Antiretroviral Treatment Failure Research Articles

HIV-1 pretreatment drug resistance negatively impacts outcomes of first-line antiretroviral treatment.

Pretreatment drug resistance (PDR) prevalence in sub-Saharan Africa is rising, but evidence of its impact on efavirenz (EFV)-based antiretroviral treatment (ART) is inconclusive. We determined the impact of PDR on outcomes of EFV-based ART in a subanalysis of a randomized clinical trial comparing different ART monitoring strategies implemented at a rural treatment facility in Limpopo, South Africa. Participants initiating EFV-based first-line ART (2015-2017) were enrolled and received 96 weeks follow-up. Resistance to nucleos(t)ide reverse transcriptase inhibitors (NRTIs) and non-NRTI's (NNRTIs) was retrospectively assessed by population-based sequencing. Virological failure was defined as a viral load of at least 1000 copies/ml after at least 24 weeks of ART. A total of 207 participants were included, 60.4% (125/207) of whom were female. Median age was 38.8 (interquartile range: 31.4-46.7) years. Median CD4+ cell count was 191 (interquartile range: 70-355) cells/μl. PDR was detected in 12.9% (25/194) of participants with available sequencing results; 19 had NNRTI-resistance, and six had NRTI- and NNRTI-resistance. 26.0% of participants (40/154) with sequencing results and virological follow-up developed virological failure. PDR was independently associated with failure (adjusted hazard ratio: 3.7 [95% confidence interval: 1.68.5], P = 0.002). At failure, 87.5% (7/8) of participants with PDR harboured dual-class resistant virus, versus 16.7% (4/24) of participants without PDR (P = 0.0007). Virological resuppression after failure on first-line ART occurred in 57.7% (15/26) of participants without PDR versus 14.3% (1/7) of participants with PDR (P = 0.09). PDR was detected in 13% of study participants. PDR significantly increased the risk of virological failure of EFV-based ART. Accumulation of resistance at failure and inability to achieve virological resuppression illustrates the profound impact of PDR on treatment outcomes.

Virological and Immunological Antiretroviral Treatment Failure and Predictors Among HIV Positive Adult and Adolescent Clients in Southeast Ethiopia.

BackgroundAntiretroviral therapy (ART) regimen failure is linked to an increased risk of disease progression and death, while early detection of ART failure can help to prevent the development of resistance. This study aimed to evaluate virological and immunological ART failure and predictors among HIV-positive adult and adolescent clients in southeast Ethiopia.MethodsA retrospective cohort study was implemented from January 2016 to November 30, 2020; all HIV-positive nave patients on follow-up during the study period from four hospitals were included. Virological and immunological treatment failure was the primary outcome of the study. Cox proportional hazards regression models were employed for analysis. Hazard ratios with 95% confidence intervals were reported and variables with p-values <0.05 were considered statistically significant predictors of treatment failure.ResultsA total of 641 HIV patients’ charts were reviewed, 62.6% of the study participants were females. Of the total study participants, 18.4% and 15% developed virological and immunological ART regimen treatment failure respectively. The median time to virological failure was 40 months. WHO stage IV [AHR = 4.616; 95% CI: (2.136–9.974)], WHO stage III [AHR = 2.323; 95% CI: (1.317–4.098)], poor adherence to HAART regimen [AHR = 3.097; 95% CI: (1.349–7.108)], and fair adherence [AHR = 2.058; 95% CI: (1.234–3.432)] were significantly associated with virological treatment failure among adolescent and adult study participants in southeast Ethiopia.ConclusionThe prevalence of virological treatment failure was 18.4% (95% CI: 15.4 −21.4) and the prevalence of immunological treatment failure was 15% (95% CI: 11.8–18.4). WHO clinical stage III/IV and non-adherence were independent predictors of virological ART treatment failure. Early management of clinical WHO stages and improving patients’ ART regimen adherence are important to decrease the prevalence of ART regimen treatment failure.

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.

Determinants of first-line antiretroviral treatment failure among adult patients on treatment in Mettu Karl Specialized Hospital, South West Ethiopia; a case control study.

