HIV/AIDS is the most known powerful risk factor for morbidity and mortality in the world. The greatest biological markers in HIV patients are CD4 cell count and hemoglobin level, as they are independent predictors of survival of HIV patients. The objective of this study was to investigate the common socio-demographic, clinical, and behavioral Predictor’s affecting the CD4 cell count, and hemoglobin level with survival time to default from ART treatment among HIV positive adults under ART treatment at university of Gondar comprehensive and specialized hospital, North-west Ethiopia.This study was conducted at University of Gondar comprehensive specialized hospital by using a retrospective cohort follow up study design. The source of data in this study was secondary data obtained from patients chart. Bayesian joint models were employed to get wide-ranging information about HIV/AIDS progression.From a total of 403 HIV positive adults, about 44.2% were defaulted from therapy and the rest were actively followed ART treatment. The estimate of the association parameter for the current true value of CD4 cell count , and good treatment adherence were significantly associated with higher CD4 cell count, hemoglobin level and time to default while having advanced WHO clinical stage-IV had significantly decreased CD4 cell, hemoglobin level, and time to default from treatment. Patients with HIV should be given special attention based on these important factors to improve their health and prolong their lives.The online version contains supplementary material available at 10.1186/s13104-023-06625-3. HIV/AIDS is the most known powerful risk factor for morbidity and mortality in the world . In 2020Eastern and Southern Africa region has been strongly hit by HIV/AIDS . UNAIDS Ethiopia has also one of the largest HIV infected population among sub-Saharan Africa countries . The disExcessive progression of HIV leads to decreased of immune response  as well Defaulting is Patients who did not returned to care ART treatment after their last longitudinal visit time . There a3.Otherwise, an indication of immunological failure of patients whose CD4 cell count less than 500 cells/mm3and HIV strongly affects the immune system below 100 cells/mm3 [CD4 cells are a major target for HIV patients, the virus binds to the surface of CD4 cells, enters them, and either replicates immediately, killing the cells in the process, or remains in a resting state, replicating later . For heaells/mm3 .The significance of hemoglobin level is a standalone predictive indicator of HIV progression and death beginning with ART . HemogloOn the other hand adult HIV positive patients can be low concentration of CD4 cell count and hemoglobin level below the expected healthy adults strongly leads to high HIV progression and patient’s defaults from ART treatment. CD4 cell count, hemoglobin level, and survival rates can be drastically improved by early ART initiation . HoweverMost of the previous literature conducted with CD4 cell count, hemoglobin level and time to default separately. Some of the studies done with separately indicated that predictors associated with default from ART were low body mass index, WHO clinical stage-IV, opportunistic infections, weight, alcohol drinker, rural residence , lack ofIndependent predictors for CD4 cell count were age, weight, baseline CD4 cell count, cell phone ownership, visit time, marital status, residence, and level of disclosure of the disease to family members , househo2 were associated with low hemoglobin level; on the contrary BMI between 25 to < 30 kg/m2 or BMI ≥ 30 kg/m2, smoker and alcohol addicted were associated with higher hemoglobin level overtime [3 [Further study also revealed that HIV Patients were older age, female sex, hepatitis C virus coinfection, higher virial load, 1c ART treatment, illicit drug and BMI < 18.5 kg/movertime . Other srtime [3 , tubercurtime [3 , other ortime [3 .Numerous studies were conducted as some mentioned above for analyzing predictors of CD4 cell count, hemoglobin level and time to default separately that do not considered dependencies between these two different data types  jointly. However, Bayesian joint model simultaneously estimates both the linear mixed-effects model for longitudinal data and Cox PH models for survival data and it is better suited for analyzing such data because they estimate jointly the time-to-event outcome conditional upon the longitudinal outcome .Therefore, as far as the authors’ knowledge is concerned, there is sparse of a study now conducted for CD4 cell count, hemoglobin level and survival time to default from ART treatment jointly among adult HIV positive patients. This study was undertaken with the objective was to identify common socio-demographic, clinical, and behavioral predictors affecting the CD4 cell count, and hemoglobin level with survival time to default from ART treatment among HIV positive adults under ART treatment at university of Gondar comprehensive and specialized hospital (UGCSH), Gondar Ethiopia.This study was conducted at University of Gondar comprehensive specialized hospital (UGCSH), Gondar, Ethiopia which was found in Gondar city. Since, these study area selected with regarding to large no of adult HIV positive patients to obtain relevant information about CD4 cell count, hemoglobin level, survival event, and related covariate.The study population for this study was all adult HIV positive patients treated at UGCSH.Secondary data source obtained by reviewing of the patient’s chart under the follow-up period.Patients who follow-up treatment from September 2015–March 2022 G.C.This study was considered adult HIV positive patients who attended at least a minimum of two visits time for longitudinal response, patients whose age ≥ 15 years, and started treatment within follow-up study period.This study doesn’t was considered adult HIV positive patients who attended only one visits time for longitudinal response, patients whose age < 15 years, and started treatment without follow-up study period.The data collection procedure in this retrospective cohort study was based on medical registration number (MRN) and patient’s chart. First selected patients chart by using their MRN from electronic database system and from the review of patients chart based on inclusion criteria the necessary information were retrieved by two ART data clerks who were trained on ART data management.In order to maintain the quality of collected data, one day intensive training was given for data collectors based on the aim of this study. At that time, adequacy of the checklist was evaluated and ambiguous questions are modified before the actual data collected. The necessary amendments are made on the final data collection format for completeness and consistency and the full formats are checked by ART data management.3, hemoglobin (Hgb) level/dL and time to default from ART treatment. The repeated biomarker of adult HIV positive patients CD4 cell count and hemoglobin level was measured within 6 months interval. In data collection the visit time for CD4 cell count and hemoglobin level was not the same for each patient. Therefore, we approximate every six month and the necessary information was recorded starting from baseline month, 6 month, 12 month, 18 month, 24 month, 30 month,36 month, 42 month, 48 month, 54 month, 60 month, 66 month and 72 month.The response variable for this study were CD4 cell count/mmTime to default of survival outcome was measured in month by subtracted the month of started ART treatment from month of defaulted occurrences.2, functional status, treatment adherence, WHO clinical stage, TB screen, opportunistic infection (OIs) other than TB, other comorbid condition (OCC), hematocrit, White Blood Cell, Red Blood Cell, platelet cell count, lymphocyte count, and monocyte count.The Independent variables in the current study were gender, age in year, level of education, disclosure status, tobacco addiction, alcohol addiction, weight in kg, body mass index in kg/mGender: can be classified in to male and female categories.Age in year: Age in year can be classified as 15–24, 25–34, 35–44, > 44 years.Level of education: for adult patients educational level can be categorized as Non-educated, Primary, Secondary, and Tertiary education.Disclosure: is sharing your HIV status for families, friends, or a health care setting can help with the stresses of living with HIV. However, deciding whom to tell and how to tell them can be complicated and difficult because the important thing is that you choose a place that is comfortable for HIV patients.Tobacco addiction and alcohol addiction: both are considered as substance use disorders, which are problematic patterns closely associated with HIV and other sexually transmitted diseases.Weight: HIV-infected individuals on ART have gained weight, which has been attributed to a return to health condition where appetite increases and more food is ingested along with minimal physical activity..Body mass index: body mass index (BMI) may contribute somewhat on drug metabolism and thus affects antiretroviral therapy (ART) effectiveness.in any cross-sectional or longitudinal study, baseline BMI was calculated as body weight in kilograms/(height in meters)Functional status: According to WHO standards, the functional status was rated as follows: (I) Working: Capable of carrying out routine tasks inside or outside the home. (II) Ambulatory: Capable of performing Activities of Daily Living but unable to perform any employment. C) Bedridden: Unable to carry out Activities of Daily Living.TB screen: HIV-positive individuals may or may not be TB in some conditions. Nevertheless, HIV patients have an increased risk of developing tuberculosis (TB) than non-HIV individuals. This is because HIV impairs immunity, making it more difficult for the body to fight against TB germs.WHO Clinical stage of patients: can be classified as: Stage I (asymptomatic disease), Stage II (mild disease), Stage III (advanced disease) and Stage IV (severe disease).OIs (Opportunistic infectious) disease: patients affected by different AIDS related infections like bacterial pneumonia, salmonella septicemia, fever, diarrhea, candidiasis, toxoplasmosis, wasting syndrome, and other.OCC (other comorbid condition): HIV Patient’s would be affected by different chronic illness like diabetes, hypertension, cancer disease, and anemia.Treatment adherence of patients: was classified based on WHO classification: poor adherence was classified as the percentage of the missed dose was < 85%, fair adherence the percentage of the missed dose was 85%–94%, and good Adherence was classified as the percentage of missed dose ≥ 95% .Hematocrit, White Blood Cell, Red Blood Cell, platelet cell count, lymphocyte count, and monocyte count: both can be considered as hematological parameters among HIV positive patients.In this study, Secondary data was collected by Microsoft excel, the collected data imported in to SPSS version 26 for data management and finally imported in to R- software Version 4.1.3 for statistical data analysis by considered 5% level of significance.Bayesian bivariate LMEM was used for continuous response variable for the repeated measure hemoglobin level and CD4 cell count.Cox PH model was used for survival time to default from ART treatment.Joint model was used for repeated measure hemoglobin level and CD4 cell count with survival outcome.In this study, the authors used Bayesian bivariate Linear mixed effect model (LMEM) to investigate the determinant factors that can affect CD4 cell count and hemoglobin level. Cox PH model had been used to determinant factors that affect the survival time to default from ART treatment. Finally, statistical joint model analysis was used to assess the impact of repeated measure CD4 cell count and hemoglobin level with time to default from ART treatment. Based on the complexity of the data and the desired objectives of the study, the authors considered the following three different statistical models:Females made up more than half of the patients in this study (64.5%), of which 55.4% defaulted from ART treatment during the follow-up period. Regarding age in years of patients, a large percentage of patients 182 (45.2%) were aged between 25 and 34 years, of which 135 (74.2%) defaulted throughout the study period. Furthermore, in terms of functional status, 