Transmission of HIV-1 minority-resistant variants and response to first-line antiretroviral therapy

• Published in: AIDS (London) Vol. 22; no. 12; pp. 1417 - 1423
• Main Authors: PEUCHANT, Olivia, THIEBAUT, Rodolphe, CAPDEPONT, Sophie, LAVIGNOLLE-AURILLAC, Valérie, NEAU, Didier, MORLAT, Philippe, DABIS, Francois, FLEURY, Hervé, MASQUELIER, Bernard
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 31-07-2008
• Subjects: AIDS/HIV; Anti-HIV Agents - therapeutic use; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Biological and medical sciences; CD4 Lymphocyte Count; Drug Resistance, Viral - genetics; Female; Genotype; HIV Infections - drug therapy; HIV Infections - transmission; HIV Infections - virology; HIV Protease - genetics; HIV Reverse Transcriptase - genetics; HIV-1 - drug effects; HIV-1 - genetics; HIV-1 - isolation & purification; Human immunodeficiency virus 1; Human viral diseases; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Infectious diseases; Male; Medical sciences; Mutation; Pharmacology. Drug treatments; Polymerase Chain Reaction - methods; Retrospective Studies; RNA, Viral - blood; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Viral Load; Immunopathology; Antiretroviral agent; Treatment resistance; HIV-1 virus; antiretroviral therapy; Transmission; Retroviridae; AIDS; minority variants; Immune deficiency; Lentivirus; Infection; Virus; Chemotherapy; Treatment; Viral disease; Antiviral; Human immunodeficiency virus; HIV-1 drug resistance
• ISSN: 0269-9370; 1473-5571
• DOI: 10.1097/qad.0b013e3283034953

The transmission of drug-resistant HIV-1 can impair the virological response to antiretroviral therapy. Minority-resistant variants have been detected in acute seroconverters. We investigated the clinical relevance of the detection of majority and minority-resistant variants in an observational study in antiretroviral therapy naive, recently infected patients.
We included patients infected between 1996 and 2005, with a plasma sample obtained less than 18 months after seroconversion and prior to antiretroviral therapy initiation. Majority-resistant variants were determined by direct population sequencing. Minority-resistant variants were searched by allele-specific PCR for the mutations K103N and M184V in reverse transcriptase and L90M in protease. The association between resistance and viroimmunological response to antiretroviral therapy was estimated by using a piecewise linear mixed model.
Majority-resistant variants were detected in 23/172 (13.4%) patients. Patients with majority-resistant variants had a lower mean plasma viral load and higher mean CD4 cell count at baseline compared with those without resistance. The decrease in viral load between 1 and 6 months on antiretroviral therapy was significantly steeper in patients with sensitive viruses compared with those with majority-resistant variants (P = 0.029). Minority-resistant variants were detected in 21/73 (29%) patients with wild-type viruses at sequencing analysis. The presence of minority-resistant variants did not modify baseline viral load and CD4 cell count and did not affect the changes in viral load and CD4 cell count.
The transmission of majority-resistant variants, but not minority-resistant variants, influenced the response to antiretroviral therapy in this prospective study. The detection of the transmission of minority-resistant variants warrants further clinical validation.