Line Antiretroviral Therapy Research Articles

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%.

First-line virologic-based ART treatment failure and associated factors among adult HIV Positives in Southwest Shoa, Central Ethiopia.

Background: The function of antiretroviral therapy is to enhance immunity and prevent the occurrence of opportunistic infection. But antiretroviral therapy showed a failure to manage infection after a time. Nowadays, an accepted criterion to confirm Antiretroviral therapy (ART) treatment failure is a virologic failure. Regarding this virologic failure, there are no well-addressed findings, especially in this study area. Therefore in this research, the magnitude and factors that contribute for virological ART treatment failure have been identified. Methods: Facilitybased cross-sectional study was conducted on adult patients taking ART. Data entry was conducted using Epi Data Version3 and exported to Stata SE version 14 for analysis. Bivariable logistic regression was used to find covariates significantly associated with firs line ART treatment failure. In this case, variables with P-value ≤ .25 were a candidate for multiple logistic regressions. A backward logistic regression model was used. Finally, variables with P-value ≤ .05 were considered as factors significantly associated with first-line ART treatment failure and the result was presented with a description, graph, and tables. Results: In this study, three hundred and fifty peoples were a candidate for the study and all have been involved. The magnitude of first-line ART treatment failure based on virologic criteria was 20.85%. Greater than three-fourth (84.29%) of study participants have support from somebody. Those patients who have initiated first-line ART with NVP based regimen have 1.83 times more likely to face first-line ART treatment failure as compared with those who have started with Efeverence (EFV) based regimen [AOR = 1.83, 95% CI (1.035, 3.245)]. Patients who have initiated first-line ART at the health center were 3.093 times more likely to face first-line ART treatment failure as compared those who have initiated ART at hospitals [AOR = 3.093, 95% CI (1.101, 8.685)]. Patients who have not developed a common opportunistic infection after ART initiation was 47.3% less likely to encounter first-line ART treatment failure as compared with those who have opportunistic infection [AOR = 0.527, 95% CI (0.289, 0.961)]. Conclusion: Based on virologic criteria, NVP based ART initiation, having history recorded opportunistic infection after ART initiation, being male, Institution where initiate ART, are significantly associated with the occurrences of first-line ART treatment failure. The action has to be directed on those identified factors to maintain the patient stay on First-line ART by concerned stakeholders.

Antiretroviral treatment failure and associated factors among HIV patients on the first-line antiretroviral therapy at Mizan-Tepi University teaching hospital, Southwest Ethiopia: A cross-sectional study.

The use of Antiretroviral therapy (ART) has become a standard of care for the treatment of HIV infection. The therapy restores immune function and reduces HIV-related adverse outcomes. However, treatment failure erodes this advantage and leads to an increased morbidity and compromised quality of life in HIV patients. Thus, this study aimed to assess anti-retroviral treatment failure and associated factors among HIV patients on the first line ART at Mizan-Tepi University Teaching Hospital. A cross-sectional study was undertaken among adult patient who have been on ART and attending ART Clinic of Mizan-Tepi University Teaching Hospital from September 2014 to September 2018. Data were collected retrospectively by reviewing patients’ medical charts using a standard structured questionnaire. Data were entered into Epi data version 4.0.2 and then exported to SPSS version 21.0 for analysis. To identify the predictors of anti-retroviral treatment failure, multiple stepwise backward logistic regression analysis were done. P value < .05 was considered as statistically significant. Among 221 patients included in the study, 118 (53.39%) were females. The mean weight of study participants at ART initiation was 57.04 kg. Of the 221 patients on the first line ART, 10 (4.5%) experienced treatment failure. Of these patients, 5 (50%) and 3 (30%) experienced virological failure and clinical failure, respectively. Functional status (AOR: 3, CI: [1.13–6.5], P < .001) and low baseline CD4 cell count (AOR: 4.3, CI: [3.4–10.6], P < .0001) were found to be an independent predictors of treatment failure. The rate of first-line ART treatment failure in the study setting was substantial. Functional status and low baseline CD4 cell count were found to be an independent predictors of virological, clinical and immunological failure. Therefore, more attention should be given for the lifestyle of pateints’ on ART and maximize virological tests for monitoring treatment failures.

Factors Associated with Viral Suppression Among Adolescents on Antiretroviral Therapy in Homa Bay County, Kenya: A Retrospective Cross-Sectional Study.

