to ART initiation was 31 days. The time from HIV diagnosis to first clinical visit also decreased and it was the shortest in 2012–2014 with a median of 7 days. There are very few national estimates on time from HIV diagnosis to ART initiation. In a population-based probability sample of HIV-infected adults receiving medical care in the United States (May 2004–April 2009) the median time to ART initiation was 10 months. A recent report from England available at a preprint server  counterparts. Heterosexual mode of transmission is associated with more advanced HIV disease at diagnosis in Croatia25. Still, the question on how quickly ART should be initiated after the confirmed or even suspected HIV diagnosis has been of major focus in recent years. Several randomized trials showed that rapid ART (including the same day of diagnosis) could improve patient outcomes by reducing loss to care and more rapidly achieving an undetectable viral load and thus reducing the possibility of onward HIV transmission33. Rapid ART initiation could also decrease health costs34. On the other hand, a study on the Dat'AIDS cohort showed that a longer period of time between first clinical visit and ART initiation was associated with a better 1-year retention in care13. In our study, the gap in care after early ART initiation was as frequent as in those starting ART later.The overall linkage to care in our study was within 7 days from HIV diagnosis in 54.0% and within 30 days in 86.0%, which is higher than reported in some other studiesWe used quantile regression in our analysis which is not frequently used to describe associations. The results of quantile regression are interpreted in a similar way to ordinary least squares regression, however unlike predicting the mean, quantile regression is performed at different quantiles of the dependent variable. So, this method provides a more detailed analysis of associations between variables and could be used in studies examining the timeliness of ART initiation.7 which requires two measurements. Confirmation was not required for the definition of virologic failure because of less frequent viral load monitoring, and this is also why did not use other definitions of virological failure (for example confirmed > 50 or > 200 HIV-1 RNA copies/ml). Nevertheless, as the majority of patients who failed were resuppressed to < 50 copies/ml the choice of virologic failure cut-off seems not to be of critical importance for our analysis.The inability to establish causation is a limitation of our observational study. For example, while a delay in ART initiation might cause a gap in care, this delay might also be just a consequence of the gap caused by some other factor. Nevertheless, it is encouraging that early ART initiation, without extensive counseling did not result in worse retention in care and did result in achieving a more rapid viral load suppression. While early ART initiation was initially motivated by having a subsequent visit for patients not living in Zagreb, it has been slowly adopted for all patients. Another concern is measuring time to viral suppression which is dependent on the frequency of viral load measurement, so the true time of becoming undetectable is unknown. For example, in our study the time to ART initiation decreased over time by 77.8% whereas the time to reaching an undetectable viral load decreased by 27.7%. We presented our data on durability of VL by the date of last measurement and not by a certain number of years after ART initiation. This has been done because patients might have regular ART refills at the hospital pharmacy and no viral load measurement. However, since the median time of last viral load measurement from ART initiation was quite long for rapid ART starters (> 6.0 years), we believe that we did provide data suggesting durability of VL suppression in those who start ART rapidly. Virologic failure was defined by a single plasma HIV-1 RNA > 1000 copies/ml which is more stringent that the current WHO definitionIn conclusion, our study adds to the growing data of feasibility and beneficence of early initiation of ART and questions the need of extensive counseling prior to ART initiation. Our data support current HIV care guidelines emphasizing early ART initiation. Earlier initiation of ART was not associated with a more frequent subsequent gap in care and our findings also suggest that early ART initiation may have favorable long term virologic outcomes.36. HIV resistance testing is also available but not regularly performed unless in the event of drug failure. The UHID pharmacy dispenses ART drugs for all PLWH and clinicians verify that the patient has the drugs before he or she leaves the hospital. Since 1997, patient information has been kept in an electronic database which catalogues demographic data, dates of clinic visits, prescriptions of ART drugs, CD4 counts, viral load measurements, and other biochemistry tests.Croatia has a centralized system of HIV care, and all Croatian citizens have universal health insurance. All PLWH are treated at the University Hospital for Infectious Diseases (UHID) in Zagreb where they receive regular clinical medical evaluations, including measurements of CD4 cell counts and HIV-RNA viral load35. This means that many patients at the UHID receive ART prescriptions for longer periods of time, usually six months. In a typical case, patients begin ART with a month-long prescription, then the next prescription is for two months and then for three. Three-month long ART prescriptions last until the physician is comfortable with providing the patient ART drugs for six months35. This is common when the HIV infection is well controlled and the patient requires clinical examination once or twice per year.For patients living outside of Zagreb, the centralized care system means that they must travel to the city for receiving HIV care and treatment and for many the journey may be lengthy or difficult. This led UHID physicians to adopt a policy of reducing appointment