31.64%, 77.2%, 48.2% were working, ambulatory, and bedridden patients respectively defaulted from ART treatment. Similarly, among 220 (54.6%) urban participants, 65 (29.5%) defaulted from ART treatment. Regarding the level of education, 139 (34.5%) had attended primary school education and out of them more than a half (54.64%) defaulted from ART treatment. Regarding disclosure status, more than half, 349 (86.6%), were disclosed the disease to someone of which 142 (40.69%) defaulted from ART treatment. Considering tobacco and alcohol addiction patients, around 22.4%, and 68.5%, were tobacco and alcohol addicted patients respectively defaulted from ART treatment  of which 87 (31.6%) defaulted from ART treatment. A large percentage of participants, 300 (74.4%), had good adherence status of which 41.7% defaulted from ART treatment during the follow-up period. Regarding the WHO clinical stage of participants, 224 (55.6%), 77 (19.1%), 74(18.4%), and 28 (6.9%) were stage-I, Stage-II, Stage-III, and Stage-IV, respectively. Similarly, the proportion of defaulter among HIV-TB co-infected participants was 83.9%. A significant proportion, of the study participants, 82 (20.3%), had one or more illnesses (opportunistic infections) other than TB, of which 55 (67.1%) had the outcome of defaulter. On the other hand, among the 89 (22.1%) participants who had affected by other comorbid condition (OCC)  defaulted from ART treatment, while the remaining 255 (55.8%) were censored. The overall mean and median survival time was 44.3 and 42 months respectively . Hence, model-IV (random intercept and slope model) for both repeated measure responses in the full model was well-fitted  than male patients. Good adherence patients had increased the average CD4 cell count by 6.7 per mm3 and fair adherence patients had increased the average Hemoglobin level by 0.45 g/dl as compared to poor adherence patients. Similarly, good adherence Patients had more hazard of defaulting (HR = 3.43) than poor adherence patients. The remaining joint predictors can be similarly interpreted as above. Hence, as hematocrit, weight, platelet cell count, and lymphocyte count of a patient increased, CD4 cell count, Hemoglobin level, as well as its defaulted time increased. However, advanced clinical stage of patients was low CD4 cell count, Hemoglobin level and time to default.Tables 3. Similarly, Hematocrit could be attributable to the maximizing Hemoglobin level and defaulters of patients.In our study Hematocrit was found to be a significant predictor of CD4 cell count, Hemoglobin level and time to default from ART treatment in HIV positive individuals. Hematocrit increased by one unit, the average CD4 cell count had increased by 4.5 per mm3.This result had been oppose by former study [Weight had a significant effect on CD4 cell count, Hemoglobin level and time to default from treatment. As weight of patients increased by one unit, the average CD4 cell count had increased by 0.9 per mmer study . A unit er study . Howeverer study . This miResults of the current study revealed that platelet cell count and lymphocyte count had an increment effects on CD4 cell count, and Hemoglobin level. Similarly, both predictors also increased by one unit, the hazard of defaulter were increased. This means adult HIV positive patients who had higher platelet cell count and lymphocyte count would have a higher CD4 cell count and Hemoglobin level with different increment of defaulter rates.In this study female patient is a statistically significant factor for CD4 cell count. The result of this findings support the previous literature , 33. TheThe patient’s treatment adherence was also found to be a significant factor for CD4 cell count, Hemoglobin level and time to default. The patient’s repeated measure and survival time appears to increase with their level of treatment adherence. This could be patients may have better get of their health status related with increment of CD4 cell count, Hemoglobin level and decides to default from treatment easily.In terms of WHO clinical stage; clinical stage-IV (severe disease) patients is lower CD4 cell count than clinical stage-I patients. This study supported by previous study in their result shown WHO clinical stage IV patients had a lower CD4 cell count than stage I during the follow-up period . ClinicaIn joint model the estimates of the association parameter due to the slope of CD4 cell count is positive This study indicating patients CD4 cell count and Hemoglobin level concentration increases from visit to visit, due to this increment variation patents default from treatment in different reason like patients might be feel better health condition  and might decide to default from treatment.This study revealed that high hematocrit, high weight, high platelet cell count, high lymphocyte count, female patients, and good treatment adherence had joint significant predictors on adult HIV patients’ by increment of CD4 cell count, Hemoglobin level, and time to default from ART treatment. While, advanced WHO clinical stage-IV had joint significant predictors on adult HIV patients’ by decrement of CD4 cell count, Hemoglobin level, and time to default from ART treatment. To improve their health and extend their lives, patients with HIV should be given special attention based on these important factors. This study result can be used as bench mark for policymakers and concerned health staff to be considered for application of health related issues. It is recommended that further studies should be done on HIV positive adult patients by considering other important covariates that were not included in this study.This study was based on retrospective cohort study design, the data obtained from adult HIV positive patients chart. However, some important socio-demographic and clinical predictors like nutritional status, income status, homeownership, viral load count and other hematological parameters like eosinophil, neutrophil, and basophil counts, were not available on patient’s chart at study period (Additional file Additional file 1: Table 1. Proportional assumption check.


To compare viral suppression in treatment-naïve adults starting antiretroviral therapy with dolutegravir (50mg)- and efavirenz (600mg)-based regimens.versusper-protocol. Time to viral suppression and adjusted odds ratio accompanied by 95% confidence intervals were estimated. We analyzed secondary data from Brazilian health information systems of people living with human immunodeficiency virus who started antiretroviral therapy between 2015 and 2017 in Minas Gerais, Brazil. The outcome was viral suppression, defined as the achievement of the first viral load <50 copies/mL within 12 months after initiating antiretroviral therapy. This outcome was also compared with viral load <1,000 copies/mL and analyzed in two scenarios: intention-to-treat3, and viral load <100,000 copies/mL had higher odds of viral suppression. According to the per-protocol analysis, viral suppression ≥90% was observed by considering viral load <1,000 copies/mL. Of the 2,599 participants enrolled, 77.5% were men, and the median age was 34 years. In the intention-to-treat analysis, viral suppression was 58.1% for efavirenz and 76.7% for dolutegravir. People living with HIV on dolutegravir-based regimen were more likely to achieve viral suppression  and had a shorter median time to viral suppression (p<0.0001). Antiretroviral therapy initiation within <120 days, baseline CD4⁺T-cells ≥200 cells/mm Our study demonstrated that viral suppression improved after introducing dolutegravir, although the proportion of patients with viral load <50 copies/mL was lower than expected. Improved access to routine viral load examinations and continuous surveillance of the effectiveness of antiretroviral therapy should be considered. Viral suppression is one of the goals for eradicating the acquired immunodeficiency syndrome (AIDS) epidemic by 2030. In Brazil, viral suppression is monitored by the Department of Chronic Conditions and Sexually Transmitted Infections, by considering the threshold VL as <50 copies/mL, which is frequently considered the threshold value in clinical research.-16An undetectable VL is the main objective of HIV treatment. The World Health Organization (WHO) has been monitoring PLWH with VL <1,000 copies/mL to control the risk of transmission, disease progression, and therapeutic failure.-19 despite changes in the national HIV guidelines in 2017 that recommend the use of antiretroviral regimens with dolutegravir (DTG) as the first-line treatment and the use of efavirenz-based regimens (EFV) as the alternative first-line ART. Therefore, it is important to collect ample data at the regional level to identify obstacles in the achievement of sustainably undetectable VL.Few studies have assessed the proportion of individuals who have achieved viral suppression using first-line ART in Brazil,To compare the viral suppression rates achieved with dolutegravir (50mg)- and efavirenz (600mg)-based regimens in the first 12 months of treatment and to evaluate the associated factors and time to viral suppression.+ T-cell counts.We conducted a historical cohort study of ART-naïve PLWH who started treatment with DTG- or EFV-based regimens between January 2015 and December 2017 in Minas Gerais, Brazil. The regimen containing DTG (50mg) was administered as two pills (a fixed-dose combination of tenofovir disoproxil fumarate (300mg) and lamivudine (300mg) plus other DTG pill), and the regimen containing EFV (600mg) was administered as one pill (a fixed-dose combination of tenofovir disoproxil fumarate (300mg), lamivudine (300mg), and EFV). Data were obtained from two administrative databases of the Unified Health System for HIV/AIDS of the Ministry of Health: the Medication Logistics Control System (SICLOM), which records the dispensation of ART, and the Laboratory Tests Control System (SISCEL), which records laboratory results of VL and CD4Individuals with records of VLs measured at least once within 12 months after ART initiation and baseline VLs measured within 180 days before ART initiation were included in this analysis. Individuals who did not undergo VL examinations, had undetectable baseline VL (<50 copies/mL), or were aged <18 years were excluded. Explanatory variables included demographic, laboratory, and therapeutic variables, such as age, sex, place of residence, baseline VL, baseline CD4+ T-cell count, and time to ART initiation (defined as the time from the first CD4+T-cell examination until ART initiation). The patient informed consent was not essential for inclusion in this study, since an code number was used for patient identification and the data confidentiality was ensured at all stages of the project. TheUniversidade Federal de Minas Gerais(UFMG) Research Ethics Committee approved this study on January 19, 2017 .The outcome was viral suppression, defined as the achievement of the first VL <50 copies/mL measured within 12 months after ART initiation. The proportion of individuals who achieved viral suppression was compared with an international parameter .2 and Mann-Whitney tests.We conducted a descriptive analysis of the study population. Absolute/relative frequencies and median/interquartile ranges (IQRs) were estimated. The variables were categorized using the median or other criteria based on their clinical relevance. We compared demographic and clinical characteristics at baseline by using the χTime to viral suppression was defined as the time (in days) that elapsed from ART initiation until viral suppression was achieved, according to the first record of suppressed VL. For individuals who had not achieved viral suppression within 365 days, we considered the interval between the date of the first ART administration and the date when the last VL was >50 copies/mL or when ART was switched (censored data). Antiretroviral therapy switches were defined as alterations to any antiretroviral drug in the regimen or dose adjustments. Kaplan-Meier survival curves were generated to assess the time to viral suppression. The log-rank test was used to compare survival functions with a significance level of 0.05. Intention-to-treat analysis included all the individuals who initiated first-line treatment regardless of whether they had switched or discontinued ART. The per-protocol analysis included individuals who were adherent to ART administered