Persistence of Transmitted Drug Resistance among Subjects with Primary Human Immunodeficiency Virus Infection

Abstract

Following interruption of antiretroviral therapy among individuals with acquired drug resistance, preexisting drug-sensitive virus emerges relatively rapidly. In contrast, wild-type virus is not archived in individuals infected with drug-resistant human immunodeficiency virus (HIV) and thus cannot emerge rapidly in the absence of selective drug pressure. Fourteen recently HIV-infected patients with transmitted drug-resistant virus were followed for a median of 2.1 years after the estimated date of infection (EDI) without receiving antiretroviral therapy. HIV drug resistance and pol replication capacity (RC) in longitudinal plasma samples were assayed. Resistance mutations were characterized as pure populations or mixtures. The mean time to first detection of a mixture of wild-type and drug-resistant viruses was 96 weeks (1.8 years) (95% confidence interval, 48 to 192 weeks) after the EDI. The median time to loss of detectable drug resistance using population-based assays ranged from 4.1 years (conservative estimate) to longer than the lifetime of the individual (less conservative estimate). The transmission of drugresistant virus was not associated with virus with reduced RC. Sexual transmission of HIV selects for highly fit drug-resistant variants that persist for years. The prolonged persistence of transmitted drug resistance strongly supports the routine use of HIV resistance genotyping for all newly diagnosed individuals.

Asymptomatic CMV Replication During Early Human Immunodeficiency Virus (HIV) Infection Is Associated With Lower CD4/CD8 Ratio During HIV Treatment

“…Six hundred four blood samples were collected longitudinally from 108 recently HIV-infected participants from the San Diego Primary Infection Resource Consortium [18] between October 1996 and October 2012. All participants were CMV and EBV seropositive.…”

Screening for antiretroviral drug resistance among treatment-naive human immunodeficiency virus type 1-infected individuals in Lebanon

“…Hence, first-line NNRTIs available in Lebanon will fail at controlling HIV-1 infection among these participants. M46I, known as a stable mutation hampering PI-based antiretroviral regimens [41], was not detected in any of our study participants; moreover, L90M, a frequently reported mutation, was detected in one patient. Our results indicate that the use of recommended treatment regimen will fail at controlling HIV-1 among the study participants as indicated by the type of detected HIVDR mutations.…”

Human immunodeficiency virus (HIV) in Washington, D.C.: Prevalence of antiretroviral resistance in treatment nave patients from 2007 to 2010

“…TDR mutations may have been underestimated as low prevalence mutations are not detected by most standard sequencing techniques unless the mutation is present in >10-30% of the population (Bellecave et al, 2013;Johnson et al, 2008). In some cases, the wild-type virus may become the dominant virus and certain TDR mutations may not be detected in the absence of selective drug pressure, though this may occur only after several years (Gandhi et al, 2003;Little et al, 2008;Yerly et al, 2008). It is possible the TDR rate in Washington, D.C. may be higher than the observed rate of 17%.…”