frequency when feasibleWe utilized anonymized data from the electronic UHID database. The cohort was comprised of Croatian citizens or permanent residents at least 18 years of age who arrived to the UHID for HIV treatment between 2005 and 2014 and had not yet received HIV care elsewhere. Pregnant women were excluded from the study. A total of 628 persons who initiated ART were included in the study cohort. The flow diagram for selecting the study cohort is shown in Fig. The date of HIV diagnosis was defined as the date when blood was drawn for confirmatory testing. The date of a patient’s first clinical visit was considered the starting date of care when a CD4 cell count and viral load was measured. The follow-up ended on December 31, 2017. Patients were censored at the date of their death, relocation from Croatia, or their LTFU. They were considered to have a gap in care if more than one year passed without follow-up. Patients with a gap in care were also considered LTFU if they were alive and living in Croatia and had no outpatient visit for more than 12 months without returning by December 31, 2017.The study was approved by the Ethics Committee of the University Hospital for Infectious Diseases (UHID), Zagreb, Croatia. The study was performed in accordance with the Declaration of Helsinki and Code of Medical Ethics and Deontology of the Croatian Medical Chamber. Written informed consents was obtained from all participants included in this study.HIV viral load was determined by various methods: the Cobas AmpliPrep Cobas Amlicor HIV-1 Monitor Test, Version 1 (lower detection limit 200 copies/ml), the ultrasensitive Amplicor HIV-1 Monitor test (lower detection limit 50 copies/ml), the Cobas Ampliprep/Cobas Taqman HIV-1 test, v2.0 (detection limit 20 copies/ml), all from Roche Molecular Systems, Branchburg, NJ and the Abbott RealTime HIV-1 Viral Load assay (detection limit 40 copies/ml). The Cobas AmpliPrep Cobas Amplicor HIV-1 Monitor Test, Version 1 and the ultrasensitive Amplicor HIV-1 Monitor test were used till the end of 2015. The Cobas Ampliprep/Cobas Taqman HIV-1 test was used from September 2009 till the end of study (December 2017) and the Abbott RealTime HIV-1 Viral Load assay from November 2011 till end of study.38. Virologic failure was defined as a single HIV-1 RNA of > 1000 copies/ml at any time after 6 months of ART. Clinically relevant resistance to NRTIs, NNRTIs or PIs was evaluated with Stanford University HIV Drug Resistance Database, Genotypic Resistance Interpretation Algorithm and IAS Drug Resistance Mutation list. A patient was considered to have virological failure with resistance if he harbored at least one mutation from the abovementioned algorithms.HIV resistance testing was done with HIV-1 sequencing using the TRUGENE HIV-1 Genotyping Kit  or by Sanger sequencing as previously described5 copies/mL), residence in or outside of Zagreb, whether or not clinical AIDS was present, presence of hepatitis B antigen or hepatitis C antibody positivity at inclusion into care, initial ART type, and year of entry into care. We also assessed the durability of viral load suppression by the proportion of persons with plasma HIV1-RNA < 50 and < 200 copies/ml at last follow-up measurement.The time from HIV diagnosis to ART initiation was categorized: within 7 days (“rapid”), from 8 to 30 days (“early”), from 31 days to one year (“intermediate”), and more than one year (“late”). We assessed how ART initiation timing periods were related to the following: gap in care, gender, transmission mode, CD4 count (cells per µL), HIV-RNA viral load (categorized as greater or less than 10We present our data on the study population by frequencies and percentages or median with first and third quartiles (Q1–Q3). Trends in the timeliness of ART initiation were examined by the Cochran-Armitage test. The Jonckheere-Terpstra test was used for comparison of doubly ordered variables, and the Wilcoxon-Mann–Whitney test was used for comparison of groups with continuous or ordinal variables. The incidence of gap in care before and after ART initiation was assessed by the Poisson method. Kaplan–Meier estimators were used to measure time from HIV diagnosis to antiretroviral treatment initiation and to viral suppression defined as a viral load < 50 copies/mL. Patients were censored if death (n = 15) or lost to follow-up (n = 5) occurred before reaching an undetectable viral load.3 and no clinical AIDS, (2) clinical AIDS regardless of CD4 count and (3) CD4 cell count ≥ 200 per mm3 and no clinical AIDS. Other variables included into the model were gender, residence (living in Zagreb vs outside of Zagreb), and transmission risk (MSM vs not MSM).We also conducted quantile regression analysis to study factors related to ART initiation with gap in care considered the major independent (predictor) variable. Gap in care was categorized as no gap, gap before ART, and gap after ART start. Persons with both gap before and after ART start were excluded (n = 9), so this analysis included 619 participants. The time from HIV diagnosis to ART initiation was the outcome variable (log months). Age, viral load (log10) calendar year and time to integration into care (log days) were modeled as continuous predictor variables. There were concerns about collinearity between the CD4 cell count and clinical AIDS, so we categorized those variables into three categories: (1) CD4 cell count < 200 per mmQuantile regression has the advantage to provide a more exact description of the distribution of the determinants of time to ART initiation at different quantile (percentile) levels. The coefficients were estimated for each 5 percentiles from 5 to 95th quantile of time to ART initiation. Standard errors and 95% confidence intervals (CI) were estimated using resampling with 1000 repetitions. The coefficients for each quantile were plotted as well as their 95% CI. We used SAS software system release 9.4  to perform the analyses. Two-sided P-values < 0.05 were considered significant.


