Risk factors for virological failure and subtherapeutic antiretroviral drug concentrations in HIV-positive adults treated in rural northwestern Uganda (original) (raw)
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World Journal of AIDS, 2012
Background: Since 2001, anti-retroviral therapy (ART) has been provided to over 75,000 HIV-infected patients at the USAID-Academic Model Providing Access to Healthcare (AMPATH) Partnership in western Kenya. Over 1000 of these patients have switched to second-line ART. We therefore set out to determine factors associated with first-line ART failure amongst these patients. Methods: This case controlled study matched patients (in the ratio 1:2) from the electronic AMPATH Medical Record System on the basis of age, gender, and ART initiation date. Cases were adults (≥18 years) who initiated second-line ART between January 1, 2007 and July 31, 2011 after at least one viral load measurement >5,000 copies/ml or satisfying the WHO immunological or clinical failure criteria. Controls were those on non-failing first-line ART with a CD4 count > 400 /ml within the last 12 months, at the time of case incidence. Conditional logistic regression for paired data was used to assess association. We evaluated the strength of association of risk factors using stratified Cox model. Results: Of the 1084 cases and 2149 controls included in the analysis, 62% were female. Median age was 36.5 years (IQR = 30.7-43.1); median baseline CD4 cell count was 161 /ml (IQR = 72-277); Median time to ART failure was 37 months (IQR = 24-47). Low baseline CD4 count < 50 /ml (H.R = 7.07, (95% CI = 4.92-10.15); Zidovudine based ART (H.R 1.76, 95% CI = 1.25-2.48) and imperfect ART adherence (H.R = 2.77, 95% CI = 2.20-3.49) were independently associated with treatment failure. Conclusion: In this setting, low baseline CD4 count, zidovudine-based ART and imperfect adherence are associated with first-line ART treatment failure.
Background: With a growing access to free ART, switching of ART to second line regimen has also become common following failure of first line ART regimens. Patients failing on first line ART regimens have been shown to stand a high risk of failing on subsequent second line ART regimens. The magnitude of those who are failing virologicaly on second line ART is not documented in our setting. This study was designed to assess the magnitude and correlates of second line ART treatment failure. Methods: A retrospective analysis of patients on second line ART for at least 1 year was done at Bugando care and treatment center. Information on demographic, clinical and laboratory data were collected and analyzed using STATA 11. The proportion of patients with Virological failure was calculated and potential correlates of virological failure were determined by logistic regression model. Results: In total 197 patients on second line ART were included in this study and 24 (12.18%) of them met criteria for virological failure. The odds of having virological failure on second line ART were independently associated with age of less than 30 years (AOR = 12.5, p = 0.001), being on first line for less than 3 years (AOR = 6.1, p = 0.002) and CD4 at switch to second line ART of less than 200cells/μl (AOR = 16.3, p < 0.001). Conclusion: Virological failure among patients on second line ART is common. Predictors of virological failure in this study could assist in planning for strategies to improve the outcome of this subgroup of patients including close clinical follow up of patients at risk, a continued adherence intensification and a targeted resistance testing before switching to second line ART.
BMC Infectious Diseases
Background: Few low-income countries have virological monitoring widely available. We estimated the virological durability of first-line antiretroviral therapy (ART) after five years of follow-up among adult Ugandan and Zimbabwean patients in the DART study, in which virological assays were conducted retrospectively. Methods: DART compared clinically driven monitoring with/without routine CD4 measurement. Annual plasma viral load was measured on 1,762 patients. Analytical weights were calculated based on the inverse probability of sampling. Time to virological failure, defined as the first viral load measurement ≥200 copies/mL after 48 weeks of ART, was analysed using Kaplan-Meier plots and Cox regression models. Results: Overall, 65% of DART trial patients were female. Patients initiated first-line ART at a median (interquartile range; IQR) age of 37 (32-42) and with a median CD4 cell count of 86 (32-140). After 240 weeks of ART, patients initiating dual-class nucleoside reverse-transcriptase inhibitor (NRTI)-non-nucleoside reverse-transcriptase (NNRTI) regimens containing nevirapine + zidovudine + lamivudine had a lower incidence of virological failure than patients on triple-NRTI regimens containing tenofovir + zidovudine + lamivudine (21% vs 40%; hazard ratio (HR) =0.48, 95% CI:0.38-0.62; p < 0.0001). In multivariate analyses, female patients (HR = 0.79, 95% CI: 0.65-0.95; p = 0.02), older patients (HR = 0.73 per 10 years, 95% CI: 0.64-0.84; p < 0.0001) and patients with a higher pre-ART CD4 cell count (HR = 0.64 per 100 cells/mm 3 , 95% CI: 0.54-0.75; p < 0.0001) had a lower incidence of virological failure after adjusting for adherence to ART. No difference in failure rate between the two randomised monitoring strategies was observed (p= 0.25). Conclusions: The long-term durability of virological suppression on dual-class NRTI-NNRTI first-line ART without virological monitoring is remarkable and is enabled by high-quality clinical management and a consistent drug supply. To achieve higher rates of virological suppression viral-load-informed differentiated care may be required. Trial Registration: Prospectively registered on 18/10/2000 as ISRCTN13968779.
