Both abacavir- (ABC-) based and zidovudine- (AZT-) based regimens are widely utilized for managing HIV infection in children. Unfortunately, there is a lack of data regarding their immunological response and associated risk factors in Ethiopia. P < 0.05 for slope of the random-effect linear regression was used as an indicator for the presence of association.  A retrospective hospital-based cohort study was conducted on HIV-infected children in Jimma Medical Center (JMC). A total of 179 records were reviewed by including data from November 2015 to April 2017. Data were collected on sociodemographic, clinical characteristics of patients and drug-related variables. Data analysis was done using STATA 13.1. Mixed-effect linear regression was performed to assess the difference in CD4+ changes between groups adjusting for baseline characteristics. The change in predicted CD4 count attributed to each regimen was also assessed by marginal analysis. β = 20.51, 95% CI [6.37–34.65]), P = 0.004) over time. The regimen AZT + 3TC + LPV/r tended to have an excellent predicted CD4+ lymphocyte count change relative to all other regimens, while ABC + 3TC + LPV/r had the least immunologic recovery (margins 338.0 cells/mm3 versus 249.13 cells/mm3 (P < 0.001)). Baseline CD4+ lymphocyte count, ART group, WHO clinical stages, and viral load were independent predictors for CD4+ change overtime.  Of 179 patients, 98 (54.7%) were females. The mean (±SD) duration of follow-up was 939.8 ± 478.3 and 984.92 ± 453.1 days for ABC and AZT groups, respectively. AZT group had a significant CD4+ count gain per visit compared with their ABC counterparts (( AZT-based regimens seem to have better immunological response compared to ABC-based regimens. Immunologic response was described worse in patients with a viral load of >1000copies/ml, low baseline CD4+ count, advanced WHO clinical stages, and ABC-containing regimens. Further study is needed to clarify these aspects. Currently, 1.7 million children are living with human immunodeficiency virus (HIV) and over 90% of them live in sub-Saharan Africa . EthiopiThe initiation of potent antiretroviral therapy (ART) in the mid-1990s has dramatically reduced HIV-associated morbidity and mortality –8. AntirThe earlier World Health Organization (WHO) guidelines recommended using a nucleoside reverse transcriptase inhibitor (NRTI) backbone including a thymidine analogue stavudine (d4T) or zidovudine (AZT) together with lamivudine (3TC) for paediatric HIV treatment . But in In Ethiopia, the initial ART regimen included the use of d4T as a preferred first-line NRTI for paediatric HIV treatment. In 2012, Ethiopia implemented the d4T phase-out program, and ABC became routinely used as a standard of care . CurrentA retrospective hospital-based cohort study was conducted on HIV-infected children in Jimma Medical Center (JMC). JMC is located in Jimma town, 355 km from Addis Ababa. It is currently the only teaching and specialized hospital in the Southwest region of Ethiopia. The hospital serves as a referral site and provides specialized care for Southwest Ethiopia with a catchment population of about 15 million. The study was conducted from April 10 to May 10, 2017, by including data from November 2015 to April 2017.We included HIV-infected children (<15 years) who were on ABC- and AZT-based regimens that fulfill the eligibility criteria. Patients on ABC- and AZT-based first-line regimens, having at least six months of follow-up with good adherence, whose records were legible and complete, who have CD4 count at least at the baseline and six months, and younger than 15 years were included in the study. Those transferred out within <6 months of follow-up and patients with incomplete records were excluded. The study was conducted by dividing the total sample into two major classes as ABC group and AZT group.Data were collected on sociodemographic characteristics , height (cm), and body mass index (BMI)), HIV-related factors , treatment-related factors  prophylaxis (cotrimoxazole preventive therapy (CPT) and isoniazid preventive therapy (IPT)), and antitubercular treatment), and immunological response (CD4+change).The number of patients who fulfilled the eligibility criteria for the ABC group was 87 and all of them were included. From those on AZT-based regimen, 92 eligible patients were included, making ABC-to-AZT group ratio of 1 : 1.05. Finally, a total of 179 subjects, with 87 charts of patients from the ABC group and 92 patients from the AZT group were reviewed.Since the number of patients on ABC-based regimen was limited, we included all eligible patients. A simple random sampling technique was used to select 92 patient charts for AZT-based regimens using a computer-generated random number.Data on socio-demographic, clinical, laboratory, and drugs administered were collected by record review using English version checklists. The data collection tool was carefully prepared after reviewing relevant literature studies to enable the data collectors to gather all the information required to address the study objectives. A 2-day training was provided on the data collection tool and general procedures for data collectors, i.e., 2 pharmacists (B. Pharm) and 2 nurses. Data from antiretroviral drugs and patient information sheet were collected by pharmacists, and data from ART clinic intake form, HIV care/ART follow-up, and patient sheet were collected by the nurses. The baseline body mass index of the subjects was later calculated after collection of baseline height and weight of the patient from the patient chart. Pretest was conducted on 5% of the eligible records.  Good adherence: estimated adherence level of >95%  as recor  Child: age <15 years   Lost to follow-up: refer to a patient who has missed clinical or drug pickup appointments permanently .The study was approved by the Institutional Review Board (IRB) of Jimma University. It has designated with an IRB number of IHRPGB/112/2017. The need for informed consent was waived because of the retrospective, anonymous nature of the study. During data collection, confidentiality was ensured, and for this reason, the name and address of the patient were not recorded in the data collection checklist.P < 0.05 was considered to declare a statistical significance. Marginal analysis was also conducted to see the difference among the specific regimen category.Data were double-entered into Epi-Data and exported to STATA 13.1 for cleaning and analysis. Descriptive analysis was performed, and results were presented in text, tables, and charts. Bivariate and multivariate mixed-effects linear regressions for repeated measurements were performed to assess the adjusted effect of the ART regimen and identify additional predictors of CD4+ recovery. The coefficient of mean CD4+ count with 95% confidence intervals was used as a measure of the strength of association, and thmonth of treatment. Thirty-two patients were excluded initially from either regimen due to missed CD4+ count at 6 months and 30  because of the adherence problem, and 179 patients were included in the analysis  and were treated for at least 6 months. Of these, 108 from ABC group and 212 from AZT group have a complete CD4+ count at the 6analysis .P=0.339) died.The mean ± standard deviation (SD) duration of follow-up was 939.8 + 478.3 and 984.92 + 453.1 days for the ABC and AZT groups, respectively. During the study period, a total of 4 patients (1 (1.14%) patient from the ABC group and 3 (3.3%) from the AZT group; P = 0.03). Baseline socio-demographic and clinical characteristics of the study participants are depicted in We included 179 patients, of whom 98 (54.75) were females. One hundred forty (78.2%) of the patients had a BMI of less than fifth centile, and there was a statistically significant difference between groups (3 for the ABC group and 150.5 (±42.1) cells/mm3 for the AZT group. The mean change in CD4+ lymphocyte count from baseline for the past 18 months was presented comparatively in th, 12th, and 18th months for ABC- and AZT-based regimens, respectively.The overall change in the mean standard deviation (±SD) of CD4+ lymphocyte count was 139.3 (±55.7) cells/mmAs shown in the figure, the CD4+ lymphocyte count trajectory belonging to AZT-based regimen looks steeper after the first 6 months of therapy.Patients on AZT + 3TC + NVP had the highest baseline CD4+ lymphocyte count, followed by AZT + 3TC + LPV/r and ABC + 3TC + NVP. The lowest baseline CD4+ count was recorded for ABC + 3TC + LPV/r .3 (P < 0.001 and 95% CI [46.86–59.20]) with an interclass correlation coefficient of 65.5% (P < 0.001). This implies a significant proportion of variability in CD4+ lymphocyte count change due to patient-specific factors. Among the groups, 36.73% of the variation in CD4+ lymphocyte change variability was explained by differences in ART regimens (P < 0.001).We conducted a mixed-effect linear regression using a consecutive CD4+ lymphocyte count measured over the past 18 months as an outcome variable. The slope of random-effect linear regression was used to report the overtime change in CD4+ count attributed to the predictor variables. The overall average gain in CD4+ count every six months was 53.0 cells/mmBody mass index, weight for height, ART group, baseline, CD4+ lymphocyte count, occurrence of opportunistic infections (OIs), WHO clinical staging, viral load, nutritional status, and exposure to antitubercular drugs were associated with CD4+ lymphocyte count change on binary linear regression. After adjusting for all confounders, ART group, baseline CD4+ lymphocyte count, WHO clinical stages, and viral load remained independent predictors for CD4+ lymphocyte count change.3 CD4+ count advantage every six months . Each unit increment in baseline CD4+ count will contribute to 0.55 cells/mm3 CD4 gain every half year .Therefore, patients who commenced on AZT-based regimens had a significant change in CD4+ lymphocyte count at each visit. Accordingly, patients exposed to AZT-based regimens had 20.51 cells/mmβ = −47.61[−84.27− (−10.96)] and β = −73.54[−118.27− (−28.81)]). In addition, patients with a viral load of >1000 copies/ml had 28 CD4+ lymphocyte count disadvantages every half year (β = −27.68[−47.75− (−7.61)]) ]) .3 of CD4+ lymphocyte count change, and it was 296.33 cells/mm3 CD4+ for those treated with ABC + 3TC + EFV. The change is statistically significant in either case (P < 0.001). The regimen AZT + 3TC + LPV/r tended to have an excellent predicted CD4+ lymphocyte count change relative to all other regimens, while ABC + 3TC + LPV/r performed the opposite (margins 338.0 cells/mm3 versus 249.13 cells/mm3 (P < 0.001)) ) .This study was the first ever to compare the immunological response of ABC- and AZT-based regimens among HIV-infected children in Ethiopia. The biannual analysis of mean CD4+ gain showed that the maximum gain in mean CD4+ count was attained with AZT + 3TC + LPV/r, while ABC + 3TC + LPV/r had the least immunologic recovery over the entire treatment course. The CD4+ lymphocyte count trajectory showed a linear trend. Baseline CD4+ lymphocyte count, ART group, WHO clinical stages, and viral load were independent predictors for CD4+ changes over time.th month of treatment course  and β = −73.54[−118.27− (−28.81)]). This is in agreement with studies conducted in Nigeria [β = −27.68[−47.75− (−7.61)]). This finding is consistent with the study conducted by Zhou et al. [On the contrary, patients with WHO stages III and IV were in a precarious situation in terms of their CD4+ count recovery. Every six months, patients with WHO stage III and WHO stage IV had 47.61 and 73.54 CD4+ lymphocyte count disadvantage, respectively ( Nigeria  and Tanz Nigeria , in whic Nigeria , in whicu et al. .This study had several possible limitations. Firstly, because of the retrospective nature of the study, we were not able to capture some important data such as adverse drug effects of ART. Second, as the sample size was relatively small, the power to detect definitive differences may have been limited. It was a single-site hospital-based study, and therefore, the findings may not be generalizable to the general population, and measures of adherence by health professionals that may not fit the reality are some of the limitations.In the current study, patients with AZT + 3TC + LPV/r had a better immunologic recovery. Immunologic response was described worse in patients with a viral load of >1000 copies/ml, low baseline CD4+ count, advanced WHO clinical stages, and ABC-containing regimens. Further study is needed to clarify these aspects.