To investigate the durability of the first integrase inhibitor-based regimen in a HIV geriatric multicentric prospective cohort and to explore the reasons of regimen discontinuation.This is an analysis conducted on the Geriatric Patients Living with HIV/AIDS (GEPPO) cohort, an Italian prospective observational multicentre cohort of people living with HIV with 65 years of age or more.The analysis was performed using R (version 4.0.2). The tests performed were two sided assuming a 5% significance level . The proportion of participants discontinuing the three regimens was displayed using cumulative curves.Among 1531 patients enrolled between 2017 and 2019 in the GEPPO cohort, we included 822 participants in this analysis. At baseline, median age was 69.8, the immunovirological profile good, multimorbidity was present in 42.3% of participants, while 27.4% were on polypharmacy. Overall, 483, 243 and 96 participants received DTG, RAL and EVG/c respectively as first InSTI. At the end of the follow up 6.4%, 21.1% and 22.9% participants discontinued DTG, RAL and EVG/c respectively. Using a log-rank test, EVG showed a significantly lower durability than DTG (p<0.001) or RAL (p 0.05) or both, DTG and RAL (p<0.001). Among participants who discontinued their regimen we found 0 virological failure and 56.7% simplification/deprescription.The three integrase inhibitors considered showed a good durability and no virological failures in geriatric patients such as those enrolled in the GEPPO cohort when used in a two or three drug regimen. People living with HIV (PLWH) are aging, mainly for the longer life expectancy under effective combined antiretroviral therapy (cART) and the increasing age of newly diagnosed patients , 2. GeriMultimorbidity (i.e. the presence of at least 3 co-morbidities) is often present in elderly PLWH and it is reported along with polypharmacy : both conditions have been associated with worse outcomes , 6.Moreover, there is a lack of randomized controlled trials (RCTs) designed properly to investigate efficacy and toxicity of antiretrovirals in geriatric patients living with HIV. Recently some sub-studies of RCTs including a ≥65 years old sub-group analysis were presented and only one non-randomized single arm clinical trial showing good tolerability, safety profile and immunovirological response with InSTI-based cART in geriatric PLWH both for cART experienced and naïve patients , 8.One of the methods that may empirically show the tolerability of a drug regimen is its durability. Durability, defined as the time to regimen modification, depends on major outcomes  as well as on more subtle factors such as mild side effects, the impact on quality of life, polypharmacy, comorbidities and patients’ and physicians’ choice . IntegraNozza et al [Participants were prospectively recruited between 2017 and 2019 from the Geriatric Patients Living with HIV/AIDS (GEPPO) cohort, an Italian prospective observational multicentre study characterising multimorbidity and geriatric syndromes in PLWH aged ≥65 years with a special focus on cART prescription. Participants are followed according to clinical practice and data about geriatric outcomes are recorded once a year. Regarding this study, inclusion criteria was the initiation of first InSTI-based regimen after 2017. InSTIs included in the analysis were DTG, RAL and EVG/c. Moreover, we explored the presence of multi-morbidity and polypharmacy: those conditions have been previously defined and described in the GEPPO cohort by za et al .Study primary endpoint was InSTI durability defined as time to discontinuation of first InSTI regimen; we also analyzed the reason for cART discontinuation, categorized as: 1) virological failure, 2) simplification/deprescription, 3) others (including toxicity).Continuous variables were described using median and interquartile range (IQR) while categorical variables were described with absolute frequencies and percentages. Comparisons of continuous variables among InSTI regimes were performed using Kruskal-Wallis test while Chi-squared test was used for categorical variables. The difference of InSTI discontinuation, considered as the first regimen shift and modelled as a time-to-event variable, was tested through a log-rank test and a Cox Proportional Hazard model adjusting by age, sex, multimorbidity (defined as the presence of at least 3 comorbidities) and the use of abacavir. The same analysis was conducted for the subgroup on InSTI dual regimen. Median survival is defined as the time needed for half of the participants in each regimen to discontinue the treatment. The proportion of participants discontinuing the three regimens was displayed using cumulative curves. All the test performed were two sided assuming a 5% significance level. All analyses were performed using R (version 4.0.2).Comitato Etico di Brescia”. All data were fully anonymized before the statistical analysis was performed. Written informed consent was asked at the first useful access.This study belongs to the GEPPO project. This project obtained approval by the Research Ethics Board of each individual institute belonging to the GEPPO cohort. The Research Ethics Board of the coordinating centre is the “Among 1531 patients aged ≥65 years followed in the GEPPO cohort, we included 822 participants in this analysis. At baseline  median age was 69.8 (IQR 7.4). Among study participants, 666 (81%) were males, the median CD4+ T-cell count at baseline was 