Dataset Information

Predictors of late virologic failure after initial successful suppression of HIV replication on efavirenz-based antiretroviral therapy.

ABSTRACT:

Background

Practical issues, including cost, hinder implementing virologic monitoring of patients on antiretroviral therapy (ART) in resource-limited settings. We evaluated factors that might guide monitoring frequency and efforts to prevent treatment failure after initial virologic suppression.

Methods

Participants were the 911 HIV-infected antiretroviral-naïve adults with CD4 count <300 cells/μL who started efavirenz-based ART in the international A5175/PEARLS trial and achieved HIV-1 RNA <1000 copies/mL at 24 weeks. Participant report of ART adherence was evaluated using a structured questionnaire in monthly interviews. Adherence and readily available clinical and laboratory measures were evaluated as predictors of late virologic failure (late VF: confirmed HIV-1 RNA ≥1000 copies/mL after 24 weeks).

Results

During median follow-up of 3.5 years, 82/911 participants (9%) experienced late VF. Of 516 participants reporting missed doses during the first 24 weeks of ART, 55 (11%) experienced late VF, compared with 27 (7%) of 395 participants reporting no missed doses (hazard ratio: 1.73; 95% CI: 1.08, 2.73). This difference persisted in multivariable analysis, in which lower pre-ART hemoglobin and absence of Grade ≥3 laboratory results prior to week 24 were also associated with higher risk of late VF.

Discussion

In this clinical trial, the late VF rate after successful suppression was very low. If achievable in routine clinical practice, virologic monitoring involving infrequent (e.g. annual) measurements might be considered; the implications of this for development of resistance need evaluating. Patients reporting missed doses early after ART initiation, despite achieving initial suppression, might require more frequent measurement and/or strategies for promoting adherence.

SUBMITTER: Singini I

PROVIDER: S-EPMC5276794 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Publications

Predictors of late virologic failure after initial successful suppression of HIV replication on efavirenz-based antiretroviral therapy.

Singini Isaac I Campbell Thomas B TB Smeaton Laura M LM Kumarasamy Nagalingeswaran N La Rosa Alberto A Taejareonkul Sineenart S Safren Steven A SA Flanigan Timothy P TP Hakim James G JG Hughes Michael D MD

HIV clinical trials 20160729 5

<h4>Background</h4>Practical issues, including cost, hinder implementing virologic monitoring of patients on antiretroviral therapy (ART) in resource-limited settings. We evaluated factors that might guide monitoring frequency and efforts to prevent treatment failure after initial virologic suppression.<h4>Methods</h4>Participants were the 911 HIV-infected antiretroviral-naïve adults with CD4 count <300 cells/μL who started efavirenz-based ART in the international A5175/PEARLS trial and achieved ...[more]

PMID: 27472067

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Project description:BackgroundAccess to routine virologic monitoring, critical to ensuring treatment success, remains limited in low- and middle-income countries. We report on implementation of routine viral load (VL) monitoring and risk factors for virologic failure among HIV-infected children on antiretroviral treatment (ART) in Western Kenya.MethodsRoutine VL testing was introduced in western Kenya in November 2013. We performed a case-control study among 1190 HIV-infected children ≤15 years on ART who underwent routine VL testing June 2014-May 2015. A random sample of 98 cases (virologic failure define as VL >1000 cps/mL) and 201 controls (VL <1000 cps/mL) from five facilities in three high HIV prevalence counties in Kenya were followed for a minimum of 12 months. Data from patient charts were analyzed using logistic regression to determine factors associated with failure to attain virologic suppression at initial routine and subsequent VL testing among cases.ResultsOverall, 1190 (94%) children with a median age of 8 years underwent routine VL testing of whom (37%) had virological failure. Among the 299 cases and controls, WHO stage, baseline CD4 count and time since ART initiation were not associated with virologic failure during the follow-up period. In multivariable analysis, unsuppressed children at initial test were more likely to be male (adjusted Odds Ratio (aOR) 2.1, 95% Confidence Interval (CI) 2.1-3.6) and have had an ART regimen change (aOR 2.0, CI 1.0-3.7) than controls. Of the two-thirds of children 201/299 who had a subsequent VL performed, VL suppression was greater among those suppressed at initial test 126/135 (93.3%) compared to children with virologic failure 15/66 (22.7%, p<0.0001). Among those failing at first test who achieved viral suppression in follow up, 12/15 (80%) were on a protease inhibitor (PI)-based regimen. In the multivariable analysis of children with subsequent VL testing, children on PI-based 2nd line regimens were 10-fold more likely to achieve viral suppression than children on first-line NNRTI-based ART (adjusted Odds Ratio [aOR] 0.1; 95%CI 0.0-0.4).ConclusionCoverage of initial routine viral load testing among children on ART in western Kenya is high. However, subsequent testing and virologic suppression are low in children with virologic failure on initial routine viral load test. There is an urgent need to improve management and viral load monitoring of children living with HIV experiencing treatment failure to ensure improved long-term outcomes.

