The accumulation of human immunodeficiency virus (HIV) resistance mutations can compromise treatment outcomes and promote transmission of drug-resistant virus. We conducted a study to determine the duration and evolution of genotypic drug resistance in the female genital tract among HIV-1-infected women failing first-line therapy.
Treatment failure was diagnosed based on World Health Organization (WHO) clinical or immunologic criteria, and second-line therapy was initiated. Stored plasma and genital samples were tested to determine the presence and timing of virologic failure and emergence of drug resistance. The median duration of genital shedding of genotypically resistant virus prior to regimen switch was estimated.
Nineteen of 184 women were diagnosed with treatment failure, of whom 12 (63.2%) had confirmed virologic failure at the switch date. All 12 women with virologic failure (viral load, 5855–1 086 500 copies/mL) had dual-class resistance in plasma. Seven of the 12 (58.3%) had genital HIV-1 RNA levels high enough to amplify (673–116 494 copies/swab), all with dual-class resistance. The median time from detection of resistance in stored samples to regimen switch was 895 days (95% confidence interval [CI], 130–1414 days) for plasma and 629 days (95% CI, 341–984 days) for genital tract secretions.
Among women diagnosed with treatment failure using WHO clinical or immunologic criteria, over half had virologic failure confirmed in stored samples. Resistant HIV-1 RNA was shed in the genital tract at detectable levels for ≈1.7 years before failure diagnosis, with steady accumulation of mutations. These findings add urgency to the ongoing scale-up of viral load testing in resource-limited settings.
Below: Percentage of women tested who had specific resistance mutations detected in (A) plasma and (B) genital tract secretions at the switch to second-line therapy. Each type of mutation is on the x-axis. The y-axis shows the percentage of samples in which this mutation was detected or not detected in each compartment, for all participating women (n = 12). In B, the percentage of samples that could not be amplified (5 of 12) is shown and included across the spectrum of mutations. Abbreviations: NNRTI, nonnucleoside reverse-transcriptase inhibitor; NRTI, nucleoside/nucleotide reverse-transcriptase inhibitor; PI, protease inhibitor; TAM, thymidine analog mutation.
Full article at: http://goo.gl/Vu4OTy
By: Susan M. Graham,1,2,3,4,5 Vrasha Chohan,1,6 Keshet Ronen,3,6 Ruth W. Deya,1 Linnet N. Masese,1 Kishor N. Mandaliya,3 Norbert M. Peshu,4 Dara A. Lehman,3,6 R. Scott McClelland,1,2,3,5 and Julie Overbaugh6
1Departments of, Medicine
3Global Health, University of Washington, Seattle
4Centre for Geographic Medicine and Research – Coast, Kenya Medical Research Institute, Kilifi
5Institute of Tropical and Infectious Diseases, University of Nairobi, Kenya
6Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, Washington
Correspondence: S. M. Graham, University of Washington, Box 359909, 325 Ninth Avenue, Seattle, WA 98104-2499
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