Antiretroviral therapy has dramatically reduced Human Immunodeficiency Virus related morbidity and mortality. It has also transformed HIV infection into a manageable chronic condition. However, first-line antiretroviral treatment failure continues to grow especially in resource limited settings. Despite this, determinants of first-line antiretroviral treatment failure are not well studied in Ethiopia. To identify determinants of first-line antiretroviral treatment failure among adult patients on antiretroviral therapy in Mettu Karl Specialized Hospital, South West Ethiopia, in 2020. A hospital based case-control study was conducted from October to November 2020. Simple random sampling technique was used to select participants. Interviewer administered questionnaire and record review were used for data collection. Data were entered into epi data version 3.1 and exported to SPSS version 20 for analysis. Bivariable and multivariable logistic regression analysis were used. At the end, variables with P-value < 0.05 at 95% confidence intervals for adjusted odds ratio were considered statistically significant determinants of first line treatment failure. A total of 113 cases and 339 controls were included in the study with response rate of 98.6%. Sixty-four (56.6%) of cases and 183 (54.0%) of controls were females. Baseline WHO clinical stage III and IV (AOR = 1.909, 95% CI: (1.103, 3.305), baseline body mass index<18.5kg/m2(AOR = 2.208,95% CI:(1.257,3.877),baseline CD4 cell count <100cells/mm3 (AOR = 3.016, 95% CI: (1.734, 5.246), having history of TB co-infection (AOR = 1.855, 95% CI: (1.027, 3.353), having history of lost to follow up (AOR = 3.235, 95% CI: (1.096, 9.551), poor adherence to medication (AOR = 7.597, 95% CI: (4.059, 14.219) and initiation of treatment after two years of diagnosis with HIV (AOR = 4.979, 95% CI: (2.039, 12.158) were determinants of first-line antiretroviral treatment failure. In this study several variables were found to be determinants of first-line antiretroviral treatment failure. Concerned bodies should give more attention to early diagnosis of HIV, early enrollment in chronic HIV care and early initiation of ART before patients develop advanced WHO clinical stages. In addition, focus has to be given for patients with low CD4 count. Regular screening for TB, counseling on optimal adherence to medication and enhancing nutritional status of patients with low body mass index are also crucial to prevent first-line antiretroviral treatment failure.

Анализ частоты формирования мутаций резистентности ВИЧ, ассоциированных с устойчивостью к антиретровирусным препаратам

Актуальность. В Украине проводится широкомасштабная антиретровирусная терапия (АРТ) больных ВИЧ-инфекцией. Необходимо постоянное наблюдение за развитием устойчивости ВИЧ к антиретровирусным препаратам (АРВП). Цель: проанализировать влияние продолжительности АРТ, возраста и пола пациентов на частоту формирования мутаций резистентности (МР) ВИЧ к АРВП разных классов. Материал и методы. Исследовали образцы плазмы крови ВИЧ-инфицированных пациентов с вирусологической неэффективностью АРТ. Секвенирование генома ВИЧ проводили на тест-системах ViroSeqTM Genotyping System v.2.1 (Celera Diagnostics, США) согласно инструкции производителя. Результаты. Достоверно чаще (р ≤ 0,05) МР ВИЧ к АРВП выявлялись у ВИЧ-инфицированных мужчин (59,70 %), чем у женщин (40,3 %). Установлено, что в 59,9 % случаев вирусологическая неэффективность АРТ была обусловлена формированием МР ВИЧ хотя бы к одному из АРВП. Среди МР ВИЧ к ненуклеозидным ингибиторам обратной транскриптазы наиболее распространенными были G190S (75,8 %); K101E (72,7%); Y181C (68,1 %); K103N (38,8 %); среди МР к нуклеозидным ингибиторам обратной транскриптазы преобладали: M184V (69 %), K65R (61 %), D67N (20 %). МР ВИЧ к ингибитору протеазы встречались редко. Выводы. Показано, что продолжительность АРТ и возраст пациентов существенного влияния на устойчивость ВИЧ к АРВП не оказывали. Решающее значение имел генетический барьер АРВП: на фоне приема препаратов с низким генетическим барьером частота выявления МР ВИЧ составляла 5,3 %; прием препаратов с высоким генетическим барьером сопровождался формированием МР ВИЧ значительно реже — в 1,1 % случаев. Доказано, что биоповеденческие особенности пациентов-мужчин являются фактором, ассоциирующимся с повышенным риском формирования МР ВИЧ к АРВП.

