Reduced Antiretroviral Drug Susceptibility Among Patients With Primary HIV Infection

• Published in: JAMA : the journal of the American Medical Association 1999-09, Vol.282 (12), p.1142-1149
• Main Authors: Little, Susan J, Daar, Eric S, D'Aquila, Richard T, Keiser, Philip H, Connick, Elizabeth, Whitcomb, Jeannette M, Hellmann, Nicholas S, Petropoulos, Christos J, Sutton, Lorraine, Pitt, Jacqui A, Rosenberg, Eric S, Koup, Richard A, Walker, Bruce D, Richman, Douglas D
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; AIDS/HIV; Anti-HIV Agents - pharmacology; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Biological and medical sciences; Demographics; Drug resistance; Drug Resistance, Microbial - genetics; Drug therapy; Female; HIV; HIV Infections - drug therapy; HIV Infections - epidemiology; HIV Infections - transmission; HIV Infections - virology; HIV Protease - genetics; HIV Protease Inhibitors - pharmacology; HIV Reverse Transcriptase - genetics; HIV-1 - drug effects; HIV-1 - genetics; Human immunodeficiency virus; Humans; Male; Medical sciences; Middle Aged; Mutation; Pharmacology. Drug treatments; Polymorphism, Genetic; Retrospective Studies; Reverse Transcriptase Inhibitors - pharmacology; Risk Factors; Studies
• ISSN: 0098-7484; 1538-3598
• DOI: 10.1001/jama.282.12.1142

CONTEXT The transmission of drug-resistant human immunodeficiency virus (HIV) has been documented, but the prevalence of such transmission is unknown. OBJECTIVE To assess the spectrum and frequency of antiretroviral susceptibility among subjects with primary HIV infection. DESIGN, SETTING, AND PATIENTS Retrospective analysis of 141 subjects identified from clinical research centers in 5 major metropolitan areas, enrolled from 1989 to 1998, with HIV seroconversion within the preceding 12 months and no more than 7 days' prior antiretroviral (ARV) therapy. MAIN OUTCOME MEASURES Phenotypic and genotypic ARV susceptibility of HIV from plasma samples. RESULTS The transmission of drug-resistant HIV as assessed by a greater than 10-fold reduction in ARV susceptibility to 1 or more drugs was observed in 3 (2%) of 141 subjects, including to a nonnucleoside reverse transcriptase inhibitor in 1 patient and to a nucleoside reverse transcriptase inhibitor and a protease inhibitor in 2 patients. Population-based sequence analysis of these 3 samples identified multidrug-resistance mutations in reverse transcriptase (M184V, T215Y, K219K/R) and protease (L10I/V, K20R, M36I, M46I, G48V, L63P, A71T, V77I, V82T, I84V, L90M) in the 2 latter patient samples, along with numerous polymorphisms. A reduction in susceptibility of greater than 2.5- to 10-fold to 1 or more drugs was observed in viral isolates from 36 patients (26%). Sequence analysis of these 36 samples identified well-characterized drug resistance mutation in reverse transcriptase and protease in only 1 of these patients. CONCLUSIONS Reductions in drug susceptibility of more than 10-fold were rare among this cohort of recently HIV-infected subjects and were distributed among each of the 3 major classes of ARV drugs tested. Reductions in susceptibility of more than 2.5- to 10-fold to certain ARV drugs of unknown clinical significance were highly prevalent among newly infected patients. Resistance testing may be warranted to monitor the frequency of drug resistance over time and to assess the potential for geographic variability.