Resistance Testing for Management of HIV Virologic Failure in Sub-Saharan Africa : An Unblinded Randomized Controlled Trial
Mark J Siedner, Mahomed-Yunus S Moosa, Suzanne McCluskey, Rebecca F Gilbert, Selvan Pillay, Isaac Aturinda, Kevin Ard, Winnie Muyindike, Nicholas Musinguzi, Godfrey Masette, Melendhran Pillay, Pravikrishnen Moodley, Jaysingh Brijkumar, Tamlyn Rautenberg, Gavin George, Rajesh T Gandhi, Brent A Johnson, Henry Sunpath, Mwebesa B Bwana, Vincent C Marconi, Mark J Siedner, Mahomed-Yunus S Moosa, Suzanne McCluskey, Rebecca F Gilbert, Selvan Pillay, Isaac Aturinda, Kevin Ard, Winnie Muyindike, Nicholas Musinguzi, Godfrey Masette, Melendhran Pillay, Pravikrishnen Moodley, Jaysingh Brijkumar, Tamlyn Rautenberg, Gavin George, Rajesh T Gandhi, Brent A Johnson, Henry Sunpath, Mwebesa B Bwana, Vincent C Marconi
Abstract
Background: Virologic failure in HIV predicts the development of drug resistance and mortality. Genotypic resistance testing (GRT), which is the standard of care after virologic failure in high-income settings, is rarely implemented in sub-Saharan Africa.
Objective: To estimate the effectiveness of GRT for improving virologic suppression rates among people with HIV in sub-Saharan Africa for whom first-line therapy fails.
Design: Pragmatic, unblinded, randomized controlled trial. (ClinicalTrials.gov: NCT02787499).
Setting: Ambulatory HIV clinics in the public sector in Uganda and South Africa.
Patients: Adults receiving first-line antiretroviral therapy with a recent HIV RNA viral load of 1000 copies/mL or higher.
Intervention: Participants were randomly assigned to receive standard of care (SOC), including adherence counseling sessions and repeated viral load testing, or immediate GRT.
Measurements: The primary outcome of interest was achievement of an HIV RNA viral load below 200 copies/mL 9 months after enrollment.
Results: The trial enrolled 840 persons, divided equally between countries. Approximately half (51%) were women. Most (72%) were receiving a regimen of tenofovir, emtricitabine, and efavirenz at enrollment. The rate of virologic suppression did not differ 9 months after enrollment between the GRT group (63% [263 of 417]) and SOC group (61% [256 of 423]; odds ratio [OR], 1.11 [95% CI, 0.83 to 1.49]; P = 0.46). Among participants with persistent failure (HIV RNA viral load ≥1000 copies/mL) at 9 months, the prevalence of drug resistance was higher in the SOC group (76% [78 of 103] vs. 59% [48 of 82]; OR, 2.30 [CI, 1.22 to 4.35]; P = 0.014). Other secondary outcomes, including 9-month survival and retention in care, were similar between groups.
Limitation: Participants were receiving nonnucleoside reverse transcriptase inhibitor-based therapy at enrollment, limiting the generalizability of the findings.
Conclusion: The addition of GRT to routine care after first-line virologic failure in Uganda and South Africa did not improve rates of resuppression.
Primary funding source: The President's Emergency Plan for AIDS Relief and the National Institute of Allergy and Infectious Diseases.
Conflict of interest statement
Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M21-2229.
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Source: PubMed