Project description:BackgroundContemporary data on the immunologic, haematologic and virologic responses and predictors of virologic failure after initiation of free antiretroviral treatment in Cameroon are needed to evaluate the current treatment-monitoring algorithm and to complement efforts to scale-up and improve on the management of HIV infections.MethodsThis was a cross-sectional study conducted between October 2010 and June 2012. A total of 951 participants aged 18-74 years were recruited from selected approved HIV treatment centres of the Northwest and Southwest regions. This comprised 247 males and 704 females. Demographic, self-reported risk behaviours and socioeconomic data were obtained using a structured questionnaire. Full blood and CD4 + T-cell counts were done using standard automated techniques. Determination of viral load (VL) was done using Abbott RealTime HIV-1 m2000™ system. Data was analysed using SPSS version 17. The statistical significance level was P < 0.05.ResultsThe median duration of antiretroviral therapy (ART) was 24 months. The population mean CD4 + T-cell count was 255.3 cells/μL [95% CI, 236.8 - 273.9]. Overall, 45.9%, 43.8% and 10.2% of the participants had CD4 + T-cell counts of < 200 cells/μL, 200-499 cells/μL and > 500 cells/μL respectively. Anaemia was present in 26.2% of the participants with 62.3%, 25.7% and 12% described as mild, moderate and severe anaemia respectively. Virologic failure occurred in 23.2% of the participants with 12.3% having VL > 10,000 RNA copies/mL. Meanwhile 76.8% of patients attained adequate viral suppression with 40.8% having undetectable viral load. The age group 18-29 years (p = 0.024), co-infection with tuberculosis (p = 0.014), anaemia (p = 0.028) and distance from the treatment centre (p = 0.011) independently predicted virologic failure.ConclusionThe majority of the participants achieved adequate viral suppression after ≥ 6 months of ART. Despite these favourable immuno-haematologic and virologic outcomes, the National AIDS Control Program should step-up efforts to improve on antiretroviral drug distribution, as well as proper assessment and management of anaemia, foster early diagnosis and treatment of tuberculosis and enhance treatment adherence counselling especially in younger patients.

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.

Project description:BackgroundTreatment management after repeated failure of antiretroviral therapy (ART) is difficult due to resistance and adherence challenges. For people who have failed non-nucleoside reverse transcriptase inhibitor-(NNRTI-) and protease inhibitor-(PI-) based regimens with no or limited resistance, remaining on PI-based ART is an option. Using data from an ART strategy trial (A5288) in low/middle-income countries which included this option, we explored whether predictors can be identified distinguishing those who experienced further virologic failure from those who achieved and maintained virologic suppression.MethodsA5288 enrolled people with confirmed HIV-1 RNA ≥ 1000 copies/mL after ≥ 24 weeks of PI-based ART and prior failure on NNRTI-based ART. This analysis focused on the 278 participants with no resistance to the PI being taken and no or limited nucleoside reverse transcriptase inhibitor (NRTI) resistance, who continued their PI with flexibility to change NRTIs. Proportional hazards models were used to evaluate predictors of virologic failure during follow-up (VF: confirmed HIV-1 RNA ≥ 1000 copies/mL at ≥ 24 weeks of follow-up).Results56% of participants were female. At study entry, median age was 40 years, time on ART 7.8 years, CD4 count 169 cells/mm3, HIV-1 RNA 20,444 copies/mL; and 37% had NRTI resistance. The estimated proportion experiencing VF increased from 39% at week 24 to 60% at week 96. In multivariable analysis, significant predictors at study entry of VF were higher HIV-1 RNA (adjusted hazard ratio: 2.20 for ≥ 10,000 versus < 10,000 copies/mL), lower age (1.96 for < 30 versus ≥ 30 years), NRTI resistance (1.74 for present versus absent), lower CD4 count (1.73 for < 200 versus ≥ 200 cells/mm3), and shorter ART duration (1.62 for < 10 versus ≥ 10 years). There was a strong trend in proportion with VF at week 96 with the number of these five risk factors that a participant had, varying from 8% for zero, to 31%, 40%, 73%, and 100% for one, two, three, and four/five. Only 13% of participants developed new NRTI or PI resistance mutations.ConclusionA simple count of five predictors might have value for identifying risk of continued VF. Novel antiretroviral and adherence support interventions are needed to improve virologic outcomes for higher risk individuals.

Dataset Information

Predictors of late virologic failure after initial successful suppression of HIV replication on efavirenz-based antiretroviral therapy.

Background

Methods

Results

Discussion

Publications

Predictors of late virologic failure after initial successful suppression of HIV replication on efavirenz-based antiretroviral therapy.

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