With the current widespread use of dolutegravir in low-income countries, the understanding of the impact of nucleoside reverse transcriptase inhibitor (NRTI-) associated mutations on the efficacy of dolutegravir-containing antiretroviral therapy (ART) is of utmost importance. We describe a rare case of a patient with pre-existing M184V/I mutation and virological failure on a dolutegravir/lamivudine/abacavir regimen with the emergence of integrase strand transfer inhibitor resistance mutations. Additional risk factors, which may have triggered the virological failure, included suboptimal adherence and low nadir CD4+ cell count. This case illustrates that dolutegravir-containing triple-therapy should be prescribed with caution to patients with pre-existing M184V/I mutation and poor efficacy of the reverse transcriptase inhibitor backbone. In addition, this case highlights the need for viral load monitoring in patients on dolutegravir-containing regimens in settings with a high prevalence of the M184V/I mutation such as in low-income countries. Infection with the human immunodeficiency virus type 1 (HIV-1) can be very efficiently treated with combination antiretroviral therapy (cART), however, this success can be jeopardized by the emergence of HIV-1 drug resistance. Dolutegravir (DTG) is a second-generation integrase strand transfer inhibitor (INSTI) often used as a component of preferred cART due to its favorable properties, including a high genetic barrier to resistance, good tolerability and safety profile, and low potential for drug-drug interactions ,3,4,5,6.With the current widespread use of DTG in low-income countries, the understanding of the impact of nucleoside reverse transcriptase inhibitor (NRTI-) associated mutations on the efficacy of dolutegravir-containing ART is of utmost importance . The M18Here we describe a rare case of a patient with a pre-existing M184V/I mutation who failed on the ABC/3TC/DTG regimen with the emergence of resistance to all currently licensed INSTIs including the second-generation INSTIs DTG and bictegravir (BIC).A 45-year-old man who has sex with men was diagnosed with HIV-1 infection in March 1997. The CD4+ cell count at the time of diagnosis revealed 325 cells per microliter (µL) blood with an HIV-1 viral load of 94,267 copies (cp) per milliliter (mL) plasma. His medical history was remarkable for chronic depression and intermittent illicit drug use. ART consisting of nelfinavir (NFV), 3TC, and stavudine (d4T) was initiated and virus suppression below the limit of quantification of 50 cp/mL plasma was achieved six months later . AccordiFollowing the SSITT trial, the patient remained off ART until October 2008. At that time, the CD4+ cell count had decreased to a nadir of 167 cells/µL blood with a viral load of 114,000 cp/mL plasma and the patient had developed candida esophagitis. Prior to developing symptoms, he did not want to reinitiate treatment although this was recommended according to treatment guidelines at that time [This is a rare case of a patient with pre-existing M184V/I mutation and virological failure on a DTG/3TC/ABC regimen with the emergence of INSTI resistance mutations. Most likely, the virological failure was triggered by suboptimal adherence and a low nadir CD4+ cell count.Virological failure with the emergence of resistance to INSTIs on a DTG-based triple-therapy is a rare event with only a few cases published so far ,3,4,5,6.The learning points of this case are manifold: Firstly, this case illustrates that patients with a low CD4+ cell count nadir, pre-existing NRTI-associated mutations, and poor adherence are not candidates for a DTG-containing regimen with limited efficacy of the NRTI-backbone, at least not without close monitoring of the viral load. Other INSTIs with a lower resistance barrier than DTG, such as elvitegravir (EVG) in the co-formulation EVG/cobicistat/FTC/TAF, showed to be effective in maintaining viral suppression despite archived M184V/I mutations at week 24 in a prospective open-label study. However, in this study-population the median nadir CD4+ cell count was high (724 cells/µL blood), the sample size was small, and the observational period was rather short . FurtherOur case has several limitations. Firstly, DTG drug levels were not measured at the time of virological failure and therefore suboptimal adherence as an important co-factor for the virological failure cannot be proven. However, self-reported adherence of missed doses of ART—as systematically collected in these patients within the Swiss HIV Cohort Study—is a good predictor for poor adherence and associated with an increased risk of both viral failure and death . Hence, In conclusion, we describe a rare case of a virological failure on the DTG/3TC/ABC regimen with the emergence of resistance to all INSTIs in a patient with pre-existing M184V/I mutation. Other risk factors, which may have triggered the virological failure, included suboptimal adherence and a low nadir CD4+ cell count. This case illustrates that DTG/3TC/ABC should be prescribed with caution to patients with pre-existing M184V/I mutation, a low CD4 cell count, and/or poor adherence. Even more caution in this patient population is probably indicated when DTG/3TC containing dual regimens are planned. In addition, this case questions the current understanding of DTG as a drug with high resistance barrier similar to contemporary boosted PIs and highlights the need for close viral load monitoring in countries with a high prevalence of NRTI-mutations.


There 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.A 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.The 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  or protease inhibitor (PI)-based regimens  relative to integrase strand transfer inhibitor (InSTI)-based regimens were significantly associated with ART discontinuation. ART initiated at a later period (2015-Feb 2017)  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).ART 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. Combination antiretroviral therapy (ART) has significantly reduced the morbidity and mortality of persons living with HIV (PLWH) . The ratSeveral cohort studies found that various factors might lead to an earlier modification of the initial ART, such as multiple-tablet regimens, more than once daily dosing, injection drug use, treatment with a protease inhibitor (PI) or a high baseline viral load , 2, 6–8.The study protocol was approved by the local ethical review board of the Marmara University School of Medicine .This was a retrospective follow-up study conducted within the HIV-TR cohort including 25 tertiary care hospital clinics in 13 cities from different geographic regions in Turkey. The HIV-TR cohort covers approximately one-third of PLWH receiving treatment in Turkey. All treatment-naive adult patients (aged ≥ 18 years) who were registered in the HIV-TR cohort and who started ART between January 1, 2011, and February 28, 2017, were included. Demographic, clinical, laboratory and treatment data extracted from medical records of patients were recorded retrospectively by a web-based data collection system. Patients whose treatment initiation and discontinuation dates were available were eligible for analysis. The outcome was defined as the time to the first modification or stopping of ART during the first year of treatment. Treatment modification was defined as a change in at least one antiretroviral drug in the regimen excluding dose alterations. A stop was defined as the discontinuation of all drugs in the regimen for at least 30 days. The term discontinuation will be used throughout this article for the modification/stopping of treatment because the number of patients stopping ART was few. Reasons for discontinuation were classified as listed in the coded form in the web-based database, including intolerance/toxicity, poor compliance, immunological failure, virologic failure, treatment simplification, drug interactions, pregnancy-related issues, new CDC stage C disease, provider’s decision, patient’s willingness, prevention of future toxicities and others as documented by the clinician. Only the first modification for each patient within 1 year of treatment initiation was included in the analyses. If more than one reason was recorded, the primary reason given by the investigator was included in the analyses. ART regimens were defined according to their classes as follows: 2 nucleoside analogue reverse transcriptase inhibitor (NRTI)s + a 3rd agent  28–45), and the baseline median CD4 cell count was 346 cells/mmThe median age significantly dropped, and the number of transmissions between men who have sex with men (MSM) increased in the second study period compared to the first. The composition of antiretroviral regimens changed significantly over time, mostly because of the introduction of new drugs . EFV/TDF/FTC and lopinavir (LPV)/ritonavir (r)/TDF/FTC were more commonly prescribed in 2011–2014, while the two InSTI-based regimens (elvitegravir/cobicistat (EVG/c)/TDF/FTC and DTG/TDF/FTC) were more common in the second period  within the 12-month follow-up period, with the regimen being modified in 337 (11.2%) and stopped in 14 (0.5%) patients. Twenty-eight patients died before any change in regimen (0.9%). The baseline characteristics of patients who discontinued or continued their ART during the first year are shown in Table The main reason for discontinuation of initial regimen was intolerance/toxicity (45.0%), followed by treatment simplification (9.7%), patient’s willingness (7.4%), poor compliance (7.1%), prevention of future toxicities (6.0%), virologic failure (5.4%), and clinician’s preference (5.4%). The reasons for discontinuation by study period are shown in Table ART discontinuation within the first year of treatment was slightly lower  during the 2015–Feb 2017 period compared to 2011-2014 [12.9% ]  than with NNRTI-based regimens (6.6% [95% CI 5.0–8.3]) and PI-based regimens (7.5% [95% CI 6.0–9.2]) (p < 0.001)  and non-InSTI regimens were associated with intolerance/toxicity-related discontinuation (Table The most commonly prescribed NNRTI- and PI-based regimens during the study period were significantly more likely to be discontinued for intolerance/toxicity compared to InSTI based regimen-elvitegravir/cobicistat/tenofovir disoproxil fumarate/emtricitabine (EVG/c/TDF/FTC). However, there was no significant difference between EVG/c/TDF/FTC and other InSTI-based regimens, including dolutegravir/tenofovir disoproxil fumarate/emtricitabine (DTG/TDF/FTC) and raltegravir/tenofovir disoproxil fumarate/emtricitabine (RAL/TDF/FTC) Table . While aThe rate of discontinuation for intolerance/toxicity decreased over time (6.1% for 2011–2014 vs. 4.4% for 2015–Feb 2017), while modification for treatment simplification displayed an increasing trend . Virologic failure was not commonly reported as a reason for treatment change and decreased over time significantly Table . In the This retrospective cohort analysis examined the trend and factors associated with discontinuation of the initial antiretroviral regimen during the first year of antiretroviral therapy in the Turkish HIV-TR cohort from 2011 to 2017. The cumulative incidence of and reasons