BackgroundDespite the success in initiating adolescents living with HIV on antiretroviral therapy (ART), questions remain about factors affecting viral suppression. In Kenya, only 63% of adolescents (aged 10–19 years) on ART had achieved viral suppression in 2016. We investigated factors associated with viral suppression among adolescents initiated on ART before November 30, 2017 in Homa Bay County, Kenya.MethodsA retrospective cross-sectional analysis of 908 adolescents registered on ART for at least 6 months and with at least one documented viral load in the last 12 months, in six health facilities in Homa Bay County was conducted. Data were extracted from the electronic medical records and exported into an excel spreadsheet. Bivariate and multivariate logistic regression analyses were conducted to identify factors associated with viral suppression and adjust for confounding, using Stata 12.0.ResultsOut of all participants, 80% (726) had achieved viral suppression (<1,000 copies of viral RNA/mL of blood at latest viral load count). After adjusting for other covariates, adolescents with good adherence to ART (AOR=2.3, 95% CI=1.38–3.84) and a most recent CD4 count of above 500 cells/mm3 (AOR=1.87, 95% CI=1.13–3.08), were more likely to be virally suppressed. Adolescents on second line ART treatment (AOR=0.45, 95% CI=0.28–0.73) and having inadequate adherence to ART (AOR=0.26, 95% CI=0.11–63) were less likely to be virally suppressed.ConclusionViral suppression for adolescents on ART in this study is significantly higher than the national prevalence in 2016 (80% vs 63%), but it is still below the WHO target of 90%. Enhanced adherence support for adolescents on ART should be implemented to improve long-term adherence. Specific interventions are needed to “rescue” adolescents on second-line ART regimens who may have a history of poor adherence.

Effect of azithromycin on incidence of acute respiratory exacerbations in children with HIV taking antiretroviral therapy and co-morbid chronic lung disease: a secondary analysis of the BREATHE trial.

BackgroundIn the BREATHE trial weekly azithromycin decreased the rate of acute respiratory exacerbations (AREs) compared to placebo among children and adolescents with HIV-associated chronic lung disease (CLD) taking antiretroviral therapy (ART). The aim of this analysis was to identify risk factors associated with AREs and mediators of the effect of azithromycin on AREs.MethodsThe primary outcome of this analysis was the rate of AREs by study arm up to 49 weeks. We analysed rates using Poisson regression with random intercepts. Interaction terms were fitted for potential effect modifiers. Participants were recruited from Zimbabwe and Malawi between15 June 2016 and 4 September 2018.FindingsWe analysed data from 345 participants (171 allocated to azithromycin and 174 allocated to placebo). Rates of AREs were higher among those with an abnormally high respiratory rate at baseline (adjusted rate ratio (aRR) 2.08 95% CI 1.10-3.95 p-value 0.02) and among those with a CD4 cell count <200 cells/mm3 (aRR 2.71; 95% CI 1.27-5.76; p-value 0.008). We found some evidence for variation in the effect of azithromycin by sex (p-value for interaction=0.07); males had a greater reduction in the rate of ARE with azithromycin treatment than females. We found that azithromycin had a greater impact on reducing AREs in participants with chronic respiratory symptoms at baseline, those on 1st line ART, with a FEV1 score >-2 and participants without baseline resistance to azithromycin. However, there was no statistical evidence for interaction due to low statistical power.InterpretationThese may represent subgroups who may benefit the most from treatment with weekly azithromycin, which could help guide targeted treatment.FundingThere was no funding source for this post hoc analysis.

Magnitude and associated factors of anemia among AZT based HAART experienced adult HIV patients at University of Gondar Comprehensive Specialized Referral Hospital, Northwest, Ethiopia, 2019: a retrospective cohort study

BackgroundAnemia is the most common hematologic abnormalities in AIDS patients usually associated with disease progression and poor clinical outcomes. Zidovudine (AZT), which is one of the nucleoside reverse transcriptase inhibitor drug families of the first line antiretroviral therapy regimen for HIV/AIDS patients, causes anemia due to early long-term of higher-dose therapy. This study was aimed to assess the magnitude and associated factors of anemia among AZT containing HAART experienced adult HIV/ADIS patients at University of Gondar Comprehensive Specialized Referral Hospital, northwest, Ethiopia, 2019.MethodsA retrospective cohort study was conducted among a total of 320 adult AZT based HAART experienced HIV/AIDS patients from January 2016 to December 2018. Systematic random sampling technique was used to select the patients’ charts. All required data for this study were extracted from patients’ medical charts. Data were coded, cleared and entered into Epi Info version 3.5.3, and transformed to SPSS version 20 for analysis. Descriptive statistics, bivariable and multivariable logistic regression models were fitted to identify associated factors of anemia and P-value < 0.05 was considered as statistically significance.ResultsA total of 320 adult AZT based HAART experienced HIV/AIDS patients’ charts were assessed. Of the total patients, 198 (61.9%) were females and 133 (41.6%) were within the age range of 35–45 years. More than half, 237(76.9%) of the patients were from the urban area and 186 (58.1%) were on WHO clinical stage III at the baseline. The prevalence of anemia was 50% (95% CI 44.7–55.0%), 44.1% (95% CI 38.4–50.0%), 35.6% (95% CI 30.3–40.6%), 40% (95% CI 34.4–45.6%), 40.6% (95% CI 35.0–46.3) and 39.1% (95% CI 33.4–44.1%) at baseline, 6 months, 12 months, 18 months, 24 months and 30 months of follow-up period, respectively. The overall prevalence of anemia was 41.6%. Anemia had significant association with WHO clinical stage and base line Hgb values.ConclusionsA significant number of participants were anemic in this study. WHO clinical stage and baseline Hgb value were the contributing factors for anemia among these patients. Therefore, anemia needs an immediate intervention on associated factor to improve the anemic status and living condition of HIV patient.

