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.

Persistent SARS-CoV-2 infection and intra-host evolution in association with advanced HIV infection

While most people effectively clear SARS-CoV-2, there are several reports of prolonged infection in immunosuppressed individuals. Here we present a case of prolonged infection of greater than 6 months with the shedding of high titter SARS-CoV-2 in an individual with advanced HIV and antiretroviral treatment failure. Through whole-genome sequencing at multiple time points, we demonstrate the early emergence of the E484K substitution associated with escape from neutralizing antibodies, followed by other escape mutations and the N501Y substitution found in most variants of concern. This provides support to the hypothesis of intra-host evolution as one mechanism for the emergence of SARS-CoV-2 variants with immune evasion properties.

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.

Factors associated with antiretroviral treatment failure among people living with HIV on antiretroviral therapy in resource-poor settings: a systematic review and metaanalysis

Background Despite the increase in the number of people accessing antiretroviral therapy (ART), there is limited data regarding treatment failure and its related factors among HIV-positive individuals enrolled in HIV care in resource-poor settings. This review aimed to identify factors associated with antiretroviral treatment failure among individuals living with HIV on ART in resource-poor settings. Methods We conducted a comprehensive search on MEDLINE (PubMed), Excerpta Medica Database (EMBASE), Cochrane Central Register of Controlled Trials (CENTRAL), World Health Organization’s (WHO’s) library database, and Latin American and Caribbean Health Sciences Literature (LILACS). We included observational studies (cohort, case-control, and cross-sectional studies) where adolescents and adults living with HIV were on antiretroviral treatment regardless of the ART regimen. The primary outcomes of interest were immunological, virological, and clinical failure. Some of the secondary outcomes were mm3 opportunistic infections, WHO clinical stage, and socio-demographic factors. We screened titles, abstracts, and the full texts of relevant articles in duplicate. Disagreements were resolved by consensus. We analyzed the data by doing a meta-analysis to pool the results for each outcome of interest. Results Antiretroviral failure was nearly 6 times higher among patients who had poor adherence to treatment as compared to patients with a good treatment adherence (OR = 5.90, 95% CI 3.50, 9.94, moderate strength of evidence). The likelihood of the treatment failure was almost 5 times higher among patients with CD4 < 200 cells/mm3 compared to those with CD4 ≥ 200 CD4 cells/mm3 (OR = 4.82, 95% CI 2.44, 9.52, low strength of evidence). This result shows that poor adherence and CD4 count below < 200 cells/mm3 are significantly associated with treatment failure among HIV-positive patients on ART in a resource-limited setting. Conclusion This review highlights that low CD4 counts and poor adherence to ART were associated to ART treatment failure. There is a need for healthcare workers and HIV program implementers to focus on patients who have these characteristics in order to prevent ART treatment failure. Systematic review registration The systematic review protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO), registration number: 2019 CRD42019136538.

Detection of Antiretroviral treatment failure among adult HIV-1 patients on anti-retroviral therapy for 12 +/- 3 months attending different Voluntary Counseling Testing and treatment centers in Khartoum state, Sudan

Objective: Small number of people on antiretroviral therapy and their virological status in Sudan is lacking. This study aimed to determine the viral load for adult HIV-1 patients who were on antiretroviral therapy for 12+/- 3 months attending different Voluntary Counseling Testing and treatment centers (VCT/ART) in Khartoum state, Sudan.Results: out of 112 adult HIV-1 patients included in this study, only 17.9% (20/112) showed unsuppressed viral load (treatment failure). The majority of them from Omdurman VCT/ART center 80% (16/20), followed by Khartoum VCT/ART center 15% (3/20), Bahri VCT/ART center 5% (1/20) and non from Elban Gadeid VCT/ART center. All of them were on the first line of treatment. Most of them 30% (6/20) on 39-48 years old age group, the majority of them 55%(11/20) on stage 3 WHO clinical staging.