as first-line treatment and did not switch their ART. We selected possibly adherent individuals who had received ARTs 12 times within one year, since during the study period the Medication Dispensing Units commonly dispensed ART monthly. The variables were stratified into subgroups to assess the statistical differences in the occurrence of viral suppression according to the ART administered.The analysis considered intention-to-treat (ITT) and per-protocol concepts to compare “real-world” and “controlled” scenarios of drug utilization, respectively.Univariate and multivariate analyses were performed using logistic regression to determine the association between viral suppression and putative risk factors. Variables with p≤0.20 in the univariate analyses were selected for inclusion in the final model. Backward stepwise regression was used to obtain the final model (variables with p<0.05) adjusted for age and sex to control for demographic characteristics, expressed as adjusted odds ratio (aOR) accompanied by 95% confidence intervals (95%CI). Model goodness-of-fit was assessed using the Hosmer-Lemeshow test. Analyses were conducted using the SAS software version 9.4 .Between January 2015 and December 2017, 13,234 PLWH in Minas Gerais started first-line ART. We excluded 5,666 (42.8%) individuals who did not undergo VL examinations or were aged <18 years. Of the remaining 7,568 individuals, 65.7% were excluded because of the absence of VL records  or presence of undetectable VLs before starting ART (n=43). A total of 2,599 individuals were included in the ITT analysis . The per-protocol analysis accounted for 559 individuals; 350 and 209 individuals were treated with EFV- and DTG-based ART, respectively .3 (IQR: 146-507), and median baseline VL was 4.7 log10copies/mL (IQR: 4.2-5.3). The median time to ART initiation was 34 days (IQR: 20-71) and 17.7% of the included study participants took ≥120 days after the first CD4+ T-cell examination to start ART. Approximately 34% (n=886) and 66%  of the patients started first-line treatment with DTG-and EFV-based regimens, respectively (⁺T-cell count and VL were 281 cells/mm3 (IQR: 121-461) and 4.9 log10copies/mL (IQR: 4.4-5.5), respectively, in PLWH following the DTG-based regimen and 343 cells/mm3 (IQR: 164-530) and 4.6 log10copies/mL (IQR: 4.1-5.2), respectively, in PLWH following the EFV-based regimen (p<0.0001).Most study participants were men (77.5%), and 57.8% of the participants lived in the countryside or neighboring cities. The median age was 34 years (IQR: 27-43), median baseline CD4⁺ T-cell count was 322 cells/mmctively . The meversus181 days [95%CI: 174-195], p<0.0001). No significant differences were observed in the per-protocol analysis results .+ T-cell count, and baseline VL. Antiretroviral therapy switching in first-line treatment occurred in 5% and 9.2% of the PLWH following the DTG- and EFV-based regimens, respectively. According to the per-protocol analysis (n=559), viral suppression was observed in 83.7% and 74.0% of the PLWH following the DTG- and EFV-based regimens, respectively, with increases of 13.0% and 16.0%, respectively, when considering VL <1,000 copies/mL. No significant difference was observed between the ART regimen groups in terms of the percentage of PLWH with viral suppression when the CD4+ T-cell count <200 cells/mm3, sex was female, age was >35 years , and baseline VL ≥100,000 copies/mL  was 76.7% (95%CI: 75.1-78.3) and 58.1% (95%CI: 56.8-59.4), respectively. Comparing PLWH with VL <1,000 copies/mL and those with VL <50 copies/mL , viral suppression was observed in 89.4% (12.7% increase) of the PLWH following the DTG-based regimen and in 76.8% (18.7% increase) of those following the EFV-based regimen. Viral suppression was observed in a higher percentage of PLWH following the DTG-based regimen than in those following the EFV-based regimen (p<0.05), even when stratified by age, sex, baseline CD4pies/mL .+ T-cell count, baseline VL <100,000 copies/mL, and time to ART initiation were also maintained in the final model. In the per-protocol analysis, DTG-based regimen  and baseline VL <100,000 copies/mL  were independently associated with viral suppression  was achieved in 90.5% of the cases that follow DTG-based regimens, even when controlling adherence.This higher proportion of individuals with viral suppression compared to that in our study is due to methodological specificities and the high heterogeneity of the HIV-infected population across Brazil. Therefore, we highlighted the importance of analysis at the regional level.The introduction of fixed-dose combinations involving EFV plus lamivudine and tenofovir disoproxil fumarate demonstrated better results in terms of viral suppression within the first six months after initiating ART in the state capital, compared to multiple doses and drug formulations.+ T-cell counts. Despite these characteristics, viral suppression was achieved in a higher proportion of the PLWH following the DTG-based regimen compared with those following the EFV-based regimen. The superiority of DTG-containing ART over EFV-containing ART has also been verified in clinical trials;,24 however, there was a lower difference 6% and 7% between the groups. Particularly in real-world scenarios, the improvement of ART adherence remains challenging,,25 indicating the importance of monitoring adherence via readily accessible dispensation of existing drugs to achieve better treatment outcomes.We found that individuals who started treatment with the DTG-based regimen presented with higher baseline VL and lower baseline CD4,26 which could explain the higher incidences of switching and lower annual dispensation rates observed with EFV-containing ART. Nervous system or psychiatric disorders are frequently reported among patients following an EFV (600mg)-based regimen.,27 Brazil’s pharmacovigilance system has reported that the main adverse effects of DTG were nausea, diarrhea, and headache. Dolutegravir-based regimens have also been associated with nervous system disorders, such as insomnia;-31 however, the rates of drug discontinuation are among the lowest in real-world scenarios.The use of low-dose EFV (400mg) has demonstrated a reduction in ART discontinuation owing to adverse effects,33 and this drug preparation has already been recommended by the World Health Organization as an alternative regimen.Therefore, low-dose EFV could be considered as an alternative to first-line ART in low-and middle-income countries with a low prevalence of pretreatment non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance, considering genotyped individuals without pretreatment resistance. Of note, EFV 400mg has not been made available in Brazil and the country is not among those with high pretreatment resistance to EFV. However, low-dose EFV would be indicated in genotyped individuals without pretreatment resistance.Higher switching rates were observed among individuals who started treatment with EFV-based regimens. Adverse effects and drug resistance leading to ART discontinuation have been reported more frequently with EFV-based regimens than with DTG-based regimens, In our study, achievement of viral suppression in ≥90% of the PLWH by 12 months was observed only when considering the same criterion  and controlled adherence and/or changes in the first-line regimen. This finding can be reinforced by the data on diagnosed individuals who are not receiving adequate treatment. In addition, because even low but persistent viremia increases the risk of virological failure,,39 this criterion may not indicate long-term therapeutic effectiveness.According to the Joint United Nations Programme on HIV/AIDS (UNAIDS) mission to achieve the 90-90-90 target in Brazil, 85% of the PLWH knew their status, 77% could access treatment, and 94% exhibited viral suppression by 2018. In 2020, Brazil achieved percentages of 88-81-95, considering a VL of <1,000 copies/mL.3, and the individuals were female and/or older. The NAMSAL study reported that a higher baseline VL  decreased the efficacy below 60% for both regimens, with a higher proportion of individuals receiving EFV-containing ART (400mg) achieving viral suppression compared with those receiving DTG-containing ART. Therefore, the predominance of certain baseline characteristics can influence the effectiveness of first-line ART. Another study observed that initiating ART within <120 days is a predictor of viral suppression. We observed that the individuals with baseline CD4⁺ T-cell count ≥200 cells/mm3 were more likely to achieve viral suppression, demonstrating that low immunological profile before starting ART may be an obstacle to viral suppression as shown in other studies.,42 The association between baseline VL  and viral suppression was observed in this study in both the ITT and per-protocol analyses. In addition, high baseline VL levels may be associated with viral blips and virological failures. Health services must recognize that these variables may affect therapeutic effectiveness and therefore prioritize the availability of antiretroviral drugs for individuals immediately after HIV diagnosis, in addition to routine monitoring and support for adherence.A comparison of the per-protocol and ITT scenarios showed that higher proportions of individuals considered adherents exhibited viral suppression, and subgroup differences were detected to a lesser extent. Similarly, in a randomized, double-blind and phase III study, DTG-based regimens achieved viral suppression in a higher proportion of the study population than EFV-based regimens without significant differences between groups when baseline VL >100,000 copies/mL, baseline CD4⁺ T-cell count <200 cells/mmA randomized clinical trial observed that individuals achieved undetectable levels of VL in approximately 28 days with DTG-containing ART and in 84 days with EFV. The shorter time to achieve viral suppression is because VL is assessed more frequently in clinical trials than in routine clinical practice.In the ITT analysis included in this study, individuals who initiated ART by following the DTG-based regimen achieved viral suppression earlier than those following the EFV-based regimen. However, no differences were observed in the per-protocol analysis, which does not reflect clinical practice. Another retrospective study observed that the median time to viral suppression was 60 days among individuals on DTG-containing ART or other integrase strand transfer inhibitors (INSTIs) compared to 137 days among those on EFV- or other NNRTI-based ART, when controlling adherence.,46 In addition, individuals living >200km away from the municipality of the pharmacy may be less likely to achieve viral suppression. Thus, it has been clearly demonstrated that the difficulty in accessing health services can influence the process of retention, adherence, and sustained viral suppression.PLWH who lived in the countryside or in other neighboring cities were significantly less likely to achieve viral suppression compared to those living in the state capital according to the univariate analysis. Others studies have shown that important differences in viral suppression can be observed depending on the place of residence or the size of the municipality. thus justifying the absence of some of the data and preventing the estimation of more accurate viral suppression rates. VL monitoring is important for understanding the factors that prevent viral suppression, leading to virological failure,12; however, it is not always performed in due course. In many low- and middle-income countries, PLWH have inadequate access to routine VL tests. Therefore, improving the patient’s access to VL monitoring and therapeutic education in clinical practice is of crucial importance.In this study, we observed that 93.4%  of the individuals started ART with EFV or DTG. Approximately 40% of the individuals did not have a VL record available for analysis. Minas Gerais has the greatest access to private healthcare (>20%) among all Brazilian states,-51 and weight gain, are associated with DTG. Among PLWH with tuberculosis, the use of twice-daily DTG rather than EFV is recommended when pretreatment genotyping within less than two weeks is not possible. In pregnant PLWH, the current data detailing the low incidence of DTG-induced neural tube defects have been reassuring so far.Nevertheless, continued surveillance of the association of DTG-based regimens with neural tube defects and metabolic alterations is required. Additionally, DTG is more expensive than EFV; however, DTG-based regimens may be more cost-effective.,55 In this study, we collected data from the period before the COVID-19 pandemic as the pandemic-imposed constraints on HIV care services may influence our results otherwise.The ART regimens investigated in this study were selected in accordance with the current recommendations, which have been updated according to emerging evidence on their efficacy, effectiveness, and safety. Recent studies have reported that metabolic abnormalities, including hyperglycemiaNevertheless, this study has some limitations. Assuming higher rates of viral suppression with DTG-based regimens among individuals linked to private health centers, our results may have been underestimated. Viral load examination results of individuals followed in the private health network are often not filled in ART prescription forms, which prevents recording to SICLOM during the ART dispensing. In addition, the records of the VL examinations represent access to the examinations rather than the actual moment of viral suppression. Therefore, the time required for viral suppression should be cautiously interpreted. Despite these limitations, our study adds to the real-world evidence of the benefits of DTG-based regimens, thus providing guidance for future clinical decisions. Further larger and long-term studies that evaluate the routine clinical practice are required to assess the ART effectiveness given the constant update of national HIV guidelines, but it will mainly require improvements in access and recording VL examinations.