Rapid HIV-1 drug resistance testing in a resource limited setting: the Pan Degenerate Amplification and Adaptation assay (PANDAA).

Introductionpre-treatment drug resistance (PDR) can compromise the 3rd 95-95-95 global target for viral load suppression. The high complexity and cost of genotyping assays limits routine testing in many resource limited settings (RLS). We assessed the performance of a rapid HIV-1 drug resistance assay, the Pan Degenerate Amplification and Adaptation (PANDAA) assay when screening for significant HIV-1 drug resistance mutations (DRMs) such as K65R, K103NS, M184VI, Y181C and G190A. Methods: we used previously generated amplicons from a cross-sectional study conducted between October 2018 and February 2020 of HIV-1 infected antiretroviral therapy (ART)-naïve or those reinitiating 1st line ART (18 years or older). The performance of the PANDAA assay in screening K65R, K103NS, M184VI, Y181C, and G190A mutations compared to the reference assay, Sanger sequencing was evaluated by Cohen´s kappa coefficient on Stata version 14 (StataCorp LP, College Station, TX, USA).Resultsone hundred and twenty samples previously characterized by Sanger sequencing were assessed using PANDAA. PDR was found in 14% (17/120). PDR to non-nucleoside reverse transcriptase inhibitors (NNRTIs) was higher at 13% (16/120) than PDR to nucleotide reverse transcriptase inhibitors (NRTIs), 3% (3/120). The PANDAA assay showed a strong agreement with the reference assay, i.e. Sanger sequencing for all five target DRMs (kappa (95%CI); 0.93 (0.78-0.98)) and NNRTI DRMs (kappa (95%CI); 0.93 (0.77-0.980), and a perfect agreement for NRTI DRMs (kappa (95%CI); 1.00 (0.54-1.00)).Conclusionthe PANDAA assay is a simple and rapid method to identify significant HIV DRMs in plasma samples as an alternative to Sanger sequencing in many RLS.

Virological failure among HIV infected individuals on antiretroviral therapy in Pune, India: a cross-sectional study

Background: It is important to identify and manage determinants of virological failure among HIV infected individuals on treatment for achieving viral suppression. This study aimed to identify proportion and factors associated with virological failure among HIV infected individuals receiving first line antiretroviral therapy (ART).Methods: A total of 2670 adult HIV infected individuals attending ART centre at ICMR-National AIDS Research Institute, between January 2005 and June 2019 and having their recent viral load done after implementation of guidelines on routine viral load testing were included. Data were reviewed and analysed.Results: Of the 2670 people living with HIV (PLHIV) on first line antiretroviral therapy, 48% were male and 69% were more than 40 years of age. Mean baseline CD4 count at ART initiation was 252 cells/mm3 (SD:210, IQR 116-313) Overall, 13% (340/2670) of the participants showed virological failure. In multivariate analyses, participants with younger age and males retained significant association. Those with baseline CD4 counts of less than or equal to 500 cells/mm3 at treatment initiation (adjusted OR 1.71; 95% CI 1.08-2.70; p=0.022) and ART adherence ≤95% within last three months of recent viral load determination (adjusted OR 1.55, 95% CI of AOR 1.04-2.32; p=0.031) had higher risk for virological failure as compared to others. PLHIV with ART substitution due to various reasons were almost twice as likely to have virological failure (adjusted OR 1.83, 95% CI 1.44-2.33; p&lt;0.001).Conclusions: It is crucial to focus on factors leading to virological failure among HIV infected individuals attending ART centre. Early linkage to treatment and ART initiation along with adherence counselling at every follow up visit play an important role in mitigating virological failure.

Rate and predictors of HIV virological failure among adults on first-line antiretroviral treatment in Dar Es Salaam, Tanzania.

