Mark J Siedner1, Mahomed-Yunus S Moosa2, Suzanne McCluskey3, Rebecca F Gilbert4, Selvan Pillay2, Isaac Aturinda5, Kevin Ard3, Winnie Muyindike5, Nicholas Musinguzi5, Godfrey Masette5, Melendhran Pillay6, Pravikrishnen Moodley6, Jaysingh Brijkumar2, Tamlyn Rautenberg7, Gavin George2, Rajesh T Gandhi3, Brent A Johnson8, Henry Sunpath2, Mwebesa B Bwana5, Vincent C Marconi9. 1. Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, Mbarara University of Science and Technology, Mbarara, Uganda, Africa Health Research Institute, KwaZulu-Natal, South Africa, and University of KwaZulu-Natal, Durban, South Africa (M.J.S.). 2. University of KwaZulu-Natal, Durban, South Africa (M.S.M., S.P., J.B., G.G., H.S.). 3. Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (S.M., K.A., R.T.G.). 4. Massachusetts General Hospital, Boston, Massachusetts (R.F.G.). 5. Mbarara University of Science and Technology, Mbarara, Uganda (I.A., W.M., N.M., G.M., M.B.B.). 6. National Health Laboratory Service, Durban, South Africa (M.P., P.M.). 7. Griffith University, Brisbane, Queensland, Australia (T.R.). 8. University of Rochester, Rochester, New York (B.A.J.). 9. Emory University School of Medicine and Rollins School of Public Health, Atlanta, Georgia (V.C.M.).
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.
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.
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