+T-cell count, and low viral load, were predictors of viral suppression, although first-line antiretroviral therapy with dolutegravir exhibited greater effectiveness, even with worse immunological and virological patient profiles, compared with efavirenz. Higher rates of viral suppression were attained with efavirenz-based regimens when adherence and antiretroviral therapy alterations were controlled ; however, these rates were lower than those attained with dolutegravir-based regimens. Nevertheless, the incidence of viral suppression  was lower than the global target, which reinforces the importance of evaluating treatment guidelines and their impact on clinical outcomes in real-world scenarios as well as improving public access to routine viral load examinations.In conclusion, viral suppression was more likely to be achieved or achieved earlier with dolutegravir-based regimens in a real-world scenario. Some baseline characteristics, such as early initiation of antiretroviral therapy, high CD4


The incidence of progressive multifocal leukoencephalopathy (PML) in people living with HIV (PLWH) is 2%-4%. Currently, there is no effective therapeutic strategy for the treatment of PML in PLWH, resulting in a mortality of up to 50%. This study aimed to identify risk factors of death and prognostic markers in people living with HIV with PML.A retrospective cohort study of AIDS-related PML individuals was conducted from January 1, 2015, to October 1, 2022, in Shanghai, China. PLWH who were diagnosed with PML for the first time were included. Kaplan-Meier curve and Cox regression were used to analyze the survival and its predictors. Levels of inflammatory markers and immune checkpoint inhibitors in blood and cerebrospinal fluid (CSF) were measured in the prestored samples using bead-based multiplex assay Indolamine 2,3-dioxygenase was determined using ELISA.Twenty of 71 subjects had initiated antiretroviral therapy (ART) before PML onset and no patients discontinued ART during this period. In total, 34 patients (47.9%) had opportunistic infections (OIs), the median CD4+ T cell count was 73.0 (33.0-149.0) cells/μL. The estimated probability of survival at six months was 78% . OIs, low CD4+ T cell count were associated with lower estimated six-month survival . Indolamine 2,3-dioxygenase activity in CSF of non-survivors group were higher than survivors group (p<0.05).The survival rate of AIDS-related PML in the modern ART era was higher than the survival rate a decade ago. Low CD4+T cell count, OIs, were all associated with death of individuals with AIDS-related PML. The role of IDO in AIDS-related PML warrant further investigation. Over thBefore the advent of antiretroviral therapy (ART), the incidence of PML in PLWH was 2%-4% and PML is recorded a mortality rate for 90% of PLWH . The surRisk factors and predictors of mortality in patients with AIDS-related PML have to be identified to improve patient management and accelerate the development of new therapies. Nevertheless, researches with larger samples on immune checkpoints and cytokines in CSF and plasma from AIDS-related PML patients are still lacking . In addiHerein, we analyzed the clinical outcome and measured levels of immune checkpoints and inflammatory markers in plasma and CSF to determinate the survival and prognostic factors of PML in PLWH.22.1This retrospective study was conducted in the Department of Infectious Diseases and Immunology of the Shanghai Public Health Clinical Center (SPHCC), Shanghai, China. Experiments were approved by the ethics committee of the SPHCC  in strict conformity with the ethical guidelines of the Declaration of Helsinki. Written informed consent was obtained from all study participants.All PLWH with progressive neurological systems or typical magnetic resonance imaging (MRI) findings and presented to SPHCC between January 1,2015 and October 1,2022 were included on initial review. CSF and plasma samples were collected and immediately stored at -80°C until analysis.2.2Clinical data of 71 AIDS-related PML individuals were collected. The following characteristics were collected from the hospital information system: gender, age, comorbidities, opportunistic infections (OIs), CD4+ T cell count, CD8+ T cell count, HIV viral load, CSF glucose, CSF chloride, CSF protein, ART regimen, JC-virus viral load, the time from the initiation of ART to PML onset, delay in PML diagnosis and clinical features.The inclusion criteria were as follows: (1) HIV-1 infection confirmed by Western blotting; (2) patients had neuropathologic demonstration of the typical histopathologic triad  or the techniques to show the presence of JC virus; (3) patients had at least one PML clinical symptoms  or imaging manifestations . The exclusion criteria were patients younger than 18 years.The definitive diagnosis of PML requires positive brain biopsy or clinical and radiographic criteria consistent with demonstrating the presence of the JC virus in CSF. Patients who had clinical and radiological findings coupled with PML but for whom lumbar puncture and brain biopsy was not performed were categorized as possible PML cases . We defiThe immune reconstitution inflammatory syndrome (IRIS) diagnosis was defined as typical presentation or paradoxical rapid worsening of PML after initiation of HAART (within 90 days) together with a sharp decrease in plasma HIV-1 viral load and increase in CD4+ T cell count with exclusion of other diseases. Comorbidities were defined based on the Charlson Comorbidity Index , which i2.3Bead-based multiplex assay was performed to detect inflammation cytokines/chemokines levels on plasma and CSF samples from different donors. We used the Human Inflammation Panel 1  to determine IL-1β, IFN-α2, IFN-γ, TNF-α, MCP-1 (CCL2), IL-6, IL-8 (CXCL8), IL-10, IL-12p70, IL-17A, IL-18, IL-23, and IL-33;and the Human Immune Checkpoint Panel 1 (10-plex) to determine sCD25 (IL-2Ra), 4-1BB, B7.2 (CD86), Free Active TGF-β1, CTLA-4, PD-L1, PD-1, Tim-3, LAG-3, and Galectin-9.Multiplex assays were done following the manufacturers’ instructions. Data were collected and analyzed using LEGENDplex software v8.0 .Kynurenine (Kyn) and Tryptophan (Trp) are quantitatively determined by ELISA , respectively. The Kyn : Trp (K:T) ratio were calculated to indicate the activity of the inducible enzyme indolamine 2,3-dioxygenase (IDO).2.4www.r-project.org), GraphPad Prism version 8.3.1  and SPSS statistics 21.0 . The Shapiro-Wilk test was used to test the normality of data distribution. Normally distributed data were reported as the means and standard deviation (mean ± SD). Non-normally distributed data were presented as the medians and interquartile range (IQR). Categorical variables were summarized with frequency counts and presented as a rate (%).Statistical analysis was performed using R software, version4.2.0  patients were confirmed PML: JC virus DNA was detected in CSF in all cases and brain biopsy confirmed the diagnosis in one case. Of all the patients, 88.7% were male, and the median age was 35.0 (29.0-36.0) years. The median time to diagnosis was 30(21-90) days. In total, 34 patients (47.9%) had OIs, and 17 (23.9%) had comorbidities. In addition, the median CD4+ T cell count was 73.0 (33.0-149.0) cells/μL, and the median HIV viral load was 4.6(3.3-5.4) log10 copies/ml. Twenty (28.2%) patients had received ART before PML onset, and 12 patients of them had received it for more than 6 months Table 1.3.2After a median of 19 (16-33) months follow-up, 15 patients (21.1%) died despite receiving ART, and 9 patients (12.7%) were lost to follow-up. The lifetable method showed a survival rate of 78.0% [95% confidential intervals (CIs): 0.63-0.85]at 6 months,78.0% (95%CIs: 0.77-0.96) at 1 year,72% (95%CIs: 0.45-0.81) at 3 years Table 2.The variables including OIs, CD4+ T cell count, CSF glucose, IRIS, age, confirmed PML and comorbidity were included in a stepwise multivariate Cox proportional hazards model. There was no interaction between OIs and low CD4+ T cell count  Table 2.3.3The levels of inflammatory markers and soluble immune checkpoint inhibitors were obtained in 31 plasma samples and 11 CSF samples at the diagnosis of PML. There was no significant difference in levels of immune checkpoint and inflammatory biomarkers in plasma between the survivors group and the non-survivors group Table 3.4The introduction of ART two decades ago greatly revolutionized treatment and allowed the reversion of HIV induced immunosuppression, increasing PML one-year survival from 10% to almost 50% . Our stuWe found higher mortality in patients with CD4+ T cell count ≤50 cells/μL compared with those with higher CD4+ T cell count, which was consistent with the previous reports . TherefoThe three most commonly HIV-related OIs were bacterial pneumonia, cytomegalovirus and nontuberculous mycobacteria among the study participants. A systematic review estimated that during the first year of ART, the incidences of all OIs declined to <2% in low- and middle-Income countries, except for unspecified tuberculosis, pneumonia tuberculosis, herpes zoster, and oral candidiasis, which remained the most common OIs . HoweverIn recent years, PD-1 inhibitors have been reported to be effective in PML patients in some cases . HoweverWe found that only IDO activity in CSF of non-survivor group in CSF was slightly higher than in survivors group among the measured immune checkpoints and inflammatory markers. IDO is produced by dendritic cells and regulatory T cells and affects T cell differentiation toward regulatory T cells and away from helper cells (Th-17) . PreviouThere are also some limitations in our study including its retrospective nature. We have missing data for JC virus and HIV viral load, which previous studies  have sho5The survival rate of AIDS-related PML in the modern ART era was higher than it was a decade ago. Low CD4+T cell count, OIs, were all associated with death of individuals with AIDS-related PML. The role of IDO in AIDS-related PML warrant further investigation.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.This study has been approved by Shanghai Public Health Clinical Center in China and informed consent was obtained from the patient involved. The approval number is 2021-S051-01. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study.JC and RZ conducted the study conception and design. RJ collected the data of patients. RJ and JC analyzed and interpreted the data. RJ wrote the manuscript. ZS and RJ contributed to the experiments. JC critically revised and finally approved the manuscript. RZ, XM TQ, JS, ZW, WS, YT,JY,SX and BZ supervised the project. All authors contributed to the article and approved the submitted version.