for regimen discontinuation were described. The results suggest a decline in all-cause and intolerance/toxicity-associated regimen discontinuation over the study period in the cohort. There was a significant rise in the median CD4 cell count at ART initiation, which reflects the recent changes in the recommendations of major guidelines for initiation of ART regardless of CD4 count . On the The 12-month probability of continuing initial ART regimens was similar over time, with a slight increase during the second period (from 81.4% in 2011–2014 to 85.4% in 2015–Feb 2017). Overall, drug intolerance/toxicity was the main reason for discontinuation of first-line ART, consistent with many other reports , 17. TheThe median duration of first-line ART regimens is variable in different settings depending on geographic area and income, treatment periods and availability of drugs. In the past, particularly in resource-rich settings, the probability of treatment change during the first year of treatment was high. The Swiss cohort study reported 37.0% and 45.6% treatment modifications among treatment-naive patients during 1995–1998 and 2000–2005, respectively , 19% in The decision by the patient or the healthcare provider to stop or change an ART regimen will depend to some extent on the availability of alternatives. Although many drugs in major ART classes were available and accessible without any restrictions in Turkey throughout the study period, non-availability of some drugs and formulations in the earlier periods might have been a reason to prevent modification due to toxicity/intolerance in patients with mild side effects. Because we studied only the initial modifications of treatment within the first year, the role of new drug availability on the patient’s willingness and providers’ preference was expected to be limited and contributed to the durability in the last period of the study. Thus, our results are mostly valid for the time period studied in our country and may not be applicable to other countries. Recent studies from Germany reported that most changes within the first year were not driven by virologic failure or adverse events, but were strategic such as preventing future toxicities with increasing options of modern ART , 12. We Various studies have reported that gender, age, transmission mode, treatment period, specific drugs or ART regimen may be major factors for discontinuation of first-line ART regimens , 10, 22.This study is limited by lack of data on the level of adherence and comorbidities influencing regimen durability. On the other hand, the results may be generalized to the country level because the vast majority of geographic regions were represented in the study. In addition, it was possible to assess almost all reasons for ART discontinuations because the database included a specific section for that. The HIV prevalence is low in Turkey, and care of PLWH is linked to infectious disease units, where drugs are freely available for the vast majority of patients. When a patient is linked to care, retention in care is high, as reflected by the low rates of LTFU in this study. Very few patients are IDUs or are co-infected with HCV. All of this might have contributed to the favourable outcomes in this study regardless of treatment discontinuation. On the other hand, the observational design of our study resulted in differences for baseline characteristics of patients and treatment options in two study periods. Prescribing patterns and provider preferences may change over time. Therefore, unmeasured factors may be associated with regimen discontinuation in two different time periods in our study.In conclusion, similar rates of ART discontinuation in the first year were observed in our cohort compared to those from other middle-income countries. This study suggests that all-cause discontinuation and discontinuation due to intolerance/toxicity within the first year of ART have decreased over time, most likely associated with the better tolerability and dosing convenience of newer, mostly InSTI-based regimens. Non-InSTI-based regimens, the early ART initiation period (2011–2014) and older patients (> 45 years old) were associated with a higher risk of ART discontinuation. Our results suggest that the treatment discontinuations were well managed and did not lead to poor virologic outcomes.Additional file 1: Table S1. TRIPOD Checklist: Prediction Model Development and Validation.Additional file 2: Figure S1. Prescribing patterns for initial ART in the HIV-TR cohort between 2011 and Feb 2017.Additional file 3: Table S2. Pretreatment virological and immunological characteristics of patients receiving InSTI-, PI- and NNRTI-based regimens.Additional file 4: Table S3. Pretreatment characteristics of patients receiving STR and non-STR InSTI.


Mongolia has a low incidence of human immunodeficiency virus (HIV) infection, with 281 cases reported at the end of 2019 and an estimated incidence rate of <0.01 cases per 1000 population.However, no study has analyzed the association between antiretroviral therapy (ART) outcomes and pretreatment characteristics of patients with HIV/acquired immunodeficiency syndrome (AIDS) in Mongolia. This retrospective study aimed to determine the survival, CD4 T cell recovery, and immune reconstitution pattern during ART in HIV patients and to determine baseline patient characteristics associated with ART outcomes. Based on three different World Health Organization (WHO) guidelines, we analyzed the 3-year observation data of 166 patients with HIV/AIDS who received treatment between 2010 and 2017. An increase of >50 cells/μL indicated CD4 T cell count recovery, and a cell count of ≥500 cells/μL in patients with a baseline cell count of <500 cells/μL indicated immune reconstitution. In this study, the 3- and 1-year mortality rates were 5.4%  and 3.6%, respectively. A total of 83% of deaths that occurred in the observation time occurred within the first 3 months. The CD4 T cell count recovery rates at 3, 12, and 36 months were 62.7%, 80.7%, and 89.2%, respectively. The CD4 T cell count increased to >500 cells/μL in 95 of 145 (65.5%) patients with a baseline cell count of <500 cells/μL after 36 months of ART. The baseline CD4 T cell count was found to be a sensitive indicator for immune reconstitution. An advanced pretreatment clinical stage of HIV infection (as classified by the WHO classification), a low CD4 T cell count in the peripheral blood, and a high viral load before the initiation of the first-line ART accurately predicted survival, CD4 T cell count recovery, and immune reconstitution in Mongolian patients with HIV/AIDS. The human immunodeficiency virus (HIV) is a lentivirus a subgroup of retrovirus that causes HIV infection and over time acquired immunodeficiency syndrome (AIDS) , 2.Mongolia is a low incidence country for HIV infection with 281 cases reported in end of 2019 and estimated rate of less than 0.01 cases per 1000 population , 4. DespSince 1992, when was detected first case of HIV infection the HIV spread among population in the country may was sporadic until 2002 with total 3 cases, but period of 2002–2012 characterized with dramatic increase of new cases (from 10 new HIV cases in 2002 to 90 in 2012) followed with gradual decrease (30 new cases in 2017) .Highly active antiretroviral therapy (HAART) or standard antiretroviral therapy (ART) consists of the combination of at least three antiretroviral (ARV) drugs to maximally suppress the HIV virus and stop the progression of HIV disease. Huge reductions have been seen in rates of death and suffering when use is made of a potent ART regimen, particularly in early stages of the disease , 8. InitSince 1992 quit number of reports focused on epidemiological situation and response activities of HIV/AIDS in Mongolia . SeveralObjective of this retrospective study is to clarify survival, CD4 T cell recovery and immune reconstitution pattern of patients with HIV during their antiretroviral therapy and to establish a baseline patient characteristics associated with the ART outcome.According to Law on prevention of HIV infection and AIDS approved by Mongolian Parliament  in 2012 By the end of 2019 year 257 off total 281 confirmed HIV/AIDS cases in the country since 1992 were treated with one 6 different combination regimens (protocols) of ART.In this retrospective study was analyzed data of 3 year (36 months) observation of 166 HIV/AIDS patients treated from November 2010 to November 2017 according to 3 different guidelines recommended by the World Health Organization (WHO guidelines) –28. DiffBaseline demographic, behavioral and clinical data of enrolled in this study patients were collected before the initiation of ART from their medical records and shown in the Tables Ethical issues of the study and consent form were reviewed and approved in Institutional Review Board of Mongolian National University of Medical Sciences in 22 June 2018. Informed consent in written form was received in 159 patients during their ART visit in AIDS/STI division. Data of 7 patients in which AIDS-related death were occurred before ethical approval were included to the study without written consent. The Mongolian Parliament approved the Law on Prevention from Human immunodeficiency virus infection and acquired immunodeficiency syndrome in 2004, and a new version was approved in 2012. Following these laws, numerous regulations were confirmed in the form of orders from the Minister of Health and internal regulations of organizations. According to these regulations, the personal information of patients is strictly classified in order to avoid any form of discrimination. Researchers, medical personnel are prohibited from copying, photographing the personal information from medical documents of the patient. In particular, patients should not declare the closest family ties, if they do not want to. And we had no information about the next of kin for deceased patients. We stated these difficulties with a written permission from the next of kin to the Institutional Review Board. IRB approved the study design.Informed consent form were designed according to the WHO Informed Consent Form Template for Clinical Studies .Data for three year observation during first-line ART was available in 166 patients received first-line ART. 1D scheme of ART by combination of tenofovir (TDF), lamivudine (3TC) and efavirenz (EFV) was conducted in 135 patients and 1F scheme of ART by combination of tenofovir (TDF), emtricitabine (FTC) and efavirenz (EFV) were conducted in 31 patients.The term CD4 T cell count recovery to ART with responders or non-responders has an ambiguous meaning . In thisOccurrence of the immune reconstitution in patients with baseline immunosupression (with baseline CD4 T cell count less than 500 cell/μL) was considered when cell count reach the level 500 cell/μL and higher. Immune reconstitution was monitored in time 3 points after initiation of ART, same as in CD4 lymphocyte recovery cases.TM, Becton Dickinson, USA) using BD FACSCount reagent kit for enumerating absolute counts of CD4, CD8, and CD3 T lymphocytes in unlysed whole blood  [Count of T cell subsets in peripheral blood (cell/μL) of patients were performed by flow cytometry (BD FACSCount 340167) .