Monitoring resistance to first line Antiretroviral therapy (ART) is crucial in preventing accumulation of viral mutations following the implementation of the World Health Organization "treat all" initiative. We estimated the rate and predictors of virological treatment failure among adults living with HIV/AIDS in Dar es Salaam, Tanzania. A retrospective cohort study involving adults aged 18 and above receiving first line ART in Dar as Salaam between 2016 and 2018 were recruited using multistage random sampling. Clinical and laboratory data were extracted from Care and Treatment Clinic database-2 (CTC2) followed by participant's interviews. Adjusted Cox-regression modelling was used to determine independent predictors of treatment failure. A total of 340 participants with mean age of 37 were recruited. Overall, 10.59% had virological failure and the rate of failure was 5.24 (95% CI:3.72; 7.27) per 100 person-months at risk with a median failure time of 18 months. Independent predictors of treatment failure were being a male (Adjusted hazard ratio (aHR) 2.78, 95%CI:1.16;6.63), having used treatment for less than two years (aHR, 12.48, 95%CI:3.64-22.71) and co-infection with Tuberculosis (aHR 2.1, 95%CI: 1.0;5.9). HIV virological failure occurs early during treatment in this population. Male clients, co-infected with Tuberculosis were at higher risk of ART failure within two years of treatment. Substantial stride has been made towards the achievement of the last UNAIDS 90 goal but tailored counseling and close monitoring of HIV/TB co-infected male clients following ART initiation could accelerate efforts to close the gap. Further studies on pre-treatment drug resistance mutations are called for.

Factors associated with prognostic or treatment outcomes in HIV/AIDS patients with and without hypertension in Eswatini

Non-communicable diseases are increasing faster in HIV/AIDS patients than in the general population. We studied the association between hypertension and other possible confounding factors on viral load and CD4-cell counts in hypertensive and non-hypertensive HIV/AIDS patients receiving antiretroviral therapy (ART) at a large hospital in Eswatini over a 4-year period. We performed a retrospective longitudinal review of the medical records of 560 ART patients divided into non-hypertension and hypertension groups (n = 325 and n = 235) from July 27 to September 8, 2018. Generalized Estimated Equation was used to analyze the longitudinal data. Hypertensive patients were more likely to have improved CD4-cell counts than non-hypertensive patients (OR = 1.83, [1.37–2.44]). ART patients with hypertension were more likely to have detectable viral loads, though not significant (OR = 1.37 [0.77–2.43]). In non-hypertensive patients, second line ART was significantly associated with viral load (OR = 8.61 [2.93–25.34]) and adverse side effects (OR = 3.50 [1.06–11.54]), while isoniazid preventive therapy was significantly associated with CD4-cell counts (OR = 1.68 [1.16–2.45]). In hypertensive patients, factors associated with viral load were WHO HIV stage (OR = 2.84 [1.03–7.85]) and adherence (OR = 8.08 [1.33–49.04]). In both groups, CD4-cell counts significantly and steadily increased over time (p-value < 0.001). Results show a significant association between hypertension and CD4 cell counts but not viral load. In ART patients with and without hypertension, the factors associated with prognostic markers were different. More attention may need to be paid to ART patients with well controlled HIV status to monitoring and controlling of hypertension status.

Treatment outcomes in HIV infected patients older than 50 years attending an HIV clinic in Harare, Zimbabwe: A cohort study.

There is a growing number of older people living with HIV (OPLHIV). While a significant proportion of this population are adults growing into old age with HIV, there are also new infections among OPLHIV. There is a lack of data describing the outcomes of OPLHIV who commenced antiretroviral therapy (ART) after the age of 50 years in sub-Saharan Africa. We conducted a cohort study of patients who enrolled in care at Newlands Clinic in Harare, Zimbabwe, at ages ≥50 years between February 2004 and March 2020. We examined demographic characteristics, attrition, viral suppression, immunological and clinical outcomes. Specifically, we described prevalent and incident HIV-related communicable and non-communicable comorbidities. We calculated frequencies, medians, interquartile ranges (IQR), and proportions; and used Cox proportional hazards models to identify risk factors associated with death. We included 420 (57% female) who commenced ART and were followed up for a median of 5.6 years (IQR 2.4-9.9). Most of the men were married (n = 152/179, 85%) whereas women were mostly widowed (n = 125/241, 51.9%). Forty per cent (n = 167) had WHO stage 3 or 4 conditions at ART baseline. Hypertension prevalence was 15% (n = 61) at baseline, and a further 27% (n = 112) had incident hypertension during follow-up. During follow-up, 300 (71%) were retained in care, 88 (21%) died, 17 (4%) were lost to follow-up, and 15 (4%) were transferred out. Of those in care, 283 (94%) had viral loads <50 copies/ml, and 10 had viral loads >1000 copies/ml. Seven patients (1.7%) were switched to second line ART during follow-up and none were switched to third-line. Higher baseline CD4 T-cell counts were protective against mortality (p = 0.001) while male sex (aHR: 2.29, 95%CI: 1.21-4.33), being unmarried (aHR: 2.06, 95%CI: 1.13-3.78), and being unemployed (aHR: 2.01, 95%CI: 1.2-3.37) were independent independent risk factors of mortality. There was high retention in care and virologic suppression in this cohort of OPLHIV. Hypertension was a common comorbidity. Being unmarried or unemployed were significant predictors of mortality highlighting the importance of sociologic factors among OPLHIV, while better immune competence at ART commencement was protective against mortality.

