Article : Transmission of Drug-Resistant HIV by ART-Naive Individuals

Transmission of Drug-Resistant HIV by ART-Naive Individuals

Charles B. Hicks, MD reviewing Mourad R et al. AIDS 2015 Sep 24.


A phylotype-based analysis demonstrates the role of ART-naive HIV-infected individuals in the ongoing transmission of drug-resistant viruses.

What proportion of transmitted HIV drug resistance originates from antiretroviral therapy (ART)-naive sources? To find out, investigators studied sequences from the U.K. HIV Drug Resistance database, which includes samples from both ART-naive and experienced individuals.

Using a novel phylogenetic method that models transmission lineages of drug-resistance mutations (DRMs) based on genetic and trait similarities among contemporary HIV sequences, the researchers analyzed 24,550 HIV-1 subtype B sequences collected between 1997 and 2011. They estimated persistence of transmission chains using a least-squares molecular clock inference approach.

Based on this approach, about 70% of transmitted drug resistance originated from an ART-naive source (naive-to-naive transmission). The most commonly transmitted DRMs were K103N, T215D, and T215S in reverse transcriptase and L90M in protease. Reversion to wild-type virus was uncommon — for example, the K103N mutation was estimated to persist in the drug-naive population for 13.5 years. Among all DRMs found in naive-to-naive transmission chains, those with little effect on viral fitness (K103N, L90M) were relatively common; DRMs with high fitness costs (K65R, M184V) were not found. The prolonged persistence of resistance reservoirs in the ART-naive, HIV-infected population is consistent with observed resistance rates in patients with newly diagnosed HIV infection. Improved efficacy of newer ART regimens has lowered the treatment-failure rate and reduced the frequency of DRM emergence among treated patients, suggesting that an increasingly large proportion of transmitted resistance emanates from ART-naive individuals who are infected with resistant viruses and not in care.


Citation(s):

Mourad R et al. A phylotype-based analysis highlights the role of drug-naive HIV-positive individuals in the transmission of antiretroviral resistance in the UK. AIDS 2015 Sep 24; 29:1917.

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