® HIV-1 v2.0, bioMérieux SA). Were used NucliSENS EasyQ® HIV-1 v2.0 kit for NASBA®-based amplification and real time detection of HIV-1 RNA [Viral load (copy/μL) was measured by nucleic acid amplification assay  was calculated using Wald test. Receiver operating characteristics (ROC) analysis was performed to estimate sensitivity of baseline CD4 T lymphocyte count for survival, CD4 T cell count recovery and immune reconstitution in different time of the ART. The Kaplan–Meier estimator was used for analyzing the survival function and estimating CD4 T cell recovery and immune reconstitution during the time of observation.Data on survival, CD4 T cell count recovery, and immune reconstitution in patients who received first-line ART are shown in th months of antiretroviral therapy in accordance to baseline characteristics defined before initiation of the therapy and shown in the Survival rate of the HIV-1 infected patients in the end point of observation or in the 36Some baseline characteristics such as advanced disease stage, low count of peripheral blood CD4 T cells, and high replication activity before ART initiation may predict a higher risk for fatal outcomes and poor survival .We analyzed the survival of HIV-1 infected patients who received first-line ART according to the baseline characteristics using the Kaplan–Meier estimator. The survival rates of patients with advanced stage (stage IV) HIV infection before ART initiation  and pati2 = 5.836; RR = 0.478; PPV = 15.4%). The recovery rate significantly increased in the third year (p<0.001) compared with that in the first year. Advanced pretreatment clinical stage, low baseline CD4 T cell count, and diagnosis of tuberculosis (TB) after ART initiation had a higher risk of non-responsiveness and lower response rate to ART  had a reduced CD4 T cell count recovery rate during ART compared with patients with clinical stages I–III .Significant differences were found in the distribution of immune reconstitution state (CD4 T cell count: >500 cells/μL) at different observational time-points according to the baseline CD4 T cell count, clinical stage, and viral load in 145 patients with a baseline CD4 count of <500 cells/μL. The relative risk and PPV of these baseline characteristics for the development of immune reconstitution were calculated in these patients .No or a low capacity for the development of complete immune reconstitution was observed in patients with advanced stages of the disease during ART, especially in the early stages of ART.By contrast, patients with early stages of the disease (stage I) and a higher count of CD4 T cells (350–500 cells/μL) had a greater possibility of being cured from immune suppression and the possibility gradually increased during ART.Receiver operating characteristic (ROC) analysis revealed that the baseline CD4 T cell count was a sensitive predictive value for immune reconstitution , but notImmune reconstitution function during the ART in patients with baseline immunosupression was differentiated according to disease stage  and baseAn advanced pretreatment clinical stage of HIV infection (as classified by the WHO classification), a low CD4 T cell count in the peripheral blood, and a high viral load before the initiation of first-line ART were found to be accurate predictive factors for survival, CD4 T cell count recovery, and immune reconstitution in Mongolian patients with HIV/AIDS.In this study, the 3- and 1-year mortality rates were 5.4%  and 3.6%, respectively. A total of 83% of deaths that occurred in the first year occurred within the first 3 months. The 1-year mortality rate in our study was lower than that  in a South American multinational study 1996–2007), which reported that 80% of the AIDS-related deaths that occurred in the first year occurred within the first 6 months . The fir96–2007, The CD4 T cell count recovery (increase of >50 cells/μL) rate at 3, 12, and 36 months of ART were 62.7%, 80.7%, and 89.2%, respectively. The 1- and 3-year non-response rates were lower in our cohort  than in an Ethiopian cohort  . RegardiThe CD4 T cell count increased to >500 cells/μL in 65.5% (95/145) of patients with a baseline cell count of <500 cell/μL after 36 months of ART initiation in our study. The immune reconstitution rate was higher than that (47.6% at 60 months) in an early Swiss HIV cohort  and loweSome studies have reported delayed and low rate of immune reconstitution during ART, especially in early periods of the therapy in patients with advanced stages of the disease , 43. TheWe found that a high viral load  before ART initiation was associated with incomplete immune reconstitution. Although several studies have reported the association between the pretreatment viral load and immune reconstitution in patients receiving ART , some stWe found a strong association between ART outcome and the baseline CD4 count and pretreatment clinical stage of HIV/AIDS. The small number of patients we observed and the short observation period may not have allowed us to find as many predictive values as described in long-term studies performed in a large population. Furthermore, data on reduction of viral replication during therapy were insufficient for accurate analysis.An advanced pretreatment clinical stage of HIV infection (as classified by the WHO classification), a low CD4 T cell count in the peripheral blood, and a high viral load before the initiation of first-line ART were found to be accurate predictive factors for survival, CD4 T cell count recovery, and immune reconstitution in Mongolian patients with HIV/AIDS.S1 Questionnaire(DOCX)Click here for additional data file.S2 Questionnaire(DOCX)Click here for additional data file.


Abacavir (ABC) and Zidovudine (AZT) based regimens are the preferred first line nucleoside reverse transcriptase (NRTIs) backbones being widely utilized for managing HIV infection in children. However, there is a dearth of data regarding the clinical outcomes and associated risk factors in Ethiopia. We compared the proportion of mortality and the rate of occurrence of Opportunistic Infections (OIs) with ABC versus AZT -based regimens in a cohort of HIV-infected children.A 42 months retrospective cohort study was conducted. A total of 179 records were reviewed by including data from October 2014 to April 2017. Data were collected on socio-demographic, clinical characteristics of patients and drug related variables. Data were analyzed using STATA13.1. Kaplan-Meier and Cox regression were used to compare survival experience and identify independent predictors. Propensity score matching analysis was conducted to elucidate the average treatment effects of each regimen over OIs.+SD) age of the study subjects was 6.53 ± 2.83 years. Through 42 months analysis, a total of 4 patients (1 (1.14%) from ABC group and 3 (3.3%) from AZT group (p = 0.339)) were died. The incidence of opportunistic infections attributed to ABC group was 8.77/100,000 person years (py) and that of AZT was 6.9/100,000py. The incidence rate ratio (IRR) for OIs was . Baseline CD4 count , Severe acute malnutrition , and exposure to tuberculosis treatment  were the independent predictors for the development of OIs.Of 179 patients, 98 (54.7%) were females. The mean (ABC and AZT based ART regimens seem to have comparable survival benefit among HIV-infected children in Ethiopia. Therefore, both regimens might be used as an alternative in resource limited settings. Globally, an estimated 2.4 million children are living with Human Immune Virus (HIV) and 91% of them are lived in Sub-Saharan Africa . Of thesThe introduction of Antiretroviral Therapy (ART) had resulted in dramatical reduction of HIV associated morbidity and mortality in children , 6. HoweHLA-B*5701 allele, although these are rare in Africa because of a lower risk-allele prevalence  and that of AZT was 6.9/100,000py. The incidence rate ratio (IRR) was found to be 0.87, 95% CI [0.49–1.53], implying that the difference is statistically insignificant  and among those who received the actual treatment   Table . Althoug2) Table . This se2 Table .ATE Estimated average treatment effect in the population, ATET Estimated average treatment among treated, CI Confidence interval, AI Abadie-imbensAfter checking for model fitness and considering all the assumptions, a Cox-proportional hazard regression was conducted to identify predictors for the development of OIs. On bivariate Cox-regression, baseline body mass index, baseline weight for height (WFH), area of residence, baseline CD4 count, baseline viral load, WHO clinical stages, nutritional status and exposure to anti-tubercular drugs were associated with the development of OIs. After adjusting all the confounders with Cox-proportional hazard model, baseline CD4 count, exposure to anti-tubercular drugs and nutritional status remained independent predictors of OIs. Accordingly, there was a 1% reduction in the hazard of OIs development as median baseline CD4 count increased by a unit . Moreover, exposure to tuberculosis treatment had also carried significant risk of OIs, (AHR = 2.93 [1.39–6.17]) . Similarly, there was no difference in the incidence of opportunistic infection . Moreover, the finding from propensity score matching showed statistically insignificant difference of ABC based regimen’s effect on opportunistic infections . A similar finding was obtained in the CHAPAS-3 study. This RCT compared the NRTIs ABC, AZT and d4T in HIV-infected African children, and found that all three NRTIs had similar outcomes in terms of clinical, immunological and virological responses [The reported mortality between the ABC and AZT groups was statistically insignificant. There was only 1 (1.14%) death from ABC group and 3 (3.3%) deaths from AZT group . Similar findings were found from Ethiopia  and NigeHowever, paediatric patients with malnutrition had extremely high risk of having opportunistic infections , similar to studies in Ethiopia , NigeriaMoreover, exposure to tuberculosis treatment had also carried significant risk of OIs. Accordingly, patients with anti-tubercular drug treatment were three times at higher risk of having opportunistic infections . This might be related to the killing of mycobacteria by anti-tubercular drugs releasing large amounts of mycobacterial antigens, which can stimulate an exuberant inflammatory response. The resulting excessive inflammatory response leads to unmasking of an underlying occult opportunistic infections .The results of our study should be interpreted in the context of several possible limitations. Firstly, as the sample size was relatively small the power to detect definitive differences may have been limited. Measure of adherence by health professionals that may not fit to the reality, and inability to assess the occurrence of specific OIs are some of the limitations.In present study, there was no statistically significant difference in mortality and occurrence of opportunistic infections between those exposed to ABC versus AZT based regimens. Baseline CD4 count, nutritional status, and exposure to tuberculosis treatment were the independent predictors for the development of OIs. The study highlighted the need for special attention for these patients groups over the course of treatment provision.


