Immunological failure in HIV-infected adults from 2003 to 2015 in Southwest Ethiopia: a retrospective cohort study.
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ABSTRACT:
SUBMITTER: Gesesew HA
PROVIDER: S-EPMC6104792 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundAntimonials are still being used for visceral leishmaniasis (VL) treatment among HIV co-infected patients in East-Africa due to the shortage of alternative safer drugs like liposomal amphotericin B. Besides tolerability, emergence of resistance to antimonials is a major concern.ObjectivesThis study was aimed at assessing the clinical outcome of VL-HIV co-infected patients when treated with sodium stibogluconate (SSG).MethodsRetrospective patient record analysis of VL-HIV co-infected patients treated at a clinical trial site in north-west Ethiopia was done. Patients with parasitologically confirmed VL and HIV co-infection treated with SSG were included. The dose of SSG used was 20 mg Sb5 (pentavalent antimony)/kg and maximum of 850 mg Sb5 for 30 days. The clinical outcomes were defined based on the tissue aspiration results as cure or failure, and additionally the safety and mortality rates were computed.ResultsThe study included 57 patients treated with SSG and by the end of treatment only 43.9% of patients were cured. The parasitological treatment failure and the case fatality rate were 31.6% and 14.0% respectively. SSG was discontinued temporarily or permanently for 12 (21.1%) cases due to safety issues. High baseline parasite load (graded more than 4+) was significantly associated with treatment failure (odds ratio = 8.9, 95% confidence interval = .5-51.7).ConclusionSSG is not only unsafe, but also has low effectiveness for VL-HIV patients. Safe and effective alternative medications are very urgently needed. Drug sensitivity surveillance should be introduced in the region.
| S-EPMC4031116 | biostudies-literature
Project description:Immunological monitoring is part of the standard of care for patients on antiretroviral treatment. Yet, little is known about the routine implementation of immunological laboratory monitoring and utilization in clinical care in Ethiopia. This study assessed the pattern of immunological monitoring, immunological response, level of immunological treatment failure and factors related to it among patients on antiretroviral therapy in selected hospitals in southern Ethiopia. A retrospective longitudinal analytic study was conducted using documents of patients started on antiretroviral therapy. Adequacy of timely immunological monitoring was assessed every six months the first year and every one year thereafter. Immunological response was assessed every six months at cohort level. Immunological failure was based on the criteria: fall of follow-up CD4 cell count to baseline (or below), or CD4 levels persisting below 100 cells/mm3, or 50% fall from on-treatment peak value. A total of 1,321 documents of patients reviewed revealed timely immunological monitoring were inadequate. There was adequate immunological response, with pediatric patients, females, those with less advanced illness (baseline WHO Stage I or II) and those with higher baseline CD4 cell count found to have better immunological recovery. Thirty-nine patients (3%) were not evaluated for immunological failure because they had frequent treatment interruption. Despite overall adequate immunological response at group level, the prevalence of those who ever experienced immunological failure was 17.6% (n=226), while after subsequent re-evaluation it dropped to 11.5% (n=147). Having WHO Stage III/IV of the disease or a higher CD4 cell count at baseline was identified as a risk for immunological failure. Few patients with confirmed failure were switched to second line therapy. These findings highlight the magnitude of the problem of immunological failure and the gap in management. Prioritizing care for high risk patients may help in effective utilization of meager resources.
| S-EPMC4427446 | biostudies-literature
Project description:BackgroundIn 2017, 64% of children living with HIV in Zambia accessed Antiretroviral Therapy (ART). Despite expanded ART coverage, there is paucity of information on effectiveness of pediatric ART in reducing mortality. The aim of this research is to describe treatment outcomes, measure mortality rates and assess predictors of mortality among children receiving ART.MethodsUsing a retrospective cohort study design, we abstracted routinely collected clinical data from medical records of children from birth to 15 years old, who had received ART for at least 6 months at Livingstone Central Hospital in Southern Province Zambia, between January 2003 and June 2015. The primary outcome was death. Cause of death was ascertained from medical records and death certificates. Distribution of survival times according to baseline covariates were estimated using Kaplan Meier and Cox Proportional Hazards methods.ResultsOverall, 1039 children were commenced on ART during the study period. The median age at treatment initiation was 3.6 years (IQR: 1.3-8.6) and 520 (50%) children were female. Of these, 71 (7%) died, 164 (16%) were lost to follow-up, 210 (20%) transferred and 594 (56%) were actively on treatment. After 4450 person years, mortality rate was 1.6/100 (95% CI: 1.4-1.8). Mortality was highest during the first 3 months of treatment (11.7/100 (95% CI: 7.6-16.3). In multivariable proportional hazards regression, the adjusted hazards of death were highest among children aged < 1 year (aHR = 3.1 (95% CI: 1.3-6.4), compared to those aged 6-15 years, WHO stage 4 (aHR =4.8 (95% CI: 2.3-10), compared to WHO stage 1 and 2. In the sensitivity analysis to address bias due to loss to follow-up, mortality increased 5 times when we assumed that all the children who were lost to follow up died within 90 days of their last visit.ConclusionWe observed low attrition due to mortality among children on ART. Loss to follow-up was high (16%). Mortality was highest during the first 3 months of treatment. Children aged less than one year and those with advanced WHO disease stage had higher mortality. We recommend effective interventions to improve retention in care and early diagnosis of HIV in children.
