To determine immunological and virological failure and associated factors among children infected with human immunodeficiency virus receiving antiretroviral treatments at Hawassa University Hospital, Southern Ethiopia.  A hospital-based cross-sectional study was conducted among 273 HIV-infected children from July 1 to December 1, 2019. Data were collected using a structured questionnaire and review of patient records. Blood samples for viral load and CD4 count were collected. Data were analyzed using SPSS version 20. Significance group comparison was done by the Kaplan-Meier log-rank test. The Cox proportional hazard model was used to select significant factors of the variability between groups. P = 0.032). The overall viral load suppression was 196 (71.8%) with a good adherence of 226 (82.9%). Nonsuppressed HIV viral load was found to be 77 (28.2%) which had two times more viral load copies , P = 0.001) when compared to those who had suppressed viral load copies. The proportions of children who had immunological nonresponse were 45.6% (21 out of 46), 30.4% (14 out of 46), and 23.9% (11 out of 46) among children with baseline CD4 of <200, 201-500, and >500 cells/μl, respectively. Unimproved outcomes among females were noted for immunological and virological failure in this study , P = 0.038).  A total of 273 children, between the age ranges of 1 to 14 years, were included. Of these, 139 (50.9%) and 134 (49.1%) were males and females, respectively. Children from the rural area were almost five times more vulnerable for virological and immunological failure than those children from the urban area ,  In conclusion, the highly active antiretroviral treatment appeared highly effective in terms of immunological and virological long-term outcomes. However, viral suppression (71.8%) in our study was far apart from the UNAIDS target of 90% in 2020. For that reason, strengthening adherence counseling and early initiation of HAART is important. Globally, there were still 38 million people living with HIV, 690,000 AIDS-related deaths, and 1.7 million new infections at the end of 2019 [Among 38 million people living with HIV, about 1.8 million were HIV-infected children; of these, more than 80% live in Sub-Saharan Africa  In the aAs early initiation of ART has shown benefits, for this reason, WHO has recommended initiation of ART for all children (<10 years of age) and adolescents (10–19 years) living with HIV, regardless of WHO clinical stage or CD4 cell count . Based oEfficacy of highly active antiretroviral treatment (HAART) is monitored by both clinical and laboratory measures, including estimation of HIV-1 viral load and CD4 cell count, while on treatment. World Health Organization recommends viral load estimation as the preferred monitoring approach to diagnose and confirm treatment failure . HoweverAcquired immunodeficiency syndrome is a systemic disorder characterized by severe impairment and progressive damage of both cellular and humoral immunological response, hematological abnormalities, and virological failure which are strong predictors of morbidity and mortality in HIV-infected children , 9. HIV 3 [Immunological failure is defined as a fall of CD4 count to pretherapy baseline, 50% fall from the on-treatment peak value, or persistent CD4 levels below 100 cells/mm3 . Knowing3 . From th3 . Other f3  can alsoA significant number of HIV-infected patients fail to achieve sustained virological suppression and immunological recovery to HAART treatment . Even afViral load is the gold standard and most important indicator of response for HIV treatment and monitoring that could show the amount of HIV genetic material  circulatIn 2020, WHO established 90% of all people living with HIV will know their HIV status, 90% of all people with diagnosed HIV infection will receive sustained antiretroviral therapy, and 90% of all people receiving antiretroviral therapy will have viral suppression to have an undetectable HIV viral load (VL) as a global target . AchieviHIV-infected children are considered a priority group for routine viral load monitoring . A thresTherefore, this study was aimed at assessing the long-term immunological response and virological failure among children receiving HAART at HUCMHS  Pediatrics ART Clinic, Southern Ethiopia.A hospital-based cross-sectional study was conducted from July to December 2019 on 273 HIV-infected children receiving HAART.The study was done at Hawassa University Comprehensive Specialized Hospital which is one of the tertiary hospitals in the country with a catchment population of 15-22 million people and one of the largest academic institutions in Ethiopia and located at the heart of Hawassa City, the capital city of the SNNPR Regional State and 275 km from Addis Ababa, the capital city of Ethiopia. The altitude of the city is 1697 meters above sea level with the mean annual temperature and rainfall of 20.9°C and 997.6 mm, respectively. The hospital started delivering ART services in 2005 both for children and adults. Currently, there are 273 HIV-positive children enrolled in chronic follow-up care. The HIV follow-up clinic is scheduled daily, both in the morning and afternoon. The average patient census returning for follow-up was 15–20 patients per day.The source population was all children with confirmed HIV-positive status at Hawassa University College of Medicine and Health Sciences, Southern Ethiopia.HIV-infected children of less than 15 years of age who have been receiving HAART and had a follow-up at Pediatrics ART Clinic at Hawassa University Hospital who have at least two consecutive viral load values and baseline CD4 results were included in the study.Children on treatment for known immunological and virological failure and receiving transfusion treatment for the last three months of data collection and children with their incomplete information with their lost record and who do not have baseline CD4 count and without a legal guardian or unaccompanied children were excluded from the study.In this study, 273 HIV-infected children who have baseline viral load and CD4 cell count were included in the study.The sociodemographic and clinical characteristics of the study participants were collected using a pretested structured questionnaire by interview and review of patient records for baseline characteristics of the study subjects before initiation of HAART.Baseline CD4 T cell and viral load counts were taken from patient registration at enrollment of patients at 0 months to the study and after every six-month interval following HAART initiation up to 4 years of HAART treatment.The child's anthropometry results were taken from the child's record, and adherence to HAART was assessed by self-reporting by the caregiver, pill count, and on-time hospital attendance by the child or his/her caregiver. Blood was drawn for complete blood count, CD4 percentage, absolute CD4+ T cell counts, and HIV-1 viral load, once every 6 months.In the specimen collection and processing, 5 ml of blood was drawn from each participant using a Vacutainer tube containing anticoagulant ethylenediaminetetraacetic acid (EDTA) for complete blood count using hematological autoanalyzer Ruby CELL-DYN 3000 USA , and CD4 percentage and absolute CD4+ T cell counts were measured using the FACSCount flow cytometer  and plasma HIV-RNA levels were determined using Abbott Real-Time HIV-1 assay  with the lower and higher detection limit of 150 and 10,000,000 RNA copies per ml, respectively.The performance of the analyzers was controlled by running quality control material alongside the study participant's sample. To ensure the quality of data, training was given to data collectors and supervisors. A pretest was done on adult patients. The necessary feedback was offered to data collectors the next morning. The laboratory measurements were done by experienced laboratory technologists. The data collection process was supervised by the investigator. A pretest was done on adult patients.P value of ≤0.05 were included in the model and selected as variables to fit a model that best explains the variance in the equation.The data were cleaned, checked, entered, and analyzed using SPSS version 20 statistical software for analysis. Frequencies were presented to describe study participants. The association between outcome  and independent  variables was measured using the backward likelihood ratio (LR) method in the multivariable logistic regressions. The Kaplan-Meier method was used to assess the proportion of patients with virologic and immunologic failure, and Cox proportional hazards regression was used to assess the relative risk of failure of each variable. Variables with a Clinical failure is defined as the appearance or reappearance of WHO clinical stage 3 or stage 4 events after at least 24 weeks on ART in a treatment-adherent child .μl or percent CD4 cell count of <10% is for a child ≥1 year to <5 years of age, and a CD4 count of <100 cells/μl is for a child 5 years of age or older.Immunological failure and anemia are defined as developing or returning to the following age-related immunological thresholds after at least 24 weeks on ART, in a treatment-adherent child and anemia . CD4 couVirological failure is defined as a persistent HIV viral load of ≥1,000 copies/ml, after at least 24 weeks on ART, in a treatment-adherent child .This study was reviewed and approved by the Institutional Review Board (IRB) of Hawassa University College of Medicine and Health Sciences. A support letter was obtained from HUCSH Chief Clinical Director's Office, and a permission was obtained from the Pediatrics ART Clinic to collect the necessary data. An informed written consent was taken from the caretakers and assent was obtained from older children (above 8 years old) before enrollment in the study. Then, the objective of this research was explained to the study participants, and their caretakers and those willing to participate were included. To ensure confidentiality of participant's information, anonymous typing was applied. Each participant was interviewed alone to keep privacy. Test results were given to the clinicians who are working on the Pediatrics ART Clinic of the hospital for further diagnosis and management.A total of 273 HIV-infected children and their medical records at the Pediatrics ART Clinic of Hawassa University Hospital were included and reviewed to assess the sociodemographic and clinical characteristics of the study participants described in A total of 273 HIV-infected children and their medical records were reviewed to assess the baseline and 48-month characteristics of CD4 count  and virological responses. 