Time to First-Line Antiretroviral Treatment Failure and Its Predictors among HIV-Positive Children in Shashemene Town Health Facilities, Oromia Region, Ethiopia, 2019.

With expanding pediatric antiretroviral therapy access, children will begin to experience treatment failure and require second-line therapy. In resource-limited settings, treatment failure is often diagnosed based on the clinical or immunological criteria which occur way after the occurrence of virological failure. Previous limited studies have evaluated immunological and clinical failure without considering virological failure in Ethiopia. The aim of this study was to investigate time to first-line antiretroviral treatment failure and its predictors in Shashamene town health facilities with a focus on virological criteria. Methods. A retrospective cohort study was conducted in three health facilities of Shashamene town, Oromia Regional State, from March 1 to 26, 2019. Children aged less than 15 years living with HIV/AIDS that were enrolled on ART between January 1, 2011, and December 30, 2015, in Shashamene town health facilities were the study population. Data were extracted using a checklist, entered into EpiData version 3.1, and exported to SPSS version 20 for data analysis. Cox proportional hazard regression was used to determine the predictors of time to first-line treatment failure. Result. The median survival time to virological failure was 30 months with IQR of 24.42 to 44.25. Baseline WHO stages 3 and 4 with AHR = 5.69 (95% CI: 2.07–15.66) and NVP-based NNRT at initial treatment with AHR = 2.72 (1.13–6.54) were the independent predictors of time to treatment failure. Conclusion. The median survival time of first-line antiretroviral treatment failure was moderate in the study area as compared to other studies. The incidence density of treatment failure in this study was low as compared to other studies. The finding also demonstrated that children treated with nevirapine-based nonnucleoside reverse transcriptase inhibitors at initial and advanced WHO clinical stages at baseline were at higher risk of treatment failure.

Prevalence of, and Factors Influencing First Line Antiretroviral Treatment Failure among Adult HIV Patients at Antiretroviral Treatment Clinic of Mettu Karl Referral Hospital, South Western, Ethiopia: A Prospective Cross Sectional Study, 2021

Antiretroviral treatment failure is defined as progression of disease and high risk of mortality after beginning of highly active anti-retroviral therapy. First-line ART failure has emerged as a growing concern. ART failure is a major challenge to HIV/AIDS management in resource-limited settings including Ethiopia where the diagnosis and management of ART failure is a key problem. Principal factors involving fist-line antiretroviral regimen failure include poor adherence to medication, younger age, lower baseline CD4+ count and higher baseline viral load.

Understanding the co-evolutionary molecular mechanisms of resistance in the HIV-1 Gag and protease

Due to high human immunodeficiency virus type 1 (HIV-1) subtype C infections coupled with increasing antiretroviral treatment failure, the elucidation of complex drug resistance mutational patterns arising through protein co-evolution is required. Despite the inclusion of potent protease inhibitors Lopinavir (LPV) and Darunavir (DRV) in second- and third-line therapies, many patients still fail treatment due to the accumulation of mutations in protease (PR) and recently, Gag. To understand the co-evolutionary molecular mechanisms of resistance in the HIV-1 PR and Gag, we performed 100 ns molecular dynamic simulations on multidrug resistant PR’s when bound to LPV, DRV or a mutated A431V NC|p1 Gag cleavage site (CS). Here we showed that distinct changes in PR’s active site, flap and elbow regions due to several PR resistance mutations (L10F, M46I, I54V, L76V, V82A) were found to alter LPV and DRV drug binding. However, binding was significantly exacerbated when the mutant PRs were bound to the NC|p1 Gag CS. Although A431V was shown to coordinate several residues in PR, the L76V PR mutation was found to have a significant role in substrate recognition. Consequently, a greater binding affinity was observed when the mutated substrate was bound to an L76V-inclusive PR mutant (Gbind: −62.46 ± 5.75 kcal/mol) than without (Gbind: −50.34 ± 6.28 kcal/mol). These data showed that the co-selection of resistance mutations in the enzyme and substrate can simultaneously constrict regions in PR’s active site whilst flexing the flaps to allow flexible movement of the substrate and multiple, complex mechanisms of resistance to occur. Communicated by Ramaswamy H. Sarma

Comparison of CBNAAT and conventional real time RT PCR for HIV 1 viral load testing