Tanzania Medical Journal, 2010
Background: Highly active antiretroviral therapy (HAART) for the treatment of HIV infection has led to profound reductions in the incidence of mortality due to AIDS-related causes in recent years. Immunological status is common parameter used to monitor HIV treatment success in developing countries. This a crossectional retrospective follow up study was conducted to determine the prevalence of immunological treatment failure and risk factors associated to it among patients on ARV therapy at Bugando Medical Centre. Method: A crossectional Retrospective study was conducted among all patients on ART from 2005 attending BMC CTC clinic. Using standard data collection form all demographic data, adherence levels, and CD4 + counts were recorded and analyzed using SPSS 11.5 computer software to determine the prevalence and predictors of immunological failure. Results: A total of 2975 patients were on ART during the study period, in the analysis 362 patients were included and followed backwards for mean duration of 29 months. The base line CD4 of more than 100cells/µl was found in 43.6% of patients studied. A steady CD4 increase in the first 7 months, followed by slow increase in subsequent months was noted. The prevalence of immunological treatment failure was 17.1% (95% CI 17.1%±3.9). Adherence below 95% was strongly associated with immunological treatment failure (p=0.00001). There was significant association between baseline CD4 of more than 100cell/ µl and immunological treatment failure (p=0.001). No significant difference was found between Home based care (HBCP) and immunological treatment failure (p=0.06). The average time to treatment failure for the first line regimen was 20 months, with 59% of failed patients having a lag time of 5 weeks before appropriate changes in their ART regimen were done. Conclusions and recommendation: Immunological failure was significantly associated with adherence below 95% and low baseline CD4 count of less than 100cells/µl. The multi-disciplinary HIV treatment and care should reinforce adherence during each patient encounter. Strategies to maximise adherence will help to ensure treatment success. We also recommend early HIV testing and referral to care before severe immnosuppression develops. A switch to second line ARV regimen should be considered after a period of adherence intensification.
BMC Infectious Diseases, 2019
Background: In 2018 in Ethiopia, magnitude of human immunodeficiency virus Acquired Immunodeficiency Syndrome treatment failure was 15.9% and currently the number of patient receiving second line antiretroviral therapy (ART) is more increasing than those taking first line ART. Little is known about the predictors of treatment failure in the study area. Therefore; more factors that can be risk for first line ART failure have to identified to make the patients stay on first line ART for long times. Consequently, the aim of this study was to identify determinants of first line ART treatment failure among patients on ART at St. Luke referral hospital and Tulubolo General Hospital, 2019. Methods: A 1:2 unmatched case-control study was conducted among adult patients on active follow up. One new group variables was formed as group 1 for cases and group 0 for controls and then data was entered in to Epi data version 3 and exported to STATA SE version 14 for analysis. From binary logistic regression variables with p value ≤0.25 were a candidate for multiple logistic regression. At the end variables with a p-value ≤0.05 were considered as statistically significant. Result: A total of 350 (117 cases and 233 controls) patients were participated in the study. Starting ART after 2 years of being confirmed HIV positive (AOR = 3.82 95% CI 1.37,10.6), nevirapine (NVP) based initial ART (AOR = 2.77,95%CI 1.22,6.28) having history of lost to follow up (AOR 3.66,95%CI 1.44,9.27) and base line opportunistic infection (AOR = 1.97,95%CI 1.06,3.63), staying on first line ART for greater than 5 years (AOR = 3.42,95%CI 1.63,7.19) and CD4 less than100cell/ul (AOR = 2.72,95%CI 1.46,5.07) were independent determinants of first line ART treatment failure. Conclusion: Lost to follow up, staying on first line ART for greater than 5 years, presence of opportunistic infections, NVP based NNRT, late initiation of ART are determinant factors for first line ART treatment failure. The concerned bodies have to focus and act on those identified factors to maintain the patient on first line ART.
International Journal of Basic and Clinical Pharmacology, 2016
Background: Human immunodeficiency virus (HIV) presently accounts for the highest number of deaths due to any infective agent in the world. The present study assessed the one year treatment outcome following antiretroviral therapy in HIV positive, treatment naïve patients in a tertiary care hospital. Methods: Adult HIV positive, antiretroviral treatment naive patients who were started on antiretroviral therapy (ART) between 1 st January 2011 and 31 st May 2013 were included in the study. Data was collected from their case records. CD4+cell count, haemoglobin level, weight, occurrence of opportunistic infections (OIs) and adverse drug reactions (ADRs) were analysed at baseline, 6 and 12 months following start of antiretroviral therapy. Data was analysed using parametric and nonparametric tests. Results: Data of 325 patients was analysed. Overall, the median increase in CD 4 + count at 1 year after initiation of treatment was observed to be clinically significant. Patients on tenofovir based regimen showed a significantly greater increase in the median CD 4 + count (P = 1.12×10-05) and haemoglobin (P = 0.002) as compared to those on non-tenofovir based regimen. A total of 151 ADRs were recorded in the study, of which the most common were skin rash 24%, anaemia and gastrointestinal side effects 17% each. Frequency of opportunistic infections gradually declined after ART. At the end of 1 year of treatment, the cumulative loss to follow up was 7.4%. Conclusions: By following the current national guidelines, the desired immunological and clinical response following initiation of ART can be achieved while minimizing drug toxicity.
