Line Antiretroviral Therapy Research Articles

Poor Adherence and Limited Treatment Support are Risk Factors for Second Line Treatment Failure among HIV Children Under 15 Years, 2022: A Case Control Study

Title: Poor adherence and limited treatment support are risk factors associated with second line treatment failure among children under 15 years at Victoria Chitepo provincial hospital, 2022: a case control study. Background: New HIV resistance mutations have been emerging and frequently changing. HIV positive people switching to third line have been increasing in Manicaland Province. Third line anti-retroviral therapy (ART) combinations are not always available. We sort to determine the factors associated with second line treatment failure among HIV positive patients. Methods: We conducted a 1:1 unmatched case-control study among 107 case-control pairs. A case was any HIV positive individual with treatment failure confirmed by 2 viral load of ≥1000 copies/ml while a control was any HIV positive individual with a viral load of <1000/ml copies; on second line therapy at Victoria Chitepo Provincial Hospital (VCPH), in 2022. Systematic random sampling was used to select cases and controls from the line-list. Administered questionnaires were used to ascertain risk factors to second line treatment failure. Patient booklets were reviewed for demographic and clinical characteristics. Frequencies, means, medians and odds ratios were generated. Multivariate analysis and stratified analysis was performed to identify independent risk factors. Permission to proceed was sought from relevant authorities and all ethical considerations were observed. Results: Defaulting treatment (aOR=2.42, 95% CI: 1.03-5.93), missing a viral load test (aOR=5.52, 95% CI: 2.30-13.26) and being under 15 years of age (aOR=6.18, 95% CI: 1.46-26.20) were independent risk factors associated with second line treatment failure. Having a treatment support was an independent protective factor (aOR=0.30, 95% CI: 0.10-0.86). Conclusion: Poor adherence is the key drive to second line treatment failure. Good adherence is critical in children under 15 years. Treatment support promotes viral load suppression.

Failure Of Second Line ART Demands Third -Line Options For HIV-Infected Patients In Telangana, India

Back ground: The research was carried out with the aim of detecting instances of second-line antiretroviral therapy (ART) failure and exploring the potential of third-line ART treatment for individuals with HIV, incorporating the utilization of HIV viral load (VL) testing. Beginning in 2016-17, individuals living with HIV are directed to government ART centers and ART plus centers for treatment. Patients who have experienced treatment failure with second-line therapy and have been exposed to multiple NRTIs, in accordance with the Indian National ART Guidelines, are referred to the SACEP Clinic for further evaluation. If deemed eligible according to the Indian National 3rd Line ART Guidelines, these patients are enrolled and followed up for the initiation of 3rd Line ART at our center. Throughout the duration of the study, a collective of 55 individuals diagnosed with Human Immunodeficiency Virus (HIV) were identified as potentially experiencing a lack of efficacy with regards to their secondary line antiretroviral therapy (ART). Two patients in the cohort were diagnosed with both HIV and multi drug resistant tuberculosis (MDR-TB). Method: Fifty-four and a half percent of the patient sample was classified as being in WHO stage I, while 32.8% were categorized as being in stage II, and the remaining 12.7% were identified as being in WHO stage IV. Fifty-five patients who were suspected of experiencing second-line treatment failure were transitioned to third-line antiretroviral therapy. Results: All 55 patients underwent VL follow-up, with 53 of them attaining viral suppression within a median period of 6 months. However, two patients were unable to achieve viral suppression. Conclusion: However, this study describes HIV-positive patients who need third-line ART due to probable second-line ART failure.