PurposeHIV viral load testing is now recommended for monitoring of anti-retroviral treatment failure in PLHIV. Xpert® HIV-1 Viral Load is a fully automated CB-NAAT. A reduced turnaround time leads to prompt clinical management. Hence the current study was undertaken to compare Xpert® HIV-1 Viral Load with the routinely used conventional real time RT PCR. MethodsThe study was conducted in the Department of Microbiology of a tertiary care medical college after ethics committee approval. 100 HIV positive samples were tested by both CB-NAAT and conventional real time RT PCR for HIV 1 viral load. Results were analyzed using Spearman's correlation co-efficient and Bland Altman plot for agreement. The number of samples with inter assay differences in viral loads exceeding 0.5 log copies/ml was also recorded. The sensitivity, specificity, PPV and NPV as well as the possible misclassification were calculated at the clinically significant value of 1000 copies/ml. Results25 samples in each of the four groups with log 10 value of <3, 3 to <4, 4 to <5 and ≥5 respectively were included. The log difference between the groups varied from 0 to 1.54. CB-NAAT has shown a statistically significant correlation with conventional real time RT PCR by Spearman's rank correlation (R = 0.972) (P < 0.01) and acceptable level of agreement with Bland Altman plot. The sensitivity, specificity, PPV, NPV and diagnostic accuracy was 80%, 100%, 100%, 93.75% and 95% respectively. The overall concordance was 95% with an upward misclassification of 6.25% and downward misclassification of 0%. ConclusionsPoint of care technology with sample in/answer out approach makes it an excellent choice especially in resource constrained and remote settings.

Antiretroviral therapy outcomes among adolescents and young adults in a Tertiary Hospital in Kenya

Background: Limited data is available on the treatment outcomes of HIV infected adolescents and young adults (AYA) in sub-Saharan Africa. HIV-infected adolescents and young adults (AYA) are at high risk of developing antiretroviral treatment failure.&#x0D; Objective: To determine the clinical, immunological and virologic outcomes of AYA at a tertiary hospital in Kenya.&#x0D; Methodology: A longitudinal study was conducted among AYA age 10-24 years attending Kenyatta National Hospital comprehensive care center. Clinical data was abstracted from electronic medical records for study participants with at least 6 months of follow-up using a structured data abstraction sheet.&#x0D; Results: A total of 250 AYA age 10 to 24 years were included. The median age was 16 years. The median CD4 cell count was 650.6 cells/mm3 (IQR 350.7-884.0). More than half (60.6%) of AYA had a CD4 cell count higher than 500 cells/mm3. Overall, 76.9% of AYA had achieved viral suppression (viral load &lt;1000 copies/ml). There was a significant increase in virologic failure with higher age and late adolescents and young adults were more likely to have a viral load &gt; 1000 copies/ ml p&lt;0.012.&#x0D; Conclusion: The overall virologic suppression in this cohort of AYA was sub-optimal. Both immunological and virologic outcomes were worse among late adolescents (18-19 years) and young adults (20-24 years).&#x0D; Keywords: Adolescents; HIV; Kenya; virologic suppression; young adults.

Determinants of switch to paediatric second-line antiretroviral therapy after first-line failure in Cameroon.

With scale-up of antiretroviral therapy (ART) children, treatment failure and switch to subsequent ART regimens are common. Our objectives were to evaluate switching practices and identify factors associated among children and adolescents failing their first-line ART. A facility-based survey study was conducted in a cohort of children living with HIV experiencing virological failure (VF) at the Essos Hospital Centre of Yaounde, Cameroon. Data were collected using a standard questionnaire, and key variables were as follows: (a) VF defined as viral load (VL)>1000 copies/ml, (b) rate of switch to second-line and (c) reason(s) for switching ART. Odds ratio (OR) with 95% confidence interval (CI) was used to assess the association between study variables, and P<0.05 was considered statistically significant. A total of 106 children experiencing VF were enrolled: median age was 8 [interquartile range (IQR): 3-15] years; 60.38% were boys and 39.62% were orphans of one/both parents. A proportion of 69% were at the WHO clinical stage III/IV, and 13.21% were experiencing immunological failure (CD4<200 cells/mm3 ). The median duration on first-line ART was 36 [IQR: 7-157] months prior to detecting VF, and the rate of switch to second-line ART was 70.75% (75/106). Delay in switching ART after a confirmed VF was 11 [IQR: 7-16] months. After switch to second-line ART, the median time to achieve undetectable VL (<40copies/ml) was 14 [IQR: 9-21] months. Multivariate analysis revealed that only children with viral rebound (aOR=0.09; 95% CI=0.03-0.24) were less likely to be switched. Of note, being orphaned (aOR=0.35, CI=0.11-1.11), biological sex (aOR=1.77, CI=0.60-5.29) and immune status (aOR=0.19, CI=0.03-1.31, 0.09) had no significant effect on switching to second-line ART. In this paediatric population experiencing VF after about 3-4years from ART initiation, the majority are switched to second-line ART after a delay of almost one year. Delayed switch to second-line was driven essentially by viral rebound, underscoring the need for close viral monitoring.