| S-EPMC6348639 | biostudies-literature
Project description:BACKGROUND:Introduction of antiretroviral therapy (ART) in sub-Saharan Africa was a hot debate due to many concerns about adherence, logistics and resistance. Currently, it has been significantly scaled up. However as the WHO clinico-immunological approaches for initiation and monitoring of ART in the region lacks viral load determination and drug resistance monitoring, HIV infected adults and children may be at risk for "unrecognized" virologic failure and the subsequent development of antiretroviral drug resistance. This study evaluates the virological efficacy and immunological recovery of HIV/AIDS patients under ART. METHODS:Consecutive HIV-1 infected adults (N = 100) and children (N = 100) who have been receiving ART for up to 6 years at Gondar University Hospital, Ethiopia were enrolled following the WHO protocol for assessment of acquired drug resistance. Magnitude of viral suppression, genotypic drug resistance mutations and patterns of CD4+ T cell recovery were determined using standard virological and immunological methods. RESULTS:Virological suppression (HIV RNA < 40 copies/ml) was observed in 82 and 87% of adults and children on a median time of 24 months on ART, respectively. Mutation K103N conferring resistance to non nucleoside reverse transcriptase inhibitors and thymidine analogue mutations (M41L, L210W) were found only in one adult and child patient, respectively. Median CD4+ T cell count has increased from baseline 124 to 266 (IQR: 203-306) and 345 (IQR: 17-1435) to 998 (IQR: 678-2205) cells/mm3 in adults and children respectively after 12 months of ART. Nevertheless, small but significant number of clinically asymptomatic adults (16%) and children (13%) had low level viraemia (HIV-1 RNA 41-1000 copies/ml). CONCLUSIONS:Majority of both adults (82%) and children (87%) who received ART showed high viral suppression and immunological recovery. This indicates that despite limited resources in the setting virological efficacy can be sustained for a substantial length of time and also enhance immunological recovery irrespective of age. However, the presence of drug resistance mutations and low level viraemia among clinically asymptomatic patients highlights the need for virological monitoring.
| S-EPMC3900473 | biostudies-literature
Project description:The aim of this study was to compare the immunologic response to a prime-boost immunization strategy combining the 13-valent conjugate pneumococcal vaccine (PCV13) with the 23-valent polysaccharide pneumococcal vaccine (PPSV23) versus the PPSV23 alone in HIV-infected adults. HIV-infected adults were randomized to receive PCV13 at week 0 followed by PPSV23 at week 4 (n = 31, prime-boost group) or PPSV23 alone at week 4 (n = 33, PPSV23-alone group). Serotype specific IgG geometric mean concentration (GMC) and functional oposonophagocytic (OPA) geometric mean titer (GMT) were compared for 12 pneumococcal serotypes shared by both vaccines at week 8 and week 28. The prime-boost vaccine group were more likely to achieve a ≥2-fold increase in IgG GMC and a GMC >1 ug/ml at week 8 (odds ratio (OR) 2.00, 95% confidence interval (CI) 1.46-2.74, p < 0.01) and week 28 (OR 1.95, 95% CI 1.40-2.70, p < 0.01). Similarly, the prime-boost vaccine group were more likely to achieve a ≥4-fold increase in GMT at week 8 (OR 1.71, 95% CI 1.22-2.39, p < 0.01) and week 28 (OR 1.6, 95% CI 1.15-2.3, p < 0.01). This study adds to evidence supporting current pneumococcal vaccination recommendations combining the conjugate and polysaccharide pneumococcal vaccines in the United States and Europe for HIV-infected individuals.