IJCM_425A: Outcomes of Second Line Anti-Retroviral Therapy Among a cohort of people living with HIV/AIDS attending an ART Centre in Mangalore

Background: Anti-Retroviral therapy for HIV/AIDS has been effective, but the mortality rate remains to be high, resulting in the use of second line of ART treatment for better results. Objectives: 1) To estimate the number of deaths among PLHIV between the years 2011 and 2017. 2) To assess the clinical immunological and virological outcomes among these patients. 3) To find out the association of outcomes with the socio demographic characteristics. Methods: In this record-based study, medical records of PLHIV seeking treatment from an ART center associated with KMC, Attavar. between the years 2011 and 2017 were reviewed. The data was extracted using a data extraction sheet consisting of sections on demographic, clinical and treatment details of the patient. Results: The baseline median CD4 count before starting ARTs was found to be 253 (IQR 150-351). After starting second line ARTs it was found to be 461 (IQR 326-651). The correlation of CD4 count after initiation of second line ART with viral load among 34 patients measured was found to be -0.371 (P<0.05). Conclusion: The study concludes that the outcomes of second line ARTs in the present study were found to be satisfactory. The average CD4 count after the initiation of ARTs was significantly high as compared to the CD4 count before the ARTs, implying that second line ARTs had a good, long-term and positive immunological outcome on PLHIV and attending a second-line ART clinic.

Trend and factors associated with non-suppression of viral load among adolescents on ART in Tanzania: 2018-2021.

Tanzania is one of the countries with a high burden of HIV. It has an estimated 1.4 million people living with HIV in 2021. Adolescents living with HIV on antiretroviral therapy (ART) have worse treatment adherence, viral suppression, and mortality rates compared to adults. This study aim was to determine the trend of non-suppression among adolescents on ART in Tanzania from 2018 to 2021 and latest associated predictors. The study utilized data of adolescents (10-19 years) receiving ART in Tanzania mainland for the period of 2018-2021 from the National Care and Treatment Centers database. The primary outcome of interest was non-suppression of viral load, defined as a VL above 1,000 copies/ml. The study employed multivariable logistic regression models to identify factors associated with non-suppression of VL. STATA 15 statistical software was used to analyze the data. Records of 65,942 adolescents present in the CTC database Tanzania were analyzed. Approximately more than half were female 38,544 (58.5%). The proportion of non-suppression was 34.5%, 23.3%, 12.1%, and 9.7% for the years 2018-2021, respectively. After adjusting for other factors, adolescents with a history of poor adherence to ART in the last six months had higher odds of non-suppression (OR = 1.95, 95% CI = 1.64, 2.31). Adolescents on second or third line ART regimens were almost two times more likely to be non-suppressed compared to those on first-line regimens (OR = 2.85, 95% CI = 2.52, 3.23). Girls had lower odds of non-suppression compared to boys (OR = 0.91, 95% CI = 0.84, 0.98), and similarly, patients attending hospitals had lower odds compared to those attending dispensaries (OR = 0.79, 95% CI = 0.72, 0.87). Being female, having good history of adherence over the last six months, and attending hospital level was significantly associated with lower levels of non-suppression, while being on second line ART or attending lower health facilities increased the odds of non-suppression. Efforts to enhance the quality and capacity of health services at lower-level facilities (dispensaries and health centers) should be prioritized, as well as promoting gender-sensitive approaches that take into account the unique needs and experiences of adolescent girls and boys are needed to improve VL suppression among this population.

Low prevalence of archived integrase strand transfer inhibitors resistance associated mutations in Botswana before the roll out of dolutegravir based first line antiretroviral therapy.

