Magnitude and correlates of virological failure among adult HIV patients receiving PI based second line ART regimens in north western Tanzania; a case control study (original) (raw)
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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.
Second-line failure and first experience with third-line antiretroviral therapy in Mumbai, India
Global Health Action, 2014
Background: There are limited data on the failure of second-line antiretroviral therapy (ART) and the use of third-line ART in people living with HIV in resource-limited settings. Since 2011, the Médecins Sans Frontières (MSF) HIV/tuberculosis programme in Mumbai, India, has been providing third-line ART to patients in care. Objective: To describe the experiences and programmatic challenges during management of suspected secondline ART failure and third-line ART therapy for patients living with HIV, including the use of HIV viral load (VL) testing. Design: This was a retrospective, observational cohort study of patients with suspected second-line ART treatment failure, who were followed for at least 12 months between January 2011 and March 2014. Results: A total of 47 patients with suspected second-line failure met the inclusion criteria during the study period. Twenty-nine of them (62%) responded to enhanced adherence support, had a subsequent undetectable VL after a median duration of 3 months and remained on second-line ART. The other 18 patients had to be initiated on a third-line ART regimen, which consisted of darunavirÁritonavir, raltegravir, and one or more appropriate nucleoside or nucleotide reverse transcriptase inhibitors, based on the results of HIV genotype testing. Of the 13 patients for whom follow-up VL results were available, 11 achieved virological suppression after a median duration of 3 months on third-line ART (interquartile range: 2.5Á3.0). No serious treatmentrelated adverse events were recorded. Conclusions: With intensive counselling and adherence support in those suspected of failing second-line ART, unnecessary switching to more expensive third-line ART can be averted in the majority of cases. However, there is an increasing need for access to third-line ART medications such as darunavir and raltegravir, for which national ART programmes should be prepared. The cost of such medications and inadequate access to VL monitoring and HIV genotype testing are currently major barriers to optimal management of patients failing second-line ART.
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.
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.
HIV/AIDS - Research and Palliative Care
Background: Treatment failure among the population on second line antiretroviral therapy is a major public health threat. In Ethiopia there has been limited research done on second line treatment failure. Objective: To identify determinants of virologic failure among adults on second line antiretroviral therapy in six public hospitals of Wollo, Amhara regional state, northeast Ethiopia. Methods: An institution-based unmatched case-control study was conducted from February 1, 2020 to April 30, 2020 on a total of 377 clients in six public hospitals of Wollo, Amhara regional state, northeast Ethiopia. Clients whose viral load result >1,000 copies/mL in two consecutive results at least 3 month apart were cases, while ≤1,000 copies/ mL were controls. The sample size was calculated by using Epi-Info version 7. Cases (94) and controls (283) were selected using a simple random sampling method in a ratio of casesto-controls of 1:3. The model fitted and binary logistic assumptions were fulfilled with 95% confidence level and P-values<0.05 were taken as statistically significant. Results: Virologic failure was predicted by poor adherence (AOR=6.060, 95% CI=2.837-12.944), not disclosing their HIV status (AOR=4.178, 95% CI=1.431-12.198), OI (AOR=4.11, 95% CI=1.827-9.246), CD4 count <100 cells/mm 3 (AOR=3.497, 95% CI=1.233-9.923) and 100-350 cells/mm 3 (AOR=5.442, 95% CI=2.191-13.513), low BMI <16 kg/m 2 (AOR=7.223, 95% CI=2.218-23.520), and young age 15-29 years (AOR=2.898, 95% CI=1.171-7.170). Conclusion and Recommendations: Determinants of second line ART virologic failure were patients who had poor adherence to ART, not disclosed, opportunistic infection, low CD4 counts <350 cell/mm 3 , low BMI (<16 kg/m 2), and young age 15-29 year patients. Social support, disclosing their HIV status, and getting early treatment for any opportunistic infection is crucial to patients.
BMC Infectious Diseases, 2022
Background: The number of people receiving second-line antiretroviral therapy (ART) has increased as global access to ART has expanded. Data on the burden and factors associated with second-line ART virologic failure (VF) from India remain limited. Methods: We conducted cross-sectional viral load (VL) testing among adults (≥ 18 years) who were registered at a publicly funded ART center in western India between 2014 and 2015 and had received second-line ART for at least 6 months. Sociodemographic and clinical characteristics were abstracted from routinely collected programmatic data. Logistic regression evaluated factors associated with VF (defined as VL > 1000 copies/mL). Results: Among 400 participants, median age was 40 years (IQR 34-44), 71% (285/400) were male, and 15% (59/400) had VF. Relative to participants without VF, those with VF had lower median CD4 counts (230 vs 406 cells/mm 3 , p < 0.0001), lower weight at first-line failure (49 vs 52 kg, p = 0.003), were more likely to have an opportunistic infection (17% vs 3%, p < 0.0001) and less likely to have optimal ART adherence (71% vs 87%, p = 0.005). In multivariable analysis, VF was associated with opportunistic infection (aOR, 4.84; 95% CI, 1.77-13.24), lower CD4 count (aOR 4.15; 95% CI, 1.98-8.71) and lower weight at first-line failure (aOR, 2.67; 95% CI, 1.33-5.34). Conclusions: We found second-line VF in about a sixth of participants in our setting, which was associated with nearly fivefold increased odds in the context of opportunistic infection. Weight could be a useful clinical indicator for second-line VF.