Successful Use of Multidisciplinary Palliative Care in the Outpatient Treatment of Disseminated Histoplasmosis in an HIV Positive Child

Histoplasmosis is an uncommon opportunistic infection in human immunodeficiency virus (HIV) positive children. The most common form is primary disseminated histoplasmosis, characterized by persistent fever and failure to thrive. A 10-year-old HIV positive girl presented to the Baylor College of Medicine Children’s Foundation—Tanzania Mbeya Center of Excellence (COE) with ulcerated skin lesions and a violaceous facial rash. She also had persistent fevers, severe acute malnutrition, and severe anemia. At diagnosis, the patient was failing first line antiretroviral therapy (ART) with a cluster of differentiation 4 immune cells (CD4) of 24 cells/µL and an HIV viral load (VL) of 196,658 cp/mL. The patient was changed to a second line ART regimen (abacavir, lamivudine, and ritonavir-boosted lopinavir) and received nutritional support, blood transfusions, multiple antibiotics, and meticulous wound care. She also received comprehensive symptom management, psychosocial support, and emergency housing through the COE’s palliative care program. Biopsy of a lesion showed intracytoplasmic organisms consistent with Histoplasmosis capsulatum var capsulatum. The patient was treated with conventional amphotericin B and oral itraconazole and she achieved wound healing as well as immune reconstitution and HIV viral suppression. Amphotericin infusions were given as an outpatient despite the resource constraints of the setting in southwestern Tanzania. Histoplasmosis should be considered in the differential diagnosis of the immunocompromised host with unusual skin manifestations and persistent fever.

Clinical, immunologic and virologic outcomes of children and adolescents receiving second line anti-retroviral therapy in two referral hospitals in Addis Ababa, Ethiopia.

BackgroundEthiopia launched free access for antiretroviral therapy in 2005. The number of patients on second line antiretroviral treatment has increased with each passing year. The objectives of this study were to describe the clinical, immunological and virologic outcomes of children and adolescents receiving second line anti-retroviral therapy in two referral hospitals, Yekatit 12 and Zewditu Memorial Hospitals, in Addis Ababa, Ethiopia.MethodsThis was a hospital based retrospective cohort study conducted among children and adolescents aged 18 years and less and receiving a second line antiretroviral drugs. Data was collected using structured questionnaires. Means and percentages were used for nominal variables. Statistical analysis was made using statistical software–SPSS 23.0. Kaplan Meier analysis, long rank test and multivariate Cox proportion model were used to identify factors affecting survival.ResultsA total of 75 children and adolescents were studied with a mean age of 13.28 years (SD: 4) with a mean treatment period on second line regimens of 35.2 months (SD: 21.8 months). Forty-eight participants were experiencing successful measures (in all three parameters) for their second line anti-retroviral treatment. Ten had virologic treatment failure while seven had died. Both treatment failure and death rates were higher within the first two years of treatment. Poor treatment adherence (Adjusted hazard ratio: 5.1 (95% CI: 1.1–23.2; p-value = 0.02)) and advanced World Health Organization clinical stage at start of the second line antiretrovirals (Adjusted hazard ratio: 7.51 (95% CI: 1.35–18.02; p-value = 0.002)) correlated significantly with survival of children and adolescents receiving treatment.ConclusionsThe study describes clinical, immunological and virologic outcomes of second line antiretroviral treatment in a pediatric cohort under care in two hospitals in Addis Ababa, Ethiopia. Poor adherence and pre-treatment advanced clinical stages were predictors of survival.

Treatment Failure and Associated Factors among Individuals on Second Line Antiretroviral Therapy in Eastern Uganda: A Retrospective Cohort Study.