26.7% and 57.9% of children were at WHO stage 1 at baseline and 48 months of therapy, respectively. There was a good treatment adherence in 226 (82.9%) participants. Other characteristics of HIV-infected children at baseline and 48 months of HAART treatment were depicted in μl, respectively. The median and IQR CD4 cell count at baseline and 48 months of HAART treatment at different CD4 cell levels were 83 (39-172), 268 (203-311), and 379 (362-399) and 197 (185-208), 304 (274-314), and 597 (498-701) cells/μl of CD4 of ≤200, 201-500, and >500 cells/μl, respectively. The trends of the median CD4 T lymphocyte count were indicated below , measuring of viral load copies, determination of hematological parameters, and clinical data. According to this scenario, the percentage of immunological nonresponse was 16.8% (46 children out of 273 patients). The proportions of patients who had immunological nonresponse were 45.6% (21 out of 46), 30.4% (14 out of 46), and 23.9% (11 out of 46) among children with baseline CD4 of <200, 201-500, and >500 cells/ed below .Furthermore, immunological progression is indicated by the increasing trend of CD4+ T cell median percentage and IQR of 13.5 (9.3-17.8) at baseline and 21.5 (15.3-30.8) at 48 months of HAART receiving. Similarly, the mean hemoglobin level also increased from 10 mg/dl at baseline to 13.1 mg/dl at 48 months of HAART therapy.Multivariable analysis was used by the Kaplan-Meier method to assess the proportion of patients with virologic and immunologic failure, and Cox proportional hazards regression was used to assess the relative risk of failure of each variable as depicted in In the current study, we assessed the rate of viral load suppression, immunological response failure, and hematological abnormalities among children receiving HAART at Hawassa University ART Clinic for the reason that identification of such problems is essential to make interventions during drug and disease management among children receiving HAART for a prolonged duration of time .P = 0.038) which was almost 2 times more risky than males for immunological failure. Similar findings were reported from Tigray, Ethiopia [Unimproved outcomes among female children were noted for immunological and virological failure in the current study , Ethiopia , Spain [Ethiopia , and IndEthiopia . NoncompEthiopia  and ThaiEthiopia . This diP = 0.032), which is almost 5 times higher risk to develop immunological and virological failure. Inconsistency to this finding was reported from Northeast Ethiopia where being an urban resident was significantly associated with virological and immunological failure than a rural resident [Children being rural residents are statistically significant with immunological and virological failure than urban residents in our study , resident .In our study, the overall rate of nonsuppressed HIV viral load was 28.2%; this is an indicator that the suppression rate is still 71.8%, far from the 90% target to be achieved in 2020 by UNAIDS . A higheThe proportion of children with undetectable HIV-RNA in our study was 184 (63.4%) which was lower than the finding reported from Thai HIV-infected children (73%)  and a st3) (IQR) in our study at baseline and 48 months of treatment were 298 (39–453) and 512 (209-1053), respectively. A similar increasing trend was observed from other studies in Ethiopia [3. A total of 173 (63.3%) children had a CD4 T lymphocyte percentage of ≥25% at 48 months of treatment, 43 (15.8%) between 15-25%, and 57 (20.9%) less than 15% indicating the total immunologic response of 79.1% Almost similar findings were reported from Spain (62.1%) [The median CD4 cell counts (cells/mmEthiopia  indicati (62.1%) . Lower C (62.1%) .P = 0.019) compared to those at stage 1. Findings in line with our report were reported from Benin [In the current study, the risk of developing immunological and virological failure was significantly 2 times higher than children who were at WHO clinical stage 4 (om Benin .P = 0.021) than those who were in good adherence. A similar finding was reported from the Tanzanian study indicated that poor adherence was significantly associated with , P = 0.0001) [P = 0.005) [In our study, children who had poor adherence were 2 times more likely to develop immunological and virological failure ( 0.0001)  and in A= 0.005) .P = 0.001) or which is 2 times higher in virological and immunological failure than EFV-based treatment. Consistent findings were reported from Tanzania , P = 0.003) [P = 0.001) [Nevirapine-based regimen was significantly associated with virological and immunological failure compared to those children who were on EFV-based treatment , = 0.003) , Uganda -2.56, = = 0.001) . Contras= 0.001)  that ind= 0.001)  and in U= 0.001) .μl , P = 0.012), poor adherence , P = 0.021), and nevirapine-based regimen , P = 0.003). However, there were no statistical significance associations (P > 0.05) between educational status, age group, TB infection, parasitic infection, and other treatments taken during HAART.In a total of 273 patients enrolled, 43 (15.7%) met the criteria of virological failure. The odds of having virological failure were independently associated with baseline CD4 counts of <200 cells/3), poor adherence, and NVP-based regimen were significantly associated with virological suppression and immunological recovery failure in this study.In conclusion, the highly active antiretroviral treatment appeared highly effective in terms of immunological and virological long-term outcomes. However, viral suppression (71.8%) in our study was far apart from the UNAIDS target of 90%. The sustainability of viral suppression and immunological response, once attained, was also variable. Sex, residence, baseline CD4 cell count (≤200 cells/mmTherefore, adherence counseling, follow-up, early initiation of HAART, and switching from one regimen to the other regimen are important for better immune recovery and viral load suppression among HIV-infected children. It is also important for health professionals to make treatment decisions on continuation and treatment change for those receiving HAART for a prolonged period and initiation of HAART for antiretroviral-naïve children. Furthermore, large-scale cohort studies are recommended to determine virological and immunological responses and drug resistance patterns of children who are on a single-drug regimen for a long period to strengthen and explore the problem in-depth.


Limited data is available on the treatment outcomes of HIV infected adolescents and young adults (AYA) in sub-Saharan Africa. HIV-infected adolescents and young adults (AYA) are at high risk of developing antiretroviral treatment failure.To determine the clinical, immunological and virologic outcomes of AYA at a tertiary hospital in Kenya.A longitudinal study was conducted among AYA age 10–24 years attending Kenyatta National Hospital comprehensive care center. Clinical data was abstracted from electronic medical records for study participants with at least 6 months of follow-up using a structured data abstraction sheet.3. Overall, 76.9% of AYA had achieved viral suppression . There was a significant increase in virologic failure with higher age and late adolescents and young adults were more likely to have a viral load > 1000 copies/ml p<0.012.A total of 250 AYA age 10 to 24 years were included. The median age was 16 years. The median CD4 cell count was 650.6 cells/mm3 (IQR 350.7–884.0). More than half (60.6%) of AYA had a CD4 cell count higher than 500 cells/mmThe overall virologic suppression in this cohort of AYA was sub-optimal. Both immunological and virologic outcomes were worse among late adolescents (18–19 years) and young adults (20–24 years). Adolescents and young adults (AYA) represent an increasing proportion of people living with HIV in the world. Over 1.6 million adolescents age 10–19 and 5 million young people age 15–24 are living with HIV Adolescents and young adults are at high risk of developing treatment failure and drug resistance, which has dire consequences in low resource settings such as Kenya, where there are limited choices of antiretroviral regimens. Across sub-Saharan Africa, many children who were infected at birth are now becoming adolescents. The number of adolescents and young adults on antiretroviral treatment has been increasing reflecting treatment success of HIV infected children AYA have unique characteristics that predisposes them to treatment failure and drug resistance such as poor insight into the disease and treatment A longitudinal study was conducted as part of an interventional study to determine the effect of mobile phone calls on retention to care among adolescents and young adults on care and treatment at Kenyatta National Hospital Comprehensive Care Clinic between January 2017 and November 2017. A review of medical records was performed to determine the clinical, immunological and virologic outcomes in AYA 10 to 24 years on active follow.The study was carried out at Kenyatta National Hospital Comprehensive Care Centre which at the time of the study had 9,915 active HIV patients on care and treatment, among them 362 adolescents age 15–19 years and 693 children between 0–14 years. Patient's data is entered into an electronic medical records database (IQ care) during routine clinic visits. Data on clinical variables, outcomes, treatment regimens and laboratory records were abstracted from the electronic medical records data which is routinely updated at each clinic visit. AYA are typically seen in the clinic monthly or every three months for clinical monitoring, with a bi-annual viral loads and CD4 cell count monitoring.3 and virologic failure as a viral load of > 1000 copies/ml.The main study outcomes were improvement in WHO staging, immunological status and virologic failure. Immunological failure was defined as CD4 cell count < 500 cells/mmThe study was approved by Kenyatta National Hospital/University of Nairobi Ethical Review Committee (ERC) and University of Washington Institutional Review Board.Data were collected and entered into a password-protected MS-Access database. The database was set within required limits and restrictions to reduce errors. Exploratory data analysis was carried out to identify extreme values and inconsistencies. On completion of the data entry, the data was exported into SPSS Version 21.0 for analysis.Continuous values were summarized as means, medians, standard deviation and interquartile ranges. Discrete values were summarized using frequencies and percentages. Categorical variables were compared using chi-square test and Fishers exact test. Continuous variables were analyzed using Student t-test and Mann Whitney test by comparing means. A P value <0.05 was considered significant. The associations between social demographics characteristics and treatment outcomes were measured by Odds Ratios (OR).A total of 250 AYA age 10 to 24 years were included with a median age of 16 years. Of those in adolescence, 71 (28.4 %), 90 (36%) and 59 (23.6%) were in early (10–13 years), mid (14–16 years) and late adolescence (18–19 years) respectively, while 30 (12%) were young adults (20–24 years). Ratio of males 124 (49.6%) vs females 