Antiretroviral therapy outcomes among adolescents and young adults in a Tertiary hospital in Kenya.

Limited data is available on the treatment outcomes of HIV infected adolescents and young adults (AYA) in sub-Saharan Africa. HIV-infected adolescents and young adults (AYA) are at high risk of developing antiretroviral treatment failure. To determine the clinical, immunological and virologic outcomes of AYA at a tertiary hospital in Kenya. A longitudinal study was conducted among AYA age 10-24 years attending Kenyatta National Hospital comprehensive care center. Clinical data was abstracted from electronic medical records for study participants with at least 6 months of follow-up using a structured data abstraction sheet. A total of 250 AYA age 10 to 24 years were included. The median age was 16 years. The median CD4 cell count was 650.6 cells/mm3 (IQR 350.7-884.0). More than half (60.6%) of AYA had a CD4 cell count higher than 500 cells/mm3. Overall, 76.9% of AYA had achieved viral suppression (viral load <1000 copies/ml). There was a significant increase in virologic failure with higher age and late adolescents and young adults were more likely to have a viral load > 1000 copies/ml p<0.012. The overall virologic suppression in this cohort of AYA was sub-optimal. Both immunological and virologic outcomes were worse among late adolescents (18-19 years) and young adults (20-24 years).

Is there a role for doravirine in African HIV treatment programmes? A large observational resistance study in South Africa.

IntroductionDolutegravir has replaced efavirenz in most low‐ and middle‐income countries, due to better tolerability and formidable resistance profile, but dolutegravir side effects suggest alternatives are needed. We evaluated doravirine resistance in South Africa as a first step to assess whether doravirine may replace dolutegravir.MethodsA retrospective dataset was analysed for predicted doravirine susceptibility, including sequences obtained from three patient groups. First, data from 277 patients initiating antiretroviral treatment (ART) were collected between February 2013 and October 2014 as part of a national survey. Second, data from 788 patients experiencing NNRTI‐based ART failure were obtained between February 2013 and October 2014 as part of a national survey. Third, data derived from 584 patients who had genotypic drug resistance testing requested after NNRT‐based failure as part of individual patient management between January 2016 and December 2019. Pol sequences were generated using validated population‐based in‐house genotyping and submitted to Stanford HIVdb v8.9.Results and discussionLess than 5% of patients initiating ART presented with genotypic doravirine resistance, whereas most patients experiencing NNRTI‐based ART failure presented with predicted intermediate (41.0%) or high‐level resistance (43.8%) to doravirine. High‐level resistance to doravirine was commonly predicted by the presence of at least three DRMs (79.7%). The predicted resistance profile to doravirine in ART‐naïve patients is promising, but less so in those experiencing failure to first‐generation NNRTIs. Accumulation of NNRTI DRMs seems to be an important factor in the poor resistance prediction for doravirine.ConclusionsAlthough doravirine is approved as initial therapy in patients who are ART‐naïve, it is currently recommended to obtain a genotype prior to the initiation of ART. Clinical studies are needed to ascertain whether predicted resistance profiles in ART naïve and NNRTI‐treated patients translate into poor clinical outcomes, especially in settings where genotypic resistance testing is not available.