Background:ART failure is a growing public health problem and a major threat to the progress of HIV/AIDS control. In Uganda however, little is documented on treatment outcomes and their associated factors among individuals on second line ART regimen. The rapid scale-up of ART over the past has resulted in substantial reductions in morbidity and mortality. However, as millions of people must be maintained on ART for life, individuals with ART treatment failure are increasingly encountered and the numbers are expected to rise. This could be attributed to factors such as sub-standard regimens, limited access to routine viral load monitoring, treatment interruptions, suboptimal adherence, among others. The purpose of this study was to estimate 5-year cumulative treatment failure and the associated factors among individuals on second line ART regimen Eastern Uganda.Materials and methods:A retrospective analysis of 541 records of HIV positive individuals, switched to second line ART regimen from January 2012 to December 2017. Inferential statistics including the Chi square test and multivariable logistic regression analysis was applied to determine associations of treatment failure against of the selected demographic, laboratory and clinical factors was performed. Associations between treatment failure and the predictors was based on a P-value of less than 5% and confidence intervals level of 95%.Results:We reviewed 541 records of individuals on second line ART regimen, of which 350 (64.7%) were female, 226 (41.8%) were married, and 197 (36.4%) were older than 35 years. The mean age at ART initiation was 30 years (SD = 14.8), while the mean weight at ART initiation was 47 kg (SD = 18.6), (range 4-97 kg). The overall proportion of treatment failure was 23%. The cumulative mortality risk for 5 years was 12.4% and the mortality rate was 2.5 deaths per 100 individuals per year. The odds of developing treatment failure among individuals switched to ATV/r-based regimen were 44% lower as compared to individuals who were switched to LPV/r (ORadj0.56, 95% CI 0.35-0.90, P = .016). while the odds of experiencing treatment failure among individuals that used AZT at ART initiation were 43% lower as compared to individuals that used a TDF based regimen at ART initiation (ORadj0.57, 95% CI 0.33-0.98, P = .041).Conclusion:The 5 year cumulative incidence of treatment failure in a cohort of 541 individuals was 23%. The type of protease inhibitor (PI) used in second line regimen and use of AZT at ART initiation were significantly associated with treatment failure. Our study also shows that the cumulative mortality risk while on second line ART regimen was 12.4% while the mortality rate was 2.5 deaths per 100 individuals per year. Given the high level of treatment failure among individuals on second line ART regimen, yet the current ART protocols limits the use of third line ART regimens to only regional referral hospitals, the Ministry of Health should strengthen the surveillance systems for identifying individuals failing on second line ART regimen even at district hospitals and lower health facilities to facilitate timely switch to optimal regimen. The Ministry of health through the Quality Improvement Division should conduct routine onsite support supervision to sites offering ART to ensure that treatment guides and other standard of care like timely switch to appropriate regimens among others are being adhered to. Knowledge gaps identified can also be addressed through onsite Continuous Medical Educations.

A Comparison of Patients on First Line and Second Line Antiretroviral Therapy in Dar es Salaam, Tanzania

Background Understanding characteristics of patients on second-line antiretroviral therapy (ART) in comparison to patients on first-line ART is important in addressing demographic and clinical issues related to treatment failure. Broad objective We aimed to compare characteristics of patients on second line ART to those of patients on first line ART and to assess factors associated with second line ART treatment in Dar es Salaam, Tanzania. Methodology Adult patients were systematically recruited in a cross sectional study from one primary level and one secondary level HIV clinics in Dar es Salaam Tanzania. Participants’ socio-demographic and clinical characteristics were recorded. Medians and interquartile ranges were used to compare continuous variables while proportions were used to compare categorical variables. Logistic regression was used to determine factors associated with second line ART treatment. Results We recruited 102 patients from each clinic. Compared to patients on 1st line ART, significantly more patients on second line ART were employed; 90.2% vs. 72.5%, p=0.001, had been on ART for ≥60 months, 71.6% vs. 33.3%, p 60months were 2.5 and 4.4 times respectively more likely seen in patients on second line ART compared to first line ART, p<0.05. Conclusion and recommendation Majority of patients on second-line ART initiated ART with very low CD4 counts, had been on ART for more than sixty months and had changed their ART three times or more. They also had lower CD4 counts at the time of the study. Employment and duration of ART predicted likelihood of being on second-line ART. We recommend early screening for HIV and ART initiation before the immunity is severely compromised in order to reduce the burden of HIV treatment failure. Key words: First line antiretroviral therapy, Second line antiretroviral therapy, antiretroviral therapy resistance, HIV patients’ characteristics, Tanzania, ART adherence.

Family Planning Priorities for Women Living with HIV and Attitudes Towards Mandatory Family Planning Use While Taking Dolutegravir