We evaluated the prevalence of archived proviral drug resistance mutations (DRMs) associated with resistance to integrase strand transfer inhibitors (INSTIs) shortly before Botswana transitioned in 2016 to using dolutegravir (DTG)-based antiretroviral treatment in first-line regimens. We used the Stanford University HIV drug resistance database to analyze INSTI-resistance associated mutations (RAMs) in a large representative population-based cohort of adults recruited in 30 geographically dispersed communities as part of the Botswana Combination Prevention Project (BCPP) cohort from 2013 to 2018. A total of 5,144 HIV-1 proviral DNA sequences were included in our analysis; 1,281 sequences were from antiretroviral therapy (ART)-naïve individuals and 3,863 sequences were from non-nucleoside reverse transcriptase inhibitor (NNRTI) ART-experienced individuals. None of the sequences were from DTG-ART experienced participants. The overall prevalence of major INSTIs DRMs was 1.11% (95% CI 0.82-1.39%). The prevalence of INSTI DRMs in ART-naïve individuals was 1.64% (21/1,281) and 0.93% (36/3,863) in ART-experienced individuals. Major INSTI-RAMs detected in ART-naïve individuals were E138K (2/1,281; 0.16%), G140R (8/1,281;0.62%), E92G (2/1,281;0.16%), R263K (5/1,281; 0.4%), N155H (1/1,281; 0.08%), P145S (1/1,281;0.008%). Among the ART-experienced individuals, major INSTI RAMs detected were E138K (4/3,863; 0.10%), G140R (25/3,863;0.65%), G118R (2/3,863, 0.05%), R263K (4/3,863, 0.10%), T66I (1/3,863;0.03%), E138K + G140R (1/3,863, 0.03%|), G140R + R263K (1/3,863, 0.03%). High-level resistance to cabotegravir (CAB), elvitegravir (EVG), and raltegravir (RAL) was detected in 0.70, 0.16 and 0.06% of the individuals, respectively. Notably, bictegravir (BIC) and dolutegravir (DTG) showed no high-level resistance. The overall prevalence of archived INSTI RAMs in Botswana was low prior to transitioning to first-line DTG-based ART regimens, and did not differ between ART-naïve and ART-experienced individuals. Ongoing surveillance of INSTI DRMs in Botswana will allow for re-assessment of INSTI resistance risk following nationwide DTG rollout.

Should dolutegravir always be withheld in people with HIV on dolutegravir with incident diabetes mellitus? a case report

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.

Non-Alcoholic fatty liver disease and metabolic syndrome in patients with HIV/AIDS and its correlation with antiretroviral therapy and severity of disease

Introduction: Metabolic syndrome (MetS) and Non-alcoholic fatty liver disease (NAFLD) are two major causes of morbidity in chronic HIV infected patients on antiretroviral therapy (ART). This study was done on HIV infected individuals by comparing ART naive patients with patients on different ART regimens and evaluating the effect of ART on Metabolic syndrome and NAFLD.Method: It was a cross-sectional observational study done on 120 HIV infected individuals in a tertiary care centre in New Delhi. All cases with hypertension, diabetes, chronic kidney or liver disease, thyroid disorders or on any drugs except ART were excluded. The risk markers for metabolic syndrome were assessed and compared within groups on different ART regimens.Results: Metabolic syndrome and NAFLD were found to be significantly more in cases on ART as compared to ART naïve cases. Metabolic syndrome was found to be associated with type of ART protease inhibitors (ATV/r)> nonucleoside reverse transcriptase inhibitors (NNRTI) > no ART] and low CD4 cell counts (p=0.01). In those patients who were on ART, these parameters were found to be more in those on second line ART [i.e., protease inhibitor (PI)(ATV/r) based regimens] as compared to those on first line ART, [i.e., nonnucleoside reverse transcriptase inhibitors (NNRTI) based regimen]. 15% of cases on 2nd line ART (group C) had MetS as compared to 12.5% in those on 1st line ART (group B) and nil in ART naïve cases (group A). One third (34%) of all 120 cases were found to have NAFLD. A significantly higher number of cases (45%) in group C had NAFLD as compared to 32.5% in group B and 25% in group A respectively. Insulin resistance and metabolic risk markers were also significantly higher in cases on ART as compared to ART naïve.Conclusions: In HIV patients, the use of antiretroviral therapy (ART) is linked to an increase in the prevalence of metabolic risk factors, including insulin resistance, lipoatrophy and dystrophy, dyslipidaemia, and abnormalities of fat distribution. Although care of Opportunistic infections and recently CVD has received a lot of attention, it is equally important to address the metabolic abnormalities such as metabolic syndrome and NAFLD brought on by ART.

Bone mineral density among children living with HIV failing first-line anti-retroviral therapy in Uganda: A sub-study of the CHAPAS-4 trial.