Myanmar has introduced routine viral load (VL) testing for people living with HIV (PLHIV) starting first-line antiretroviral therapy (ART). The first VL test was initially scheduled at 12-months and one year later this changed to 6-months. Using routinely collected secondary data, we assessed program performance of routine VL testing at 12-months and 6-months in PLHIV starting ART in the Integrated HIV-Care Program, Myanmar, from January 2016 to December 2017. There were 7153 PLHIV scheduled for VL testing at 12-months and 1976 scheduled for VL testing at 6-months. Among those eligible for testing, the first VL test was performed in 3476 (51%) of the 12-month cohort and 952 (50%) of the 6-month cohort. In the 12-month cohort, 10% had VL > 1000 copies/mL, 79% had repeat VL tests, 42% had repeat VL > 1000 copies/mL (virologic failure) and 85% were switched to second-line ART. In the 6-month cohort, 11% had VL > 1000 copies/mL, 83% had repeat VL tests, 26% had repeat VL > 1000 copies/mL (virologic failure) and 39% were switched to second-line ART. In conclusion, half of PLHIV initiated on ART had VL testing as scheduled at 12-months or 6-months, but fewer PLHIV in the 6-month cohort were diagnosed with virologic failure and switched to second-line ART. Programmatic implications are discussed. The scale up of antiretroviral therapy (ART) has been one of the great public health success stories of our time. By June 2019, there were 24.5 million people globally receiving ART, representing 62% of all people living with HIV (PLHIV) .The response to ART in the initial years of treatment scale-up was monitored clinically and by CD4 cell count. However, the deficiencies of these methods, particularly in the high HIV-burden countries in sub-Saharan Africa ,6. GuidaIn Myanmar, the HIV epidemic is concentrated among key populations and in 2018 there were an estimated 240,000 people living with HIV (PLHIV) of whom about 167,000 (70%) were on ART ,11. In 2The International Union Against Tuberculosis and Lung Disease (The Union) has been implementing an integrated HIV care (IHC) program in Myanmar in collaboration with the national AIDS program (NAP) since 2005. The program introduced routine VL testing in January 2017. Initially, the first VL test was done at 12-months after starting ART. One year later, in January 2018, the policy changed to do the first VL test at 6-months after starting ART. Although this change has already taken place, there is no information about whether health workers have been compliant with policy or whether VL testing at 6-months identifies the same proportion of PLHIV with high VL and ART failure as compared with VL testing at 12-months. For example, it is possible in PLHIV with high baseline VL and advanced HIV-related disease that viral suppression has still not occurred by 6-months and such patients with VL > 1000 copies/mL might mistakenly be diagnosed as failing treatment. Alternatively, true virologic failures may be more common at 12-months rather than 6-months. The change in policy and practice in Myanmar between 2017 and 2018 provided an opportunity to describe and assess programmatic performance and outcomes of doing the first routine VL testing at 12-months and at 6-months.The aim of this study therefore was to describe and report on the programmatic performance and outcomes of routine VL testing at 12-months and at 6-months in PLHIV newly initiating first-line ART in the IHC Program in Myanmar. Specific objectives for PLHIV in the two cohorts, those VL tested at 12-months or those VL tested at 6-months, were to (i) describe and compare baseline characteristics, (ii) document who had VL testing, both within and outside of the scheduled times, (iii) describe the cascade and outcomes of VL testing including the diagnosis of virologic failure and switch to second-line ART and iv) assess risk factors for virologic failure amongst those who were VL tested within the scheduled time periods.This was a retrospective cohort study using routinely collected secondary data.2, is located in mainland Southeast Asia and it borders China to the northeast, India and Bangladesh to the west, Laos to east and Thailand to the east and southeast. According to the provisional results of the 2014 Census, Myanmar had a total population of about 52 million [The Republic of the Union of Myanmar, with a total surface area of 676,578 km million . Myanmar million . The couThe Union has been implementing an “Integrated HIV Care Program IHC” in collaboration with the National AIDS Program (NAP) and National Tuberculosis Program (NTP) in Mandalay Region, Sagaing Region, Magway Region, Yangon Region and Shan State since 2005. The details of the NAP and Union IHC program have been previously described .In 2018, there were 49 IHC clinics in 37 townships in Myanmar. Every month around 370 patients with a confirmed HIV diagnosis were registered for care and treatment at Union IHC clinics. After enrolment, all PLHIV were evaluated for ART eligibility and started ART if they were eligible according to the most recent national ART guidelines (which currently recommend the “HIV test and treat” approach in line with WHO guidance) . There wBefore 2017, PLHIV started on ART were monitored by CD4 cell counts and clinical assessment to decide on whether they were failing ART. Those who were judged to have failed treatment on those grounds were targeted for VL testing—PLHIV with VL > 1000 copies/mL received adherence counseling and if the repeat test still showed VL > 1000 copies/mL, a diagnosis of virologic failure was made and first-line treatment was changed to second-line treatment. In January 2017, the program introduced routine VL testing, with the first test done at 12-months after starting ART. One year later, in January 2018, the policy changed to do the first VL test at 6-months after starting ART. In brief, the procedure of VL testing involved the collection of venous or capillary whole blood or plasma at the public laboratories where IHC clinics implemented activities, with specimens then transported to the central Public Health Laboratory, Mandalay. The VL assay was performed at the central laboratory and results sent back to the clinics.The management of patients was based on the results of VL testing. In brief, if the first VL > 1000 copies/mL, enhanced adherence counseling (EAC) took place, which involved one intensive counseling session by social workers under the guidance of medical officers. A repeat VL test was performed 3–6 months later. If VL < 1000 copies/mL the patient was maintained on first-line ART. If VL > 1000 copies/mL, a diagnosis of virologic failure was made and the patient was switched to second-line therapy.Every patient registered in the IHC program had a dedicated file in which baseline and follow-up clinical details and laboratory test results were entered by the treating doctors. Patient data from each IHC clinic was entered to an electronic database of the NAP and The Union on a regular basis. Every month, these IHC electronic data were sent to a central electronic database at the Union office in Mandalay, which was maintained by a Monitoring, Evaluation, Accountability and Learning Unit. Data quality control of all electronic databases was performed at regular intervals to minimize errors with data entry and to ensure data validity and consistency.The study included all adult and pediatric PLHIV who newly started first-line ART between 1 January 2016 and 31 December 2017 in all IHC clinics, Myanmar. The study group comprised of two cohorts: PLHIV initiated on ART between 1 January 2016 and 30 June 2017 who had first VL testing scheduled at 12-months and PLHIV initiated on ART between 1 July 2017 and 31 December 2017 who had first VL testing scheduled at 6-months.Data variables: these included patient ID number, date of starting ART, type of first-line ART regimen, age, sex, marital status, mode of HIV transmission, employment, literacy status, baseline WHO clinical stage, baseline CD4-cell count, co-infection with Hepatitis B (HBsAg positive) and Hepatitis C (HCV-antibody positive), diagnosis of TB at start of ART, programmatic outcome at time of VL testing at either 12-months or 6-months , first VL test done, date of first VL test, VL > 1000 copies/mL, repeat VL test done, date of the repeat VL test, repeat VL > 1000 copies/mL, switched to second-line ART and date of switching to second-line ART. Data for the VL cascade and outcomes were censored on March 31, 2019.Operational definitions: a first viral load test done at 12-months was programmatically defined as PLHIV having a VL test done between 10 and 15 months after starting ART. A first viral load test done at 6-months was programmatically defined as PLHIV