Dolutegravir (DTG) is currently the first and second line antiretroviral therapy (ART) for women living with HIV (WLHIV). However, in 2018 Botswana Harvard AIDS Institute Partnership found that DTG exposure at conception corresponded with an increase in neural tube defects. Therefore, it is important that providers work with WLHIV to ensure they are aware of how to avoid unplanned pregnancies while on DTG. Telephone interviews were conducted with women living with HIV ages 21-59. The interviews were conducted in western Kenya, at clinical sites of the Academic Model Providing Access to Healthcare (AMPATH) program. Nineteen interview transcripts were coded using NVIVO 12. Domains included family planning use and shared decision making (SDM). Within these domains, three themes were used for this analysis: 1) tensions in ARV SDM and pregnancy, 2) decision making in family planning, and 3) decision making in family planning with DTG. The following three themes were discussed frequently: 1) When making decisions surrounding family planning, women preferred in person counseling and prioritized knowing the side effects of contraceptive methods; 2) WLHIV were often aware of the risk of HIV vertical transmission and valued preventing birth defects if told a medication may cause them; 3) When asked about using family planning while on DTG, WLHIV saw the benefit of preventing pregnancies. However, they did not believe family planning should be mandatory and preferred having a wide variety of contraceptive options. Understanding what factors influence women’s family planning choices may improve SDM between patients and providers. This is especially important when it comes to preventing pregnancies in women taking DTG. WLHIV often understood the importance of effective ARTs and wanted to prevent birth defects. Therefore, it is important to navigate SDM conversations such that WLHIV are given control of their own health decisions.

Clinical phenotype and risk factors for severe efavirenz-associated neurotoxicity amongst inpatients in Cape Town, South Africa

Background: Efavirenz, widely used as first line antiretroviral therapy (ART), is frequently associated with mild transient neuropsychiatric symptoms, usually occurring early in therapy. More severe neurotoxicity has been reported, but the clinical phenotype and risk factors are poorly defined. Methods and materials: We identified adult patients with an efavirenz concentration >4 mg/L (target 1–4 mg/L) at four hospitals in Cape Town, South Africa. Data were extracted from medical records, including clinical symptoms and signs and laboratory abnormalities at the time of efavirenz quantification; severe neurotoxicity was defined as Division of AIDS score > 3. We performed logistic regression to identify associations with neuropsychiatric symptoms and severe neurotoxicity. Results: Data were included from 82 patients: 62 had neuropsychiatric symptoms, 19 had hepatitis, and 1 had no apparent indication for efavirenz quantification. Median age was 38 years (interquartile range (IQR) 29–45), median weight 53 kg (IQR 44–63), 29 (34%) were male, and 49 (63%) patients had concomitant isoniazid exposure. Median efavirenz concentration was 12.1 mg/L (IQR 6.6–20.0). Neuropsychiatric manifestations included ataxia (n = 20) and other cerebellar signs (n = 13), psychomotor slowing (n = 24), psychosis (n = 17), mood disturbance (n = 11), and insomnia/sleep disturbance (n = 4). Compared with hepatitis, neurotoxicity was associated with male sex (adjusted odds ratio (aOR) 20.0, 95% CI 2.0–199.9), higher efavirenz concentrations (aOR 1.2 per 1 mg/L increase, 95% CI 1.0–1.4) and isoniazid exposure (aOR 5.1, 95% CI 1.1–23.5). Severe neuropsychiatric symptoms occurred in 47 (75%) patients with neurotoxicity, after a median of 25 weeks (IQR 9–175) on efavirenz-based ART. Median efavirenz concentration was 20.0 mg/L (the upper limit of assay detection, IQR 13.0–20.0) in those with severe versus 7.0 mg/L (4.5–11.8) in those with mild neurotoxicity (p < 0.01). Amongst patients with severe neurotoxicity, there was complete resolution of symptoms within 1 month in 29/31 (94%) who discontinued efavirenz and in 2/5 (40%) who underwent dose-reduction. 3-month mortality was 11% (n = 45) for patients with severe neurotoxicity. Conclusion: Cerebellar signs were the most frequent clinical manifestation of efavirenz-associated neurotoxicity. There was a concentration-effect relationship for severe neurotoxicity, which occurred late and resolved in most patients after efavirenz discontinuation.

Second line anti-retroviral therapy failure in a pediatric cohort of an Ethiopian tertiary hospital: A retrospective observational study

Background: Sub-Saharan Africa carries the largest burden of pediatric HIV infection. The extent and factors affecting the success of second line anti-retroviral treatment in the region have not been well-studied. This study aimed to determine the rate and determinants of failure of second line anti-retroviral treatment among children and adolescents on follow-up at an Ethiopian tertiary teaching hospital. Methods and materials: A retrospective observational cohort study was conducted at Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia. Structured data abstraction forms were used to collect socio-demographic, clinical and diagnostic data. Descriptive statistics and bivariate analysis were used to describe the magnitude of the problem and its associations. Results: A total of 76 children and adolescents who were taking second line anti-retroviral treatment and had at least a single viral load determination while under care were analyzed. Their mean age was 16.1 years. Failure of second line anti-retroviral drugs was seen in 14 of the 76 while 4 of them fulfilled eligibility criteria for a switch to third line anti-retroviral treatment. The mean duration till virologic failure was 17.6 months. The mean CD4 and viral load upon requirement of a third line regimen was 612.2/mm3 and 82,131.3 copies/ml. Second line antiretroviral treatment virologic failure was significantly associated with the age of the child or adolescent. Conclusion: There was a high rate of virologic failure among children and adolescents under second line anti-retroviral drugs in our hospital. Our findings also highlight the need for provision of third line second line anti-retroviral drugs. Challenges for delivering a standard care were infrequent viral load testing and delayed initiation of second line treatment after confirming failure of first line regimens.