Children living with perinatally acquired HIV (CLWH) survive into adulthood on antiretroviral therapy (ART). HIV, ART, and malnutrition can all lead to low bone mineral density (BMD). Few studies have described bone health among CLWH in Sub-Saharan Africa. We determined the prevalence and factors associated with low BMD among CLWH switching to second-line ART in the CHAPAS-4 trial (ISRCTN22964075) in Uganda. BMD was determined using dual-energy X-ray Absorptiometry (DXA). BMD Z-scores were adjusted for age, sex, height and race. Demographic characteristics were summarized using median interquartile range (IQR) for continuous variables and proportions for categorical variables. Logistic regression was used to determine the associations between each variable and low BMD. A total of 159 children were enrolled (50% male) with median age (IQR) 10 (7-12) years, median duration of first -line ART 5.2(3.3-6.8) years; CD4 count 774 (528-1083) cells/mm3, weight-for-age Z-score -1.36 (-2.19, -0.65) and body mass index Z-score (BMIZ) -1.31 (-2.06, -0.6). Low (Z-score≤ -2) total body less head (TBLH) BMD was observed in 28 (18%) children, 21(13%) had low lumbar spine (LS) BMD, and15 (9%) had both. Low TBLH BMD was associated with increasing age (adjusted odds ratio [aOR] 1.37; 95% CI: 1.13-1.65, p = 0.001), female sex (aOR: 3.8; 95% CL: 1.31-10.81, p = 0.014), low BMI (aOR 0.36:95% CI: 0.21-0.61, p<0.001), and first-line zidovudine exposure (aOR: 3.68; 95% CI: 1.25-10.8, p = 0.018). CD4 count, viral load and first- line ART duration were not associated with TBLH BMD. Low LS BMD was associated with increasing age (aOR 1.42; 95% CI: 1.16-1.74, p = 0.001) and female sex: (aOR 3.41; 95% CI: 1.18-9.8, p = 0.023). Nearly 20% CLWH failing first-line ART had low BMD which was associated with female sex, older age, first-line ZDV exposure, and low BMI. Prevention, monitoring, and implications following transition to adult care should be prioritized to identify poor bone health in HIV+adolescents entering adulthood.

Incidence and predictors of attrition among adults receiving first line anti-retroviral therapy at public health facility in Adea Berga district, Oromia, Ethiopia.

According to current estimates, there are 665,723 people in Ethiopia who have human immunodeficiency syndrome. As Ethiopia inches closer to attaining the 95/95/95 targets for treatment coverage and reaching epidemic control, however, attrition from anti-retroviral treatment is still one of the key programmatic challenges. To assess the incidence of attrition rate and its predictors among adult HIV patients receiving anti retro viral treatment at Public Health Facility in Adea Berga/Enchini District. A 6-year (June 28, 2015 to June 27, 2021) institution-based retrospective cohort study was used to recruit 540 study participants by using simple random sampling. Data were obtained from chart review, coded, entered into Epi Data, and exported to Stata 14.2 software for analysis. At least 1 month missed appointment is considered as attrition and the predictors of attrition were identified using bivariable and multivariable Cox proportional hazard models and an adjusted hazard ratio (AHR). Bivariate and multivariate analyses were conducted to find predictors of attrition, p-value < 0.05 was considered statistically significant. From the total 540 study participant, 158 (29.26%) patients were discontinuing from follow up making the incidence rate of attrition 9.50 per 100 person years .Being WHO clinical stage III or IV (AHR = 1.96,), non-practice of Appointment spacing model (AHR = 3.98), poor or fair ART adherence level (AHR = 6.47), age groups (15-24) years (AHR = 1.73) and Others ART linkage points[index case testing, tuberculosis clinic and referral from private/public health institutions] (AHR = 1.76) were significantly associated. The study showed that the incidence of attrition among adults receiving antiretroviral therapy was high. Patient sociodemographic, clinical, and treatment-related factors were significantly associated with patients on ART.

High acceptability and viral suppression rate for first-Line patients on a dolutegravir-based regimen: An early adopter study in Nigeria.

