Virologic, clinical and immunologic responses following failure of first‐line antiretroviral therapy in Haiti

Macarthur Charles,Jean W Pape,Daniel W Fitzgerald,Warren D Johnson,Roy M Gulick,Paul D Leger,Colette Guiteau,Patrice Severe,Alexandra Apollon

doi:10.7448/ias.15.2.17375

Abstract

BackgroundSince HIV-1 RNA (viral load) testing is not routinely available in Haiti, HIV-infected patients receiving antiretroviral therapy (ART) are monitored using the World Health Organization (WHO) clinical and/or immunologic criteria. Data on survival and treatment outcomes for HIV-1 infected patients who meet criteria for ART failure are limited. We conducted a retrospective study to compare survival rates for patients who experienced failure on first-line ART by clinical and/or immunologic criteria and switched to second-line ART vs. those who failed but did not switch.MethodsPatients receiving first-line ART at the GHESKIO Center in Port-au-Prince, Haiti, who met WHO clinical and immunologic criteria for failure were identified. Survival and treatment outcomes were compared in patients who switched their ART regimen and those who did not. Cox regression analysis was used to determine predictors of mortality after failure of first-line ART.ResultsOf 3126 patients who initiated ART at the GHESKIO Center between 1 March 2003 and 31 July 2008, 482 (15%) met WHO immunologic and/or clinical criteria for failure. Among those, 195 (41%) switched to second-line ART and 287 (59%) did not. According to Kaplan–Meier survival analysis, the probability of survival to 12 months after failure of first-line ART was 93% for patients who switched to second-line ART after failure and 88% for patients who did not switch. Predictors of mortality after failure of first-line ART were weight in the lowest quartile for sex, CD4 T cell count ≤ 100, adherence < 90% at the time of failure and not switching to second-line ART.ConclusionsPatients who failed first-line ART based on clinical and/or immunologic criteria and did not switch to second-line therapy faced a higher mortality than those who switched after failure. To decrease mortality, interventions to identify patients in whom ART may be failing earlier are needed urgently. In addition, there is a major need to optimize second-line antiretroviral regimens for improved potency, lower toxicity and greater convenience for patients.

Highlights

7 million HIV-infected patients in resource-poor settings have initiated antiretroviral therapy (ART) since 2003, and as many as 1 million of these patients may have virologic failure with ongoing HIV replication [1Á3]
The Development of Antiretroviral Therapy (DART) trial showed that CD4 testing led to small but significant decreases in the proportion of person-years spent with low CD4-cell counts and lower rates of HIV disease progression and death from the third year on ART as compared with clinical monitoring [10]
Study population Between 1 March 2003 and 31 July 2008, 3615 HIV-1 infected patients 13 years and older were initiated on first-line ART at the GHESKIO clinic in Port-au-Prince, Haiti, and 3126 patients were alive and in active follow-up 6 months after initiating first-line therapy and were at risk for ART failure

Summary

Introduction

7 million HIV-infected patients in resource-poor settings have initiated antiretroviral therapy (ART) since 2003, and as many as 1 million of these patients may have virologic failure with ongoing HIV replication [1Á3]. Due to a lack of HIV-1 RNA monitoring in resource-poor settings, these patients will continue on first-line ART until virologic failure progresses to a 50% decrease in CD4 T cell count (immunologic failure) or the recurrence of symptomatic HIV disease (clinical failure). Several studies suggest that where HIV RNA testing is not routinely used, switching to second-line ART is delayed and patients face a high early mortality after switching. Since HIV-1 RNA (viral load) testing is not routinely available in Haiti, HIV-infected patients receiving antiretroviral therapy (ART) are monitored using the World Health Organization (WHO) clinical and/or immunologic criteria. Conclusions: Patients who failed first-line ART based on clinical and/or immunologic criteria and did not switch to second-line therapy faced a higher mortality than those who switched after failure. There is a major need to optimize second-line antiretroviral regimens for improved potency, lower toxicity and greater convenience for patients

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Discussion

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