Overall ADR was high . TDF, potentially active in 35.7% of participants after first-line and 45.1% after second-line, suggested sub-optimal TLD-efficacy in second-line (64.3%) and third-line (54.9%). All PI/r preserved high efficacy after first-line failure while only DRV/r preserved high-level efficacy (87.9%) after second-line failure. In this resource-limited setting (RLS), ADR is high in ART-failing patients. PI/r strategies remain potent backbones for second-line ART, while only DRV/r remains very potent despite second-line failure. Though TLD use would be preferable, blind use for second- and third-line regimens may be sub-optimal  with high risk of further failure, thus suggesting strategies for selective ART switch to TLD in failing patients in RLS.Increased HIV drug resistance (HIVDR) with antiretroviral therapy (ART) rollout may jeopardize therapeutic options, especially in this era of transition to fixed-dose tenofovir-lamivudine-dolutegravir (TLD). We studied acquired HIVDR (ADR) patterns and describe potentially active drugs after first- and second-line failure in resource-limited settings (RLS) like Cameroon. A laboratory-based study with 759 patients (≥15 years) experiencing virological failure was carried out at the Chantal Biya International Reference Centre (CIRCB), Yaoundé, Cameroon. Socio-demographic, therapeutic and immunovirological data from patient records were analysed according to HIV-1 genotypic profiles. Median (IQR) ART-duration was 63 (50–308) months. Median CD4 and viremia were 153 (IQR:50–308) cells/mm Human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) remains a public health priority, with more than 84.2 million people infected and about 40.1 million related deaths since discovery .Following the global 90-90-90 targets set up in 2014 by the World Health Organisation (WHO)/UNAIDS, successful scaleup of antiretroviral therapy (ART) coverage worldwide brought 27.1 million people on treatment by the end of 2017, with a national coverage of 53.68% in Cameroon . Given tElsewhere, there have been optimizations of the therapeutic guidelines over the years, aimed at further improving treatment outcomes in people living with HIV (PLWHIV). As such, the 2019 WHO guidelines recommend the use of the fixed-dose combination tenofovir-lamivudine-dolutegravir (TLD) as the preferred standard of care in adolescents and adults in first-and third- line regimens . With thWe sought to ascertain patterns of acquired HIVDR in routine clinical practice in Cameroon between 2011 and 2019 and to describe potentially active drugs post-therapeutic failure and their adequacy with the potential use of TLD as a second- or third-line option in this resource-limited setting.We carried out a laboratory-based cross-sectional and analytical study from November 2011 to August 2019 with adults (≥15 years) who had failed first- and second-line ART, received for genotypic resistance testing (GRT) at the Chantal Biya International Reference Centre (CIRCB) for Research on HIV and AIDS Prevention and Management, Yaoundé, Cameroon.Our study was carried out at CIRCB, Yaoundé, Cameroon and included patients presenting for resistance testing from all ten regions of the country. Located in the capital city, Yaoundé, and created in 2006 with much expertise in the field of HIV/AIDS research, CIRCB offers GRT for PLWHIV at a subsidized cost.Using an estimated prevalence for HIVDR of 94%, as described by Kouamou et al. , and a 5Inclusion criteria: We included all participants aged ≥ 15 years, failing virologically  on a standard first- or second-line ART regimen after being treated for at least six months. Of note, adherence was measured using a self-reported method evaluated by the responsible clinician during clinical appointment. All participants had performed genotypic resistance testing at CIRCB.Exclusion criteria: We did not include patients who were naïve to ART or re-initiating ART (population suitable for pre-treatment HIVDR surveillance), those with undocumented ART therapies, on TB treatment (due to risk of drug interaction) or those with incomplete sequences.Participants were selected following our eligibility criteria from a pool of patients in the CIRCB antiviral resistance (CARe) database. Their socio-demographic, clinical and immunovirological data, sequences and GRT results were obtained.Enrolled patients had previously benefited from GRT following an in-house protocol as follows:® DNA Minikit; QIAGEN, Courtaboeuf, France). Using an in-house protocol and two-step polymerase chain reaction-PCR (RT-PCR and Nested-PCR), HIV-1 pol-gene (protease and reverse-transcriptase regions) was then amplified (~1600 base pairs). Using agarose gel electrophoresis, the effectiveness and integrity of PCR products was confirmed, following which the amplicons were purified. Purified products were submitted to a sequencing reaction. Products of the sequencing reaction were then gel-purified using SEPHADEX  gel to remove excess reactants and render DNA products pure. Sequencing was performed using an Applied Biosystems 3500 genetic analyzer  and sequence assembly and editing with SeqScape v2.7 (Applied Biosystems) or Recall v2.28 [First, 10 mL of blood was drawn from treatment-failing patients who presented for GRT at CIRCB. Plasma samples were then separated from whole blood and stored between −20 °C to −80 °C when samples were not to be analysed immediately. Viral RNA was extracted using a commercially available protocol after an initial two-hour centrifugation of 1 mL of plasma at 14,000 rpm to improve viral RNA concentration and thus increase PCR sensitivity. Following this step, 140 µL of plasma was retained for HIV-1 RNA extraction following the QIAGEN protocol  and REGA , were used for subtyping, with confirmations performed using molecular phylogeny after sequence alignment with BioEdit v.7.2.5 and tree inference with MEGA software v.70.107. Sequences generated for the purpose of this study were submitted to Genbank under the following accession numbers: MK580543-MK580618; JF273935-JF273965; JQ796152-JQ796169, MK867721-MK867755; and OQ985493-OQ985958.All edited sequences were interpreted using Stanford HIVdb v.9.4. to identify major DRMs and potentially active medications. Rapid subtyping tools, such as COMET  and median (interquartile range). Qualitative variables were described with frequencies and proportions stating 95% confidence intervals (CI). Associations between qualitative variables were calculated using chi square and Fischer’s exact tests where appropriate. Student’s T test was used to compare means of continuous variables between groups, and Ethical clearance was sought and obtained from the Institutional Review Board of the Faculty of Medicine and Biomedical Sciences, University of Yaoundé I (reference number 330/UYI/FMSB/VDRC/DAASR/CSD). Research authorisation was also obtained from the CIRCB directorate to carry out our study in this establishment. Confidentiality was ensured by using patient identification numbers with password-protected computers, and core ethical values were respected.n = 436 (57.4%); northwest: n = 86 (11.3%); and littoral: n = 85/745 (11.2%) regions. Of the 759 participants, 575 (75.8%) were failing non-nucleoside reverse transcriptase inhibitor (NNRTI)-based first-line ART, while 184 (24.2%) were failing protease inhibitor (PI/r)-based second-line . We retained a total of 759 participants with mean age (±SD) of 42 (±14) years. Majority of participants were female: 485/745 (63.9%). All 10 regions of the country were represented, with participants from the centre: p = 0.18).Overall, median (IQR) CD4 cell count at the time of failure was low; 153 (50–308) cells/µL. With respect to the therapeutic lines, immunological status was similar between first- and second-line treated patients (median CD4: 161 (56–315) cells/µL for first-line and 126 (39–299) cells/µL for second-line, p = 0.81; As to virological status, the overall median viral load (IQR)  was high at 138,666  copies/mL. Similarly to immunological status, there was no significant difference in the median viral load (IQR) between first- and second-line patients at 134,645  copies/mL and 142,710  copies/mL, respectively  was high at 708/759 . Prevalence of drug resistance by antiretroviral class were as follows: nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) resistance: 651/759 (85.8%); NNRTI resistance: 685/759 (90.3%); and protease inhibitor (PI/r) resistance: 105/759 (13.8%). Dual-class resistance was as follows: NRTI_NNRTI: 83.3% (632/759); NRTI_PI/r resistance: 13.4% (102/657); and NNRTI_PI/r resistance: 12.4% (94/759). Triple class resistance was 12.4% (94/459). Overall, the most prevalent mutation was M184V (75.5%), followed by K103N (47.4%) and Y181C (27.7%). See After first-line failure, overall HIVDR (presence of at least one major DRM) was 93.4% (CI 91.1–95.2%) and varied by drug class as follows: NRTI resistance: 87.7%; NNRTI resistance: 92.2%; PI/r resistance: 5%. NRTI_NNRTI dual class resistance: 86.7%. After second-line failure, overall-HIVDR was 92.9%, (95% CI 88.1–96.1%) with 80.0% resistance to NRTI, 41.8% resistance to PI/r, and 40.1% NRTI_PI/r dual-class resistance. The most prevalent PI/r resistance mutation was M46I (29.8%), followed by I54V (14.9%) and I84V (12.8%). See The bar charts to the left of 1  then G . Pure subtypes made up 24.2% of the viral subclades, while recombinant subtypes made up 75.8%. We did not find any association between HIV-1 viral clade and CD4, viral load or HIVDR occurrence  of the viral subtypes, followed by Acurrence . Thus, rWe considered effective drugs as those having a susceptibility score of <30 according to the Stanford HIVDR database. After first-line failure, irrespective of NRTI exposure, zidovudine (AZT) was potentially active in 46.1% (95% CI: 42.1–50.2%) of participants; tenofovir (TDF) in 35.7% (95% CI: 31.9–39.7%); abacavir (ABC) in 18.5% (95% CI: 15.6–21.9%); and lamivudine/emtricitabine (3TC/FTC) in 8.7% (95% CI: 10.5–21.5%). As to NNRTI, efavirenz (EFV) was potentially active in 13.2% of participants  and nevirapine (NVP) in 7.6%,  of participants .After second-line failure, AZT appeared potentially active in 35.2% (95% CI: 28.3–42.6%) of participants; tenofovir (TDF) in 45.1% (95% CI: 37.7–52.6%); ABC in 22.5% (95% CI: 16.7–29.3%); and 3TC/FTC in 15.4% (95% CI: 10.5–21.5%). Darunavir (DRV/r) appeared potentially active in 86.7% (84.8–94.8%) of participants, unlike atazanavir (ATV/r) and lopinavir (LPV/r) which appeared potentially active in 61.0% (95% CI 63.5–68.1%). See After AZT/D4T + XTC exposure in first-line treatment, few participants had virus susceptible to AZT (30.7%), TDF (41.0%) and ABC (21.0%). On the contrary, after TDF + XTC exposure, 63.1% of participants had viral susceptibility to AZT, 30.9% to TDF and 18.4% to ABC See . Note thDRV/r preserved good levels of efficacy despite PI/r history. After ATV/r and LPV/r exposure, DRV/r preserved efficacy in 96.6% and 81.0% of participants, respectively. After both ATV/r and LPV/r exposure, it preserved efficacy in 87.8% (75.2–95.4%) of participants, particularly if used at 600 mg bid. Lastly, after previous exposure to other PIs (NFV and IDV), it preserved efficacy in 60.0% of individuals .Taking into consideration the potential efficacy of TDF after first- and second-line failure (35.7% and 45.1% respectively), and considering the non-exposure to integrase strand transfer inhibitors , full TLD efficacy was predicted in 35.7% and 45.1% of patients after first- and second-line failures, respectively. With respect to drug exposure, predictive efficacy of TLD appeared lowest in patients with prior exposure to TDF-only regimens, followed by those exposed to both AZT/D4T and TDF, and highest in those exposed to AZT-only regimens . Lastly, after second-line failure, TLD predictive efficacy appears highest in those who had received only AZT/D4T-containing regimens (50.0%), followed by those who had received