Correlates of missed HIV appointments in low-resource settings: a study from Uganda

Aims: Alarming reports of antiretroviral treatment failure have recently emerged in sub-Saharan Africa. The onset of virologic failure has multiple causes but suboptimal treatment adherence is one of the leading causes. This study aimed to explore correlates of adherence to HIV appointments in community care patients living with HIV/AIDS in Uganda. Methods: Two hundred and ninety-five people living with HIV (median age 37.0 years; interquartile range 16.0; female 67.8% [n = 200]) reported whether they had missed any of their four-weekly appointments during the past 24 weeks. They also completed the Internalized AIDS-Related Stigma Scale, Generalized Anxiety Disorder-7, the Patient Health Questionnaire-9, the Alcohol-Use Disorders Identification Test, and the Physical Activity Vital Sign. Results: Thirty-three (11.2%) patients missed at least one of their six scheduled appointments in the 24-week period. The adjusted odds ratio for missing at least one of six appointments was 3.03 (95% CI: 1.21–8.43, p = 0.01) for those who were physically inactive, and 2.29 (95% CI: 0.93–5.63, p = 0.046) for those with depression. Conclusions: Targeting future rehabilitation studies for PLHIV around feelings of depression and around physical inactivity could be important in achieving optimal HIV treatment adherence.

First line antiretroviral treatment failure and associated factors among people living with HIV in northwest Ethiopia.

Anti-retroviral treatment enhances the immune status and reduces unwanted outcomes. However, development of treatment failure and drug resistance raises concern over lifelong treatments to chronic diseases such as HIV/AIDS. This study determined proportion of treatment failure (TF) and identified factors associated with TF among people living with human immunodeficiency virus (HIV) in Bahir Dar, Northwest Ethiopia. Facility based cross sectional study was carried out from November, 2017 to April, 2018. Sociodemographic and clinical data were collected using structured questioner. Blood sample was collected and analyzed for viral load, complete blood count (CBC), liver and kidney function test and CD4 count. A patient is declared as treatment failure when viral load value is higher than 1000 RNA copies/ml in two consecutive viral load analyses within three months interval. Data were entered and analyzed using SPSS version 23. To identify factors associated with TF, logistic regressions model was employed. A total of 430 people who had six months and above antiretroviral treatment (ART) follow up were enrolled in the study. Of these, 57.9% were females & the mean age was 38 years. The mean month of ART follow up was 83 months. In the first viral load analysis, 106 (24.7%) of the cohort were virologically failed. These failed people were followed for 3 months with intensive adherence support; then second viral load analysis showed a viralogical failure among 65 people of the second cohort. Thus, the overall viralogical failure or TF was 15.1%. The re-suppression rates were 41(38.7%). Male gender, people with history of drug discontinuation, poor adherence, irregular time of drug intake, multiple sexual practice showed significant association with TF. Moreover, base line and current CD4 counts of <200 cells/ml also demonstrated significant association with TF. Significant proportion of treatment failure was reported in the present study. Moreover, behavioral factors such as drug discontinuation, poor adherence, multiple sexual partner were associated with treatment failure. Hence, to avoid TF, regular patient counseling and monitoring should be in place. To identify the predictors for treatment failure, further follow-up study is desirable.

Antiretroviral Treatment Failure and Associated Factors Among HIV-Infected Children on Antiretroviral Therapy: A Retrospective Study.

BackgroundHIV/AIDS-associated morbidity and mortality have reduced since the introduction of antiretroviral therapy (ART). Treatment failure is one of the causes of mortality, morbidity, and the development of drug-resistant viral strains. Therefore, this research aims to assess the prevalence and associated factors of treatment failure among children with HIV/AIDS on antiretroviral therapy attending the University of Gondar Specialized Referral Hospital, Northwest Ethiopia.MethodsA retrospective study was conducted on 200 children registered for ART from 2005 to 2017. Data regarding patients’ socio-demographic, baseline clinical characteristics, and treatment-related information were collected through a review of their medical records. Data were entered into Epi-info version 3.5.3 and analyzed using statistical package for social sciences (SPSS) version 21 software. To summarize characteristics of the study participant’s descriptive statistics were done. Bivariable and multivariable binary logistic regression were fitted to identify factors associated with treatment failure. The odds ratio and 95% confidence interval (CI) were calculated to assess the strength of the association and P-value<0.05 in the multivariable regression was considered as statistically significant.ResultsThe prevalence of ART failure was 12.5% (95% CI: 7.88, 17.12), clinical failure was the most common followed by immunologic failure with only a small proportion having both clinical and immunologic failure. The mean time to develop treatment failure after initiation of the first-line regimen was 22.28 ± 24.00 months. Being male (AOR= 3.15; 95% CI: 1.18–8.39), co-infected with tuberculosis (TB) at baseline (AOR= 2.37; 95% CI: 1.23–8.84), being on ART for a long period (>36 months) (AOR= 1.01; 95% CI: 1.34–2.89), and regimen change (AOR=9.22; 95% CI: 3.36–25.03) were factors of ART failure.ConclusionIn this study, there is significant treatment failure among HIV-infected children. Having co-infection, being on ART for a long period, regimen change, and being male were found to be independent factors of treatment failure in children. Therefore, timely identification and monitoring of ART failure should be necessary to enhance the benefit and to prevent further complications. Prophylaxis for opportunistic infections such as co-trimoxazole preventive therapy should continue to recover the immunological status of the child.