Nigeria adopted dolutegravir (DTG) as part of first line (1L) antiretroviral therapy (ART) in 2017. However, there is limited documented experience using DTG in sub-Saharan Africa. Our study assessed DTG acceptability from the patient's perspective as well as treatment outcomes at 3 high-volume facilities in Nigeria. This is a mixed method prospective cohort study with 12 months of follow-up between July 2017 and January 2019. Patients who had intolerance or contraindications to non-nucleoside reverse-transcriptase inhibitors were included. Patient acceptability was assessed through one-on-one interviews at 2, 6, and 12 months following DTG initiation. ART-experienced participants were asked about side effects and regimen preference compared to their previous regimen. Viral load (VL) and CD4+ cell count tests were assessed according to the national schedule. Data were analysed in MS Excel and SAS 9.4. A total of 271 participants were enrolled on the study, the median age of participants was 45 years, 62% were female. 229 (206 ART-experienced, 23 ART-naive) of enrolled participants were interviewed at 12 months. 99.5% of ART-experienced study participants preferred DTG to their previous regimen. 32% of particpants reported at least one side effect. "Increase in appetite" was most frequently reported (15%), followed by insomnia (10%) and bad dreams (10%). Average adherence as measured by drug pick-up was 99% and 3% reported a missed dose in the 3 days preceding their interview. Among participants with VL results (n = 199), 99% were virally suppressed (<1000 copies/ml), and 94% had VL <50 copies/ml at 12 months. This study is among the first to document self-reported patient experiences with DTG in sub-Saharan Africa and demonstrated high acceptability of DTG-based regimens among patients. The viral suppression rate was higher than the national average of 82%. Our findings support the recommendation of DTG-based regimen as the preferred 1L ART.

CD4-T Cells as a Predictor of Immune Status and Its Outcomes Following Second-Line Combination Antiretroviral Therapy in Adult HIV-1 Infected Patients Attending Apin/Juth HIV Clinic in Jos, Plateau State, Nigeria

Deficiency in immune cell number or activity is a cardinal feature of HIV. Second line antiretroviral therapy is geared towards improving immune cell activity and improving treatment outcomes. More people are now accessing free combination antiretroviral therapy through public health programmes in resource limited settings. There is currently no third line therapy for patients failing second line therapy in most of these programmes and data on effectiveness of second line antiretroviral therapy are limited. To adequately address and prepare for this scenario, critical assessments of the outcomes of second-line cART are needed. This is a retrospective cohort study of patients accessing second line cART at the APIN/ JUTH, Jos adult HIV clinic from 2004 to 2018, to determine the proportion of patients failing second line cART, to evaluate time to immunologic failure, time to lost to follow up and time to death using Kaplan Meier estimates. Immunological failure occurs when there is a fall of CD4 counts to pre-therapy baseline (or below) or 50% fall from the on-treatment peak value (if known) or persistent CD4 levels below 100 cells/mm 3 6 months after ART initiation. A total of 285 patients were included in the study, with a mean age of 45±9.5 years. Females where 194 (68.1%) All the patients were on boosted protease inhibitor, the predominant combination antiretroviral therapy for second line regimen was Lopinavir boosted with ritonavir in combination with Tenofovir, Lamivudine and Zidovudine (43.9%). The baseline CD4 count was 134 (IQR 54-272). The CD4 count increased to 339 (IQR213-498) at 72 weeks. In conclusion, Second line cART immunologic failure rates are low in our cohort and patient stay longer on cART before failure. Keywords: CD4 cells, Immunologic failure, Antiretroviral therapy DOI: 10.7176/JHMN/107-02 Publication date: April 30 th 2023

Comorbidities and New Onset of Type 2 Diabetes Mellitus among Women Living with HIV Receiving Antiretroviral Therapy in Lagos, Nigeria