having a VL test between 4 and 9 months after starting ART. In each case the time range was there to allow for PLHIV having difficulties in accessing clinics. VL tests done outside of these times were defined as unscheduled tests.Source of data on patient characteristics and laboratory results including VL was the central electronic database of the NAP and The Union in Mandalay.Data collection: Data were collected by exporting the data in the central electronic data base to an EXCEL file in April 2019.p-value < 0.2 in bivariate analysis were included in an adjusted logistic regression model. Levels of significance were set at 5% .Data were exported from the EXCEL file into STATA and analyzed using STATA . Frequencies and proportions were used to summarize categorical variables and medians and interquartile ranges (IQR) used to summarize continuous variables. There were two cohorts of PLHIV: (i) those with first VL testing at 12-months after initiating ART and (ii) those with first VL testing at 6-months after initiating ART. Characteristics of PLHIV, viral load testing and outcomes between the two cohorts were compared using Pearson’s chi-square test and chi square test for trend. Baseline risk factors associated with the diagnosis of virologic failure (VL > 1000 copies/mL on repeat VL testing) in those who were tested for VL at 12-months or 6-months were analyzed using risk ratios (RR) and 95% confidence intervals (CI). Factors that showed associations with Permission for the study was obtained from the National AIDS Program (NAP). Ethics approval was obtained from the Ethical Review Committee, Department of Medical Research, Myanmar (Ethics/DMR/2018/131) and the Ethics Advisory Group, International Union Against Tuberculosis and Lung Disease, Paris, France (EAG number: 46/18). Data were collected in a designed format  with no patient names and confidentiality was maintained by keeping patients’ files in a lockable cabinet and electronic data securely in a password protected computer. As secondary data were used, the need for informed patient consent was waived.There were 9129 PLHIV initiated on ART between 1 January 2016 and 31 December 2017: these included 7153 PLHIV who had VL testing scheduled for 12-months and 1976 who had VL testing scheduled for 6-months. Demographic and clinical characteristics of PLHIV in the two cohorts are shown in VL testing at and outside of the scheduled times is shown in The cascade of VL testing in the 12-month cohort is shown in The cascade of VL testing in the 6-month cohort is shown in p < 0.001. Of the 17 PLHIV in the 12-month cohort with virologic failure who did not switch, 11 (65%) died or were lost to follow-up or transferred-out, which was similar to 6 (43%) of 14 PLHIV in the 6-month cohort who died or were lost to follow-up . There were no substantial changes in the main conclusions presented above for either of the two cohorts.There were four main findings from this observational cohort study on programmatic performance and outcomes of routine VL monitoring done at 12-months and at 6-months in PLHIV newly initiating ART in the IHC program in Myanmar.First, baseline demographic, clinical and immunological characteristics of both cohorts were similar with about one third of PLHIV starting ART either in WHO clinical stage 3 and 4 or with CD4 cell counts< 200 cells/µL. Before 2017, national guidelines specified that PLHIV should start ART if they were in WHO clinical stage 3 or 4 or if the CD4 count < 500 cells/µL . HoweverSecond, in both cohorts about half of PLHIV had VL testing done at the scheduled time of 12-months or 6-months according to our definition and according to policy. Of those who had VL testing done outside the scheduled time, this was more common amongst the 6-month VL testing cohort. We did not collect detailed information on when these PLHIV had non-scheduled VL tests or the reasons for this non-compliance with policy. However, we speculate that this may have been due to clinicians requesting earlier VL testing based on the need to know, for example in pregnant women, or later VL testing based on patient clinical status. While previous studies have shown that routine VL monitoring results in earlier detection of virologic failure and earlier switching to second-line ART ,22, a reThird, while only half of both cohorts had their first VL test done at the scheduled time, about 80% of PLHIV with VL > 1000 copies/mL on the first test had repeat VL tests done. This performance compares favorably with similar assessments from other countries . MoreoveFourth, risk factors for virologic failure in both cohorts were advanced HIV-related disease and/or immunosuppression. These findings are in line with previous reports ,30,31, aThe strengths of this study were the large numbers of patients initiated on ART in both cohorts, rigorous monitoring of hard milestones and end points along the VL testing cascade and the conduct and reporting of the study in line with the strengthening the reporting of observational studies in epidemiology (STROBE) guidelines .There were, however, some limitations. First, we did not collect detailed information on PLHIV who had VL testing done outside of the scheduled times. However, the main purpose of our study was to assess VL testing and VL results for those who were tested at our defined 12-month and 6-month schedules, and we were less interested in those who were tested outside of these schedules for whom the interpretation of results would have been difficult. Second, there is the possibility of a selection bias or survival bias as we only included PLHIV who were VL tested in the risk factor analysis for VL failure. To address the selection bias, we compared the characteristics between patients included in the analysis and those who were not included and found that they were similar apart from some small differences in the regions from where they came from. Thus, we concluded that the potential impact of selected bias was small. To address survival bias and the possibility that we might have misclassified those with VL failure, we conducted a sensitivity analysis by classifying those who did not have VL testing a second time as VL failure and found that there was no substantial change in results and our main conclusion stays the same. Third, we did not have information on what happened to PLHIV who did not have their first or repeat VL tests done and we did not enquire as to why those with defined virologic failure were not switched to second-line ART. Fourth, we did not record details about when and how well EAC was performed between first and repeat VL tests. Fifth, the two cohorts (the 12-month VL testing cohort and the 6-month VL testing cohort) were enrolled and managed on ART at different but consecutive time periods. It is possible that the health system and health service factors were different in 2018 compared with 2017 and 2016, although we have no evidence to suggest that this was the case. Finally, the follow-up period for repeat VL testing and switching to second-line ART was shorter for the 6-month cohort and the lack of time for these events to have happened compared with the 12-month cohort may be one of the explanations for a low proportion of the 6-month testing cohort switching to second-line ART.Despite these limitations, there are some important programmatic implications from this study. First, VL testing is key to monitoring VL suppression and has to be done to assess progress against the UNAIDS 90-90-90 targets . The polSecond, once the first VL test is done close attention must be paid to following through the VL cascade. Those who have VL > 1000 copies/mL must be referred early for good quality EAC under the guidance of medical officers and a repeat VL test must be done about 3 months later. Both primary and acquired ARV drug resistance are becoming a global problem ,9, and rFinally, how clinicians and PLHIV view the early timing of VL testing and the decision to switch to second-line ART may change as new WHO guidelines become adopted. Since this study was done, the WHO has recommended changes to first-line ART, such as the use of dolutegravir (DTG) to replace efavirenz . DTG, anThis study showed that about half of PLHIV initiated on ART had VL testing at 12-months or 6-months in line with policy, with an additional one fifth having the tests done outside of the scheduled times. In terms of the VL cascade, a similar and satisfactory pattern was seen in both cohorts up to VL retesting, but thereafter less PLHIV in the 6-month cohort were identified with virologic failure and fewer were switched to second-line ART compared with the 12-month cohort. Reasons for these findings and programmatic implications are discussed.