Uptake of antiretroviral treatment and viral suppression among men who have sex with men and transgender women in sub-Saharan Africa in an observational cohort study: HPTN 075

ObjectivesHPTN 075 enrolled men who have sex with men (MSM) and transgender women (TGW) in sub-Saharan Africa. Persons in HIV care or on antiretroviral treatment (ART) were not eligible to enroll. We evaluated antiretroviral (ARV) drug use, viral suppression, and drug resistance in this cohort over a 12-month follow-up period. MethodsAssessments included 64 participants with HIV (39 MSM, 24 TGW, and one gender not specified). ARV drugs were detected using a qualitative assay. Viral load (VL) and drug resistance testing were performed using commercial assays. ResultsOver 12 months, the proportion of participants using ARV drugs increased from 28.1% to 59.4% and the proportion with VLs <400 copies/mL increased from 21.9% to 57.8%. The rate of ART failure (detection of drugs without viral suppression) was similar at screening and 12 months (12.0% and 11.1%, respectively) and was similar among MSM and TGW. Two participants developed HIV drug resistance during follow-up. ConclusionsOver 12 months, ARV drug use in the cohort more than doubled and viral suppression increased nearly threefold without a significant increase in ART failure or drug resistance. These results suggest that ART can be successfully scaled up for HIV prevention and treatment in this high-risk population.

Performance of a True Point-of-Care Assay for HIV-1/2 Viral Load Measurement at Antenatal and Postpartum Services.

Timely viral load (VL) results during pregnancy and the postpartum period are crucial for HIV disease management and for preventing mother-to-child transmission. Point-of-care (POC) VL testing could reduce turnaround times and streamline patient management. We evaluated the diagnostic performance of the novel m-PIMA HIV-1/2 VL assay (Abbott, Chicago, IL) in Mozambique. The study was conducted in prenatal and postpartum consultation rooms in 2 primary health care clinics. Sample collection and testing on m-PIMA were performed by trained nurses. HIV-infected pregnant and postpartum women on antiretroviral treatment (ART) or ART naive were tested using both on-site m-PIMA POC and referral laboratory-based real-time VL assays. Linear regression analysis and Bland-Altman plots were used to calculate the agreement between both. Correlation between venous blood plasma POC and plasma laboratory-based VL was strong (r2 = 0.850, P < 0.01), with good agreement between the methods [overall bias 0.202 log copies/mL (95% CI: 0.366 to 0.772 log copies/mL)]. Using the threshold of 1000 copies/mL, which is used to determine ART failure, the sensitivity and specificity of the POC VL assay were 95.0% (95% CI: 91.6% to 97.3%) and 96.5% (95% CI: 94.2% to 98.0%), respectively. The correlation coefficient between the venous and capillary sample types was 0.983 (r2 = 0.966). On-site, nurse-performed POC VL testing is feasible and accurate in resource-limited primary health care settings. The operational challenge of plasma separation within clinics for POC testing was successfully overcome using minicentrifuges. The use of capillary blood could simplify the execution of the assay in a clinical environment.

Determinants of first-line antiretroviral treatment failure among adult HIV patients at Nekemte Specialized Hospital, Western Ethiopia: Unmatched case-control study.