618 cell/μl (IQR 25–75: 437.5–814.0), and 95.2% had HIV RNA <50 copies/ml. Multimorbidity was present in 356 (43.3%) participants, while 225 (27.4%) were on polypharmacy  of 16.1 (10.3–20.4), 18.3 (12.0–21.1) and 13.5 (8.5–19.9) years in the DTG, RAL and EVG/c group respectively, with significant differences among the three InSTIs .The median follow-up time, computed with KM estimator, was 12.7 months. At the end of the follow up 29 (6.0%), 52 (21.4%) and 22 (22.9%) participants discontinued DTG, RAL and EVG/c respectively. The median discontinuation time calculated as the time required to reach a drug discontinuation of 50% was 29 months for EVG and 36 months for RAL while DTG did not reach 50% discontinuation (after 36 months the proportion of participants who discontinued DTG was 23%). Using a log-rank test, EVG showed a significantly lower durability than DTG (p<0.001) or RAL (p = 0.048) or both DTG and RAL (p<0.001). The curves showing the proportion of participants discontinuing InSTI regimen are shown in An intriguing treatment option recently implemented thanks to several RCTs, are two drug regimens (2DR) InSTI-based. Analyzing this treatment choice, we found that overall 526 (64.0%) of the participants received a standard triple therapy while 195 (40.4%) received DTG-based 2DR and 58 RAL-based 2DR. Among those receiving DTG-based 2DR, for 89 (45.6%) participant the second drug was lamivudine (3TC), for 47 (24.1%) rilpivirine (RPV), and for 59 (30.3%) other agents. Durability of InSTI-based 2DR is shown in Among participants who discontinued their regimen (103) we found 0 (0%) virological failure, 59 (56.7%) simplification/deprescription, 11 (25.9%) other reasons, including 4 adverse events and 1 participant’s preference. For the remaining 33 participants, data regarding the reason of InSTI discontinuation are missing, although among them 4 participants changed molecules in the InSTI class.This longitudinal study in geriatric PLWH demonstrated a good durability of InSTI-based regimens analysed with a particularly good performance of DTG-based regimens (regardless of accompanying drugs).Geriatric Patients Living with HIV/AIDS (GEPPO) is a prospective observational cohort including consecutive HIV-positive geriatric patients in care at 11 HIV clinics all over Italy compared with a HIV-negative control group. The aim is monitoring the health status of geriatric PLWH as well as study how the common geriatric care model applies to PLWH [The 822 participants at GEPPO cohort also enrolled in this study were long standing cART experienced with a median history of more than 10 years of antiretroviral drugs and presenting a good immunovirological profile. Aging is usually associated with a higher tendency to treatment adherence , 13.et al. did not observe a weight gain in participant switching from tenofovir diproxil fumarate to tenofovir alafenamide nor from a InSTI-free cART to a DTG-based regimen [As expected, in a cohort of people with a median age of 70 years, multimorbidity and polypharmacy were common findings . It is well known that these two factors should be carefully considered when choosing an ART regimen: if virological suppression is achieved, NRTI-sparing, unboosted regimens are emerging as intriguing treatment options as well as the possibility to simplify to dual therapy should be considered [ regimen .The emerging interest on DTG-based 2DR has been extensively investigated in RCTs when DTG was combined/co-formulated with RPV or 3TC . These rEaton et al. [These data are confirmed in our cohort. None of the participants discontinued due to virological failure, while 56.7% for simplification/deprescription, and 25.9% for toxicity. These data are in line with what found by n et al. .These data may also be put in the perspective of the fourth 90% target recently suggested as outcome in the HIV treatment cascade. Switching ARV in geriatric PLWH is mainly driven by a proactive strategy to avoid polypharmacy in a de-prescribing approach, often applied in general geriatric population . In thisEVG and RAL also showed a good durability (29 and 36 months respectively), though they were less preferred in GEPPO cohort in comparison to DTG. A few hypotheses may be provided.EVG is necessarily boosted with cobicistat which strongly inhibit CYP3A4 displaying a higher EVG risk of DDIs, producing concerns in the context of polypharmacy. RAL discontinuation may be due to high pill burden regardless of the once a day RAL formulation which has been recently released. To note RAL anyway showed a good durability, higher than EVG.In geriatric PLWH deprescription options should be the standard of care. This process implies therapy review with the goal of medication reconciliation and medication prioritizations to prevent unnecessary drug prescriptions. In this context 2DR and 3DR unboosted STR regimens should be prioritised . Recent Several limitations of our study should be acknowledged: missing data, short follow up, only one time-point per year, and the observational design, unable sometimes to evaluate the clinical decisions.Although the three InSTI considered showed some differences in this geriatric cohort of patients, all of them had a durability of more than two years with no virological failures. In geriatric patients such as those enrolled in the GEPPO cohort 2DR and 3DR unboosted STR regimens are favoured and display long term durability.S1 Data(XLSX)Click here for additional data file.