126 (50.4%) was almost 1. Majority of the study participants 226 (90.4%) had a parent as the primary caregiver while the rest had guardians. Almost half; 120 (48.2%) attended clinics unaccompanied, while (90) 36.1%, 23 (9.2%), (6) 2.4% 10 (4.0%) were accompanied by their mothers, fathers, siblings and guardians respectively. About two thirds 169 (67.6%) attended all clinics as scheduled while a third 81( 32.4%) missed their scheduled clinics. There was no statistical difference on attendance of scheduled clinic visits among the various age groups (p=0.764).st line antiretroviral regimen, while 77 (30.8%) were on their 2nd line regimen as per the national guidelines in Kenya. The most frequent ART regimen combination at ART initiation comprised of two nucleoside reverse transcriptase inhibitors (NRTIs); [zidovudine or abacavir or tenofovir or stavudine] plus lamivudine and one non-nucleoside reverse transcriptase inhibitor (NNRTI), nevirapine or efavirenz. Only a third ( 33 (13.2%) were initiated on a protease inhibitor-based regimen. On the current ART regimen; majority 171 (68.4%) were on two nucleoside reverse transcriptase inhibitors (NRTIs); [zidovudine or abacavir or tenofovir plus lamivudine] and one non-nucleoside reverse transcriptase inhibitor (NNRTI), [nevirapine or efavirenz]. Seventy seven (30.8%) were on a protease inhibitor-based regimen while two (0.8%) were on an integrase inhibitor-based regimen. . The majority of 173 (69.2%) were on a 13 Vs. <500 cells/mm3) p=1.000 and no significant changes in viral loads (<1000 copies/ml Vs. >= 1000 copies/ml) p=1.000. (The results are shown in Treatment outcomes 6 months after enrollment into the study showed that the mean body weight (SD) significantly increased from 46.3 (12.7) to 50.5 (11.1) p<0.001, the WHO clinical staging significantly deteriorated from stage I towards stage IV p=0.003, there was no significant change in CD4 cell count , 28 (11.5%) were in WHO clinical stage II, 19 (7.8%) in WHO clinical stage III and 3 (1.2) in WHO clinical stage IV. At 6 months of the study there was no significant association in improvement in WHO clinical staging depending on gender, adolescent age group or the primary caregiver. Although not statistically significant, AYA who missed clinic appointments were more likely to move to an advanced WHO stage compared to those who did not miss appointments . Those that had their regimen substituted were more likely to be in an advanced WHO clinical stage compared to those that were not OR 0.3 (95% CI 0.1–0.8), 1.0 (CI 95%) p=0.01. (The results are summarized in 3 (IQR 350.7–884.0). Considering all age categories, more than half (60.6%) of AYA had a CD4 cell count with more than 500 cells/mm3. There was a decrease in CD4 cell count with higher age, with 92.3 % of early adolescents (10–13 years), 62.2 % of mid adolescents (14–17 years), 38.8 % of late adolescents (18–19 years) and only 23.3 % of young adults having a CD4 cell count above 500 cells/mm3 p<0.001.  while young adults were more likely to have a CD4 cell count of less than 500 cells/mm3 (OR 0.2 (0.1–0.5 p<0.001).  76.9% of adolescents and young adults had a viral load <1000 copies/ml, while 93 (39.4%) had a viral load of >1000 copies/ml. There was a significant likelihood of virologic failure with higher age; with young adults more likely to have a viral load > 1000 copies/ml p<0.012.  where mid and late adolescents had poor immunologic, virologic outcomes and poor adherence to treatment17. In the same study viral suppression was poorest in mid adolescents at any point time of ART. The poor immunological and virologic outcomes could be explained by less adherence support during transition to adult HIV programs leading to poor adherence to ART, less support from parents and guardians and complexities associated with the developmental stages of adolescence and young adulthood.Median CD4 cell count was 650 cells/mm18At our last assessment at 6 months, a larger proportion of AYA in our study (79.4%) were in WHO clinical stage I, while 11.5%,7.8% and 1.2 % were in WHO clinical stage II, III and IV respectively. Thus majority of the adolescents were stable with absence of recent opportunistic infections. However on further analysis, during the six months study period, there was significant deterioration in the clinical staging from WHO clinical stage I to IV. The finding of having a majority of HIV infected adolescents being stable was also found in a longitudinal study by Allison et al where they found 85% of adolescents in there cohort to be stable. This was a cross-sectional study that utilized routinely collected clinical outcome data from an electronic medical records system as part of a clinical trial. The study involved a single site which is a tertiary teaching hospital thus the results may have limited generalizability. However this study provides an insight into the treatment outcomes of HIV infected adolescents and identifies the age categories that need special attention during care and treatment for that age group.Viral load suppression in this cohort of adolescents was suboptimal with late adolescents (18–19 years) and young adults (20–24 years) being more likely to have virologic failure. Interventions in this program should targets adolescents and young adults with special focus to late adolescents and young adults to improve treatment outcomes.


Single-tablet regimens (STRs) should be considered for patients with HIV/AIDS to increase medication compliance and improve clinical outcomes. This study compared variations in the prescription trends between STRs and multiple-tablet regimens (MTRs) for treatment-naïve patients with HIV/AIDS after the approval of the new STRs, a proxy indicator for improvement in medication adherence. The medical and pharmacy claim data were retrospectively obtained from the Health Insurance Review and Assessment service, which contains basic information on the patients’ sociodemographic characteristics and treatment information for the entire Korean population. From 2013 to 2018, a total of 6737 patients with HIV/AIDS were included. Most patients were men  and insured through the National Health Insurance . The mean number of pills in their antiretroviral treatment regimens decreased from 2.8 ± 1.2 in 2013 to 1.2 ± 1.0 in 2018. After the first STR (EVG/c/TDF/FTC) was approved in 2014, prescription transitions from MTR to STR were observed among more than 38% of patients. In 2018, most treatment-naïve patients were prescribed STRs (91.2%). There was a time lag for STR prescription trends in non-metropolitan hospitals compared with those in metropolitan cities. Our data provide a valuable perspective for evaluating ART regimen prescription patterns on a national scale. This achievement was made possible in part thanks to the Joint United Nations Program on HIV/AIDS2. The goal of the program, called the 90–90–90 target, was to diagnose 90% of all HIV-positive persons, provide antiretroviral therapy (ART) for 90% of those diagnosed with HIV/AIDS, and achieve viral suppression for 90% of patients on medication by 20202.Over the 30 years since the human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) was first recognized, the HIV/AIDS epidemic has remarkably transitioned from a fatal disease to a chronic illness with patients living with HIV/AIDS4. Early ART regimens were based on the administration of more than 20 pills, 3 times a day. Standard ART recommendations stipulate that the regimen contains at least 3 active drugs from 2 or more classes. In most cases, this consists of partial regimens combining 2 nucleoside reverse transcriptase inhibitors (NRTIs)—zidovudine (ZDV)/lamivudine (3TC), abacavir (ABC)/lamivudine (3TC), or tenofovir (TDF)/emtricitabine (FTC)—and 1 of the following: boosted protease inhibitor (PI) (lopinavir/ritonavir), nonnucleoside reverse transcriptase inhibitors (NNRTIs) (efavirenz or rilpivirine), or integrase strand transfer inhibitors (INSTIs) 6. Such multiple-tablet regimens are certainly not easy for adherence by patients with HIV/AIDS. Regimen characteristics, such as the complexity of the treatment regimen, long treatment duration, and frequent medication changes, have been associated with medication non-adherence7. Therefore, the World Health Organization (WHO) has recommended using simplified fixed-dose combination regimens for common chronic diseases, such as hypertension, tuberculosis, and HIV infection. Today, once-a-day antiretroviral treatment is recognized as the standard medication for people living with HIV/AIDS8.The key to viral suppression is maintaining a potent and sustainable regimen to which people living with HIV/AIDS can easily adhere. In this sense, guidelines from the United States Department of Health and Human Services and the European AIDS Clinical Society recommend ART with combination regimens and emphasize adherence to the ART for all individuals infected with HIV/AIDS10. The first STR that combined TDF, FTC, and efavirenz (EFV) became available globally in 2006. Many medical professionals believed that the STRs would not only reduce the patients’ pill burden and improve their quality of life but also improve medication adherence and, consequently, the probability of virologic suppression. Retention in care and virologic suppression has been achieved in the patients started on STRs12. Patients on STRs were more likely to achieve good medication adherence and had fewer hospital admissions than patients on multi-tablet regimens (MTRs)13. Increases in STR prescriptions were significantly associated with medication adherence14, which led to improved quality of life and better clinical outcomes among patients with HIV/AIDS15. Given that adherence is an essential feature in the prevention of the emergence and replication of drug-resistant strains of HIV, STRs have become an important tool to manage appropriate medication adherence19.The fixed-dose combinations represented by single-tablet regimens (STRs) should be considered for patients with HIV/AIDS to increase medication compliance and, consequently, improve their clinical outcomes20. About 1100 new patients with HIV/AIDS cases have emerged every year since 2013. To optimize ART for patients, the STR strategy was proposed in Korea, too. The first STR combining TDF, FTC, cobicistat (c), and elvitegravir (EVG) was approved in 2014 in Korea. During the 10 years between 2007 and 2018, the time when this research was conducted, there were 4 STRs available: (1) elvitegravir (EVG)/cobicistat (c)/tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) (approved in March 2014); (2) rilpivirine (RPV)/TDF/FTC (approved in December 2014); (3) dolutegravir (DTG)/ABC/3TC (approved in November 2015); and (4) EVG/C/tenofovir alafenamide fumarate (TAF)/FTC (approved in February 2017). This study compared variations in the prescription trends between STRs and MTRs for treatment-naïve patients with HIV/AIDS