Background: There is limited gender stratified data in many type 2 diabetes mellitus (T2DM) studies in Africa. This study aimed to determine the prevalence of Comorbidities, New Onset of T2DM and risk factors influencing predisposition to T2DM among women living with HIV (WLWH) and receiving Antiretroviral Therapies. Methods: This was a cross-sectional study of females who were 15 years and above with HIV and/or without pulmonary TB attending HIV and TB DOTS clinics in Lagos, Nigeria from January 2019 to October 2021. The socio-demographic data of participants were obtained using questionnaire. Participants who were not known diabetic cases were tested for diabetes based on WHO and ADA standards using glycated haemoglobin (HbA1c) test, fasting plasma glucose and 2 hour 75 g oral glucose post prandial test. CD4 and CD8 counts were carried out using flow cytometer and their cytokines’ levels were determine using ELISA technique. HIV positive patients with signs and symptoms of TB (presumptive TB) were tested using sputum smear microscopy method and gene X-pert technique. We measured Body mass index (BMI) using International System of Units (kg/m2). Information on age, gender, Antiretroviral therapy (ART), values of CD4, weight, height, viral load and cholesterol test results less than 6 months were obtained from the patients’ folders. Results: A total of 187 WLWH were studied. Their mean age was 41.93±10.32 years. Fifty-five (27.9%) had BMI values of ≥ 30 kg/m2. Twenty-one (11.2%) had impaired glucose level. Those with T2DM at baseline were 5(2.7%), 17(9.1%) later developed T2DM. There was strong association between newly developed T2DM and obesity odd ratio (OR) 8.21(95% CI 1.30-51.99), interleukin (IL-): IL-6 OR 4.50 (95% CI 0.58-35.15), viral load with OR as 1.34(0.48-3.75), knowledge of diabetes OR 2.24 (95% CI 0.43-11.62), consumption of alcohol OR 2.03(95% CI 0.60-6.90). Twenty (10.7%) WLWH developed pulmonary TB while receiving ART. Co-morbidities recorded were: HIV/T2DM 14(7.5%), HIV/TB 21(11.2%), HIV/TB/T2DM 7(3.7%). A total of 42(22.7%) were on 2nd line ART. Conclusion: Prevalence of HIV/TB co-infection, HIV/T2DM comorbidity and HIV/TB/T2DM multimorbidity were high. Also the prevalence of incident TB and new cases of T2DM among the study population were high. There was positive association between development of T2DM while receiving ART and obesity, IL-6, knowledge of diabetes and alcohol consumption. Protease inhibitors were found to influence the development of T2DM among WLWH while receiving ART. Recommendation: There is need for promoting awareness of T2DM and its risk factors among WLWH who are receiving ART.

TDF-3TC-DTG or TDF-3TC-EFZ First Line Antiretroviral Therapy Protocols and Their Relation to Salivary Biochemical Constituents in HIV-1 Infected Patients in Yaoundé, Cameroon

TDF-3TC-DTG or TDF-3TC-EFZ First Line Antiretroviral Therapy Protocols and Their Relation to Salivary Biochemical Constituents in HIV-1 Infected Patients in Yaoundé, Cameroon

Incidence, survival time and associated factors of virological failure among adult HIV/AIDS patients on first line antiretroviral therapy in St. Paul's Hospital Millennium Medical College-A retrospective cohort study.

Human Immune deficiency Virus or Acquired Immune deficiency Syndrome (HIV/AIDS) is a pandemic affecting millions around the world. The 2020 the Joint United Nations Programme on HIV/AIDS report stated that the estimated number of people living with HIV (PLHIV) is 38 million globally by 2019. Ethiopia is among HIV high burden countries in Africa. By 2021, PLHIV in Ethiopia is estimated to be 754, 256. Globally out of 25.4 million PLHIV on ART, 41% reported virally non-suppressed. According to UNAIDS, the estimated viral non-suppression in Ethiopia is about 27%. A hospital based retrospective cohort study was conducted among 323 patients who were enrolled to ART from July 2016 to December 2020. The medical records of study participants were selected using simple random sampling technique & data was collected using data extraction checklist. The collected data was entered and cleaned using SPSS V.25. Kaplan-Meier is used to estimate the cumulative hazard of virological failure at different time points. During bivariate analysis variables with p<0.25 were taken for Multivariate Cox regression analysis to assess predictors of virological failure & statistically significant association was declared at p<0.05 with 95% confidence interval. The overall incidence rate of virological failure was 1.75 per 1000 months of observations. The mean survival time of virological failure was 14.80 months. Disclosure of sero-status (AHR = 0.038, 95% CI: 0.008-018), poor adherence (AHR = 4.24, 95% CI: 1.04-16), having OIs (Opportunistic infections) (AHR = 4.59, 95% CI: 1.17-18) and use of cotrimoxazole (CPT) prophylaxis (AHR = 0.13, 95% CI: 0.026-0.68) have shown statistically significant association with virological failure. The incidence of virological failure among patients on first line ART in St. Paul's hospital is low. Disclosure of sero-status, poor adherence, having OIs and use of CPT prophylaxis were associated with virological failure. Therefore, a due attention needs to be given to these factors in order to minimize virological failure in patients on ART.