We aimed to assess the overall cardiovascular and metabolic effect of the switch to three different single tablet regimens (STRs)  in a cohort of people living with HIV/AIDS (PLWH) under effective ART.All PLWH aged above 18 years on antiretroviral treatment with an HIV-RNA < 50 cp/mL at the time of the switch to TAF/FTC/RPV, TAF/FTC/EVG/cobi and ABC/3TC/DTG were retrospectively included in the analysis. Framingham risk score modification after 12 months from the switch such as lipid profile and body weight modification were assessed. The change from baseline to 12 months in mean cardiovascular risk and body weight in each of the STR’s group were assessed by means of Wilcoxon signed-rank test whereas a mixed regression model was used to assess variation in lipid levels.Five-hundred and sixty PLWH were switched to an STR regimen of whom 170 (30.4%) to TAF/FTC/EVG/cobi, 191 (34.1%) to TAF/FTC/RPV and 199 (35.5%) to ABC/3TC/DTG.p = 0.610] whereas a significant increment was observed in PLWH switched to TAF/FTC/EVG/cobi  and TAF/FTC/RPV . In addition, a significant variation in the mean body weight from baseline to 12 months was observed in PLWH switched to TAF/FTC/EVG/cobi  and TAF/FTC/RPV  whereas no difference was observed in those switched to ABC/3TC/DTG .No difference in the Framingham cardiovascular risk score was observed after 12 months from the switch in each of the STR’s groups. No significant overtime variation in mean total cholesterol levels from baseline to 12 months was observed for PLWH switched to ABC/3TC/DTG [200 (SD 38) mg/dl vs 201 (SD 35) mg/dl; No difference in the cardiovascular risk after 1 year from the switch to these STRs were observed. PLWH switched to TAF/FTC/EVG/cobi and TAF/FTC/RPV showed an increase in total cholesterol levels and body weight 12 months after the switch. The progressive development of more convenient and effective antiretroviral regimens has turned an invariably fatal illness into a manageable chronic condition . For sevThe development and implementation of single tablet regimens (STRs) have been demonstrated to improve both adherence and convenience of drug uptake reducing the possible barriers to antiretroviral treatment related to pill burden or more than once a day antiretroviral administration –8. The fThe advent of new STR combinations based on abacavir (ABC) or tenofovir alafenamide (TAF) helped to overcome this untoward drug effects –17. NeveThe overall cardiovascular risk modification after the switch to different STRs have not yet clearly elucidated. In the present study we aimed to assess the overall cardiovascular and metabolic effect of the switch to three different STRs  in a cohort of people living with HIV/AIDS (PLWH) under effective ART.Monocentric retrospective observational study.The study was conducted on the outpatient cohort of PLWH of the 3rd Infectious Diseases Division of Luigi Sacco Hospital, Milan, Italy, between December 2015 and June 2019.All PLWH aged above 18 years on antiretroviral treatment with an HIV-RNA < 50 cp/mL at the time of the switch to TAF/FTC/RPV, TAF/FTC/EVG/cobi and ABC/3TC/DTG were included in the analysis excluding naïve patients and those with an HIV-RNA > 50 cp/mL at the time of the switch.Outcomes: cardiovascular risk assessed by Framingham risk score  at 12 moExposure: STRs Predictors: we included in the analysis potential confounders such as age, gender, switch from TDF, PIs, INIs, RTV or cobi containing regimens, years on antiretroviral treatment, CD4 cell counts at the time of the switch, statin and other lipid lowering agents  exposure.demographic and clinical data comprehensive of age, gender, HIV risk exposure.clinical data comprehensive of year of HIV diagnosis, antiretroviral history, years on antiretroviral treatment, AIDS diagnosis, HCV and/or HBV coinfection, CD4 cell count, CD4 cell count nadir, HIV-RNA determination, smoking habits, lipid lowering agents  and aspirin.Metabolic data comprehensive of Framingham score at the time of the switch and after 12 months, total cholesterol, triglycerides, HDL cholesterol and body weight.Reason leading to the switch of one of the investigated STRs.The data were extracted from an electronic database which included clinical and laboratory data. Al sensitive data have been anonymized and subsequently collected at the time of the switch and after 6 and 12 months from the switch:Due to the retrospective nature of the study the analysis is exposed to selection and channelling bias. Moreover, it is possible that bias could be introduced by missing data. The monocentric design could limit the generalizability of our findings.The primary outcome was the assessment of Framingham risk score modification at 12 months after the switch in the different STRs.The secondary outcomes were the change at 12 months in body weight and the modification at 6 and 12 months of total cholesterol, triglycerides and HDL levels according to the different STR and the identification of potential predictors/effect modifiers.The study population is considered to be representative of the cohort of PLWH actually followed at our outpatient clinic.Statistical analysis: the data were identified and categorized according to be continous or categorical variables according to the objective of the study. A descriptive statistical analysis was performed and an inferential one assuming a significance level of α = 0.05.The analysis of cardiovascular risk was performed comparing the Framingham risk score at baseline and 12 months thereafter in each of the STR’s group by means of Wilcoxon signed-rank test.The dependent variable was for each analysis was: total cholesterol, triglycerides and body weight, respectively. Patients who introduced or modified a lipid lowering treatment during the study period were excluded.The variations within each STR’s group in total cholesterol, triglycerides and HDL cholesterol were evaluated trough a multivariable linear mixed effects regression model. The SAS PROC MIXED with random intercept was used to account for repeated measures. The intra individual variance was analysed through an autoregressive correlation of the first order.As covariates in the final model for lipid levels modification were included: age, gender, switch from TDF, PIs, INIs, baseline lipid levels, statin or lipid lowering agents’ exposure and adjusted for time effect after