after the approval of the new STRs, a proxy indicator for improvement in medication adherence, using the national insurance claims data in Korea.In Korea, the incidence of HIV/AIDS has consistently increased since the first case of HIV/AIDS infection in 1985Table Since the approval of the first STR, EVG/c/TDF/FTC, in 2014, four STRs have become available sequentially (Supplementary Table After the first STR (EVG/c/TDF/FTC) was approved in 2014, prescription transitions from MTR to STR were observed by more than 38% of patients, whereas NNRTI-based and PI-based MTR rates were reduced by 18.6% and 19.9%, respectively, in 2014. The proportion of patients initiating ART with STRs increased to 86.7% in 2016 after DTG/ABC/3TC was approved. In 2018, most patients who started ART were prescribed STR  as their first HIV/AIDS treatment medication  with one INSTI-based agent (EVG). In the same year, the second single-complex combination, RPV/TDF/FTC, was approved. It contains an NNRTI (RPV) with the same combination of 2 NRTIs (TDF and FTC). Notwithstanding, EVG/c/TDF/FTC, the first approved STR, was the most frequently prescribed STR from 2014 to 2015. INSTI-based regimens containing the novel ingredients DTG or EVG replaced previously preferred MTRs. EVG/c/TDF/FTC has been replaced by EVG/c/TAF/FTC since 2017. Notably, there were no RPV/TDF/FTC prescriptions for treatment-naïve patients after its approval in 2014. Eventually, RPV/TDF/FTC, which had not been claimed for reimbursements for 2 years, was deleted from the National Formulary list in 201725. On the other hand, elvitegravir (EVG) is a recently developed INSTI, and it has been recognized for its excellent efficacy and tolerability. Additionally, it is rarely associated with treatment resistance. EVG/c/TDF/FTC can be prescribed to all patients regardless of HIV-RNA levels, and thus, clinicians have selected EVG/c/TDF/FTC for various patient groups. Furthermore, RPV/TDF/FTC must be taken with at least 400 cal of food, whereas EVG/c/TDF/FTC prescriptions have no restrictions on concomitant food intake26. These disadvantages associated with specific ART regimens can affect the choices of clinicians who consider medication adherence and convenience.Physicians favored EVG/c/TDF/FTC over RPV/TDF/FTC because of the latter’s limited and complex indications. Moreover, RPV/TDF/FTC has been associated with high virologic failure rates and drug-resistant mutations, with failures occurring among patients with baseline HIV-RNA viral loads > 100,000 copies/mL or CD4 cell counts < 200 mm25. EVG/c/TAF/FTC, which was approved in 2017 in Korea, reduced the adverse effects of the previously approved EVG/c/TDF/FTC. TAF is a tenofovir prodrug that results in a 90% reduction in plasma tenofovir concentrations compared with TDF, and it is, therefore, associated with fewer tenofovir-related adverse effects in the kidneys and bone19. As soon as DTG/3TC/ABC was approved, its prescription rate increased rapidly because of its better therapeutic effects; however, no such increase was observed for EVG/c/TAF/FTC. These findings imply that both convenience and improvements in therapeutic scope are important considerations for physicians and patients deciding on ART regimens.We observed a remarkable change in ART prescription patterns after the launch of DTG/ABC/3TC and EVG/c/TAF/FTC. Dolutegravir (DTG) is a second-generation INSTI and is highly active against drug-resistant HIV strains, including strains resistant to first-generation INSTIs. DTG/ABC/3TC is recommended for once-daily treatment and can be taken more easily, with or without food27. There is a higher proportion of young people in metropolitan areas, so new STRs, which can be taken more easily and have fewer adverse effects, may be preferred by younger patients in these areas. The general pattern of ART prescription trend changes was similar in non-metropolitan areas relative to that observed in metropolitan areas—declining MTR prescriptions and increased uptake of STR—albeit with a time lag in non-metropolitan areas.STR prescription rates were higher in metropolitan areas than elsewhere between 2014 to 2016. This pattern may be due to demographic factors29. Second, we were unable to evaluate whether the ART choices were the clinically optimal regimen , as we only relied on insurance claims data for reimbursement purposes.This study had some limitations. First, we did not include clinical outcomes showing how the STRs increased patient compliance, influenced virologic suppression, or reduced tolerance. However, previous studies have demonstrated STRs are important determinants of medication adherenceDespite these caveats, our data provide a valuable perspective for evaluating ART regimen prescription patterns on a national scale, compared with studies using data on ART regimens from medical records in selected clinics. Our results imply that the preferences among the single fixed-dose combination options are determined not only based on administration convenience  but also fewer adverse effects. Although newer regimens are preferred, a new effective ingredient (DTG) was selected more frequently than an alternative component (TAF), despite the latter’s smaller adverse effect profile.As HIV/AIDS patients get older over time, they are likely to develop comorbidities. Therefore, additional studies are warranted to clarify the relationship between medication adherence and clinical outcomes, including the adverse effects of ART medication and comorbidities, such as diabetes and dyslipidemia. We need to continue efforts to optimize ART adherence to manage HIV/AIDS as a chronic disease, particularly for patients with multiple comorbidities and psychosocial difficulties.31. Furthermore, all medical institutions and local pharmacies are compulsory participants of the National Health Insurance and National Medical Aid programs. All medical expenditures within the National Health Insurance and National Medical Aid programs are monitored for reimbursement by the HIRA. The HIRA claims database contains basic information on patients’ sociodemographic characteristics and information on diagnoses, prescriptions, or diagnostic procedures, and it covers the entire Korean population of approximately 50 million individuals32.The medical and pharmacy claims database was retrospectively obtained from the Health Insurance Review and Assessment (HIRA) service. In Korea, 97% of the total population are the mandatory beneficiaries of National Health Insurance, and the remaining 3% are recipients of the National Medical Aid program, the public assistance system for health services for people in the lowest economic bracket33. With the internal code in the first visit, out-of-pocket payments are waived for patients with HIV. Those who were prescribed at least 1 ART prescription during 2007–2018  remained. Third, we excluded individuals who started ART before 2013 (n = 6240), given that the first STR, EVG/c/TDF/FTC, was approved in March 2014 in Korea. Then, we excluded those under 20 years of age (n = 230), those who received ART prescriptions for pre-exposure prophylaxis (PrEP) or incomplete prescriptions  (n = 208), and those who switched regimens within 2 weeks from the ART initiation (n = 233). Among the remaining 13,648 patients, 6737 patients were considered as HIV/AIDS treatment-naïve and included in the final sample for the present study , over 10 years, between 2007 and 2018 . Second, among these, we excluded individuals who did not have a specified internal code for HIV/AIDS, indicating rare diseases, i.e., V103, in the first medical claim with an HIV/AIDS diagnosis  or ART prescription (n = 1585)34. We separately identified ART initiation dates at outpatient visits and during hospital admissions. Index regimens were grouped as an STR versus MTR based on the number of pills in the regimen. Based on the treatment guidelines for initial ART administration to consist of 2 NRTIs combined with a third agent, we categorized MTR types, such as NNRTI, boosted PI or PI-based, INSTI, and NRTI-sparing (boosted protease inhibitor plus INSTI)28. The medical institutions were categorized as tertiary general hospitals, which are designated by government accreditation every three years based on the proportion of severe diseases versus others. Hospital locations were grouped as metropolitan areas, including the capital city, versus other regions35.Sociodemographic characteristics were accessed at the initial ART prescription, which was used as the index date for each subject. The analyzed sociodemographic characteristics included sex, age, and national health insurance premium level as a proxy for income. Age at the index date was categorized by 10-year intervals starting at 20 years of age2 test. All analyses were performed using Stata 15 .All descriptive results are given as total numbers and percentages. Comparisons of percentages were performed using the χThis study was approved by the Institutional Review Board of Yonsei University, which waived the requirement for informed consent due to the study’s use of existing secondary claims data obtained from HIRA . The study was performed in accordance with relevant guidelines and regulations.Supplementary Figure 1.Supplementary Figure 2.Supplementary Table 1.Supplementary Legends.


Patients were excluded if they were on third-line ART < 6 months or received RAL and/or ETV and/or DTG before starting third-line ART. A retrospective evaluation of adults ≥18 years old on third-line ART regimens at UTH between January 2012 to June 30, 2020 was conducted. Patients were referred for second-line virologic failure defined as HIV RNA VL > 1000 copies/mL on two consecutive measurements after 6 months on second-line ART.10 3.60 and 3.33, respectively. The immunologic response revealed 49 (56.3%) had CD4 increase with mean increase of 61.1 cells/mm3. (See Table 1.)A total of 539 patients were included; 231 males (42.9%) and 308 (57.1%) females. The mean age of third-line initiation was 29.8 years; mean time from ART initiation to third-line initiation was 9.9 years. Out of 25 combination 349 (64.7%) received DTG, 272 (50.5%) DRV/r, 85(15.8%) ETR, and 49 (9.1%) RAL. There were 215 (39.9%) genotypes; common mutations were to zidovudine (80%), non-nucleoside reverse transcriptase inhibitors (NNRTIs) (78%), and protease inhibitors (PIs) (41%). Patients with at least one viral load and CD4 upon third-line initiation was 296 (54.9%) and 350 (64.9%), respectively. Among patients with sufficient data , VL suppression increased from 44 (38%) patients at baseline to 53 (46%) at next available follow-up; with mean baseline VL and follow-up VL of logWe found moderate improvements in VL suppression and immunologic response. Nearly all third-line patients had genotypic resistance to first-line NNRTI and nearly half to second-line PI regimens. Quality improvement measures are needed to improve viral load timing following ART changes to better assess regimen efficacy.All Authors: No reported disclosures


