Opportunistic infections among schoolchildren who were on antiretroviral therapy in Ethiopia: a systematic review and meta-analysis.

BackgroundDespite significant efforts to enhance access to antiretroviral therapy (ART), opportunistic infections among children on ART remain a major concern in low-income countries, including Ethiopia. Currently, there are no pooled estimates of opportunistic infections incidence among children on ART in Ethiopia. Consequently, this review aimed to determine the pooled incidence and identify the predictors of opportunistic infections among children under 15 years of age on ART, addressing the existing information gap.MethodsThis systematic review followed the PRISMA guidelines, and relevant studies were obtained from the PubMed, CINAHL, Scopus, EMBASE, and Google Scholar databases. Data analysis for pooled estimates of incidence and predictors of opportunistic infections was conducted via STATA 17 software with random-effects model. Heterogeneity was evaluated via Cochrane's Q-test and the I2 statistic, and publication bias was assessed through funnel plots and Egger's test.ResultsOf the 5,631 studies identified, 20 studies involving 9,196 participants were included in the meta-analysis. The pooled incidence of opportunistic infections among children under 15 years of age on antiretroviral therapy was 5.61 per 100 person-years (95% CI: 4.37–6.86), based on 36,716.4 person-years of observation. Predictors of opportunistic infections included advanced WHO clinical stage (HR 1.45, 95% CI: 1.35–1.55), poor ART adherence (HR 1.49, 95% CI: 1.35–1.63), lack of isoniazid (HR 1.56, 95% CI: 1.40–1.74) and cotrimoxazole preventive therapy (HR 1.56, 95% CI: 1.38–1.66), malnutrition (HR 1.50, 95% CI: 1.34–1.67), and severe immunosuppression (HR 1.39, 95% CI: 1.27–1.51).ConclusionThe incidence of opportunistic infections in this review was high, highlighting the need for intensified efforts to achieve the 2030 target. Moreover, advanced WHO clinical stage, poor adherence, lack of isoniazid and cotrimoxazole preventive therapy, malnutrition, and severe immunosuppression were identified as predictors of opportunistic infections. This suggests that early initiation of ART, regular nutritional assessments, intensive follow-up and monitoring, and a multidisciplinary approach need be prioritized to address the identified predictors.

To evaluate the relation between CD4 and HIV RNA levels at the onset of specific opportunistic infections (OIs) in HIV-infected patients. The OIs occurring between June 1996 and December 1998 were retrospectively reviewed, considering only the episodes of major and minor OIs in patients with simultaneously available CD4 and plasma HIV RNA determinations before clinical onset who had been untreated or on stable antiretroviral therapy (ART) for at least 2 months. Two hundred seventy-four episodes of different OIs were considered in 216 patients; the median CD4 count was 35 cells/mm3 (range: 0-1154 cells/mm(3)), and the median HIV RNA count was 5.1 log cp/mL (range: < 1.9-6.7 log copies/ml). The different HIV RNA levels were significantly associated with different OIs regardless of CD4 and ART (p < .0001), even when only those occurring in patients with a CD4 count of < or = 50 cells/mm(3) were considered (p = .0049). Kaposi sarcoma, esophageal candidiasis, oropharyngeal candidiasis, and Mycobacterium avium complex disease were associated with significantly above-average median HIV RNA levels, and varicella-zoster virus infection was associated with below-average levels. Different OIs are associated at their onset with significantly different HIV RNA levels, regardless of CD4 cell counts and ART.

Factors associated with anti-retroviral therapy (ART) adherence among adult people living with HIV (PLWH): A 5-year retrospective multi-centre study in Kumasi, Ghana.