the switch.The analysis of body weight was performed comparing the baseline and 12 months’ values in each of the STR’s group by means of Wilcoxon signed-rank test.If the modification in body weight 12 months after the switch were found to be statistical significant a general linear model was built to assess factors associated to the overtime change in body weight. A logarithmic transformation with natural logarithm was applied to body weight .As covariates in the final model of body weight, and lipid levels modification were included: age, gender, switch from TDF, PIs, INIs, RTV or cobi, years on antiretroviral treatment, CD4 cell counts at the time of the switch.P values of < 0.05 were considered statistical significant.All of the statistical analyses were made using SAS software, version 9.4, and differences with - Sample size estimate: to evidence a between means (baseline and 12 months thereafter) minimum difference of at least 3.5% assuming a standard deviation of 11 in the cardiovascular risk assessed by Framingham risk score in each STR’s group   it has bp = 0.003, respectively). Patients switched to ABC/3TC/DTG were more frequently switched from a PI-based regimens and less frequently from a regimen containing TDF when compared to those switched to TAF/FTC/EVG/cobi and TAF/FTC/RPV .During the study period 560 PLWH were switched to one of the investigated STRs: 170 (30.4%) to TAF/FTC/EVG/cobi, 191 (34.1%) to TAF/FTC/RPV, and 199 (35.5%) to ABC/3TC/DTG. Characteristics of patients at the time of the switch are reported in Table The main reason of switch toward an STR was related to simplification driven by concomitant comorbidities [323 (57.6%) patients] followed by simplification to improve adherence [155 (27.7%) patients], other reasons [62 (11.1%) patients] and drug-drug interactions [20 (3.6%) patients].p = 0.691); 12.4% [Standard Deviation (SD) 11] and 12.3% (SD 11.1) from the switch to TAF/FTC/EVG/cobi (p = 0.124); 11.3% [Standard Deviation (SD) 11.9] and 12.6% (SD 12.5) from the switch to TAF/FTC/RPV (p = 0.089), respectively.No difference in the Framingham cardiovascular risk score was observed after 12 months from the switch in each of the STR’s groups  mg/dl vs 208 (SD 40) mg/dl; p < 0.0001] and TAF/FTC/RPV .No significant overtime variation in mean total cholesterol levels from baseline to 12 months was observed for PLWH switched to ABC/3TC/DTG  whereas no differences were observed in those switching to TAF/FTC/EVG/cobi  and TAF/FTC/RPV .A significant reduction in mean triglycerides levels was observed for PLWH switched to ABC/3TC/DTG from baseline to 12 months .A significant slight increase in mean HDL levels from baseline to 12 months were observed in all the STR’s groups  and statin exposure  was observed for total cholesterol modification in PLWH switched to TAF/FTC/EVG/cobi, whereas switching from a TDF containing regimen  and statin exposure  resulted independently associated to total cholesterol modification in those switching to TAF/FTC/RPV.In the multivariable model a correlation between female gender  whereas no statistical significant difference was observed in those switched to ABC/3TC/DTG .The comparison of body weight at the time of the switch to one of the investigated STRs and after 12 months are depicted in Fig. p < 0.001), CD4 cell count (per 200 more) , the switch from a TDF containing regimen  and the switch from an INI containing regimens  was observed.In the general linear model restricted to PLWH switched to TAF/FTC/EVG/cobi an association between body weight variation at 12 months and male gender  and the switch from an RTV/cobi containing regimen  was observed.In the general linear model restricted to PLWH switched to TAF/FTC/RPV an association between body weight variation at 12 months and the switch from a PI containing regimen  and this association was confirmed to be independent in the multivariable model restricted to patients switched to TAF/FTC/RPV. This finding is expected considering the possible TDF statin-like effect  with an In a recent conference presentation Mallon and co-workers showed an independent effect of a switch from TDF to TAF on weight gain irrespectively of being concomitantly switched to an INI-containing regimen . In addiA low prescription of statin such as of aspirin was observed in our cohort. This finding is in line with previous reports of low statin use in PLWH mainly caused by a combination of fear to drug-drug interaction and unproven expected higher incidence of adverse events in PLWH –37. ThisOur study has several limitations. First, the retrospective design could have introduced bias into the analysis related to missed data. Second, the choice of the switch was based on clinical judgement and, although the demographic characteristics of the three group were not significantly different, some unbalancing between groups were present and this makes the between groups comparisons unfeasible. Third, the Framingham risk score does not take into account the potential role of ABC as a potential independent additive risk factor for cardiovascular risk. Fourth, considering the observational nature of our study no causality link could be inferred between the switch to one of the different STRs and the investigated outcomes but only associations that should be carefully interpreted in light of potential residual confounders that have not been taken into account into the analysis. In the end, the monocentric design limits the generalizability of our findings to other settings. Nevertheless, the study population included in the present study is overall representative of PLWH attending our HIV outpatient clinic.No difference in the cardiovascular risk after 1 year from the switch to ABC/3TC/DTG, TAF/FTC/EVG/cobi and TAF/FTC/RPV were observed. PLWH switched to TAF/FTC/EVG/cobi and TAF/FTC/RPV showed an increase in total cholesterol levels and body weight 12 months after the switch although the overall impact on the cardiovascular risk assessed by Framingham risk score seems to be limited. An important gap in preventing cardiovascular risk in a high-risk population by means of pharmacological interventions (i.e. lipid lowering agents and aspirin) was found. These observations highlight the need of proactive intervention to reduce the long term cardiovascular risk in the same way we are proactive in simplify ART regimens.


