Stability of transmitted drug-resistant HIV-1 species

Abstract

Since transmitted resistance can be detected years after infection, it is now worthwhile carrying out resistance tests on newly diagnosed patients in which it is known that the level of transmitted resistance in the population warrants such testing.

HIV, transmitted drug resistance, and the paradox of preexposure prophylaxis

“…The main experimental parameters for specifying PrEP regimens were: (i) efficacy in preventing infections with wild-type strains (range: 30-90%); (ii) relative efficacy in preventing infection with resistant strains (range: zero to half as efficient against resistant strains compared with wild-type); (iii) degree of PrEP-induced reduction of viremia during primary infection (range: no reduction to 2log 10 ); (iv) rate of emergence of resistance in infected individuals on PrEP (range: 10-99% per y); and (v) reversion rates of resistant strains (that were acquired when an individual was taking PrEP) to wild-type strains (range: 6 mo or less). We also assumed resistant strains acquired through sexual transmission could revert and that reversion would take at least 2 y, as has been observed in empirical studies (5,(36)(37)(38).…”

The Fitness Cost of Mutations Associated with Human Immunodeficiency Virus Type 1 Drug Resistance Is Modulated by Mutational Interactions

“…However, in vivo observations do not always show the expected relationship between fitness cost and persistence, and a range of persistence for the same mutation has been noted among patients infected with multidrug-resistant viruses. For instance, M184V mutants have been found to persist between 4 and 16 months after primary infection, while persistence of K103N can range between 1 and 3 years (2,3,5,17). We hypothesize that mutational interactions in multidrug-resistant viruses might modulate the fitness cost of resistance mutations and might influence the rate of reversion and persistence of mutations.…”

“…Compensatory evolution through the acquisition of additional mutations generally results in partial restorations of viral fitness (19). Despite the accumulation of compensatory mutations, drug-resistant viruses tend to replicate less efficiently than wild-type viruses.The transmission of drug-resistant mutants with diminished fitness and the evolution of these viruses in the absence of drug are typically associated with the reversion and loss of resistance mutations (3,9,22). Different rates of persistence and reversion of mutations have been documented in vivo and have usually been explained by the impact of mutations on viral fitness.…”

“…The transmission of drug-resistant mutants with diminished fitness and the evolution of these viruses in the absence of drug are typically associated with the reversion and loss of resistance mutations (3,9,22). Different rates of persistence and reversion of mutations have been documented in vivo and have usually been explained by the impact of mutations on viral fitness.…”

Protection against Rectal Transmission of an Emtricitabine-Resistant Simian/Human Immunodeficiency Virus SHIV162p3M184VMutant by Intermittent Prophylaxis with Truvada

“…Assessing the impact of circulating M184V viruses on PrEP efficacy in humans is difficult and often not feasible because it requires sampling early during infection and M184V tends to rapidly revert and become undetectable due to its high fitness costs (3,6,9,28). Reversion of M184V to the wild type (WT) limits the accurate assessment of the impact of this mutation on PrEP effectiveness.…”