BackgroundAs the use of antiretroviral therapy (ART) increases, the issue of treatment failure is still a global challenge, particularly in a resource limited settings including Ethiopia. The results of former studies in Ethiopia were highly variable and inconsistent across studies. Thus, this systematic review and meta-analysis intended to provide the pooled estimation of treatment failure and associated factors among children on antiretroviral therapy.MethodsWe searched international databases (i.e., PubMed, Google Scholar, Web of Science, Ethiopian Universities’ online repository library, Scopus, and the Cochrane Library) during the period of February 30 to April 7, 2021. All identified observational studies reporting the proportion of treatment failure among HIV positive children in Ethiopia were included. Heterogeneity of the studies was checked using I2 test and Cochrane Q test statistics. We run Begg’s regression test to assess publication bias. A random-effects meta-analysis model was performed to estimate the pooled prevalence of treatment failure.ResultsThe estimated pooled prevalence of treatment failure among children in Ethiopia was 12.34 (95%CI: 8.59, 16.10). Subgroup analysis of this review showed that the highest prevalence was observed in Addis Ababa (15.92%), followed by Oromia region (14.47%). Poor ART adherence (AOR = 2.53, CI: 2.03, 4.97), advanced WHO clinical staging (AOR = 1.66, CI: 1.24, 3.21), and opportunistic infections (AOR = 2.64 CI: 2.19, 4.31 were found to be significantly associated factors with childhood treatment failure.ConclusionsThis study revealed that treatment failure among children on ART was high in Ethiopia. Poor ART adherence, advanced WHO clinical staging, opportunistic infections, and low level of CD4 cell counts increased the risk of treatment failure.

As the use of antiretroviral therapy (ART) increases, the issue of treatment failure is still a global challenge, particularly in a resource limited settings including Ethiopia. The results of former studies in Ethiopia were highly variable and inconsistent across studies. Thus, this systematic review and meta-analysis intended to provide the pooled estimation of treatment failure and associated factors among children on antiretroviral therapy. We searched international databases (i.e., PubMed, Google Scholar, Web of Science, Ethiopian Universities' online repository library, Scopus, and the Cochrane Library) during the period of February 30 to April 7, 2021. All identified observational studies reporting the proportion of treatment failure among HIV positive children in Ethiopia were included. Heterogeneity of the studies was checked using I2 test and Cochrane Q test statistics. We run Begg's regression test to assess publication bias. A random-effects meta-analysis model was performed to estimate the pooled prevalence of treatment failure. The estimated pooled prevalence of treatment failure among children in Ethiopia was 12.34 (95%CI: 8.59, 16.10). Subgroup analysis of this review showed that the highest prevalence was observed in Addis Ababa (15.92%), followed by Oromia region (14.47%). Poor ART adherence (AOR = 2.53, CI: 2.03, 4.97), advanced WHO clinical staging (AOR = 1.66, CI: 1.24, 3.21), and opportunistic infections (AOR = 2.64 CI: 2.19, 4.31 were found to be significantly associated factors with childhood treatment failure. This study revealed that treatment failure among children on ART was high in Ethiopia. Poor ART adherence, advanced WHO clinical staging, opportunistic infections, and low level of CD4 cell counts increased the risk of treatment failure.

6539 Background: Dendritic cells are key antigen presenting cells which coordinate immune responses against infections. We investigated the correlation between DC reconstitution after HSCT and the onset of OI. Methods: We prospectively studied immune reconstitution of DC in 124 patients with predominantly high-risk hematopoetic malignancies. Peripheral blood underwent flow cytometry analysis for DC, defined as lineage negative, HLA-DR+, CD11c+ and CD123+. Cluster analysis demonstrated patients at engraftment with high DC (&gt;6.92/mm3) (n =68), low DC (n=56), and at 60 days with high DC (&gt;3.95/mm3) (n=48), and low DC (n=43). Primary study endpoint was onset of OI, defined as viral and invasive fungal (proven and probable) OI within 6 months of HSCT. A cox proportional hazard multivariate model was adjusted for important covariates, including age, transplant conditioning (myeloablative vs. non-myeloablative), graft source (peripheral blood vs. bone marrow), donor-type (HLA-matched related vs. unrelated), and ANC. Results: Patients with low DC at engraftment had significantly increased onset of acute grade II-IV GVHD by Kaplan-Meier analysis (p=0.004). Patients with onset of GVHD prior to day 60 were less likely to have high DC (32% with GVHD, 72% without GVHD) (p=0.001). Furthermore, low DC at 60 days was adversely associated with: time to viral OI (p=0.04), time to composite of viral OI and death (p=0.02), time to viral or fungal OI (p=0.009), and time to composite of viral or fungal OI and death (p=0.02). In the Cox model, low DC at 60 days, was associated with a 3.7 relative risk (RR) (1.2, 11.8) for onset of OI. Patients with onset of OI prior to day 60 were significantly less likely to have high DC (41% with OI, 61% without OI) (p=0.05). Conclusions: This study emphasizes the clinical importance of measuring DC after transplant. Patients with low DC reconstitution are at an increased risk of OI and death. Measuring DC, and further understanding of the likely complex factors involved in DC reconstitution, may provide rationale towards future therapeutic immune interventions. No significant financial relationships to disclose.