Endothelial glycocalyx improvement after six months and one-year of antiretroviral therapy in treatment naive patients with human immunodeficiency virus

Abstract Background Chronic inflammation induced by Human Immunodeficiency Virus (HIV) plays a key role in the development of early cardiovascular (CV) disease. The impact of currently recommended first line antiretroviral therapy (ART) on CV risk early after treatment initiation is still under investigation. We aimed to explore any treatment-induced changes in endothelial function through endothelial glycocalyx measurement (EG) in treatment naïve HIV patients' one year post HIV treatment initiation by different ART agents. Methods We estimated endothelial function by endothelial glycocalyx integrity measurement in 58 recently diagnosed and treatment naïve HIV patients (mean age=38+10 years, 91% males, 61% smokers) at baseline and at 1-year post ART initiation (integrase or protease inhibitors). Increased perfusion boundary region (PBR) of the sublingual arterial microvessels (ranged from 5–25 micrometers) using Sideview Darkfield imaging (Microscan, Glycocheck) was measured as a non-invasive accurate index of reduced EG thickness. Results From a total population of 54 HIV patients, 35 patients were randomly treated by the newer integrase inhibitor Dolutegravir (Group A, mean age = 37±10 years, 89% males, 54% smokers) while 22 patients by the older protease inhibitor Darunavir/Cobicistat (Group B, mean age = 38±10 years, 95% males, 74% smokers). No differences were found between groups regarding age, weight, lipid profile (LDL-C, HDL-C, triglycerides), office (SBP, DBP) and central (cBP) blood pressure. We found that weight (76±14 vs. 81±16 kg, p&amp;lt;0.001), SBP (125±12 vs. 130±14 mmHg, p=0.003) and cBP (116±12 vs. 121±12 mmHg, p=0.001) were increased in the entire HIV population, at 1 year post-treatment. At 6 months evaluation, PBR5–25 was decreased in the entire HIV population and Group A (2.18±0.3 μm vs. 2.05±0.3 μm, p=0.01 and 2.19±0.3 μm vs. 2.02±0.3 μm, p=0.02, respectively). However, at 1-year post treatment evaluation, PBR5–25 was decreased in all groups, total HIV population, Group A and Group B (2.18±0.3 μm vs. 1.96±0.3 μm, p&amp;lt;0.001, 2.19±0.3 μm vs. 1.93±0.3 μm, p=0.003 and 2.17±0.3 vs. 1.99±0.3, p=0.04, respectively). Conclusions Endothelial function, estimated by endothelial glycocalyx integrity, is improved in newly diagnosed and treatment naïve HIV patients, evaluated at 6 and 12 months post-treatment initiation by integrase or protease inhibitors despite weight and blood pressure increase. Funding Acknowledgement Type of funding sources: None.

Opsoclonus Myoclonus Ataxia Syndrome in a HIV Patient as a rare presentation of CSF escape: A Case Report

Cerebrospinal fluid escape is an uncommon phenomenon seen in patients where there is discordance in plasma and cerebrospinal fluid viral load. The presentation of this condition can range from being asymptomatic to the patient showing cognitive dysfunction. In addition, it can also be associated with various opportunistic neurological infections. Opsoclonus Myoclonus Ataxia is very rare entity classically associated with neuroblastoma or viral illness. Opsoclonus Myoclonus Ataxia Syndrome (OMAS) has previously been described as a presentation of Human Immunodeficiency Virus cerebrospinal fluid escape very rarely. We report a case of 55 years old patient diagnosed with HIV/AIDS, who was on first line antiretroviral therapy and presented with Opsoclonus Myoclonus Ataxia Syndrome associated with Cerebral Fluid (CSF) Escape, along with the review of the literature. Moreover, in this article, we're providing a postulation for the plausible cause behind cerebrospinal fluid escape leading to the Opsoclonus Myoclonus Ataxia Syndrome. Keywords: HIV/AIDS, CSF Escape, Opsoclonus Myoclonus Ataxia Syndrome.

