 |
|
|
| |
Resistance Testing Did Not Boost HIV
Control Rates in Randomized African Trial
|
| |
| |
CROI 2021, Conference on Retroviruses and Opportunistic Infections, March 6-10, 2021
Mark Mascolini
Genotypic resistance testing after first-line antiretroviral failure did not lift virologic suppression rates when compared with standard care after 9 months in an 840-person randomized trial in public clinics of Uganda and South Africa [1]. But people who got resistance testing had lower rates of antiretroviral resistance at the end of the trial.
In high-income countries, genotypic resistance testing is standard practice to guide management after virologic failure. But in low-income regions guidelines typically recommend adherence counseling and continued viral load monitoring to inform management. Researchers in the United States, Uganda, and South Africa observed that genotypic resistance testing has some advantages that may now support adoption of this strategy in low-income countries, including falling cost of genotyping, rising cost of second-line regimens, and use of resistance testing as an adherence tool.
A team from Massachusetts General Hospital, Mbarara University, and the University of KwaZulu-Natal planned the REVAMP study as an open-label randomized trial "to assess effectiveness and cost-effectiveness of resistance testing after first-line failure in sub-Saharan Africa." Researchers recruited participants at 5 public clinics in Mbarara and Durban who met the following inclusion criteria: (1) first-line antiretroviral therapy (ART) for at least 5 months, (2) a viral load of 1000 copies or more in the past 3 months, (3) no prior use of protease inhibitors, and (4) no known resistance to antiretrovirals. They excluded people already eligible for second-line therapy by local guidelines. If people became eligible for a second regimen during the trial because genotyping found resistant virus, they switched to a new regimen immediately.
Researchers randomized participants to standard care (with adherence counseling and viral load monitoring to guide care) or to resistance testing (with genotypic resistance testing guiding care). The primary outcome was reaching a viral load below 200 copies 9 months after enrollment, with death and loss from observation counted as viral load failures. The trial was powered to detect a 10% difference in that outcome between study arms.
Among 423 people enrolled in the standard-care arm and 417 enrolled in the resistance-testing arm, half in each group received care in Uganda and half in South Africa, median ages was 37 in each group, and about half in each group were women. Median ART duration stood at 3.5 years in the standard-care group and 3.0 years in the resistance-testing group. Three quarters of participants in each group were taking efavirenz plus tenofovir (TDF) and emtricitabine (FTC) or lamivudine (3TC). Most of the rest were taking a nevirapine regimen.
After 9 months the resistance-testing group did not differ significantly from the standard-care group in the primary outcome (viral load below 200 copies, 63% vs 61%, P = 0.45) or in several secondary outcomes: viral load below limit of detection (P = 0.41), viral suppression on first-line therapy (P = 0.10), retention in care (P = 0.61), or 9-month survival (P = 0.18). A significantly higher proportion in the resistance-testing group than the standard-care group had virologic failure without emergence of antiretroviral resistance (about 40% vs 25%, P = 0.01). All analyses were intention-to-treat.
Among men statistical analysis saw a trend toward more likely attainment of a viral load below 200 copies with resistance testing than with standard care (odds ratio 1.37, 95% confidence interval 0.91 to 2.08). But that association went in the opposite direction among women (odds ratio 0.85, 95% confidence interval 0.56 to 1.28).
Although genotypic resistance testing in Ugandans and South Africans with a viral load above 1000 copies on first-line antiretroviral therapy did not favor reaching a sub-200 viral load at 9 months compared with standard care, the REVAMP team noted that people randomized to the resistance-assay arm ended up with fewer antiretroviral resistance mutations, which could affect longer-term antiretroviral response. The researchers noted that cost-effectiveness analyses of the main finding are underway.
Reference
1. Siedner M, Moosa MY, McCluskey S, et al. Randomized trial of resistance testing for virologic failure in sub-Saharan Africa. CROI 2021, Conference on Retroviruses and Opportunistic Infections, March 6-10, 2021. Abstract 95.
|
| |
|
|
|
|
|