Introduction of tenofovir (TDF) plus lamivudine (3TC) and dolutegravir (DTG) in first- and second-line HIV treatment regimens in South Africa warrants characterization of acquired HIV-1 drug resistance (ADR) mutations that could impact DTG-based antiretroviral therapy (ART). In this study, we sought to determine prevalence of ADR mutations and their potential impact on susceptibility to drugs used in combination with DTG among HIV-positive adults (≥ 18 years) accessing routine care at a selected ART facility in KwaZulu-Natal, South Africa.reverse transcriptase and protease genes by Sanger sequencing and assessed ADR. We characterized the effect of ADR mutations on the predicted susceptibility to drugs used in combination with DTG.We enrolled adult participants in a cross-sectional study between May and September 2019. Eligible participants had a most recent documented viral load (VL) ≥ 1000 copies/mL after at least 6 months on ART. We genotyped HIV-1 From 143 participants enrolled, we obtained sequence data for 115 (80%), and 92.2% (95% CI 85.7–96.4) had ADR. The proportion with ADR was similar for participants on first-line ART  and those on second-line ART , and was present for the single participant on third-line ART. Approximately 89% (62/70) of those on first-line ART had dual class NRTI and NNRTI resistance and only six (13.6%) of those on second-line ART had major PI mutations. Most participants (82%) with first-line viraemia maintained susceptibility to Zidovudine (AZT), and the majority of them had lost susceptibility to TDF (71%) and 3TC (84%). Approximately two in every five TDF-treated individuals had thymidine analogue mutations (TAMs).Susceptibility to AZT among most participants with first-line viraemia suggests that a new second-line regimen of AZT + 3TC + DTG could be effective. However, atypical occurrence of TAMs in TDF-treated individuals suggests a less effective AZT + 3TC + DTG regimen in a subpopulation of patients. As most patients with first-line viraemia had at least low-level resistance to TDF and 3TC, identifying viraemia before switch to TDF + 3TC + DTG is important to avoid DTG functional monotherapy. These findings highlight a need for close monitoring of outcomes on new standardized treatment regimens.The online version contains supplementary material available at 10.1186/s12981-021-00393-5. The ambitious Joint United Nations Programme on HIV/AIDS (UNAIDS) 95–95–95 targets and HIV test-and-treat all approach have resulted in an increase in number of patients receiving ART , 2. DespIn South Africa, adult HIV infected individuals were previously initiated on ART with a fixed dose combination of TDF plus emtricitabine (FTC) and efavirenz (EFV), whilst protease inhibitors (PIs) and INSTIs were reserved for second-line and third-line ART, respectively . In lineViral load (VL) testing remains the standard of care for monitoring patients on ART, with 2 consecutive VLs ≥ 1000 copies per millimeter (cp/mL) done at least 3 months apart (with enhanced adherence support) considered as virological failure . Given kThe first South African national drug resistance survey amongst adults failing first-line NNRTI-containing ART showed that almost all participants (96%) had drug resistant mutations after receiving ART for at least 6 months and having two consecutive VLs ≥ 1000 cp/mL . The finTherefore, as part of the CAPRISA Advanced Clinical Care Programme, we conducted a study of HIV-1 ADR at the East Boom Community Health Centre, a public health facility in uMgungundlovu District Municipality, KZN, South Africa. This study aimed to determine prevalence of ADR in participants receiving ART with viraemia (i.e. having at least one VL ≥ 1000 cp/mL after receiving ART for at least 6 months) and to assess susceptibility of the virus to drugs used in combination with DTG in preferred subsequent ART regimens.We conducted a cross-sectional study on ADR among HIV-positive adults ≥ 18 years) accessing routine care at East Boom Community Health Centre in Pietermaritzburg, in the uMgungundlovu district (a HIV hyper-endemic setting), in central KZN, between May and September 2019. Briefly, we interrogated the routine HIV programme database (TIER.net) and weekly reports of elevated VLs from the National Health Laboratory Service to identify individuals that might be eligible to participate. At the time of searching for eligible participants in March 2019, 11,609 patients were actively receiving a documented ART regimen and 192 were eligible based on our inclusion criteria  was collected from each eligible participant and the samples were sent to the CAPRISA laboratory for plasma separation and then to the KwaZulu-Natal Research Innovation and Sequencing Platform (KRISP) laboratory at the University of KwaZulu-Natal, for HIV-1 drug resistance testing. Additional file pol Sanger sequencing on plasma samples using the Applied Biosystems HIV-1 Genotyping Kit according to manufacturer’s instructions  and the median duration on the current regimen for those on second-line ART was 21 months (IQR 7–48). Only one participant was currently on third-line ART and none of the participants were receiving a DTG-based regimen at time of enrolment. Table Overall, 106/115 had at least one drug resistance mutation . The proportion with resistance was similar for participants on first-line ART  and those on second-line ART . Of those on first-line ART, 62/70 (88.6%) had dual class NRTI & NNRTI resistance. The patterns of drug class-specific resistance are shown in Additional file Several participants with viraemia on first-line ART had atypical NRTI resistance patterns, i.e. 28/68 (41.2%) participants with viraemia on TDF + FTC + EFV had at least one TAM. In most cases (21/28) the TAMs were present without the K65R mutation; and of these cases (17/28), there was only a single TAM detected. The two most frequently observed TAMs were D67N (n = 18) and K219E/Q (n = 16). Despite this observation, in most participants with viraemia on first-line TDF + FTC + EFV , the virus was predicted to be susceptible to zidovudine (AZT). In contrast, the virus was predicted to be susceptible to tenofovir (TDF) in only 20 cases (29.4%) and susceptible to abacavir (ABC) in only nine cases (13.2%)  of first-line ADR , 15, relOver 40% of participants failing first-line TDF regimens already had the K65R mutation that alone causes high-level resistance to TDF and intermediate resistance to XTC . If VL tIn keeping with other studies from South Africa, a minority of adults with viraemia on second-line PI-based regimens had major PI resistance mutations , 20. In Given that most of the participants had the NNRTI mutation K103NS  of the participants with viraemia in this study already had ADR mutations with 80% (92/115) having dual class NRTI- and NNRTI-resistance at time of genotyping, suggesting the need to consider early VL monitoring and switching of ART regimens. This is supported by a recent HIV Synthesis Model that showed reduction in mortality when a single VL ≥ 1000 cp/mL after at least 6-months of ART is considered a criteria for virologic failure on first-line efavirenz based treatment . SecondlResistance profiles among first-line viraemic participants with ADR suggests that the new standard second-line regimen of AZT + 3TC + DTG would be effective. However, the atypical occurrence of TAMs in TDF-treated individuals could mean a less effective AZT + 3TC + DTG regimen in a subpopulation of patients, and studies assessing mechanisms resulting in TAMs among patients not receiving thymidine analogues are warranted. Given that most patients with first-line viraemia had at least low-level resistance to TDF and 3TC, identifying viraemic patients (including those with low-level viraemia) before switching them to TLD is of vital importance to the success of subsequent ART. We believe these findings have wide relevance across South Africa and in most low and middle-income countries that follow standard HIV-1 treatment recommendations by the WHO . OverallAdditional file 1: Figure S1. Study flow diagram from participant selection to reporting of results in the acquired HIV drug resistance study in KwaZulu-Natal (KZN) province, South Africa, May–September 2019. Table S1. Comparison of participant characteristics among samples excluded and included in final analysis in the acquired HIV drug resistance study in KwaZulu-Natal (KZN) province, South Africa, May–September 2019. Table S2. Patterns of drug class resistance among participants on first- and second-line ART in the acquired HIV drug resistance study in KwaZulu-Natal (KZN) province, South Africa, May–September 2019. Table S3. Prevalence of specific acquired drug resistance mutations in the acquired HIV drug resistance study in KwaZulu-Natal (KZN) province, South Africa, May–September 2019. Table S4. Relationship between patient characteristics and acquired drug resistance using multivariable logistic regression.


During the COVID-19 pandemic, we realized the importance of limiting in-clinic interactions with patients who were stable on antiretroviral therapy to promote social distancing. Our HIV clinic adopted telemedicine practices, in line with the HHS Interim Guidance for COVID-19 and Persons With HIV. Several HIV clinics reported lower viral suppression rates during the pandemic. We aim to describe the implementation process as well as year one outcomes of telemedicine at our clinic.In March 2020, we created telemedicine protocols; we also designed and continuously updated algorithms for determining patient eligibility for telemedicine based on recent viral loads and last clinic visit. We monitored outcomes through electronic medical record chart reviews between May 1, 2020, and April 30, 2021. We collected patient demographics, and federal poverty level (FPL) information. We collected baseline and post-intervention rates of viral load suppression , medical visit frequency  and lost to care .We conducted a total of 2298 ambulatory medical visits; 1642 were in person and 656 (29%) were telemedicine visits. Out of those, 2177 were follow up visits . There was no difference of telemedicine utilization based on race (28% in African Americans vs. 32% in Whites); ethnicity (30% in Hispanic vs. 30% in Hon-Hispanic); gender ; or FPL (28% in FPL < 200% vs. 31% in FPL >200%). By the end of April 2021, overall clinic VLS rate was 94%, MVF was 48%, and there were 40 patients LOC compared to 92%, 49%, and 43 patients in April 2020, respectively.Telemedicine was a safe alternative to routine in-person HIV care during the COVID-19 pandemic. We observed similar rates of utilization across demographic and FPL status. Applying selection criteria, viral suppression and retention in care rates were not adversely impacted by shift to telemedicine modality. All Authors: No reported disclosures