TDF-only regimens (47.0%) and those who had received both TDF and AZT/D4T (35.1%).3 and median viral load, 138,666 copies/mL) suggests late detection of failure, which could also explain the high levels of ADR observed. Moreover, the high viral load (5log) and low CD4 count observed after first- and second-line failure in our context is different from values obtained in western countries (moderate level viremia that is in the order of 3log) but more like in patients with advanced failure and higher risk of clinical progression and death [The scalability of ART comes with expected increases in HIVDR in a resource-limited setting (RLS). Our study aimed at describing the patterns of HIVDR in patients failing ART in Cameroon between 2011 and 2019. Overall rates of ADR were high in these patients, with 93.3% presenting with at least one major DRM. These results are not surprising as HIVDR constitutes the major reason for patients failing ART in Cameroon. The development of these resistances in the clinical context could be favoured by poor adherence to ART, stock ruptures, sub-therapeutic blood levels of drug , poor prescription practices and intrinsic viral factors, amongst others . In addind death ,23. Takind death ,25,26. Tnd death . In thisnd death . With thnd death . HIV-1 gIn patients failing first-line therapy, rates of ADR were high (93.4%), with similar trends across the drug classes with 97.7% for NRTI, 92.2% for NNRTI and 86.7% for NRTI_NNRTI dual-class resistance. These results are similar to those obtained in Taiwan by Tsai et al. in 2017 and Manasa et al. in South Africa ,31. ThisAs concerns potentially active regimes after first-line failure, AZT preserved efficacy in 46% of patients, TDF in 35.7% and ABC in 18.5%. In this era of transition to TLD, this highlights the risk of sub-optimal therapy in about 65% of patients, given the poor efficacy of TDF . Though many studies have shown good efficacy of TLD despite NRTI resistance, clinical monitoring of this group of patients is crucial in order to evaluate the long-term efficacy of such regimens and also permit opportune detection of failure ,17. ThisAfter second-line failure, all commonly used NRTIs in our context  appeared to be effective only in a low proportion of participants . This indicates that care needs to be taken in choosing subsequent NRTI-accompanying drugs following second-line failure with the need for genotypic resistance testing. This also highlights the fact that blind transitions to TLD in patients failing second-line therapy in our context may be sub-optimal in about half of patients. Interestingly, DRV/r remained effective in the majority of patients (96.6%), even after second-line failure and despite the risks of cross-resistance by mutations to ATV/r and LPV/r. Therefore, DRV/r remains recyclable in third-line regimens in our context [In this resource-limited setting, using WHO guidelines for ART management and laboratory-based HIVDR surveillance, rates of ADR are very high after first- and second-line failures, favoured by long treatment duration and late failure detection. After an NNRTI-based first-line, PI/r and a substituted NRTI-accompanying molecule may be sufficient in second-line treatment, especially with a well-documented treatment history, but may need GRT guidance in cases of the first-line use of thymidine analogues. After second-line failure, DRV/r remains very effective, thus representing a great option for third-line regimens. Lastly, TLD may be sub-optimal  when used blindly as a second- or third-line regimen. This calls for cautious monitoring and use by designing a sequential algorithm for switching heavily treated failing patients to TLD, especially those with previous exposure to TDF-containing regimens. These measures will ensure the long-term efficacy of TLD in resource-limited settings.


Dolutegravir (DTG), an integrase strand transfer inhibitor is currently the recommended first and second line anti-retroviral therapy (ART) anchor agent by the World Health Organization due to its favorable side effect profile, high efficacy and genetic barrier to resistance.Despite its very good side effect profile, there have been multiple case reports of ART experienced patients developing hyperglycemia within weeks to a few months after switching to DTG preceded by weight loss. At population level, however, DTG as well as other integrase inhibitors have been demonstrated to have a reduced risk of incident diabetes mellitus (T2DM) compared to other HIV drug classes.Following multiple similar reports of accelerated hyperglycemia in Uganda during the first pilot year of DTG use, the Uganda Ministry of Health recommended withholding dolutegravir in all patients who develop diabetes. Whether this recommendation should be applied to all patients with incident T2DM remains to be demonstrated.We present a clinical case of an HIV positive ART naïve man who was diagnosed with T2DM after 36 weeks on DTG. We describe changes in blood glucose, glycated hemoglobin, insulin resistance and pancreatic beta cell function before and after withholding DTG. We demonstrated that he was phenotypically different from the reported cases of accelerated hyperglycemia and he continued to have worsening insulin resistance despite withholding DTG. His blood glucose improved with dietary T2DM management. It is possible he had an inherent risk of developing T2DM independent of his exposure to DTG. This put in question whether DTG should universally be withheld in PLHIV with incident T2DM in Uganda. Integrase strand transfer inhibitors (INSTIs) block integrase (an HIV enzyme) responsible for integration of viral DNA into the DNA of the host cell . The WorGLucose Metabolism changes in Ugandan HIV patients on Dolutegravir, GLUMED study) evaluating glucose metabolism changes in anti-retroviral therapy (ART) naïve PWH on tenofovir/ lamivudine/ DTG (TDF/3TC/ DTG) for 48 weeks . Th. Th4]. TThe patient we present had an asymptomatic onset of glucose intolerance over 36 weeks (diagnosed on a routine study visit) and gained weight before diabetes diagnosis in contrast to the above group of patients. Various factors such as immune reconstitution, improved appetite as well as dolutegravir itself could have contributed to the weight gain , 18]. O. O18]. OThe patient did not monitor his blood glucose at home after T2DM diagnosis hence the glucose measurements we documented were the only ones taken on study visit days. This is a single case report hence conclusions drawn much as insightful may not be generalizable to a larger population. Despite that, the patient was meticulously followed up with pertinent clinical data at the different time points.In conclusion, this case report suggests that dolutegravir may not have to be universally withheld in ART naïve PWH who develop diabetes mellitus but the decision made on a case-by-case basis. More research is however needed to ascertain the pathogenesis of accelerated hyperglycemia in a section of PWH on integrase inhibitors to inform clinical decisions on which PWH need drug substitution, if any. This is programmatically pertinent especially in sub-Saharan Africa where DTG is first line therapy in most HIV treatment programs and there is wide spread primary resistance to alternative drug classes like NNRTIs .


The initiation of anti-retroviral therapy (ART) effectively restores immune function and reduces HIV-related morbidity and mortality. However, virologic failure while on ART may lead to increased morbidity and compromised quality of life. The aim of this study was to determine the prevalence and determinants of early virologic failure (VF) among HIV patients on first-line ART enrolled at the Research Institute for Tropical Medicine, Philippines.A retrospective cohort study was conducted involving treatment-naive HIV patients who were started on ART during the period of January 2004 – December 2018. Early virologic failure was defined as HIV-1 viral load of > 1,000 copies / ml of plasma blood taken within 6 months or more of first-line ART. Data regarding patients’ sociodemographic profile, baseline clinical characteristics, and treatment-related information were collected through database review. Data were analyzed using STATA 15.0. Descriptive statistics, cross-tabulations, and univariate and multivariate logistic regressions were utilized. P < 0.05 was used to determine clinical significance.3 (SD 204.19). The average time from ART initiation to the first VL determination was 4 years (SD 28.62). A total of 72 (3.79 %) subjects were found to have virologic failure. Multivariate logistic regression showed that patients with age 15-20 years were 5-6 times more likely to have VF  while patients with baseline CD4 count of < 50 cells/mm3 were 3 times  more likely to have virologic failure.Among the 1900 subjects included in this study, 1839 were males (96.79 %). The mean age at ART initiation was 30.36 years (SD 6.89) with a baseline CD4 count of 232.30 cells / mm3. Presence of these factors should be used as a marker for intensified adherence counselling especially in the absence of reliable or readily available viral load monitoring.The prevalence of early virologic failure among HIV patients on first-line anti-retroviral therapy is 3.79 %, relatively lower compared to other published data. Early virologic failure was most likely to occur among patients 15-20 years old and/or those with baseline CD4 count below 50 cells/mmAll Authors: No reported disclosures


It is necessary to identify simple biomarkers that can efficiently predict the efficacy of long-term antiretroviral therapy (ART) against human immunodeficiency virus (HIV), especially in underdeveloped countries. We characterized the dynamic changes in plasma interleukin-18 (IL-18) and assessed its performance as a predictor of long-term virological response.This was a retrospective cohort study of HIV-1-infected patients enrolled in a randomized controlled trial with a follow-up of 144  weeks of ART. Enzyme-linked immunosorbent assay was performed to evaluate plasma IL-18. Long-term virological response was defined as HIV-1 RNA <20 copies/mL at week 144.Among the 173 enrolled patients, the long-term virological response rate was 93.1%. Patients with a long-term virological response had significantly lower levels of week 24 IL-18 than non-responders. We defined 64  pg./mL, with a maximum sum of sensitivity and specificity, as the optimal cutoff value of week 24 IL-18 level to predict long-term virological response. After adjusting for age, gender, baseline CD4+ T-cell count, baseline CD4/CD8 ratio, baseline HIV-1 RNA level, HIV-1 genotype and treatment strategy, we found that lower week 24 IL-18 level  was the only independent predictor of long-term virological response.Early on-treatment plasma IL-18 could act as a promising indicator for long-term virological response in patients with HIV-1 infection. Chronic immune activation and inflammation may represent a potential mechanism; further validation is necessary. Maintaining viral suppression through effective antiretroviral therapy (ART) is critical for reducing morbidity and mortality in this population. However, obstacles to fully controlling HIV include patient compliance, drug resistance and drug–drug interactions. In addition, many HIV services, such as testing and monitoring, have been disrupted during the coronavirus disease 2019 epidemic. Therefore, more efforts are needed to identify useful predictors of treatment efficacy. Identifying these predictors can help to optimize ART in real-world clinical practices, thereby contributing to reaching the new proposed global 95-95-95 targets set by the Joint United Nations Program on HIV and AIDS (UNAIDS).Previous studies have shown that specific biomarkers of inflammation are associated with increased mortality and morbidity, including clinical treatment failure, incident active tuberculosis and other longer-term outcomes, such as cardiovascular disease, in