HIV-1 proviral resistance mutations: usefulness in clinical practice

Area of Science:

• Virology
• Molecular Biology
• Infectious Diseases

Background:

• Transmitted HIV strains can carry drug resistance mutations.
• Current detection methods analyze HIV-1 drug resistance mutations in plasma viral RNA.
• HIV-1 proviral DNA, persisting in infected cells, presents an alternative detection marker.

Purpose of the Study:

• To assess the prevalence and persistence of HIV-1 drug resistance mutations in CD4 cell DNA.
• To compare DNA-based detection with standard RNA genotyping.
• To evaluate the impact of pre-existing mutations on treatment outcomes.

Main Methods:

• Prospective study of 69 treatment-naïve patients initiating protease inhibitor (PI) or nonnucleoside reverse transcriptase inhibitor (NNRTI) therapy.
• Analysis of HIV-1 drug resistance mutations in CD4 cell DNA and plasma viral RNA before and after therapy.
• Follow-up of 40 patients to assess mutation persistence for at least one year.

Main Results:

• A higher proportion of mutations were detected in CD4 cell DNA (90%) compared to plasma RNA (66%) before therapy.
• Four key mutations were exclusively found in CD4 cell DNA.
• Detected mutations persisted for at least one year in 40 followed patients.
• New key mutations emerged in CD4 cells during successful treatment.

Conclusions:

• HIV-1 DNA genotyping detected a significantly higher proportion of drug resistance mutations than standard RNA genotyping.
• Detected mutations persisted for at least one year, irrespective of therapy.
• Pre-existing resistance mutations did not compromise treatment outcomes if the specific drug was not used.
• HIV-1 DNA analysis is valuable for chronic infections and therapy switching in patients with undetectable viremia.