BackgroundPeople living with HIV/AIDS (PLWHA) are frequently confronted with severe social issues such as rejection, abandonment, criticism, and stigma. This would negatively affect their quality of life. Several studies have been conducted so far to assess factors affecting the health-related quality of life among people living with HIV/AIDS who are on antiretroviral therapy (ART) in Ethiopia. However, to our knowledge, there is no previous study that has summarized the results of the studies that investigated health-related quality of life (HRQOL) among PLWHA in Ethiopia. Therefore, the purpose of this review was to estimate the pooled prevalence of HRQOL and its association with social support among people living with HIV/AIDS (PLWHA) on ART in Ethiopia.MethodsA systematic search was carried out using several electronic databases (PubMed, Science Direct, Web of Science, and Cochrane electronic), Google Scholar, Google, and a manual search of the literature on health-related quality of life among people living with HIV/AIDS who are on ART. A Microsoft Excel data extraction sheet was used to extract pertinent data from an individual study. To assess the heterogeneity of primary articles, the Cochrane Q test statistics and the I2 test were carried out, and a random effects meta-analysis was used to estimate the pooled prevalence of HRQOL.ResultOut of the 493 articles reviewed, ten with a total of 3257 study participants were eligible for meta-analysis. The pooled prevalence of HRQOL among people living with HIV/AIDS who are on antiretroviral therapy in Ethiopia was 45.27%. We found that strong perceived social support was significantly associated with higher levels of subjectively perceived HRQOL. PLWHA who were on ART and had good social support were four times more likely to report higher HRQOL when compared to their counterparts [AOR = 4.01, 95% CI 3.07–5.23].ConclusionA substantial number of PLWHA had poor HRQOL in Ethiopia. Social support was significantly associated with HRQOL among people living with HIV/AIDS. Hence, it’s recommended to encourage suitable intervention at every follow-up visit, and psycho-social support is also warranted to improve the quality of life.

IntroductionThe emergence of First-line Antiretroviral Therapy (ART) regimens fails; it necessitates the use of more costly and less tolerable second-line medications. Therefore, it is crucial to identify and address factors that increase the likelihood of first-line ART regimen failure in children. Although numerous primary studies have examined the incidence of first-line ART failure among HIV-infected children in Ethiopia, national-level data on the onset and predictors remain inconsistent. Hence, this study was conducted to fill the gaps in determining the onset of first-line ART failure and its predictors among HIV-infected children in Ethiopia.MethodsArticles related to our topic of interest were searched using a systematic approach in national and international electronic databases. The retrospective follow-up cohort studies published in English up to 2022 were included. The data were extracted using a Microsoft Excel spread sheet and exported into Stata™ Version 17.0 for further management and analysis. The level of heterogeneity was quantified using I2 test together with a 95% confidence interval (CI). The incidence of the primary estimates was estimated using a random effects model in the Dersimonian-Lairedmethod. Subgroup analysis, Meta regression, and sensitivity analysis were computed to identify the source of heterogeneity but not explained. The predictors of first-line ART failure were explained using relative risk (RR) with 95% confidence interval (CI).ResultsTen studies having a total of 5446 children were included. The pooled onset of first-line ART failure was 3.18 (95% CI: 1.91, 4.44) per 100 child-years of observations. Those study participants who began ART at an advanced WHO clinical stage at ART initiation had a 3.05 (95% CI: 1.47, 6.36), having poor ART adherence had a 2.19 (95% CI: 1.29, 3.70), and having TB-HIV coinfection at ART initiation had a 1.43 (95% CI: 1.06, 1.94) times higher chance of experiencing first-line ART failure than their corresponding counterparts.ConclusionThe onset of first-line ART failure was high to achieve the 2030 UNAIDS target of ending the AIDS epidemic. Advanced WHO clinical stage, poor first-line ART adherence, and having TB-HIV coinfection were identified predictors. Hence, community HIV screening should continue to strengthen early ART initiation, and the attention of ART adherence should be kept to achieve ending the AIDS epidemic. The baseline tests and diagnosis, like TB diagnosis should be maintained for HIV-infected children while they begin ART.