HIV-infected patients –5. AlthoIn this study, we aimed to further characterize the dynamic changes in IL-18 for up to 144 weeks and to assess the performance of IL-18 as a predictor of long-term virological response.2.2.1.This was a retrospective cohort study consisting of HIV-infected patients enrolled in a randomized, controlled, open-label, noninferiority trial (ALTERLL study) , 9. The This study was approved by the Ethics Committee of Guangzhou Eighth People’s Hospital  and registered with the Chinese Clinical Trial Registry, number ChiCTR1900024611. Written informed consent was obtained from all patients.2.2.CD3 + CD4 + CD8−) count and CD8+ T lymphocyte (CD3 + CD4 − CD8+) count were measured using a BD CantoII flow cytometer with CD3/CD4/CD8 trichrome fluorescence reagent from BD according to the instructions. BD Multitest™ CD3/CD8/CD45/CD4 IMK Kit used in this study contains FITC-labeled CD3, clone SK7; PE-labeled CD8, clone SK1; PerCP-labeled CD45, clone 2D1 (HLe-1); and APC-labeled CD4, clone SK3. Plasma HIV-1 RNA load was quantified using the Roche COBAS-TaqMan Assay , and the detection limit was 20 copies/mL. Long-term virological response was defined as HIV-1 RNA <20 copies/mL at week 144 of treatment. Subgenotypes of the HIV-1 virus were tested with the standard strains selected from the Los Alamos HIV database using Bioedit and MEGA5 software, and mutation sites were identified using the Stanford HIV-resistant database  of two parameters were calculated. The optimal cutoff value of plasma IL-18 was identified using the Youden index. Logistic regression analysis was used to determine predictors of long-term virological response. All statistical tests were 2-sided. Statistical significance was taken as p < 0.05. All analyses were performed with SPSS software, version 26.0 .Data are expressed as counts and percentages for categorical variables and as medians and interquartile ranges (IQRs) for continuous variables. Qualitative and quantitative differences were analyzed using 3.3.1.10 copies/mL; approximately half of the patients had CD4+ T-cell counts less than 350/μL; and 30.1 and 44.5% of the patients were infected with HIV-1 genotypes CRF01_AE and CRF07_BC, respectively. The rates of viral suppression (HIV-1 RNA <20 copies/mL) reached 92.5% at week 48 and were maintained at 93.1% until week 144 of ART. Additionally, the viral load among patients with detectable HIV-1 RNA decreased from 4.4 to 1.6 log10 copies/mL.A total of 173 patients were enrolled in this study. The demographic, virological and clinical characteristics of the patients are shown in 3.2.F = 70.356, p value <0.001).At baseline, the median level of plasma IL-18 was 65.4 (IQR 47.7–88.9) pg./mL. The levels of IL-18 decreased after initiating ART, reached a nadir at week 12 (53.7 [IQR 39.5–76.8] pg./mL) and week 24 (53.8 [IQR 40.0–70.5] pg./mL), and thereafter increased significantly to 96.1 (IQR 66.6–139.5) pg./mL at week 144 . The dynp values <0.05).Levels of IL-18 among patients with and without long-term virological response were further analyzed as shown in 3.3.We studied the early on-treatment (defined as initiation of ART within 24 weeks) plasma IL-18 levels and changes at week 12 and week 24 to evaluate the predictive performance for long-term virological response using receiver operating characteristic (ROC) curves. The AUROC of the IL-18 level was highest at week 24  and higher than the IL-18 change from baseline to week 12 or week 24 . By summ3.4.10 HIV-1 RNA level  and lower week 24 IL-18 level  were associated with virological response. In the multivariate analysis, lower week 24 IL-18 level  was the only independent predictor for long-term virological response.To further evaluate baseline and early on-treatment characteristics in predicting long-term virological response, a logistic regression analysis was conducted with the inclusion of age, gender, baseline CD4+ T-cell count, baseline CD4/CD8 ratio, baseline HIV-1 RNA level, HIV-1 genotypes, ART strategy and week 24 IL-18 level in the model . In the 3.5.10 HIV-1 RNA than non-responders (median 4.3 vs. 4.8 log10 copies/mL). 10 copies/mL) and week 24 IL-18 . The rates of long-term virological response were high (98.9 and 100.0%) among patients with week 24 IL-18 ≤ 64 pg./mL and quite low (85.7 and 70.0%) among patients with week 24 IL-18 > 64 pg./mL, irrespective of baseline HIV-1 RNA levels.Patients with long-term virological response had lower levels of baseline log4.p value = 0.950). In addition, the absolute levels of IL-18 at most visits and dynamic changes were similar in different treatment groups (data not shown). The patients with good viral control had significantly lower levels of week 24 IL-18, which is consistent with previous studies , National Natural Science Foundation of China (grant number: 82072265), Basic and applied basic research project jointly funded by Guangzhou University (College) (grant number: 202201020285 and 202201020276), Science and Technology Program of Guangzhou (grant number: 202102020074).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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. 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To assess the demographic, clinical, and survival profile of people living with HIV.p-values were presented to show the significance. The log-rank test was used to determine the significance of the Kaplan–Meier survival curve.A retrospective cohort study was conducted among patients enrolled at a single antiretroviral therapy center in North Karnataka. A total of 11,099 were recruited from April 2007 to January 2020, out of which 3,676 were excluded and the final 7,423 entries were subjected to analysis. The outcome of interest was the time to death in months of people living with HIV on antiretroviral therapy (ART). The clinical and demographic characteristics were examined as potential risk factors for survival analysis. To investigate the factors that influence the mortality of patients using ART, univariate and multivariate Cox regression were performed. Hazard ratio (HR), 95% confidence interval (CI), and Out of 7,423 HIV-positive people, majority were female (51.4%), heterosexual typology (89.2%), and in the age group 31–45 years (45.5%). The risk of death in male patients was 1.24 times higher (95% CI: 1.14–1.35) than female patients. Patients with age >45 were 1.67 times more likely to die than patients ≤30 (95% CI: 1.50–1.91). In the multivariable analysis, the hazards of mortality increased by 3.11 times (95% CI: 2.09–2.79) in patients with baseline CD4 count ≤50 as compared to those who had baseline CD4 count >200. The risk of death in patients who were diagnosed with TB was 1.30 times more (95% CI: 1.19–1.42) than in those who did not have TB. The survival probabilities at 3 and 90 months were more in female patients  compared with male patients , respectively.This study proved that age, sex, baseline CD4 count, and tuberculosis (TB) status act as risk factors for mortality among people with HIV. Prevention strategies, control measures, and program planning should be done based on the sociodemographic determinants of mortality. In this context, accurate data on the causes of death are of great importance and should help to define priorities in the prevention and management of lethal comorbidities. Such evidence has come from previous prospective studies on people with HIV  . TB was There are few studies on mortality at an early stage among PLHIV soon after the initiation of ART which is unlikely to be caused due to drug efficacy –15. ThisA retrospective descriptive cohort study was conducted in a single antiretroviral therapy (ART) center, District hospital, Koppal, India, which is the largest and single facility in the district providing screening and treatment facilities for people living with HIV. The study population was the people with HIV receiving ART from the study setting. The study was conducted from April 2007 to January 2020. The data retrieved were regarding the age, gender, HIV diagnosis, treatment status, lab parameters, tuberculosis co-infection, and survival status.A total of 11,099 patients enrolled in the ART center from different districts of North Karnataka were included in the study. Standard ART and anti-TB therapy registries, electronic formats, patient medical records (cards), and intake forms were used as data sources. Five nurses with training and experience working in the ART and TB clinics at the hospital were involved in the data extraction process. To assure data quality, an experienced supervisor followed up on the extraction processes. Throughout the data extraction process, the researchers and the supervisor continuously checked the checklists for consistency and completeness. A total of 3,676 people were excluded from the study due to the non-availability of complete data, mismatch between the date of registration, death, initiation of ART, and missing values . Data anp-values are presented to show the significance. p-value <0.05 was considered statistically significant. RStudio Version 1.3.1093 was used for statistical analysis  along with 95% CI and analysis .The study received ethics approval and waiver of written informed consent from the institutional human ethical committee, Koppal Institute of medical sciences, Koppal, with No. KIMS-Koppal/IEC/53/2020-21.3 and 5.7% had a CD4 count of <50 mm3. Only 1,538 (20.7%) patients were diagnosed with TB. Among 1,538 patients with TB, the majority (41.2%) had pulmonary TB , 40.2% had extrapulmonary TB , and 18.6% had pulmonary tuberculosis . A-TLE was the most common ART regimen used by 62.3% of patients, followed by A-ZLN among 15.8% and A-SLN among 12.8% of patients. The remaining 9.4% of patients were on other miscellaneous ART regimens.A total of 7,423 people living with HIV were included in the analysis. 3, respectively. The death rate among female sex workers (FSWs), men who have sex with men (MSM), and heterosexuals was 40.5, 38.2, and 34.3%, respectively. Death was high among patients with TB (43.2%) as compared to patients without TB (29.7%). The mortality rate was high (73.3%) in the initial 3 months after the start of ART, and it was 63.4, 41.3, and 15.5% at 4–6 months, 7 months−1 year, and >5 years, respectively  died, and 5,009 (67.5%) were censored. The overall median follow-up time for the patients who died was 11 months (IQR 3–30 months), while it was 36 months for the censored patients (IQR 18–61 months). The death rate was high among transgender people (39.4%) followed by male patients (39.0%) and least among female patients (26.4%). In patients with an age of more than 45, the death rate was 42.5%, followed by 36.4% in 31–34 years and 24% in patients aged <30 years. The death rate was noted to be 57.5, 44.9, and 21.9% among patients with a CD4 count of <50, 51–200, and >200 mmectively .p-value < 0.05). It is observed in a multivariate analysis that the risk of death increased 2.41 times more (95% CI: 2.09–2.79) in patients with baseline CD count ≤50 mm3 as compared to those who had CD count >200 mm3. The risk of death in male patients was 1.24 times higher (95% CI: 1.14–1.35) as compared to female patients. Patients with age >45 were 1.67 times more likely to die (95% CI: 1.50–1.91) than those ≤30 years, and people between 31 and 40 years were 1.28 times more likely to die (95% CI: 1.16–1.41). The risk of death in patients who were diagnosed with TB was 1.30 times more (95% CI: 1.19–1.42) than in those without TB. Mortality was considerably less with A-TLE , A-ZLN , and other ART  regimens, as compared to A-SLN.p-value <0.001) in median survival times were observed with gender, age group, baseline CD4 count, TB status, and ART regimen. As compared to male patients , the median survival time in months was higher among female patients  and transgender population . With regard to the age group, the median survival time decreased with increasing age, while the median survival time increased in patients with a baseline CD4 count of >200 mm3. As compared to people without TB , people with TB had lower median survival time . As compared to people on the A-TLE regimen , people on A-SLN had significantly median lower survival time . In comparison, people with A-ZLN  and other regimens  had higher median survival time  among the study participants, followed by mother-to-child transmission. Similar findings were observed in previous studies by Kumawat et al.  (87.67%)Among the study participants, 20.7% had tuberculosis. A previous study has shown that 10.66% of the 300 participants had tuberculosis . SuperadSex, age group, baseline CD4 count, and TB diagnosis showed a statistically significant relationship with mortality in people with HIV. Our study's finding that male patients have a 1.24 times higher risk of death (95% CI: 1.14–1.35) than female patients builds on previous studies that has shown that men with HIV have a higher risk of death. The findings we present are also consistent with broader health and survival disparities experienced by men around the world at all ages , 31.Mortality was noted to be higher in people with HIV who were more than 45 years (42.8%) compared to ≤30 years (24.1%) and 1.67 times (CI 1.48–1.88) higher and older age group. The age-specific deaths observed in our study are consistent with other studies that found higher mortality in patients aged >50 or 55 years compared to patients aged <50 or 55 years, respectively, with longer follow-up , 33. A s3  and 2.11 times (95% CI: 1.94–2.30) in patients with baseline CD4 count ≤50 and baseline CD4 count 51–200, respectively, as compared to those who had baseline CD4 count >200. A similar retrospective cohort study done in Oromia region, Ethiopia, on a large population of 2,775 individuals with HIV reported lower mortality  among individuals with CD4 count compared to people living with HIV with CD4 count more than 200 cells/mm3 . Several3 . Suppres3 . This is3 .The overall survival probabilities among people with HIV declined over follow-up time with regard to various risk factors such as age, sex, CD4 count, and TB status . The surThe survival probability of people with HIV receiving different ART regimens declined over time from 95% at 3 months to 71% at 90 months with the A-TLE regimen. A retrospective cohort study done in China reported the cumulative survival rate at 1, 2, 3, 4, and 5 years, of 97.1, 93.4, 90.6, 88.8, and 86.0%, respectively . A similVarious similar research studies were carried out in the African region –39, but The median survival time was higher in female patients in the age group ≤30 years, patients with baseline CD4 count >200, and patients who were not diagnosed with TB. Tuberculosis was found to be one of the risk factors for mortality in people with HIV. This study has created evidence on the role of age, sex, baseline CD4 count, and TB status as risk factors for deaths among HIV-positive individuals. The finding of survival probabilities with different treatment regimens is the first of its kind for Karnataka state that can help Karnataka State AIDS Prevention and Control Society (KSAPS) to make policy changes with regard to treatment regimens. The National AIDS Control Organization must, therefore, work to create a cutting-edge health system that will give ART at higher CD4 cell count thresholds and put an emphasis on early discovery, testing, sustainable treatment, and enhanced retention.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.The ethical review committee of the Koppal Institute of Medical Sciences had approved the study experiment (data collection) which was in accordance with institutional ethical guidelines in the purview of the declaration of Helsinki.RAS has conceptualized the study and played primary role in compiling, analysis, and interpretation of the data. RAS, MSA, SKH, and MM did the manuscript preparation. BAA and MZA did the manuscript editing. MSA, SKH, and MM approved the final draft. RKA, MBA, and MMA did the data cleaning and data analysis. BAA, RAS, MA, and MAA have contributed in fine tuning of the proposal, manuscript write up, editing, and review. All the authors take complete responsibility for the content of the manuscript, read, and approved final version of the manuscript.


Thanks to the modern ARV regimens and the fact that the morbidity and mortality of metabolic syndrome increases with age, clinicians are continuously researching effective and safe antiretroviral regimens with low impact on the lipid profile. Doravirine (DOR) is the latest non-nucleoside reverse-transcriptase inhibitor (NNRTI) that shows long-term safety and tolerability and a favorable lipid profile. The aim of this study is to assess the impact of DOR-based three-drug regimens on the lipid profile in clinical practice. We retrospectively analyzed a cohort of 38 treatment-experienced, virologically suppressed people living with HIV (PLWH) switching to this regimen, following the eligibility criteria. We carried out comparison analysis of immunological and metabolic parameters between baseline and 48 weeks of follow up. In our cohort of treatment-experienced, virologically suppressed PLWH, three-drug regimens with DOR showed good efficacy and a positive profile on lipid metabolism at 48 weeks of follow up. Non-communicable diseases are the real emerging issues among aging people living with HIV (PLWH) on antiretroviral treatment ; among tDoravirine (DOR) is the latest non-nucleoside reverse-transcriptase inhibitor (NNRTI) to be introduced for the treatment of HIV-1 infection and has been recommended as part of three-drug regimens by international guidelines for the treatment of HIV-1 infection . DOR is Doravirine has an in vitro resistance profile that is distinct from other NNRTI molecules and retains activity against viruses containing the most frequently transmitted NNRTI mutations ,6. TheseResults from a randomized, active-controlled, double-blind, noninferiority phase 3 trial DRIVE-AHEAD continue to support DOR/3TC/TDF efficacy and its favorable lipid profile at 96 weeks of follow up, compared to EFV/FTC/TDF, as demonstrated at week 48 . In a muThe aim of this study is to assess the impact of DOR-based regimens on the lipid profile in clinical practice during a follow-up time of 48 weeks.We retrospectively analyzed a cohort of 38 treatment-experienced, virologically suppressed PLWH who switched to a DOR-based 3-drug regimen. We collected clinical history and viroimmunologic and metabolic parameters such as HIV-RNA (copies/mL), T-CD4+ lymphocyte cell count, low-density lipoprotein (LDL) value, total cholesterol, and triglycerides, both at baseline and at 48 weeks of follow up. We applied the following eligibility criteria: patient’s informed consent to data collection, adult age (≥18 years-old), and being on stable ARV with viral suppression (HIV-RNA < 50 copies/mL) at the moment of switch (baseline). We carried out comparative analysis of immunological and metabolic parameters between baseline and 48 weeks via parametric and nonparametric tests and searched for predictors by linear regression. We also analyzed the time to virological failure  or interruption of the regime  via Kaplan–Meier survival analysis, using the Cox Regression Analysis to search for predictors.We analyzed a cohort of 38 PLWH: 23 (60.5%) were males, with a median age of 53 years (IQR 46–59) and a median time from HIV diagnosis of 14.3 years (IQR 5.8–21.8). The median time of ARV exposure was 12.2 years (IQR 5.5–18.8) and median time of virological suppression was 8.4 years (IQR 3.9–16.1). All PLWH started an XTC/TDF + DOR regimen, except one of them who started DOR plus FTC/TAF. The major reason for switching to a doravirine-based regimen in our population was the need for a simplified strategy . Full population characteristics are shown in During a follow-up time of 42.79 patient-years of follow up (PYFU), we observed one VF, a rate of 2.3 per 100 PYFU. The probability of maintaining virological suppression at 48 weeks was 96.9%. We did not find any predictor of VF in our regression analyses.Regarding treatment discontinuations, we recorded three TD during 43.24 PYFU: one due to hypersensitivity reaction and two due to simplification to a 2DR. The estimated probability of maintaining the DOR-based regimen was 91.7% at 48 weeks. We did not find any predictor of TD in our regression analyses.3, p = 0.011), not associated with significant changes in the CD4/CD8 Ratio. Regarding metabolic parameters, LDL, HDL, and triglycerides median values at baseline are shown in p = 0.001) and a trend in the reduction in triglycerides . The only predictor of the reduction in total cholesterol was baseline total cholesterol .Regarding immunological parameters, we observed a reduction in absolute CD4+ count at 48 weeks  not associated with significant changes in the CD4/CD8 ratio. Based on the small number of patients enrolled, the short follow-up time, and the non-change in the CD4/CD8 ratio, the resulting median reduction in CD4+ cell count should not be a concern. We aim to continue the follow up until 144 weeks post-treatment to clarify whether this reduction in CD4+ cell count is confirmed.Our data also highlight a positive profile on lipid metabolism, resulting in a median reduction of −17 mg/dL of total cholesterol at 48 weeks of follow up. We also found a reduction in absolute CD4+ cell count, with a median reduction of −37 cell/mmMetabolic syndrome is especially concerning in PLWH, even those on stable ARV treatment, given the multiple overlapping risk factors with the seronegative population. HIV infection itself represents a cardiovascular risk factor, due to the HIV-associated low-grade-inflammation and immune dysregulation ,13,14,15Lifestyle interventions on PLWH are the first steps needed, leading to reducing the common risk factors such as smoking, drug abuse, and physical inactivity; this can also lead to a reduction in the combination of pharmacotherapies with lipid-lowering medications including statins and fibrates for dyslipidemia, and mitigate CVD risk. The European Society of Cardiology guidelines recommend lipid-lowering therapy to reduce low-density lipoprotein cholesterol to <70 mg/dL in PLWH .In PLWH with metabolic syndrome, reducing cholesterol and triglycerides values is mandatory in order to obtain a reduction in the inflammation degree and the risk of atherosclerotic plaque formation ,13.For all these mechanisms mentioned above, using ARV regimens with low impact on metabolic parameters and on the lipid profile is crucial in HIV infection management, and could also lead to finding the optimal combination strategy to improve the quality of life and life expectancy of PLWH .Given the current issues and the aging PLWH population, our results can help in developing tailored therapy, choosing the adequate ARV regimen, and improving clinicians’ ability to deliver optimal preventive care.The main limitations of our study are the small sample size, the limited follow up, and the lack of a control group. However, real-life data are particularly needed, given their impact on the day-to-day activity of clinical healthcare providers.In conclusion, our data show the favorable metabolic profile of a two NRTI + DOR regimen in PLWH, leading to a significant reduction in total cholesterol in as soon as 48 weeks. More studies are needed, adding to the current literature, to quantify the benefits of switching to a DOR-based regimen in terms of reducing cardiovascular risk, and reducing the number of cardiovascular events in PLWH.In conclusion, our data show the favorable metabolic profile of a two NRTI + DOR regimen in PLWHIV, leading to a significant reduction in total cholesterol in as soon as 48 weeks. More studies are needed, adding to the current literature, to quantify the benefits of switching to a DOR-based regimen in terms of reducing cardiovascular risk, and reducing the number of cardiovascular events in PLWHIV.