Objective:In Ethiopia, only a few studies were conducted to determine factors contributing to antiretroviral treatment failure, in general, and there are no published data in the study area, in particular. Thus, the aim of the study was to assess the determinants of first-line treatment failure among adult HIV patients on antiretroviral treatment at Nekemte Specialized Hospital, western Ethiopia.Methods:The hospital-based 1:2 unmatched case–control study was conducted in Nekemte Specialized Hospital from 1 August to 30 September, 2019, on 252 HIV-positive patients receiving antiretroviral treatment (86 cases and 166 controls). Cases were selected from patients who were switched to second-line antiretroviral treatment regimen after first-line antiretroviral treatment failure. Controls were from those who are on the first-line antiretroviral regimens for at least 6 months. Data were collected by two trained clinical nurses. Record review and an interviewer-administered questionnaire were used to collect data. Data were entered into Epi-Data, version 7.2.2, and then exported to SPSS, version 25, for analysis. The association between treatment failure and each covariate was assessed by bivariate analysis to identify candidate variables at p value < 0.25. All candidate variables were entered into multivariate analysis done in stepwise backward likelihood ratio to declare statistical significance association at p value < 0.05, 95% confidence interval.Results:Data from a total of 252 (86 cases and 166 controls) patients were extracted at a response rate of 98.4%. Statistically higher odds of first-line treatment failure were observed among those who started treatment at an advanced stage (Baseline World Health Organization stage 3 o r4 (adjusted odds ratio = 3.12, 95% confidence interval: 1.55–6.26), lower Baseline CD4 count < 100 cells (adjusted odds ratio = 3.06, 95 % confidence interval: 1.45–6.50), lack of participation in a support group (adjusted odds ratio = 4.03, 95% confidence interval: 1.98–8.21), history of antiretroviral treatment discontinuation for greater than 1 month (adjusted odds ratio = 2.36, 95% confidence interval: 1.17–4.78) and poor adherence to antiretroviral treatment (adjusted odds ratio = 3.09, 95% confidence interval: 1.54–6.19).Conclusion:Antiretroviral treatment initiation at an advanced stage, lower CD4 count, no participation in a support group, and poor adherence were determinants of treatment first-line antiretroviral treatment failure. Therefore, health care providers and program developers should give special attention to; early diagnosis and start of treatment, encouraging patients to participate in a support group, trace patients early, and attentively follow patients to improve their adherence to antiretroviral treatment.

Time to First-Line Antiretroviral Treatment Failure and its Predictors for Seropositive Children Treated in Public Hospitals, North West Ethiopia 2021

The magnitudes of Anti-Retroviral Treatment (ART) failure for adult people living with HIV (PLWH) were exhaustively studied; however, time to treatment failure among seropositive children was overlooked, and this study aimed to assess time to first-Line Antiretroviral treatment Failure for seropositive children. Methods: Facility-based retrospective follow-up study was conducted since 1 January 2016-30 December 2020. EPI- DATA version 3.2 and STATA/14 software were used for data entry and analysis, respectively. Proportional hazard assumption was checked for each variable and no variable was found with Schoenfeld residual test <0.05. Categorical variables at bi-variables Cox regression were assessed for candidates transferred at P-value <0.25 for multivariable Cox regression to claiming predictors associated for TB incidence rate at 95% CI at P<0.005. Results: A total of 710 recorded of ART files were reviewed with 96 children (13.5%) (95% CI: 11.2, 16.3) had developed treatment failures. The overall incidence rate of treatment failure was found 4.098 (95% CI: 3.35 to 5.02) per 1000 Person Month. Children being orphaned (AHR: 4.3, 95% CI: 2.17, 7.7), WHO stage III and IV (AHR: 3.5, 95% CI: 1.8, 7.4), Poor ART adherence 3.27 (AHR:3.27, 95% CI:1.54, 4.8), ART follow-up duration ≥ 72 months (AHR: 2.28, 95% CI: 1.2, 5.2), Missed CPT 6.7 (AHR-6.7; 95% CI: 3.6, 8.4), AZT-3TC-NVP 6.5 (AHR=6.5; 95% CI: 3.2, 18.2), AZT-3TC-EFV 2.9 (AHR=2.89, 95% CI: 2.89, 10.1) were associated with treatment failures. Conclusion: Sixty-two percent of treatment failures were occurred after 72 months of ART follow up with a higher incidence of treatment failures, which is unacceptable as compared with slandered reference <10%. Being a seropositive child ≥ 70 month on ART, WHO stage III and IV, ART regiment (AZT-3TC-NVP and AZT-3TC-EFV), Poor ART adherence, missing CPT, and orphanages were associated with treatment failure.