Analysis of HIV-1 reverse transcriptase and protease sequences in paired plasma and lymphoid tissue specimens from HIV-1 infected individuals

Objectives: To determine how representative the genotype of HIV-1 circulati ng in plasma is of the genotype of the virus present in lymphoid tissue. Methods: Paired plasma and tonsillar tissue samples were prospectively obta ined from patients with various levels of plasma HIV-1 RNA who were receivi ng combination antiretroviral therapy. HIV-1 reverse transcriptase and prot ease sequences were amplified from plasma and lymphoid tissue specimens by nested polymerase chain reaction and analyzed using an automated sequencing system. Results were compared with consensus HIV-1 sequences to determine whether drug-resistance mutations were present in the regions analyzed. Results: HIV-1 protease sequences were compared in 11 plasma/tissue pairs o btained from eight patients; HIV reverse transcriptase sequences were compa red in 12 plasma/ tissue pairs obtained from nine patients. Sequence homolo gy between plasma and tissue RNA, tissue RNA and DNA, and plasma and tissue DNA ranged from 97% to 100%. Few discrepancies were found when the percent age of mutant sequences at resistance codons was compared among paired samp les. In most instances, tissue RNA or plasma contained a higher percentage of mutant sequences than did tissue DNA. Conclusion: The genotype of plasma HIV-1 is similar to the genotype of the virus in lymphoid tissue. Resistance studies using plasma samples should pr ovide accurate information regarding the genotype of HIV-1 in lymphoid tiss ues. (C) 2001 Lippincott Williams & Wilkins.