Assessing the paradox between transmitted and acquired HIV-1 drug resistance in the Swiss HIV Cohort Study from 1998 to 2012.

BACKGROUND  Transmitted HIV-1 drug-resistance mutations(TDR) are transmitted from treatment-failing or treatment-naïve patients. Although prevalence of drug-resistance in treatment-failing patients has declined in developed countries, TDR prevalence has not. Mechanisms causing this paradox are poorly explored. METHODS  We included recently-infected, treatment-naïve patients with genotypic-resistance-tests performed ≤1year post-infection and <2013. Potential risk factors for TDR were analyzed using logistic regression. Association of TDR prevalences with population viral load(PVL) from treatment-patients during 1997-2011 was estimated with Poisson regression for all TDR and individually for most frequent resistance-mutations against each drug class(M184V/L90M/K103N). RESULTS  We included 2421 recently-infected, treatment-naïve patients and 5399 treatment-failing patients. TDR prevalence fluctuated considerably over time. Two opposing developments could explain these fluctuations: generally continuous increases in TDR(Odds Ratio[OR]=1.13,p=0.010), punctuated by sharp decreases when new drug-classes were introduced. Overall, TDR prevalence increased with decreasing PVL(Rate Ratio[RR]=0.91/1000Log10-PVL,p=0.033). Additionally, we observed that the transmitted high-fitness-cost mutation M184V was positively associated with PVL of treatment-failing patients carrying M184V(RR=1.50/100Log10-PVL,p<0.001). Such association was absent and negative for K103N(RR-K103N=1.00/100Log10-PVL,p=0.99) and L90M(RR-L90M=0.75/100Log10-PVL,p=0.022), respectively. CONCLUSIONS  Transmission of antiretroviral drug-resistance is temporarily reduced by the introduction of new drug classes and driven by treatment-failing and treatment-naïve patients. These findings suggest a continuous need for new drugs, early detection/treatment of HIV-1-infection.