Although good adherence to antiretroviral therapy (ART) is essential for successful treatment outcomes, some patients may have specific personal barriers to ART adherence. To study specific personal barriers to ART adherence. Quantitative data on patients' health status, ART adherence, CD4 cell counts and viral loads were collected, and qualitative data on life experiences of five patients with poor ART outcomes and adherence were also collected. Out of 35 patients with poor immunological and virological ART outcomes, 17 (49%) also had poor ART adherence. Patient 1 had no living child and did not disclose her HIV serostatus to her spouse because she wanted to have a child. Patient 2 was an orphan with neither social nor family support. Patient 3 stopped ART when she conceived, returned to the study clinic when pregnant again and was sickly. She was switched to second-line ART with satisfactory outcomes. Patient 4, a 14 year old orphan had missed ART for 2 months when his treatment supporter was away. Patient 5 aged 66 years stopped ART which he blamed for his erectile dysfunction. ART adherence counselling should target specific personal barriers to ART adherence like: lack of family support, health and sexual life concerns, desire to have children and family instability.

This study was aimed at developing a risk score prediction model for bacteriologically confirmed tuberculosis (TB) among adults with HIV receiving antiretroviral therapy in Ethiopia. An institutional-based retrospective follow-up study was conducted among 569 adults with HIV on ART. We used demographic and clinical prognostic factors to develop a risk prediction model. Model performance was evaluated by discrimination and calibration using the area under the receiver operating characteristic (AUROC) curve and calibration plot. Bootstrapping was used for internal validation. A decision curve analysis was used to evaluate the clinical utility. Opportunistic infection, functional status, anemia, isoniazid preventive therapy, and WHO clinical stages were used to develop risk prediction. The AUROC curve of the original model was 87.53% [95% confidence interval (CI): 83.88-91.25] and the calibration plot ( P -value = 0.51). After internal validation, the AUROC curve of 86.61% (95% CI: 82.92-90.29%) was comparable with the original model, with an optimism coefficient of 0.0096 and good calibration ( P -value = 0.10). Our model revealed excellent sensitivity (92.65%) and negative predictive value (NPV) (98.60%) with very good specificity (70.06%) and accuracy (72.76%). After validation, accuracy (74.85%) and specificity (76.27%) were improved, but sensitivity (86.76%) and NPV (97.66%) were relatively reduced. The risk prediction model had a net benefit up to 7.5 threshold probabilities. This prognostic model had very good performance. Moreover, it had very good sensitivity and excellent NPV. The model could help clinicians use risk estimation and stratification for early diagnosis and treatment to improve patient outcomes and quality of life.

Depression consistently emerges as a significant predictor of poor antiretroviral therapy (ART) adherence among adult people living with human immunodeficiency virus (PLHIV). However, a gap exists regarding how social support and depressive symptoms can interact to influence ART adherence among adult PLHIV in South Africa (SA). To investigate the interaction between social support and depressive symptoms on ART adherence among adult PLHIV. A tertiary hospital in Durban, KwaZulu-Natal province of SA. Utilising a quantitative cross-sectional research design along with time location sampling technique (TLS); the study recruited 201 adult patients enrolled in an ART programme. The results indicated that depressive symptoms were significantly associated with ART adherence with and without the interaction (B = -0.105; odds ratios [OR] 0.901; 95% confidence intervals [CI] = 0.827, 0.981; p = 0.016), while social support was not significantly associated with ART adherence (B = 0.007; OR 1.007; 95%CI = 0.989, 1.025; p = 0.475). However, a statistically significant interaction was found between social support and depressive symptoms (B = -0.006; OR 0.994; 95%CI = 0.989, 1.000; p = 0.037) on ART adherence. Based on the results, depressive symptoms significantly influenced ART adherence. However, social support did not buffer the adverse effects of clinical depression associated with poor ART adherence. This study provides an evidence-based approach to address gaps in the mental health and social well-being of PLHIV in the context of ART adherence.

Incidence and Type of Opportunistic Infections during Ibrutinib Treatment at a Single Academic Center