Anti-retroviral treatment enhances the immune status and reduces unwanted outcomes. However, development of treatment failure and drug resistance raises concern over lifelong treatments to chronic diseases such as HIV/AIDS.This study determined proportion of treatment failure (TF) and identified factors associated with TF among people living with human immunodeficiency virus (HIV) in Bahir Dar, Northwest Ethiopia.Facility based cross sectional study was carried out from November, 2017 to April, 2018. Sociodemographic and clinical data were collected using structured questioner. Blood sample was collected and analyzed for viral load, complete blood count (CBC), liver and kidney function test and CD4 count. A patient is declared as treatment failure when viral load value is higher than 1000 RNA copies/ml in two consecutive viral load analyses within three months interval. Data were entered and analyzed using SPSS version 23. To identify factors associated with TF, logistic regressions model was employed.A total of 430 people who had six months and above antiretroviral treatment (ART) follow up were enrolled in the study. Of these, 57.9% were females & the mean age was 38 years. The mean month of ART follow up was 83 months. In the first viral load analysis, 106 (24.7%) of the cohort were virologically failed. These failed people were followed for 3 months with intensive adherence support; then second viral load analysis showed a viralogical failure among 65 people of the second cohort. Thus, the overall viralogical failure or TF was 15.1%. The re-suppression rates were 41(38.7%). Male gender, people with history of drug discontinuation, poor adherence, irregular time of drug intake, multiple sexual practice showed significant association with TF. Moreover, base line and current CD4 counts of <200 cells/ml also demonstrated significant association with TF.Significant proportion of treatment failure was reported in the present study. Moreover, behavioral factors such as drug discontinuation, poor adherence, multiple sexual partner were associated with treatment failure. Hence, to avoid TF, regular patient counseling and monitoring should be in place. To identify the predictors for treatment failure, further follow-up study is desirable. Human immunodeficiency virus (HIV) is a cause of acquired immune deficiency syndrome (AIDS). Based on World Health Organization (WHO) report of 2015, 36.7 million people were living with HIV. In the same year, the disease claimed nearly 2.3 million new infections and 1.6 million death, respectively First-line ART regimen is a cocktail of two nucleoside reverse-transcriptase inhibitors (NRTIs) plus a non-nucleoside reverse-transcriptase inhibitor (NNRTI). Of these, tenofovir disoproxil fumarate (TDF) with 3TC or emtricitabine (FTC) and efavirenz (EFV) as a fixeddose combination is recommended as the preferred option to initiate ARTWhile the rapid development of sensitive and specific point of care diagnostic technique is one of the success stories in the history of HIV; development of curative treatment and vaccine could not be a reality. Recently, the clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated nuclease 9 (Cas9) system has been engineered as an effective gene-editing technology with the potential to treat HIV-1/AIDS. It can be used to target cellular co-factors or HIV-1 genome to reduce HIV-1 infection and clear the provirus, as well as to induce transcriptional activation of latent virus in latent viral reservoirs for elimination 3) and clinically  for the year 2020 set a target known as 90-90-90. This is to test, to have sustained ART and to achieve viral suppressions rate of 90% of the eligible people Based on nationwide survey of Ethiopia, the prevalence of transmitted drug resistance (TDR) was 3.9%323Several lines of evidences showed that, poor adherencePeriodic surveillance is required for monitoring the prevalence of TF. Hence, the aim of this study was to determine the prevalence of first-line ART TF and identify factors associated with TF. This study also calculatedthe added value of second viral load on avoiding premature switching to the second line treatment.A facility based cross sectional study was conducted from November, 2017 to April, 2018 at three ART sites in Bahir Dar City administration namely; Felege Hiwot Referral Hospital (FHRH), Han Health Center and Adinas General Hospital. More than 6300, 2000 and 200 patients were on ART at the three health facilities, respectively.All people living with HIV (PLWHIV) in Bahir Dar city administration were the source population and those who attended ART follow up at the three health facilities during the study period were the study population. PLWHIV who had ART follow-up period of at least 6 months were included. Only those on first line ART were included.Sample size was determined using single population proportion formulaWhere, n= sample size; p=prevalence taking 31.2% prevalence of TF based viral load test in Addis Ababa 15; z=1.96= statistic level of confidence; D = margin of error taking 5%; adding 10% non-response rate finally reached to 430. Sample size was proportionally allocated to the three study sites. Patients who gave written consent and ascent were consecutively enrolled until the required sample size obtained.Virological treatment Failure (VTF) or simply TFwas the dependent variable.Sociodemographic and baseline clinical data were