Data on HIV treatment outcomes in people who inject drugs (PWID) in the Asia‐Pacific are sparse despite the high burden of drug use. We assessed immunological and virological responses, AIDS‐defining events and mortality among PWID receiving antiretroviral therapy (ART).We investigated HIV treatment outcomes among people who acquired HIV via injecting drug use in the TREAT Asia HIV Observational Database (TAHOD) between January 2003 and March 2019. Trends in CD4 count and viral suppression  were assessed. Factors associated with mean CD4 changes were analysed using repeated measures linear regression, and combined AIDS event and mortality were analysed using survival analysis.Of 622 PWID from 12 countries in the Asia‐Pacific, 93% were male and the median age at ART initiation was 31 years . The median pre‐ART CD4 count was 71 cells/µL. CD4 counts increased over time, with a mean difference of 401  cells/µL at year‐10 (n = 78). Higher follow‐up HIV viral load and pre‐ART CD4 counts were associated with smaller increases in CD4 counts. Among 361 PWID with ≥1 viral load after six months on ART, proportions with VS were 82%, 88% and 93% at 2‐, 5‐ and 10‐years following ART initiation. There were 52 new AIDS‐defining events and 50 deaths during 3347 person‐years of follow‐up (PYS) . Previous AIDS or TB diagnosis, lower current CD4 count and adherence <95% were associated with combined new AIDS‐defining event and death.Despite improved outcomes over time, our findings highlight the need for rapid ART initiation and adherence support among PWID within Asian settings. In a multi‐stage systematic review, it was estimated that there were nearly 4 million people who inject drugs (PWID) reside within the east and southeast Asia, with a population prevalence of 0.25%  [The HIV cascade of care is a useful framework to monitor people living with HIV (PLHIV) from the first point of diagnosis to the ultimate goal of achieving high levels of HIV RNA‐1 viral load suppression . BetweenThe causes of suboptimal treatment outcomes and mortalities are likely multifactorial, including adherence problem , 9, oppoDespite the need to identify and target key interventions, little is known regarding HIV‐related treatment outcomes among HIV‐positive PWID living in the Asia‐Pacific region. The few studies that previously evaluated treatment outcomes among PWID in the region were cross‐sectional and had a short duration of follow‐up , 16, 17.22.1This study is a longitudinal analysis evaluating HIV treatment outcomes among HIV‐positive PWID who have started ART. PLHIV who reported injecting drug use at enrolment as their primary mode of HIV acquisition in the TAHOD cohort between January 2003 and March 2019 were included. TAHOD is a multi‐site observational cohort study which includes 21 participating sites from 12 countries in the Asia‐Pacific region. Details of the cohort and its methods have been reported in previous studies , 19, 20.2.2The first part of the study was to evaluate immunological and virological responses up to 10 years after ART initiation. Immunological and virological responses were measured by CD4 changes and the proportion of individuals with HIV viral suppression after ART initiation respectively. To measure immunological changes, we included patients with available baseline CD4 counts, defined as the latest pre‐ART CD4 count within six months of treatment initiation. Viral suppression (VS) was defined as HIV‐1 RNA <1000 copies/mL. As a sensitivity analysis, the threshold of 400 copies/mL was used to define VS.The second part of the study was to explore a combined endpoint of AIDS‐defining events and all‐cause mortality and incidence of TB. AIDS‐defining events were defined as having a condition from the modified CDC AIDS‐indicator list, including tuberculosis (TB) or an AIDS‐related cancer. All‐cause mortality was defined as AIDS‐ and non‐AIDS‐related deaths. Causes of death were based on the review of the standardized Cause of Death (CoDe) form outlined by the D:A:D study . ParticiWe considered a range of sociodemographic variables, including age , sex, and country income level (low‐middle and high income). Self‐reported adherence was collected during follow‐up visits from the visual analogue scale [2.3Participants with at least one CD4 measurement after six months on ART were included in the CD4 outcome analysis. Factors associated with CD4 changes up to 10 years from ART initiation were evaluated using repeated measure linear regression  with exchangeable correlation matrix using robust covariance estimation), adjusting for site and time on ART. The proportion of patients with VL suppression was analysed descriptively. Participants with at least one viral load measurement after six months on ART were included.Risk factors for TB, and combined AIDS‐defining event and death were evaluated by Cox proportional hazard models. Crude incidence rates of combined AIDS/death and new TB events were reported per 100 persons years (/100 PYS). TB incident cases were analysed as a separate outcome and also included in the AIDS events/death analysis.p < 0.10 were fitted in the multivariable models using a backward stepwise selection process. Covariates with p < 0.05 in the multivariable models were considered significant. Given the potential disparities in healthcare systems across the sites, analyses were stratified by site. As a sensitivity analysis, factors associated with CD4 changes over time were also analysed using linear mixed effect models with a random intercept on patients. All analyses were performed using SAS software version 9.4  and STATA software version 14.2 .Survival time was left truncated at ART initiation or cohort entry, whichever occurred last, and ended on the outcome of interest. Patients who did not experience the outcome were lost to follow‐up, or transferred out were censored on their last visit date. Covariates from the univariable analysis with 2.4Ethics approvals were obtained from respective local ethics committees of all TAHOD‐participating sites, the Kirby Institute  and TREAT Asia/amfAR (coordinating centre). Informed consent was waived unless specified by the local institutional review board at each participating site.33.1Among 8622 participants with known first ART start date enrolled in the cohort until March 2019, 622 PWID (7.2%) were identified  cells/µL among 435 PWID (70%) who had a CD4 count available before ART initiation. An overall increase in CD4 was observed up to 10 years after ART initiation Figure . Among 7p Figure . Figure p = 0.002) and >100,000 copies/mL  compared with viral load ≤400 copies/mL, pre‐ART CD4 51 to 100 cells/µL , 101 to 200 cells/µL  and >200 cells/µL  compared with CD4 ≤50 cells/µL. The adherence variable was not included in the analysis of CD4 changes due to multicollinearity with HIV viral load . We did not find an association with past AIDS or TB diagnosis, age at ART initiation, year of ART initiation, initial ART regimen and time‐updated BMI  in the first year of ART initiation, to 82% (115/140), 88% (82/93) and 93% (63/68) at 3, 5 and 10 years after starting of ART. In a sensitivity analysis when the threshold was used as 400 copies/mL, the proportion of VS remained the same as 1000 copies/mL. The proportion of VS over different years of ART initiation was comparable: 85%, 87% and 88% during years of <2005, 2005 to 2010 and >2010 respectively. In addition, 12 of the 25 PWID who did not have HIV VS at year 1 (48%) had died or LTFU by year 10, compared to 47 of 115 PWID who had VS (41%).3.3p = 0.01), current CD4 ≤50 cells/µL  and CD4 of 51 to 100 cells/µL  and ART adherence of ≤95%  were associated with incidence of new AIDS event or death /100 PYS , current age , ART adherence ≤95%  and current CD4  were associated with TB diagnosis /100 PYS. Past TB diagnosis  among the PWID population was estimated to have enormous health economic impacts at country, regional and even global level, according to the Global Burden of Disease Study . In our Lower CD4 count was shown to be associated with new AIDS events or death in our study. Previous studies have suggested poorer treatment outcomes of PWID especially those with low CD4 count. Our study results are consistent with previous studies that demonstrated individuals with current CD4 counts less than 200 cells/µL having a higher risk for developing new AIDS events/death after ART initiation . Our stuWe have evaluated TB as a separate outcome in this study. PWID tend to be at a greater risk of developing TB and are more likely to not be retained within the TB treatment programme . TB inciLike other non‐PWID participants in the cohort , 32, theThis study has several limitations. First, participants were designated as PWID based on the presumptive HIV mode of transmission defined at their enrolment in the cohort, and no data were collected regarding ongoing drug use or utilization of methadone therapy among our study participants. Therefore, we could not evaluate the impact of current illicit drug use on HIV treatment outcomes. The majority of PWID included in the study started ART in 2005 to 2010, which potentially limits the generalizability of our findings to the “treatment for all” period when ART is recommended after HIV diagnosis regardless of CD4 threshold, and when less toxic regimens became available. Another limitation is that the study group consists of a small number of PWID aged older than 50 years and a small number who were initiated with a PI‐based regimen as first‐line ART combination. As such, the generalizability of our findings to the general PWID is limited. Finally, we were not able to account for unobserved confounders within our cohort.5There has been improvement in immunological and virological responses after ART initiation among PWID. Earlier treatment initiation and implementation of adherence support programmes could benefit PWID within the region. Also, in the Asia‐Pacific region, routine HBV and HCV screening and treatment for this marginalized population with easy access to healthcare services are also critical. Policies enhancing HIV management, adherence support and prevention services tailored for the needs of PWID, and harm reduction services should be more widely adopted to control the HIV transmission in this population group.The authors declare no conflict of interest related to this work.W.M.H., A.J. and A.A. contributed to study’s conception and design. W.M.H. and A.J. analysed the data. W.M.H. wrote the first draft. A.J., N.A.M.S., J.Y.C., B.V.H., J.R. and A.A. interpreted the data and critically reviewed the manuscript. All the authors have substantially contributed to the study and have reviewed and approved the manuscript.Table S1. Incidence rate tuberculosis and its associated factors among PWIDTable S2. Factors associated with CD4 changes over 10 years after ART initiation using random effect modelsClick here for additional data file.