Early viral load monitoring predicts virological failure among HIV-infected individuals on anti-retroviral therapy - A single centre experience

Background: Global estimates for people living with Human immunodeficiency virus (HIV) at 2017 was between 31.1 to 43.9 million. In Malaysia, people living with HIV (PLHIV) was reported to be 75,040 and 41,430 (55.2%) are on Anti-Retroviral Therapy (ART). ART is an effective treatment in reduction of mortality and maintain quality of life in PLHIV. HIV viral load (VL) monitoring is recommended while on ART. The frequency of monitoring of VL is important and at the same time costly. In this study, we evaluate the predictive value of VL testing at one year of ART after initiation of first line ART to identify risks of future virological failure (VF). This would enable appropriate resource allocation depends on risk of VF. Methods and materials: This is a retrospective study analyse HIV-infected adult aged 18 years and ART naïve from 2007 to 2015. All cases were initiated on first-line ART and attended at least 1 clinical follow up and have 1 VL done at 12th month of treatment. Non-citizen and cases transferred care to other centres were excluded. Cases outcomes are categorized into favourable (i.e. remained on first line therapy at 5 year of follow up) and non-favourable (i.e. loss to follow-up (LFU), VF and death). Results: Overall 1525 cases had VL done at 12th month post ART. The majority (81.1%) were male, aged 17 to 77-year-old with median of 37.14-year-old. 71.3% had initial CD4 count below 250cells/uL. At 12th month post ART, 79.8% (n = 1217) had VL < 40 copies/mL, 11.3% (n = 172) had VL 40 to 500 copies/mL and 8.9% had VL more than 500 copies/mL. At 60th month, 76.7% (n = 1170) had favourable outcome and 23.3% (n = 355) had non-favourable outcome. Non-favourable outcomes include 186 (12.2%) VF, 109 (7.1%) LFU and 60 (3.9%) death. 12th month VL suppressed showed statistically significant in favourable outcome at 60 months follow up. Conclusion: Viral load measurement at 12th months post ART predicts future risk of virological failure. This would enable clinicians to use different monitoring strategies based on the viral load at 12th months, especially in resource limited settings.

Magnitude of first line antiretroviral therapy treatment failure and associated factors among adult patients on ART in South West Shoa, Central Ethiopia.

BackgroundFirst-line antiretroviral treatment failure has become a public health concern in high, low and middle-income countries with high mortality and morbidity In Ethiopia, around 710,000 peoples were living with HIV and 420,000 of them were receiving ART in 2017. Little is known about the magnitude of first-line ART treatment failure and its associated factors in Ethiopia, particularly in the study area. Therefore, this study was aimed to find the magnitude of first-line ART treatment failure and its associated factors among adult patients attending ART clinic at Southwest shoa zone public hospitals.MethodsInstitutions based cross-sectional study was employed from February 1 to April 2, 2019. An interviewer administered questionnaire was used to collect data from 350 adult patients on ART using a systematic random sampling technique. The collected data were coded and entered into Epidata version 3 and exported to STATA SE version 14 for analysis. Bivariable and multivariable logistic regression was done to identify factors associated with first-line ART treatment failure. At 95% confidence level strength of association was measured using Odds ratio. Variables with a p-value of ≤ 0.25 in the bivariable analysis were considered as a candidate variable for multivariable analysis. To get the final variables step-wise backward selection procedure was used and those in the final model were selected at a p-value <0.05. Finally, texts, simple frequency tables, and figures were used to present the findings.ResultsIn this study the magnitude of first-line ART treatment failure was 33.42%. Absence of baseline opportunistic infection AOR = 0.362 (95%CI0.178, 0.735), Staying on first-line ART for <5 years AOR = 0.47 (95%CI 0.252, 0.878), Nevirapine containing ART regimen AOR = 3.07 (95%CI 1.677, 5.63), Baseline CD4 count ≥100 cells/mm3 AOR = 0.299 (95%CI 0.152 0.591), absence of opportunistic infections after ART initiation AOR = 0.257 (95%CI 0.142, .467), time taking greater than an one-hour to reach health facility AOR 1.85 (95%CI 1.022 3.367) were significantly associated with first-line ART treatment failure.ConclusionThe magnitude of first-line ART treatment failure was high in the study area. Base-line opportunistic infection, duration on first-line ART, NVP based ART, Baseline CD4 count level, OI after ART initiation, and time it takes to reach health facility were independent determinants of first-line ART treatment failure.