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

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

Moving forward with dolutegravir in children weighing less than 20 kg

Dolutegravir was recommended as first line antiretroviral therapy (ART) across all ages by WHO in 2018. At that time, no dosing data was available for children living with HIV weighing less than 15 kg and appropriate formulations were not available in high burden settings.1 There was also no evidence of superior outcomes in children living with HIV.1 With approximately 800 000 children living with HIV not receiving ART and low viral suppression rates,2 robust child friendly dolutegravir-based regimens will allow for once daily dosing, align with adult guidelines, and improve outcomes.

Virologic failure in people living with HIV in 1st line ART: A 10-year Mexican population-based study.

BackgroundIn Mexico, the number of people living with HIV (PLWH) receiving antiretroviral therapy (ART) has increased in the last 20 years. The elimination of a CD4 threshold to initiate publicly funded ART was a major policy implemented in 2014. The study objective was to assess the determinants of Virologic Failure (VF) in Mexican PLWH on first-line ART between 2008 and 2017 and to evaluate the effects of changes following the 2014 policy.MethodsA 10-year patient-level data analysis was conducted using the Mexican SALVAR database. The main outcome was the proportion of PLWH with VF. A multivariable logistic regression was conducted to identify the association between covariates and VF before and after the 2014 policy implementation.ResultsWe found a lower proportion of people with VF in 2014–2017 compared with 2008–2013 (50% vs 33%, p<0.001). The multivariable analysis showed a reduction in the odds of virologic failure after 2014 (Odds ratio: 0.50 [95% CI: 0.48–0.51]). Place of treatment and level of deprivation were significant predictors of VF in during 2014–2017, but not before.ConclusionThis study indicates that, by lowering threshold levels of CD4 required for treatment initiation in Mexico, a higher number of PLWH initiated treatment during 2014–2017, compared to 2008–2013 and the odds of VF were reduced.

A comparative study on early treatment outcome and adverse drug reaction profile of two protease inhibitor-based antiretroviral regimens in human immunodeficiency virus patients at a tertiary care teaching hospital, Rajasthan

Introduction: Second-line antiretroviral therapy (ART) regimens are used when patients develop treatment failure from first-line drug regimens. The present study is aimed to compare treatment outcome in terms of clinical, virological, and immunological effectiveness over 1 year of follow-up in human immunodeficiency virus (HIV) patients, switched to various second-line ART regimens and to assess adverse drug reactions (ADRs). Materials and Methods: A longitudinal observational study was conducted at ART center, SMS Hospital, Jaipur, after approval from Institutional Research Review Board. One hundred HIV positive patients, resistant to first line ART, switched to either of the 2 s line ART regimens were followed for 1 year for early treatment outcomes and any ADRs. Results: Out of 97 patients enrolled 65 patients received Tenofovir and 32 patients received Zidovudine (ZDV) along with lamivudine and Atazanavir/ritonavir. There was significant increment in CD4 count from the baseline value (202.51–438.52 cells/mm3) after 12 months of therapy. On comparison, CD4 cell rise was not significantly different between the two groups. However, Plasma viral load suppression was achieved insignificantly more number of patients in ZDV group than in tenofovir group: 31 (96.9%) versus 57 (87.7%), respectively. Opportunistic infections (OI) were seen in 21.5% and 28.1% patients respectively at the time of switching of second-line ART. Out of 59 ADRs reported, nausea, vomiting, diarrhea, hyperbilirubinemia, dyslipidemia, and anemia were most common. Conclusion: Nonadherence, drug resistance, and treatment failure are the major challenges in controlling HIV disease. Our study shows that both the second-line regimens were comparable in improvement in CD4 count and viral load suppression with 1 year success rate of 90.7%.