Elite controllers (EC) are a rare group of HIV‐1‐positive individuals who suppress viral loads (VL) to undetectable levels with elevated CD4 T‐cell counts in the absence of ART. While rates of short‐ and mid‐term progression have been described in these patients, few studies have focused on their long‐term outcome This study aims to describe the virological and immunological behaviour in a cohort of elite controllers followed up for a median of 17 years in the University Hospital, and to identify factors that may be related to disease progression.We conducted a descriptive, prospective and single‐centre study of all HIV‐positive adults recorded in the University Hospital database who met the definition criteria for EC. EC were defined as patients having two consecutive undetectable VL without ART for at least one year. Patients were followed from baseline up to December 2019, to the development of a progression event  or to the censoring date (lost to follow‐up or initiation of ART). Predictive models of progression were calculated.Fifty‐nine EC were identified with a median follow‐up of 17 years contributing 1033 PYFU. The median (95% CI) time duration from HIV‐1 diagnosis to disease progression was four (1.7 to 6.3) years. Forty‐nine (83%) presented progression to the composite end‐point, 44 (74.6%) lost viral control, 39 (66.1%) lost immunological control, two developed AIDS and two died. Only 10 patients (16.9%) did not show progression of any kind. Independent predictors of virological progression were sexual risk of HIV‐1 acquisition and VL blips during the first year of follow‐up (baseline). The only independent predictor detected for progression to a composite end‐point was VL blips during the first year of follow‐up (baseline).The rate of long‐term progression in EC was very high. Only a minority of patients did not show clinical progression after a median of 17 years of follow‐up. These results should be taken in account when considering EC as a model of HIV‐1 remission. Although the ultimate elimination of HIV reservoirs remains a distant goal, the existence of elite controllers (EC) has guided the creation of a plausible model of functional cure. Elite controllers are HIV‐1‐positive individuals who spontaneously suppress viraemia to undetectable viral loads (< 50 copies/mL) while maintaining elevated CD4 cell counts without receiving antiretroviral therapy. These patients are rare, representing only 0.2 ‐ 0.5% of HIV‐1‐positive cases . Models for predicting baseline markers associated with virological, immunological or combined HIV‐1 disease progression included all the available baseline characteristics of the patients: age, sex, risk for HIV‐1 acquisition, hepatitis C virus (HCV) serology, HCV cure during the follow‐up  or no detectable HCV replication after 12 weeks of treatment, nadir CD4+ T‐cell count, zenith viral load (VL), baseline CD4+ cell count and baseline VL defined as the first measurement during follow‐up at our centre, and total years of follow‐up. The years of follow‐up were estimated using the date of diagnosis as the starting point.3 or time to combined progression, involving an AIDS‐defining event, death, starting ART, and virological or CD4 progression). To calculate time to combined progression, the limiting factor was set as the first of the progression events to occur. Subsequently, potential determinants of clinical events were studied using Cox regression models. The significant variables selected in the univariate analysis were included in the multivariate analysis using a stepwise forward  method. All statistical analyses were performed using SPSS software version 25 .A univariate analysis by Kaplan–Meier estimates, log‐rank tests and proportional hazard models was performed to analyse the influence of the different variables on the time to study end‐points  lost virological control and two (3.4%) died. As various VL tests and detection limits had been used, we standardized the blipping using 200 copies/mL as the definition in a sensitivity analysis, which confirmed the results (data not shown). In the two patients who died, the cause of death was cirrhosis in one and unknown in the other. Of the 44 patients who experienced virological failure, 36 (81.9%) also presented concomitant immunological failure, two of whom presented AIDS‐defining events (one pulmonary tuberculosis and the other lymph node tuberculosis). Only 10 patients (16.9%) did not show progression of any kind during the follow‐up. Fifty percent of the patients without progression were males with a median (IQR) age of 55 years old (40 to 60), 60% were coinfected by HCV, and the medians (IQR) of baseline and nadir CD4 T cell count were 872 (678 to 1066) and 736 (524 to 835) respectively. In these patients the median (IQR) length of follow‐up was 20 years (5 to 29); five had been followed up for more than 25 years (range 25 to 35 years).Among the 863 patients included in the first search for two undetectable viral loads without ART in the Hospital Clínic HIV database, 59 elite controllers were identified. Patients were followed up for a median of 17 years (IQR 9 to 25), thus contributing 1033 PYFU. The main characteristics of the EC in this study are summarized in Table 3.2The univariate analysis reflected that the age below the median (≤38 years old), parenteral group risk for HIV‐1 acquisition, HCV infection, baseline CD4+ T cell levels above the median and the absence of viral load blips in the first year of follow‐up (baseline) had a significant impact on virological progression. All these variables were associated with a longer maintenance of undetectable viral load levels. Nadir CD4+ T cell levels above the median showed a trend towards persistent viral control. In the multivariate analysis, variables which proved to be independent predictors of VL progression were sexual group risk for HIV‐1 acquisition [HR 2.2 (1.1 to 4.2)] and the presence of viral load blips in the first year of follow‐up (baseline) [HR of 2.1 (1.1 to 4.0)]. All the results are displayed in Tables 3.33 met our criteria for progression. This isolated CD4+ reduction lasted for less than one year, was not lower than 400 cells/mm3 and was not recorded in any of the subsequent determinations. Removal of these six patients from the progression group reduced the immunological failure rate to 55.9%, closer to the 48% reported in the literature  showing that patients with viral load blips in the first year of follow‐up (baseline) were more likely to present progression of HIV infection. Specific data are shown in Table  to 4.6] 4In this study, we outline the main demographic characteristics of elite controllers at the University Hospital, the evolution of their viral, immunological and combined infection control, and also the evolution of the variables that predicted disease progression. In our cohort, rates of loss of spontaneous HIV‐1 control due to an increase in viral load or a reduction in CD4+ T cell count were notably higher than in previous studies, even though we used the same definition for elite control. While one study report incidence rates for viral and combined progression of 24% and 53%, respectively, with a median of 7 years of follow‐up  after a Interestingly, 10 patients (16.9%) did not show progression of any kind and five of these were followed up longer than 25 years. Casado et al. [Regarding the variables that predicted persistent viral load control, elite controllers with a sexual risk of HIV‐1 acquisition or with the presence of viral load blips in the first year of follow‐up (baseline) were twice as likely not to maintain long‐term virological control. Previous studies of these variables have reported similar results , 18. It 3 for longer. The latter result can be attributed to the effect of interferon alpha, the first treatment to appear for HCV, which caused a temporary reduction in CD4+ T cell levels and thus affected our results [Our immunological failure rates did not identify any independent risk factors for control maintenance. However, there was a trend for patients with an absence of viral load blips in the first year of follow‐up (baseline) and for those who were not cured of HCV to maintain CD4+ T cell counts above 500 cells/mm results .With regard to the combined loss of EC status the only independent risk factor observed was the absence of viral load blips in the first year of follow‐up (baseline). Patients with undetectable viral loads since the beginning of follow‐up had an OR of 2.5 1.3 to 4.6) for a longer survival time until all‐cause progression. A longer period of viral suppression was related to lower rates of disease progression, in agreement with previous studies [.3 to 4.6Several limitations of this study should be noted. First, because the date of HIV infection was not known, we assumed that patients had been elite controllers since the year of diagnosis. This same assumption was made for patients with the absence of viral load blips in the first year of follow‐up (baseline). Second, despite our rigorous efforts to record CD4+ T cells and VL determinations every six months, not all HIV patients regularly attended their medical appointments. However, as this was not the case for most measurements, we were able to assume that the data collected were representative of six‐month sequences. Finally, with regard to HCV IgG‐positive patients with negative RNA, no distinction between spontaneous clearance or medical treatment was made at the time of analysis. This was the case in four out of 16 cured patients who did not undergo HCV treatment.5The frequency of disease progression in elite controllers was much higher than expected. After a median of 17 years of follow‐up, only 17% of patients did not present combined disease progression. Our study raises the question of whether this proportion will decrease further with longer follow‐up further. However, it seems that a small proportion of patients maintain EC status for more than 25 years and may represent cases of spontaneous functional HIV‐1 cure. These data should be taken in account when considering EC as a model of HIV‐1 remission.The authors do not have a commercial or other association that might pose a conflict of interest.“MB, IF, FE and AU performed the research. MB, MP, LL and FG designed the research study. MB, FG and FG analysed the data. MB, LL and FG wrote the paper.”


The UNAIDS 2020 Global strategy to reduce the transmission of HIV includes ensuring HIV viral load (VL) testing coverage of at least 90% on all patients on antiretroviral therapy (ART). Routine VL monitoring has been shown to result in earlier detection of treatment failure, timely regimen switches, promotion of adherence to treatment and improved survival. We wanted to assess the introduction of the wellness anniversary in improving routine viral load monitoring.We retrospectively assessed effects of the wellness anniversary on routine VL coverage, timeliness and suppression rates.The month when the patient initiated ART was designated as the wellness anniversary. On the anniversary month a package of care, which included a routine VL, was delivered. We conducted a retrospective chart audit to assess VL coverage and timeliness between two time periods, from January 2016 to December 2016 (pre-implementation) and from January 2017 to December 2017 (post-implementation).Timeliness of VL testing improved from 27.5% in the pre-implementation cohort to 49.7% in the post-implementation cohort. Our study showed high VL testing coverage before the implementation of the wellness anniversary with an average of 98.3% VL. There was a significant correlation between timeliness and VL suppression (VLS) in the post-implementation group.Implementation of the wellness anniversary may improve timeliness of routine VL testing in settings with high VL coverage. Studies looking at the effect of timeliness on VLS and clinical outcomes are needed. In 2016, approximately 78% of people on ART in South Africa were virally suppressed, which translates into about 47% of all people living with HIV.2South Africa has the largest HIV epidemic in the world, with about 7.2 million people living with HIV in 2017.3 Routine HIV VL monitoring has been shown to improve earlier detection of treatment failure, timely regimen switches, promoting adherence to treatment and survival.4 However, the effect of timeliness of routine VL monitoring on the positive effects of routine VL monitoring is unknown. The World Health Organization (WHO) guidelines from 2013 recommended HIV VL monitoring as a preferred method to monitor treatment response.5 In South Africa, routine VL monitoring was rolled out in 2004. Testing intervals are currently at 6 months, 12 months and every 12 months thereafter if patients are suppressed. Routine HIV VL coverage in patients on ART in South Africa was approximately 72% prior to the implementation of the WHO guidelines and 75% by 2015, with 78% VL suppression (VLS).6 Factors that were found to contribute to low HIV VL testing coverage in low- and middle-income countries (LMIC) included poor adherence to WHO guidelines, low levels of staff training and lack of funding.7 However, the challenges preventing increased HIV VL coverage in South Africa may be different compared to most Sub-Saharan African countries. Quality improvement projects (QIP) have the potential to improve HIV VL coverage, such as QIP reported by Kekana et al., although the scalability of these interventions may be limited.8 Sunpath et al. also showed increased VL completion after the implementation of the VL champion in low- and high-traffic ARV clinics.9 Improved HIV VL coverage together with active tracing has been implemented in resource-poor