| S-EPMC5007521 | biostudies-literature
Project description:ObjectivesThere are few data on ART failure rates and drug resistance from Tanzania, where there is a wide diversity of non-B HIV subtypes. We assessed rates and predictors of virological failure in HIV-infected Tanzanians and describe drug resistance patterns in a subgroup of these patients.MethodsART-naive, HIV-1-infected adults enrolled in a randomized controlled trial between November 2006 and 2008 and on ≥24 weeks of first-line NNRTI-containing ART were included. Population-based genotyping of HIV-1 protease and reverse transcriptase was performed on stored plasma from patients with virological failure (viral load >1000 copies/mL at ≥24 weeks of ART) and at baseline, where available.ResultsA total of 2403 patients [median (IQR) age 37 (32-43) years; 70% female] were studied. The median (IQR) baseline CD4+ T cell count was 128 (62-190) cells/μL. Predominant HIV subtypes were A, C and D (92.2%). The overall rate of virological failure was 14.9% (95% CI 13.2%-16.1%). In adjusted analyses, significant predictors of virological failure were lower CD4+ T cell count (P = 0.01) and non-adherence to ART (P < 0.01). Drug resistance mutations were present in 87/115 samples (75.7%); the most common were M184V/I (52.2%) and K103N (35%). Thymidine analogue mutations were uncommon (5.2%). The prevalence of mutations in 45 samples pre-ART was 22%.ConclusionsHigh levels of early ART failure and drug resistance were observed among Tanzanian HIV-1-infected adults enrolled in a well-monitored study. Initiating treatment early and ensuring optimal adherence are vital for the success and durability of first-line ART in these settings.
| S-EPMC4896406 | biostudies-literature
Project description:Due to the limited availability of viral load testing for treatment outcome monitoring in resource limited settings, identifying predictive factors of antiretroviral treatment failure will help in selecting clients who will benefit most from the targeted use of viral load monitoring. Little is known about the predictors of treatment failure in the study area. This study was conducted to determine factors that predict first-line antiretroviral therapy failure among HIV-infected adult clients at Woldia Hospital, Northeast Ethiopia. For this study, antiretroviral therapy treatment failure was defined as the fulfillment of clinical and/or immunological criteria set by WHO.Case-control study was carried out from November to December 2014. Cases were adult clients who were on failing first line regimen and on active follow up while controls were those adult clients on a non-failing first-line regimen for 36 months and above and on active follow up. Data was entered in to Epi Info version 7 and was exported to SPSS version 20 for analysis. Binary logistic regression model was used to identify predictors of ART failure.A total of 59 cases and 245 controls were included in the analysis. Sixty three percent of the participants were females and the median age at ART enrollment was 33 years (IQR; 28, 40). The median baseline CD4count was not significantly different among cases and controls (105 (IQR = 60-174)vs.131 (IQR = 72.5-189.0); p = 0.301). The median peak CD4 count in the failure group (230 (IQR = 123-387)) was significantly low compared to the non-failure group (463 (IQR = 348.5-577)) [p < 0.001]. High peak CD4count (AOR = 0.993; 95% CI 0.990, 0.996) and longer duration on ART (AOR = 0.923; 95% CI 0.893, 0.954) were protective of treatment failure. In addition stavudine based regimen (AOR = 3.47; 95% CI 1.343, 10.555), low baseline BMI (AOR = 2.75; 95% CI 1.012, 7.457), unemployment (AOR = 4.93; 95% CI 1.493, 16.305) and formal educational level (AOR = 5.15; 95% CI 1.534, 17.276) were independently significant predictors of treatment failure.In this setting low peak CD4count, shorter duration on first line ART, d4T based regimen, low baseline BMI, unemployment and formal educational level were significantly associated with increased treatment failure. Retaining patients on their initial first line regimen with appropriate follow up and improving their socioeconomic status through various livelihood initiatives should be strengthened.
| S-EPMC5667926 | biostudies-literature
Project description:PurposeThis cross-sectional study took place in the integrated tuberculosis (TB) clinic of a large outpatient clinic for HIV-infected patients in Kampala, Uganda. The purpose of this study was to describe the proportion of TB/HIV co-infected adults with virological failure, type and frequency of HIV drug resistance-associated mutations, and the proportion of patients with suboptimal efavirenz levels.MethodsHIV-1 plasma viral loads, CD4 cell count measurements, and efavirenz serum concentrations were done in TB/HIV co-infected adults. Genotypic resistance testing was performed in case of confirmed virological failure.ResultsAfter a median time on ART of 6 months, virological failure was found in 22/152 patients (14.5%). Of 147 participants with available efavirenz serum concentration, 26 (17.6%) had at least one value below the reference range, including 20/21 (95.2%) patients with confirmed virological failure. Genotypic resistance testing was available for 16/22 (72.7%) patients, of which 15 (93.8%) had at least one major mutation, most commonly M184V (81.2%) and K103NS (68.8%).ConclusionWe found a high proportion of TB/HIV co-infected patients with virological failure, the majority of which had developed relevant resistance-mutations after a median time on anti-retroviral treatment (ART) of 6 months. Virological monitoring should be prioritized in TB/HIV co-infected patients in resource-limited settings.