captured by ART nurses using a pretested questionnaire. Baseline CD4 value, WHO stage, months of ART follow up and baseline regimens were extracted from ART registration log book.Blood sample was collected in duplicate using vacutainer sample collection apparatus from each participant. For serum glutamic pyruvic transaminase (SGPT), serum glutamic oxaloacetic transaminase (SGOT) and creatinine analysis, 5 ml of blood was collected with serum separator tube containing gel. For plasma viral load (PVL), CD4 and complete blood count (CBC) tests, 4 ml of whole blood was collected with K3 EDTA anticoagulant coated vacuum test tubeThe RNA was extracted from 200 µl of plasma sample using Abbott m2000sp automated equipment. Then 50 µl of RNA sample-eluate and 50 µl master mix  have been combined and run for amplification. The target sequence for HIV-1 is in the pol Integrase region of the HIV-1 genome. The target RNA region converted to cDNA by the reverse transcriptase activity of the thermostable rTth DNA polymerase.Briefly, the HIV-1 and internal control (IC) reverse primers anneal to their respective targets at 59oc for 30 min for reveres transcription. The optimum denaturation, annealing and extension temperature and time were at 92°c for 30 second, 56°c 20 second respectively. Hybridization and detection take place at 35°c. The amount of HIV-1 target sequence is measured through the use of fluorescent-labeled oligonucleotide probes. The amplification cycle at which fluorescent signal detected by the Abbott m2000rt is proportional to the log of the HIV-1 RNA concentration present in the original sampleThe data were entered and scrutinized using SPSS . The information was summarized using frequency, percentage and mean. Moreover, logistic regression was computed to identify factors associated with TF. P-value of ≤ 0.05 considered statistically significant.The questionnaires were pre-tested and validated. Internal quality controls (IQC) and calibration have been done at every reagent lot changed. Viral load Abbott M2000 machine was monitored with negative, low positive and high positive controls at every session run of viral load.A total of 430 PLWHIV and who took first-line ART drugs for six and more months were recruited. Of these, 249 (57.9%) were female, 396 (92.1%) were urban dwellers. The mean age of participants was 38 years (ranges 12–67 years). Of the total 430 participants, 44(10.2%) and 119(27.7%) had current and previous history of tuberculosis (TB), respectively. Diabetes mellitus (DM) was reported from 10 (2.3%) of the participants. Ninety-four percent of the patients did not have history of dependency, 116(27%) had history of multiple sexual partner, 123(28.6 %) used condom regularly. The average length of stay on ART was 83 months (Range: 6–184 months) .At baseline, 267(62.1%) of the participants were at WHO stage 3. Remarkably, at the time of data collection, 426 (99.1%) of PLWHIV were at WHO stage treatment 1 (T1) showing clinical improvement. Twenty-one percent of the participants have history of treatment interruption and that of 43% disclosed irregularity on medication time. With regard to adherence, 333(77.4 %) of patients were with good (>95%) adherence and 97(22.6%) were with sub-optimal adherence (<95%) .Closer inspection of the 6 (± 1.9) cells/mm3 and that of the mean hemoglobin value was 13.5 g/dl (±2.3). The mean value of SGPT and creatinine were 33.6 IU/l (±25.6) and 0.8 mg/dl (±0.3), respectively. No significant differences were found between treatment failed and none treatment failed groups with regard to complete blood cell count, creatinine value, SGPT and hemoglobin value in the present study.The mean CD4 value of the participant was 455 (±278) and 267.6 cells/mm3 (+-234.5) at the time of study and baseline, respectively. The mean WBC counts was 6.2 x10Together, in the present study, TF is associated with gender, treatment discontinuation habit, irregular time of medication intake, poor adherence, low CD4 value (<200 cells/ml) at current and baseline and sexual behavior.The study revealed that first line HIV TF was 15.1%. Based on WHO definition of TF, this prevalence report is considered as high 11Male gender showed significant association with treatment failure . This result was in line with previous studies from Ethiopia, Bale With successive increases in sexual contacts, there was also an increase in TF . This might be due to exchange of mutated virus and sub types between sexual contacts Overall, these results indicate that irregular time of medication, drug discontinuation, poor adherence, multiple sexual history, male gender, baseline and current CD4 count<200 were significantly associated with first line HIV TF.Human immune deficiency virus drug resistance test was not done which could distinguish drug resistance from clinical failure. Moreover, time of enrollment on ART was not accounted for, which poses major concerns in terms of bias in the estimates.In general, first line HIV treatment failure was gauged at 15.1% and re-suppression rate after intensive adherence was 38.7%. Male gender, drug holidays, multiple sexual partner, sub-optimal adherence, lower baseline and current CD4 counts were the potential factors responsible for TF. Hence, sustained counseling and advice should be given targeting risk groups such as male, interrupter, people having low CD4 value. To identify the driving factor, follow-up study is desirable.