HIV/AIDS : Research and Palliative Care, 2022
Virological suppression for persons living with HIV (PLHIV) on antiretroviral therapy (ART) reached 85% at the end of 2018, still falling short of the UNAIDS target of 95%. In Ethiopia, there were studies on treatment failure focusing on viral suppression and immunological failure of ART users, but none of them have addressed virological failure for second-line regimens. Objective: This study was aimed to estimate the incidence and predictors of virological failure among HIV patients who were switched to second-line ART at the selected public hospitals in Addis Ababa. Methods: An institutional-based retrospective follow-up study was conducted from September 2018 to January 2021 at public hospitals in Addis Ababa. The sample size was determined by using the Schoenfeld formula. Data entry were done by Epi Data version-4.6.0.0 and exported to R-software version-4.1.0 for analysis. Kaplan-Meier methods were used to compare the survival estimates. Cox proportional hazard model was used to identify predictors of virological failure and model adequacy was checked by using the Cox-Snell residuals plot. Results: Overall 44 (12.22%) HIV/AIDS patients developed virological failure with incidence density of 3.57/1000 Person-Month (PM) with 95% CI of [2.65-4.79]. Age >45 years (AHR=0.36, 95% CI: 0.12-0.99), CD4 count <100cell/mm 3 (AHR=3.02, 95% CI: 1.17-7.78), TB co-infection (AHR=2.48, 95% CI: 1.10-6.33), ATV/r-based second-line regimen (AHR=0.27, 95% CI: 0.11-0.70), and poor adherence at the start of second-line ART (AHR=6.18, 95% CI: 1.93-19.76) were the significant predictors of virological failure. Conclusion: A high incidence of virological failure was noticed. The rate of virological failure was higher for patients who had poor ART adherence, small CD4count, and TB co-infection. Therefore, targeted HIV care interventions shall be provided to young ages and efforts stepped up to improve adherence to ART, which helps to increase immunity and suppress viral replication. In addition, prevention and early detection of TB co-infection are crucial to the patients.
Antiviral Therapy, 2011
Background-More patients in resource-limited settings are starting 2 nd-line ART following 1 st-line ART failure. We aimed to describe predictors of lack of virologic suppression in HIVinfected patients on 2nd-line ART in a roll-out program in South Africa. Methods-Retrospective analysis was performed on an adult HIV treatment cohort who started 2 nd-line ART (lopinavir/ritonavir, didanosine, and zidovudine) after virologic failure of 1 st-line ART (2 consecutive HIV RNA >1000 copies/ml). Predictors of week-24 lack of suppression (HIV RNA > 400 copies/ml) on 2 nd-line ART were determined by bivariate analysis where missing equals failure. A multivariable model adjusted for gender, age, and time to ART switch. We tested these findings in sensitivity analyses defining lack of suppression at week-24 as HIV RNA > 1000 and > 5000 copies/ml. Results-Of 6,339 patients on ART, 202 started 2 nd-line ART. At week-24 an estimated 41% (95% CI 34-47%) did not achieve virologic suppression. Female sex (adjusted OR=2.25; 95% CI, 1.03-4.88) and time to ART switch, (adjusted OR=1.07; 95% CI, 1.01-1.14 for each additional month) increased the risk of lack of virologic suppression. Age, CD4 count, and HIV RNA at 2 ndline ART initiation did not predict this outcome. In multivariate models, these findings were insensitive to the definition of lack of virologic suppression. Conclusions-A substantial number of HIV-infected patients do not achieve virologic suppression by week-24 of 2 nd-line ART. Women and patients with delayed start of 2 nd-line ART after 1 st-line ART failure were at an increased risk of lack of virologic suppression.
2012
Objectives-To measure rates and predictors of virologic failure and switch to second-line ART in South Africa. Design-Observational cohort study Methods-We included ART-naïve adult patients initiated on public-sector ART (Jan 2000-July 2008) at five sites in South Africa who completed ≥6 months of follow-up. We estimated cumulative risk of virologic failure (viral load ≥400 copies/ml with confirmation above varying thresholds) and switching to second-line ART. Results-19,645 patients (29,935 person-years) had a median of 1.3 years of study follow-up (1.8 years on ART) and a median CD4 count of 96 (IQR:40-159) cells/μl at ART initiation. 9.9% (4.5/100 person-years) failed ART in median 16 (IQR:12-23) months since ART initiation, with median 2.9 (IQR:1.8-5.0) months between first elevated and confirmatory viral loads. By survival analysis, using a confirmatory threshold of 400 copies/ml, 16.9% (95%CI:15.4-18.6%) failed by