Journal of the International AIDS Society, 2012
Introduction: Clinical outcome is an important determinant of programme success. This study aims to evaluate patients' baseline characteristics as well as level of care associated with lost to follow-up (LTFU) and mortality of patients on antiretroviral treatment (ART). Methods: Retrospective cohort study using routine service data of adult patients initiated on ART in 2007 in 10 selected hospitals in Nigeria. We captured data using an electronic medical record system and analyzed using Stata. Outcome measures were probability of being alive and retained in care at 12, 24 and 36 months on ART. Potential predictors associated with time to mortality and time to LTFU were assessed using competing risks regression models. Results: After 12 months on therapy, 85% of patients were alive and on ART. Survival decreased to 81.2% and 76.1% at 24 and 36 months, respectively. Median CD4 count for patients at ART start, 12, 18 and 24 months were 152 (interquartile range, IQR: 75 to 242), 312 (IQR: 194 to 450), 344 (IQR: 227 to 501) and 372 (IQR: 246 to 517) cells/ml, respectively. Competing risk regression showed that patients' baseline characteristics significantly associated with LTFU were male (adjusted sub-hazard ratio, sHR 01.24 [95% CI: 1.08 to 1.42]), ambulatory functional status (adjusted sHR01.25 [95% CI: 1.01 to 1.54]), World Health Organization (WHO) clinical Stage II (adjusted sHR01.31 [95% CI: 1.08 to 1.59]) and care in a secondary site (adjusted sHR 00.76 [95% CI: 0.66 to 0.87]). Those associated with mortality include CD4 count B50 cells/ml (adjusted sHR02.84 [95% CI: 1.20 to 6.71]), WHO clinical Stage III (adjusted sHR 02.67 [95% CI: 1.26 to 5.65]) and Stage IV (adjusted sHR 05.04 [95% CI: 1.93 to 13.16]) and care in a secondary site (adjusted sHR02.21 [95% CI: 1.30 to 3.77]).
Clinical Journal of HIV & AIDS
Background: Kenya has recorded a high burden of HIV with 1.5 million HIV + persons by 2015. With the adoption of 2016 ART guideline in Kenya all PLHIV now qualify for antiretroviral (ART) irrespective of WHO clinical stage, cd4 count, age gender, pregnancy status, co-infected status thus increasing the number of patients likely to develop resistance. Once a patient develops resistance to first line, they are put on second line ART regimen which is more expensive and less tolerable. This study seeks to establish the duration of time patients put on first line ART take before developing virological failure and factors influencing it as a step towards guiding the management in adequate planning and budget allocation for management of these patients. Study objective: To assess virological failure among HIV patients on first line ART at Kenyatta National Referral Hospital Comprehensive Care Centre between the years 2009-2016. Methods: This was a retrospective cohort study conducted at Kenyatta National Referral Hospital Comprehensive Care Centre (KNH-CCC) between 2009 and 2016 with 3 years accrual and 6 years observation periods. The main exposure was poor adherence to first line ART treatment. HIV infected patients were enrolled and initiated into first line ART at the center between 2009 and 2010. A total of 1470 patients were selected through simple random sampling from the list of these patients in CCC database with complete follow-up records. Data collection and analysis: A structured data abstraction tool was used for extracting sociodemographic, clinical and virological data from medical records data of the selected patients. The data ware entered and stored in Microsoft Access 2013. Data cleaning, coding and analysis was done using STATA version 13 SE. The main outcome was the virological failure time. The Kaplan-Meier estimator was used to estimate the survival function. Log-rank tests were used to compare the survival functions between patients based on adherence to treatment and first line HAART combinations. Log-rank statistic and corresponding p-value was reported. Results: Generally patients sampled comprised of age 2 months to 72 years where 75% of the patients were below age 42.10% of the patients were pediatric while adults composed of 90% having female patient being almost double of the men on follow up. At enrolment clients classified in WHO (3 and 4) were 42.2% and 99% of patients were reported to have been screened for TB, 13% of patients on follow up had NCD were 64% of patients were having EFV based regimen and 35.8% had NVP based regimen. Poor adherence was reported by 34.8% of patients and 75% of patients had CD4 of less than 600 cell/ml, with 19.7% of patient reported being obese and 11% were underweight. Kaplan Meier estimates indicate that 50% of adult patient failed by 36 months after ART initiation for adult's patients and for pediatric would fail by 42 months after being started on ART. Log rank tests showed that the failure rate differed significantly with relation to age, adherence and regiment type. Adults had 61% risk of virological failure at next time compared to pediatric, patient started on NVP had 18% reduced risk of virological failure compared to ones started on EFV based. Good adherence reduced chance of virological failure by 26% by the next time. Conclusion: Patients being started on first line ART at KNH-CCC their failure time depended on age, adherence and type of regimen (EFV or NVP) where in general pediatric had longer period on first line compared to adults patients.