settings and has shown to lead towards better clinical outcomes and increased retention in care.10The UNAIDS 2020 Global strategy to reduce the transmission of HIV includes ensuring HIV viral load (VL) testing coverage of at least 90% on all patients on ART.11 HIV VLS has been shown to reduce HIV transmission and improve life expectancy in people living with HIV.12 Early VLS in children is associated with better growth, immune and viral responses and psychosocial outcomes.13 Good self-reported adherence has been associated with engaged and motivated caregivers, disclosure of child and caregiver status, knowledge of ART and good patient–caregiver–healthcare provider relationships, which result in better outcomes.14 Interventions that have been shown to enhance adherence include directly observed therapy by family members, personalised treatment plans, medication diaries, convenient and pleasant clinic appointments and community-based adherence support.16 Decentralised models of ART delivery may also lead to improved virologic outcomes.17 The effects of timely VL testing on treatment outcomes is unknown.Viral load suppression in children from LMIC is lower when compared to adults in LMIC and children in high-income countries.There are multiple measures in place at the clinic to improve adherence to treatment and ensure timely VL testing including active tracing of defaulters, peer-led support groups and WhatsApp groups supervised by social workers. We implemented the wellness anniversary to ensure delivery of an annual standardised holistic package of care. We aimed to assess the effectiveness of the wellness anniversary in improving VL testing coverage and timeliness of testing.We conducted a retrospective comprehensive chart audit to assess two time periods, from January 2016 to December 2016 (pre-implementation) and from January 2017 to December 2017 (post-implementation). The primary objective was to assess and compare the coverage and timeliness of HIV VL testing between the two time periods. Secondary objectives were to describe and assess the association of VL testing coverage and timeliness with patient demographics, and to describe and assess the association of VL testing coverage and timeliness with short-term treatment outcomes.The study was conducted in King Edward VIII Hospital (KEH), Philani Family Clinic, which is a combined adult and paediatric HIV clinic in an urban area. The clinic covers a wide area which includes peri-urban and urban areas. The clinic offers both general paediatric HIV treatment services and tertiary services. The general services are provided by one permanent medical officer, a part-time medical officer and a rotating medical intern, while the tertiary service is provided by the paediatric infectious disease (ID) team once a week. All routine HIV-infected children and adolescents are initiated and followed up by the general service. The tertiary service is a referral clinic for both the general clinic and a large part of KwaZulu-Natal province. The patients managed by the ID team are referred back to the general clinic or the referring hospital with resolution of the referring problem. The audit largely focuses on the patients attending chronic follow-up in the general clinic.The study was conducted on all children below 19 years who attend the paediatric and adolescent HIV clinic in King Edward Hospital. We excluded children who were lost to follow up, children who were transferred out to other ART sites, children who died in the pre-implementation period and children who turned 19 years in the post-implementation period.The study sample included all the patients who were attending the HIV clinic and met the inclusion and/or exclusion criteria during the two study periods.We implemented a QIP at KEH in June 2016 to improve the quality of care in our patients on ART. This project involved introducing the concept of ‘wellness anniversary’ for patients and healthcare workers, to use the month of ART initiation as an annual reminder to have their VL test taken as part of a holistic package of annual assessments which included safety laboratory tests, weight, height and developmental screening. Prior to this, the clinic implemented a VL register to track VLs performed and to follow up results on a weekly basis. The effectiveness of the VL register was not assessed. The project was discussed with the management, nursing staff, counsellors and social workers working at the clinic to ensure commitment from the clinic team. Maternal Adolescent and Child Health (MatCH), a non-governmental organisation, provided the colour-coded anniversary month stickers. The nurses at the weighing station educated the patients on the aims of the wellness anniversary month. They identified the anniversary month and attached the stickers on the outpatient file and the ART clinic file. The patient was also informed about when their anniversary month was. The patients who had a VL done more than 6 months before the anniversary month and were suppressed received the package of care on their anniversary month. The patients who were not suppressed were tested according to the guideline for treatment failure. The implementation was ongoing as new patients were initiated on ART during the study period.A list of all the participants and their folder numbers was generated from the Tier.net database. Files were retrieved from the filing room according to the list, file audits were performed, and data were entered in the data collection Microsoft Excel spreadsheet. Duplication of patients’ records, patients transferred out to other sites, patients lost to follow up, and deceased patients were removed from the database.HIV VL testing was assessed by presence of results on the results sheet in the patient’s chart or the result log in the clinical chart or a specimen lab sticker in the file, or the note of the doctor’s order for the test. VL results that were not in the patient’s files were traced on the National Health Laboratory Services Trakcare system. Absolute VL results were recorded to assess the outcomes. VLs results were categorised as follows: ‘lower than detectable level’ (LTDL) if less than 50 copies per millilitre (cp/mL), ‘50–999 cp/mL’, ‘1000 cp/mL and above’, ‘None’ if no VL was done in the audit period, and ‘Not Applicable’ if a VL was not due either because the patient is on a holding regimen or has recently initiated ART and 6 months on treatment has not passed by the end of the audit.Viral load coverage was assessed by the proportion of patients with at least one routine VL testing performed in the 12 months within the study period. Timeliness was described by how promptly the patient received testing once due for testing (i.e. 12 months after the prior VL). We considered VLs which were done a month before, on or after the wellness anniversary as timely. The analysis for timeliness was performed on patients with 2 VLs or performed in a 12-month period as patients needed a maximum of two VLs in a period of 12 months as per the testing guidelines. Patients with more than two VLs were likely to have treatment failure and more frequent VL testing. Short-term clinical outcomes were assessed by HIV VLS.p-values.Statistical analysis was done by looking at means, medians and standard deviations. Measures for statistical significance used were Pearson’s chi squared test and All patients were included for file review to reduce selection bias. There was no blinding to reduce bias when files were reviewed.Ethics approval was obtained from the Biostatistics Research Council (BREC) of the University of KwaZulu-Natal . Gatekeeper approval was obtained from King Edward VIII Hospital and the Department of Health.We reviewed 1468 patient folders. The pre-implementation dataset excluded 387 patients that were lost to follow-up, 209 patients that were transferred out and 24 patients that died. The final number of patients included for analysis was 850 in the pre-implementation group. The post-implementation dataset excluded 38 patients that turned 19 before the end of the audit, 24 patients that were lost to follow-up and 23 patients that were transferred out. We ended up with 765 patients in the post-implementation group.The baseline VL coverage was 98.3% in the pre-implementation group and 97.8% in the post-implementation group. There was 100% coverage in the 0–3-year age group in the post-implementation audit .Viral load suppression was 86.5% in the pre-implementation group and 84.4% in the post-implementation group. The suppression rates in the 0–3-year age group were distinctly lower with 56.8% VLS in the pre-implementation group and 69% post-implementation. Suppression rates in the > 3–10 years were 87.7% and 85.7% in the pre- and post-implementation groups, respectively.p-value of 0.001 (Viral load timeliness was 27.5% in the pre-implementation group and 49.7% in the post-implementation group . There wof 0.001 .Our study showed a high VL testing coverage at this urban paediatric HIV clinic before implementation of the wellness anniversary with an average of 98.3% VL coverage pre-implementation of the wellness anniversary. This was attributed to an already existing system of tracking all the patients that are due for VL testing, as well as defaulters who have not returned for their results.4 The wellness anniversary intervention did not have a significant positive or negative effect on the VL coverage in the clinic, with a post implementation overall coverage of 97.8%. This may be attributed to high baseline VL coverage. The patients who did not have VLs done were mostly patients with anniversary months in December or January when patients return to family homes outside of the city during the holidays.Routine VL monitoring has been associated with better clinical outcomes.Timeliness of VL tests was low in our paediatric and adolescent patients with an average of 27.5% done timeously before implementation. This improved to 49.7% in patients who had suppressed VLs after the implementation of the wellness anniversary. This analysis was only on patients with VLs below 1000. There was particularly low timeliness in January and December in both groups which we have attributed to the holiday season. During this period the pharmacy dispenses 2 months’ supply of treatment for patients with good adherence and treatment response. Some patients also go on holiday during this period. The timeliness of VL testing was expected to correlate with early detection of treatment failure and timely intervention which should lead to higher virological suppression rates and less drug resistance. However, the results did not show this, as overall suppression rates did not improve.18 Maternal ART and early infant diagnosis are likely to improve this, with more infants with lower VLs at ART initiation and earlier VLS. There was a statistically significant increase in VLS in the patients who had timely VLs in the post-implementation group. This may be attributed to the fact that patients with suppressed VLs only need 12 monthly VLs, which may be the bulk of patients who subsequently had timely VLs. Further, patients may have been better able to anticipate the date of the VL testing during the implementation and may have re-enforced adherence resulting in improved VLS. Studies looking at regimen switches and re-suppression as a result of timely VL testing may be more conclusive to show the effect of timely VL testing.The overall VLS rate was above 80% in the pre-implementation group, which is higher than the cascaded target of 72.9% set by the UNAIDS 2020 strategy. There was no overall improvement in suppression rates in our study. The 0–3 year age group had a particularly low suppression rate and improved after implementation. Time to suppression in this group may be affected by factors such as high baseline VL, poor tolerability of syrups and caregiver-related issues.Although our study consisted of a comprehensive chart review of a large cohort of patients, limitations include that we did not record ART regimens the patients were on and whether there was an increase in ART regimen switches with the timely VL testing. Implementation of the wellness anniversary had both patient-related and staff-related obstacles, which may be overcome easily even in LMIC setting ART clinics. Patients were initially concerned with the possible stigma expressed by other patients because of a visible sticker on their clinical charts, which required a change in the position of the sticker so that it was less visible. The process of addressing concerns also helped with patient engagement and ownership of their treatment monitoring which may contribute to retention-in-care. Once the initial phase of rolling out the wellness anniversary was completed, the responsibility of assigning the wellness anniversary and putting the stickers on the files was assigned to the doctors. Patients that were transferred from other institutions often did not have detailed transfer letters, and patients could not recall the month they commenced ART. The month of transfer ended up being their wellness anniversary. We would recommend that assigning the wellness anniversary should also be flexible to accommodate the patient’s and caregiver’s lifestyles such as avoiding routine monitoring in school-going children during school holiday months. We feel that these findings are generalisable to other large paediatric and adolescent clinics and offer a low-cost strategy to improve the VL testing.The implementation of the wellness anniversary in the setting of a clinic with a high VL coverage may improve timeliness of VL tests done. Further studies are needed to assess the effects of timely VLs on VLS and clinical outcomes.