IntroductionHuman immunodeficiency virus (HIV) infection results in a gradual depletion of immune function, particularly CD4 cells. The CD4 assessment plays a significant role in assessing treatment responses and clinical decision-making for patients on combination antiretroviral therapy (ART) in resource-limited settings. However, new data on CD4 count changes are scarce; the volatility of CD4 counts after initiation of ART over time remains largely uncharacterized. This study aimed to identify the predictors of CD4 changes over time among HIV-infected children who began ART in Amhara, Ethiopia.MethodsA retrospective follow-up study was performed. A total of 983 HIV-infected children who initiated ART in government hospitals in the Amhara region between 2010 and 2016 were included using a simple random sampling technique. Data were extracted using a structured checklist. An exploratory data analysis was carried out to explain individual and average profile plots. The linear mixed model was used to identify the CD4 change count predictors over time. Variables with p value < 0.05 were considered statistically significant in a multivariable linear mixed regression analysis.ResultsThe mean CD4 count of the participants was 465.1 cells/mm3 with an average CD4 count increase of 30.06 cells/mm3 over 6 months from baseline CD4 count and ART initiation. Childhood age (β = − 0.015; 95% Cl − 0.021, − 0.009), opportunistic infection at ART initiation (β = − 0.044, 95% CI − 0.085, − 0.004), hemoglobin level (β = 0.013; 95% CI 0.004, 0.022), and baseline WHO clinical stage II (β = − 0.046, 95% CI − 0.091, − 0.0003) were significant predictors of CD4 changes over time.ConclusionsThe average CD4 count increase was sufficient in HIV patients who began combined antiretroviral therapy over time. The younger age of the infant, the higher baseline level of hemoglobin, the baseline WHO clinical stage II, and opportunistic infections led to changes in CD4 counts. As a result, timely diagnosis and treatment of opportunistic infections will reduce the risk of opportunistic infections.

Background: People living with HIV/AIDS (PLWHA) are more likely to experience a psychiatric disorder in their lifetime when compared to the general population. is can greatly a ect adherence to the centerpiece of HIV treatment, antiretroviral therapy (ART), and the course that the illness can take. Depression and substance use are the two most common psychiatric disorders in PLWHA. is cross-sectional study examined rates of depression, substance use, adherence to ART and HIV biomarkers on a sample of HIV-positive patients serviced by a general medical clinic, Clinica de Familia La Romana (CFLR) in the Dominican Republic (DR). Methods: A cross-sectional, questionnaire-based study was conducted in a clinic with a special program for PLWHA in La Romana, DR, over four weeks in Fall 2015. The questionnaire included demographic information and scales for assessing adherence, depression and substance use: the Morisky Medication Adherence Scale (MMAS- 4), Patient Health Questionnaire-2 and -9 (PHQ-2 and -9) and CAGE-AID, respectively. Open-ended, exploratory questions on the experience of living with HIV/AIDS were posed to every fourth or fifth participant. Additionally, two important biomarkers for measuring HIV progression and severity, CD4 cell counts and HIV-RNA viral loads (most recent value within the last six months), were extracted from the medical chart. Data analysis was carried out using the Statistical Package of Social Sciences (SPSS) software. Results: 89 participants were involved in the study. The mean age was 40.0 years old (SD 10.9) with an almost equal distribution of women and men; two participants self-identified as transgender. 80 participants (89.9%) scored positively on the PHQ-2, which means they met at least one of the two major criteria for depression: loss of interest in activities and depressed mood. The mean PHQ-9 for those who scored positive on the PHQ-2 was 10.6 (SD 4.7; threshold of 10 for major depression). Those with good ART adherence had a mean PHQ-9 of 9.4 (SD 5.0) while the mean for those with poor ART adherence was 11.2 (SD: 4.4). 27 participants (30.3%) fit criterion for severe alcohol or drug use (> 2). Participants endorsing drug use in their lifetime used marijuana (n=8) and cocaine (n=5). Based on the MMAS-4, 41.3% of those on ART had good adherence (score=0), whereas 58.7% had poor adherence (score > 1). Dominican origin and the completion of at least primary school were associated with good adherence (p-value = 0.04 and p-value = 0.03, respectively). Being female was associated with increased PHQ-9 scores (p-value = 0.01) as well as undetectable viral loads (p-value = 0.03); being male was associated with increased alcohol or drug use (p-value < 0.01). In the exploratory questions, most individuals reported acquiring HIV from a spouse or known romantic partner and reported being diagnosed after personally falling ill or witnessing their partner do so. Major concerns were inability to nd work, loneliness and fear of discrimination. Conclusions: Depressive symptoms and substance use were common factors that impacted ART adherence in a sample of PLWHA treated at Clinica de Familia La Romana in the Dominican Republic. Using validated measures to implement screening for depression and substance use could help identify those requiring diagnosis and appropriate care within the constraints of this low-resource clinic.

Incidences and factors associated with viral suppression or rebound among HIV patients on combination antiretroviral therapy from three counties in Kenya