Potential drug–drug interactions (PDDIs) commonly occur because of aging and comorbidities in people living with human immunodeficiency virus . Protease inhibitors and non-nucleoside reverse transcriptase inhibitors have been reported to cause PDDIs in these patients. However, there are few reports of PDDIs in the era of treatment using integrase strand transfer inhibitors. Therefore, we investigated PDDIs in Japanese PLWH receiving antiretroviral drugs (ARVs).This was a cross-sectional observational study conducted in Japanese outpatients. All eligible patients who had received ARV therapy for at least 48 weeks were enrolled. The primary endpoint was the incidence of PDDIs detected using the Lexicomp® interface.P <  0.001). Furthermore, the proportion of patients on polypharmacy was significantly higher in those with PDDIs than in those without PDDIs .Of the 71 eligible patients, 51 (71.8%) were prescribed concomitant non-ARV medications. In 21 patients (29.6%), PDDIs with the potential to reduce the effects of ARVs occurred, although the HIV load was suppressed in all cases. Polypharmacy (the use of ≥5 non-ARVs) was observed in 25 patients (35.2%). There was a significantly higher median number of non-ARV medications in the PDDI group than in the non-PDDI group (6 vs. 3, The incidence of PDDIs is relatively high in Japanese PLWH, even in the era of treatment using integrase strand transfer inhibitors. Therefore, it is important for patients and health care providers to be constantly aware of PDDIs associated with ARV treatment.The online version contains supplementary material available at 10.1186/s40780-021-00226-7. In recent years, the number of elderly people living with human immunodeficiency virus  has been increasing, and problems related to comorbidities and concomitant drugs have garnered increasing attention , 2. A prP-value of < 0.05. All analyses were performed using StatMate IV . The study was approved (312–161) by the ethical review board of Sapporo Medical University, Japan.This cross-sectional observational study was conducted in Japanese outpatients aged 20 years or older who were prescribed ARVs between January 1, 2019, and April 30, 2019, in Sapporo Medical University Hospital. All eligible patients who had received antiretroviral therapy (ART) for at least 48 weeks were enrolled. Data from the patients’ last visit were used. The primary endpoint was the incidence of PDDIs detected using the Lexicomp® interface. We defined PDDIs that occurred between ARVs and non-ARVs as DDIs classified as Rank D (consider therapy modification) or Rank X (avoid combination) in the Lexicomp interface. Viral load suppression was defined as an HIV load of < 50 copies/mL, based on the FDA Snapshot Algorithm. The FDA Snapshot algorithm defines the success of ART by a viral load < 50 copies/mL. We calculated the proportion of patients with viral load suppression and compared clinical characteristics between patients with and without PDDIs. At the time of data collection, we did not analyze the changes in the ART regimen within a 48-week period before the visit. Concomitant medications were defined as medications received together for more than 2 weeks. Topical medications with the expectation of local action were not included. In addition, medications prescribed at other hospitals were not included in the analysis. Each component of fixed-dose combination medications  was counted and analyzed separately. In contrast, herbal medicines and mixtures of probiotics were counted as one drug each even if they contained two or more ingredients. Polypharmacy was defined as the use of five or more medications [P <  0.001) (Table P < 0.003) and polypharmacy  were associated with the occurrence of PDDIs.The characteristics of the study population are described in Table The results of this study indicate the following. PDDIs are common in the Japanese population using INSTIs. In addition, PDDIs between INSTIs and polyvalent cations that could reduce the effects of ARVs occurred, although the HIV load was suppressed in all cases. The prevalence of PDDIs in our study 29.6%) was within the range reported in previous HIV cohort studies 17–45%) [% [5–7, 9.6% was wThe present results support the findings of previous drug-utilization studies demonstrating that the number of medications prescribed is associated with the occurrence of PDDIs –21. PresThe results of our study are valuable in identifying new issues in HIV treatment with INSTIs in Japan. Furthermore, it is interesting that poor viral control was not reported in any of the patients with PDDIs between INSTIs and polyvalent cations. The effects of PDDIs involving INSTIs and polyvalent cations can be minimized by ensuring adequate intervals between the times at which these medications are taken . NotablyThere are several important limitations to this study. No conclusions regarding cause and effect can be drawn from this study due to its cross-sectional design. We were unable to analyze the duration of use of the concomitant medications that caused the PDDIs and medications prescribed in other hospitals. Additionally, our study included no information on the changes in the ART regimen within a 48-week period before the visit at the time of data collection. In the future, we will conduct a longitudinal study using the best possible medication history including prescriptions from other hospitals to address these issues. Another limitation of this study is the small number of participants. This limitation should be resolved in the future by performing a multicenter study. In addition, the study was conducted in a single center; thus, the results might be vulnerable to center bias, and it may be difficult to extrapolate them to other related settings, except for the part where most of our subjects chose ARVs from treatment guideline recommendations .In conclusion, the incidence of PDDIs involving INSTIs and non-ARVs is relatively high in Japanese PLWH. Many guidelines recommend the use of INSTIs; therefore, their use is expected to increase in the future. In addition, the risk of PDDIs among PLWH increases with aging as they use more gastrointestinal and osteoporotic drugs. We conclude that appropriate prescribing strategies and patient education regarding PDDIs are important to avoid virologic failure.Additional file 1: Table S1. Drug classes concurrently prescribed with ARVs.


In the “treat all” era, there are few data on the nature of HIV clinical progression in middle-income countries. The aim of the current study was to prospectively analyze the clinical progression of HIV and its indicators among men in China with acute HIV who have sex with men.via periodic pooled nucleic acid amplification testing, and they were assigned to an AHI prospective cohort in Beijing and Shenyang, China. Rapid progression was defined as two consecutive CD4+ T cell counts < 350/µL within 3–24 months post-infection. Kaplan−Meier and Cox-regression analyses were conducted to identify predictors of rapid progression.From 2009–2014 a total of 400 men with acute HIV infection (AHI) were identified among 7,893 men who have sex with men + T cell count < 500/μL , higher baseline HIV viral load , acute symptoms lasting ≥ 2 weeks , higher body mass index , higher HIV viral load , set point viral load at 3 months , each 100-cell/μL decrease in CD4+ T cell count at 3 months , and baseline routine blood tests including white blood cell count < 5.32, hemoglobin ≥ 151, mean corpuscular hemoglobin ≥ 30.5, hemoglobin concentration ≥ 342, mean platelet count ≥ 342, lymphocytes ≥ 1.98, and mixed cell count ≥ 0.4 .Among 400 men with AHI 46.5% were rapid progressors, 35.1% reached rapid progressor status by 12 months post-infection, and 63.9% reached rapid progressor status by 24 months. Rapid progression was associated with herpes simplex-2 virus coinfection , baseline CD4+ T cell counts, and high set point viral load in acute infection stage. Rapid progression can be identified via simple indicators such as body mass index and routine blood test parameters in low and middle-income countries.Almost half of the patients underwent rapid clinical progression within 2 years after HIV infection. A treat-all policy is necessary and should be strengthened globally. Rapid progression was correlated with herpes simplex-2 virus coinfection, depression, low CD4 A “treat all” policy was recommended by the World Health Organization in 2016 to achieve the global aim of eliminating AIDS by 2030 . A compr+ T cell count. Thus, it is intuitive to link the rapidity of disease progression with high viral load and indolent disruption of CD4+ T cells, and eventual collapse of the immune system  is commonly missed or diagnosed belatedly because of the absence of virus-specific diagnostic tests in routine clinical HIV screening, and the non-specific nature of symptoms .The aim of the current study was to use a large longitudinal prospective cohort of patients with AHI to identify the proportion of RPs present and predictors of rapid progression, in a middle-income country before a treat-all policy was adopted there, to facilitate greater understanding of HIV management globally. China adopted a treat-all policy in 2016. The study cohort were collated and monitored in the years from 2009–2014, and consisted of men who have sex with men (MSM) in China. MSM accounted for one third of the annual national newly reported HIV/AIDS cases in China . Before via pooled polymerase chain reaction for HIV RNA. All HIV-negative (both antibody and RNA) participants at baseline were invited to attend follow-up assessments at 2-month intervals at designated clinics. To minimize loss-to-follow-up, a friendly reminder regarding the date of next follow-up visit was given to each participant well ahead of time. All diagnosed cases of AHI were enrolled into the China Acute HIV Infection Cohort Alliance and were followed up. All follow-up data were included in analyses until the initiation of highly-active anti-retroviral therapy (HAART).Three sampling methods were used to recruit eligible MSM attending voluntary counseling and testing centers in Beijing and Shenyang, China from 2009–2014; respondent-driven-sampling, snowball sampling, and peer referral/facility-based conventional sampling. Participants were eligible if they were born male, aged ≥ 18 years, had engaged in anal intercourse with any male in the last year, were willing to complete at least 2 years of follow-up, and provided written informed consent. Eligible HIV antibody-negative subjects in the initial screening at baseline and during the follow-up survey were both further screened A participant was considered to have AHI if they (1) seroconverted during the follow-up period and the duration between the last antibody-negative test result and the first HIV-positive test was < 6 months (2), returned a negative HIV antibody test but a positive nucleic acid amplification test, or (3) the initial range of their HIV antibody testing was 0.5–1.0 OD and it subsequently increased within 2 weeks   during a 3–24-month period post-infection. Participants were categorized as non-rapid progressors (NRPs) if they only returned 1 CD4+ T cell count of < 350 cells/µL during a 3–24-month period post-infection, or they maintained CD4+ T cell counts of > 350 cells/µL  guideline and recommended providing ART to PLWHIV with CD4+ T cell counts ≤ 500/µL, rather than ≤ 350/µL)  using a pre-tested interviewer-administered questionnaire to collect information on socio-demographic characteristics, sexual behaviors, and clinical symptoms. As per the standard guidelines the height and weight of each participant were also measured. At the end of the interview, pre-test counseling was provided and blood was collected from each participant for the required biological tests. During each follow-up visit, necessary biological, immunological, and virological tests were performed. HAART was initiated when the CD4 350/µL) .A 24-item Hamilton-Depression-Scale  was usedvia nucleic acid amplification testing  using a 24-sample mini-pool strategy. ELISA-positive but western blot-negative/indeterminate test results were tested separately for HIV RNA, with a lowest detection limit of 20 copies/mL. To exclude false-positive determinations, nucleic acid amplification and western blotting tests were repeated for each sample identified as positive during the follow-up, until HIV antibody seroconversion events occurred subsequently.A four-generation enzyme-linked immune adsorbent assay (ELISA)  was used to detect HIV antibodies at the initial screening. Positive samples were confirmed by HIV-1/2 western blotting . For detecting HIV-RNA, all ELISA-negative or western blot-negative/indeterminate samples were further assessed via both the Rapid Plasma Reagin Test  and the Treponema Pallidum Particle Agglutination Assay . HSV-2 was tested using ELISA kits  and seropositive patients were considered to be HSV-2 infected. Hepatitis was tested for using ELISA kits  for detecting serum anti-hepatitis C virus core protein IgG antibodies and anti-hepatitis B surface antigen.Syphilis and herpes simplex virus-2 (HSV-2) were two of the most prevalent sexually transmitted infections (STIs) among MSM in China, and were highly correlated with HIV seroconversion. In previous studies the prevalence of syphilis among MSM in China was 9.1% (range 7.6%–10.8%) , and theRoutine blood tests including hemoglobin (HGB), platelets (PLT), white blood cell (WBC) count, red blood cell (RBC) count, monocyte ratio (MONO%), neutrophil ratio (NEUT%), and monocyte count (MONO) were measured using a BC-6800 automatic blood analyzer  whenever AHI subjects attended a followed-up visit.