| S-EPMC5237283 | biostudies-literature
Project description:Data regarding the outcomes of HIV-infected adults with baseline renal dysfunction who start antiretroviral therapy are conflicting.We followed up a previously-published cohort of HIV-infected adult outpatients in northwest Tanzania who had high prevalence of renal dysfunction at the time of starting antiretroviral therapy (between November 2009 and February 2010). Patients had serum creatinine, proteinuria, microalbuminuria, and CD4(+) T-cell count measured at the time of antiretroviral therapy initiation and at follow-up. We used the adjusted Cockroft-Gault equation to calculate estimated glomerular filtration rates (eGFRs).In this cohort of 171 adults who had taken antiretroviral therapy for a median of two years, the prevalence of renal dysfunction (eGFR <90 mL/min/1.73 m(2)) decreased from 131/171 (76.6%) at the time of ART initiation to 50/171 (29.2%) at the time of follow-up (p<0.001). Moderate dysfunction (eGFR<60 mL/min/1.73 m(2)) decreased from 21.1% at antiretroviral therapy initiation to 1.1% at follow-up (p<0.001), as did the prevalence of microalbuminuria (72% to 44%, p<0.001). Use of tenofovir was not associated with renal dysfunction at follow-up.Mild and moderate renal dysfunction were common in this cohort of HIV-infected adults initiating antiretroviral therapy, and both significantly improved after a median follow-up time of 2 years. Our work supports the renal safety of antiretroviral therapy in African adults with mild-moderate renal dysfunction, suggesting that these regimens do not lead to renal damage in the majority of patients and that they may even improve renal function in patients with mild to moderate renal dysfunction.
| S-EPMC3935873 | biostudies-other
Project description:INTRODUCTION:The 2016 WHO consolidated guidelines on the use of antiretroviral drugs defines HIV virologic failure for low and middle income countries (LMIC) as plasma HIV-RNA ? 1000 copies/mL. We evaluated virologic failure and predictors in four African countries. MATERIALS AND METHODS:We included HIV-infected participants on a WHO recommended antiretroviral therapy (ART) regimen and enrolled in the African Cohort Study between January 2013 and October 2017. Studied outcomes were virologic failure (plasma HIV-RNA ? 1000 copies/mL at the most recent visit), viraemia (plasma HIV-RNA ? 50 copies/mL at the most recent visit); and persistent viraemia (plasma HIV-RNA ? 50 copies/mL at two consecutive visits). Generalized linear models were used to estimate relative risks with their 95% confidence intervals. RESULTS:2054 participants were included in this analysis. Viraemia, persistent viraemia and virologic failure were observed in 396 (19.3%), 160 (7.8%) and 184 (9%) participants respectively. Of the participants with persistent viraemia, only 57.5% (92/160) had confirmed virologic failure. In the multivariate analysis, attending clinical care site other than the Uganda sitebeing on 2nd line ART (aRR 1.8, 95% CI 1·28-2·66); other ART combinations not first line and not second line (aRR 3.8, 95% CI 1.18-11.9), a history of fever in the past week (aRR 3.7, 95% CI 1.69-8.05), low CD4 count (aRR 6.9, 95% CI 4.7-10.2) and missing any day of ART (aRR 1·8, 95% CI 1·27-2.57) increased the risk of virologic failure. Being on 2nd line therapy, the site where one receives care and CD4 count < 500 predicted viraemia, persistent viraemia and virologic failure. CONCLUSION:In conclusion, these findings demonstrate that HIV-infected patients established on ART for more than six months in the African setting frequently experienced viraemia while continuing to be on ART. The findings also show that being on second line, low CD4 count, missing any day of ART and history of fever in the past week remain important predictors of virologic failure that should trigger intensified adherence counselling especially in the absence of reliable or readily available viral load monitoring. Finally, clinical care sites are different calling for further analyses to elucidate on the unique features of these sites.
| S-EPMC6363169 | biostudies-literature