HIV-1 Drug Resistance Profiles in Children and Adults With Viral Load of <50 Copies/mL Receiving Combination Therapy

Abstract

Based on the samples that could be amplified, low-level viremia in children and adults receiving HAART with prolonged suppression of viremia to less than 50 copies/mL of HIV-1 RNA may result primarily from archival, pre-HAART virus, reflecting earlier treatment conditions, and does not appear to require development of new, HAART-selected mutations reflecting partial resistance to therapy. Low-level viremia below 50 copies/mL may represent less of a concern regarding impending drug failure of current HAART regimens. However, the archival drug-resistant virus may be relevant regarding future treatment strategies.

Influence of Treatment Complexity on Adherence and Incidence of Blips in HIV/HCV Coinfected Patients

“…12 Others studies suggest that the phenomenon of blips originates from activation and expansion of latently infected cells and from the appearance and selection of new drug-resistant strains. 13,14 Approximately 30% of HIV-infected patients are coinfected with hepatitis C virus (HCV). After the release of highly active antiretroviral therapy, liver disease has become the leading cause of morbidity and mortality in HIV patients.…”

Potential Implication of Residual Viremia in Patients on Effective Antiretroviral Therapy

“…19,[21][22][23][24][25][26] If the persistence of residual viremia consisting of short-lived free viruses [3][4][5][6] is the result of continuous cycles of virus replication occurring in tissues during ART, then the evolution of drug-resistant residual viruses would be prevalent, which is generally not found in patients with suppressive therapy. 10,27,28 Moreover, there is evidence demonstrating that virus replication is almost completely blocked in tissues during ART. [29][30][31] These data point to a scenario in which under optimal antiviral concentrations, residual viremia might arise as a result of persistent release of the virus at low levels from the highly stable productively infected cells.…”

“…1), except for an occasional transient rise (''blips'') in VL during therapy. 10 The underlying causes for these blips are still not clear.…”

“…[10][11][12][13][14][15] This lowlevel viremia is often termed ''residual viremia.'' The single copy vRNA detection assay can detect ranges of vRNA from 1 to 32 copies in plasma of patients with effective virus suppression by ART.…”

Characterisation, Evaluation and Clinical Significance of Latent HIV-1 Reservoirs and Therapeutic Strategies for HIV Eradication

“…The low level-viremia seen in HAART-treated adults and children was shown to be related to pre-HAART virus, with no evidence of drug-resistant mutation selection. Since there was no virus evolution, it has been suggested that no residual virus replication was occurring [100]. A novel RT-PCR method for genotyping the HIV-1 protease gene at low viral loads (5 copies/ml) revealed that children who began successful inhibitory HAART soon after birth, also did not exhibit drug-resistance mutations to the protease inhibitor nelfinavir and the virus resembled that found in resting CD4+ T-cells [101].…”