+ T cell counts were measured using a FACSCalibur flow cytometer  based on a single-platform lyse-no-wash procedure using TruCOUNT tubes and TriTEST anti-CD4-FITC/CD8-PE/CD3-PerCP reagents (BD Bioscience). Viral load (VL) was detected using COBAS AmpliPrep-COBAS AMPLICOR HIV-1 MONITOR Test, version 2.0 (CAP-CA Roche Molecular Systems Inc.) with a detection limit of 20 copies/mL. HIV VL set point was calculated by taking average of all VL values measured during 4–6 months prior to the initiation of HAART. All VL and VL set point values were log10 transformed for data analysis. For HIV-1 subtyping, the pol sequences (entire protease and 256 codons of the RT sequence) were amplified and the edited sequences were aligned against the reference sequences available in the Los Alamos database.CD42. Cox-regression analyses were performed to identify correlates of rapid progression with adjustment for socio-demographics, and adjusted hazard ratios (aHRs) and corresponding 95% confidence intervals (CIs) were calculated. Variables with p values < 0.20 in a bivariate model were included in a multivariate model. The Kaplan–Meier method was used to estimate time to reach end-points  and to determine the variation in rates among AHI cases with CD4+ T cells < 350/µL during the follow-up period across the strata of HIV genotypes/depression status/HSV-2 infection/VL at set point/duration of AHI symptoms. SAS version 9.3 was used for all statistical analyses. Graphs were prepared using SPSS 16.0 software. Midpoint between the last HIV-negative and the first HIV-positive antibody test or 14 days before HIV-RNA positive result were taken as possible time of infection , median, and interquartile range (IQR) were used to describe continuous variables. Body mass index was calculated as body weight (kg)/height (m)The Ethics Committee of The First Affiliated Hospital of China Medical University reviewed and approved the study protocol. Written informed consent was obtained from each participant before the study.The study sponsors had no role in study design, data collection, data analysis, interpretation of the data, writing the report, or the decision to submit the paper for publication.+ T cell counts < 350/μL, 291 patients with AHI who were followed up for at least 2 years were included in the Cox regression model  were excluded from the study. The remaining 7131 western blot and HIV-RNA-negative participants were invited for further follow-up assessments. Of 7131 MSM, 4170 (58.5%) returned to the study and 2961 (41.5%) were lost to follow-up. A total of 6661 person years of follow-up were observed for 4170 subjects with an HIV incidence density of 7.0 (95% CI 6.4–7.7) per 100 person years. Of the 4170 MSM, 467 were diagnosed with incident HIV infection during the study period, thus the total number of AHI cases was initially 572 Figure 12. More than 80% reported having < 3 male sex partners, and 46% had practiced both insertive and receptive sex in the last 3-months. Only 7.8% reported ever having had paid sex with a male partner. Syphilis seropositivity was detected in 119/400 (29.8%), 109/400 (27.3%) were positive for HSV-2, 24/400 (6%) were positive for hepatitis B surface antigen, and 13/400 (3.3%) were positive for anti-hepatitis C virus core protein IgG antibodies at baseline.Among a total of 400 patients with AHI the median age was 32 years (IQR 27–40), and the majority were of Han ethnicity (92.5%), had a monthly income > $350 US (52.5%), and had never been married (69.8%). One third (33.3%) had depression, and the mean body mass index was 20.3 kg/m9/L were detected in 156/400 (39.0%) patients with AHI, 218/400 (54.5%) had red cell counts < 5 × 109/L, 207/400 (51.8%) had hemoglobin < 150 g/L, and 216/400 (54.0%) had platelet counts < 200 × 109/L. The mean overall baseline CD4+ T cell count before HIV seroconversion was 752 cells/µL (SD 268.6). The mean initial CD4+ T cell count was 437 cells/µL (SD 195.6), and the mean log baseline HIV VL was 4.6 copies/mL (SD 1.1) after being diagnosed with AHI. Genetic analysis indicated that majority of patients had the CRF01_AE subtype (63.8%), followed by CRF07_BC (12.0%). During the first year post-seroconversion the mean CD4+ T cell count dropped by 32.1 cells/µL (IQR -78.5–151.7), whereas the mean annual drop was 79.3 cells/µL (IQR 2.8–151.2). The mean HIV VL was 4.3 copies/mL (SD 0.8). Approximately 62% of the patients had a history of acute symptoms, which on average lasted for < 2 weeks in 86% of cases. Fever was the most common symptom reported (49.5%), followed by malaise (31.2%).WBCs < 5 × 10+ T cell count and VL, VL at set point, annual CD4+ T cell count reduction speed post-seroconversion, and mean log baseline HIV VL differed significantly . In the RP group there were greater proportions of patients aged > 30 years, monthly incomes < $350 US, HSV-2 coinfection, depression, duration of acute symptoms ≥ 2 weeks, duration of acute symptoms ≥ 3 weeks, and symptoms of acute malaise, and baseline HIV VL, annual CD4+ T cell count reduction speed post-seroconversion, set point VL were higher. Baseline CD4+ T cell counts were lower in the RP group. In routine blood test results WBC counts, RBC counts, platelets, lymphocyte counts, and eosinophil counts were higher in RPs than in NRPs, whereas the mean platelet volume was lower (During follow-up 186/400 (46.5%) patients with AHI were identified as RPs, and 186/400 (46.5%) were identified as NRPs. In comparisons of the baseline characteristics of RPs and NRPs, there were significant differences in age, monthly income, HSV-2 coinfection, depressive scores, acute infection symptoms, baseline routine blood test items, baseline CD4as lower Table 1.+ T cell count < 350/µL. The median duration between the estimated date of infection and ART initiation was 774 days (IQR 444–1020). The median time from the estimated HIV infection date to a positive results was 30 days (IQR 24–37), and the median time between an initial indeterminate western blot result and a positive result was 52 days (IQR 38–79).The median duration between the estimated date of HIV infection and AHI detection was 38 days (IQR 30–70), and the median follow-up duration post-infection was 421 days (IQR 187–716) Table 1.+ T cell count < 500/μL, < 350/μL, and < 200/μL were 234 (IQR 105–512), 269 (IQR 127–572), and 344 (IQR 144–760). Immunological progression to a CD4+ T cell count < 350/µL at 3, 6, 12, and 24 months occurred in 9.0%, 20.1%, 35.1%, and 63.9% of participants respectively. At the same timepoints 1.8%, 3.0%, 5.6%, and 11.3% of the participants exhibited CD4+ T cell count reductions to < 200 cells/µL, and 13.3%, 32.8%, 47.8%, and 67.8% exhibited CD4+ T cell count reductions to < 500 cells/µL (During follow-up 186/400 (46%) of the patients with AHI were identified as RPs Table 1.+ T cell counts per µL were 380 ± 131, 343 ± 140, 305 ± 89, 296 ± 103, and 281 ± 62 at 90, 180, 360, 540, and 720 days post-infection in the RP group. These values were all significantly lower than the corresponding values in the NRP group at the same timepoints . During the first year after seroconversion, CD4+ T cell counts decreased, by a median of 32 cells/µL (IQR 79–152). The median overall annual decrease was 79 cells/µL (IQR 3–151).The mean respective CD410 copies/mL (vs. < 5), and persistence of symptoms ≥ 2 weeks (vs. < 2 weeks) reached the endpoint of a CD4+ T cell count < 350/μL at a significantly faster rate , HIV VL > 5 log10 copies/mL , duration of acute symptoms ≥ 2 weeks , and baseline routine blood test items ; higher body mass index  and mean platelet volume < 10.3 fL  were negatively associated with rapid progression  were associated with an increased risk of rapid progression.In Kaplan-Meier analysis participants with depression at baseline, HSV-2 coinfection at baseline, set point HIV VL ≥5 logter rate Figure 4+ T cell counts, and a high VL at baseline, and in those with a specific range of baseline routine blood test results. Via prospective follow-up identifying the nature of HIV disease progression in acutely infected MSM before the implementation of a treat-all policy, the current study demonstrates the urgency of early ART in middle and low-income countries. By combining epidemiology, clinical characteristics, immunology, and virology data, the study also quantified correlates of rapid disease progression other than genetic polymorphisms  of the patients, and was more prevalent in those with HSV-2 coinfection, depression, low CD4orphisms , rate ofA change , and priA change , 24.i.e., CD4+ T cell count < 350 cells/µL) within 2 years post-infection in the present study was 63%, which is higher than that reported in studies conducted in South West Africa (55%) and South Africa (44%)  , 26. TheConsistent with the current study, several longer time follow-up studies have reported strong associations between depression and poor clinical outcomes such as AIDS symptoms or mortality in HIV-infected individuals , 28. TheIn the present study concurrent HSV-2 infection was associated with rapid progression, though findings from previous studies are variable. It has been reported that HSV-2 coinfection increases the risk of HIV acquisition three-fold irrespective of sex, but the role of coinfection in disease progression remains unclear , 30. A ri.e., mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, lymphocyte count, absolute value of intermediate cells, and mean platelet volume) that predicted rapid disease progression but have received little attention in previous studies. The use of these routine tests could facilitate the detection of RPs among patients with AHI without treat all policy, and assist healthcare professionals with decisions regarding ART initiation, especially in settings with limited resources for CD4+ T cell testing , the National Science and Technology Major Project of China during the 13th Five-year plan period (2017ZX10201101), the Beijing Excellent Talent Plan (2018000021223ZK04), the Beijing Talent Project in the New Millennium (2020A35), the National Institutes of Health (NIAID 1R01AI114310-01), UNC-South China STD Research Training Center (FIC 1D43TW009532-01), and the UNC Center for AIDS Research (NIAID 5P30AI050410).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.