Investigators in California have found that over a quarter of their treatment-naive patients with HIV infection of unknown duration have resistance to at least one class of antiretroviral drugs. The investigators suggest that their study shows the value of using drug resistance tests as part of routine HIV care. The study is published in the February 1st edition of Clinical Infectious Diseases.
Earlier studies have shown that between 8-20% of newly infected HIV-positive individuals have primary drug resistance. HIV treatment guidelines, such as those of the International AIDS Society, recommend that patients who were known to have been infected with HIV within the previous year should have a resistance test to see if primary resistance is present.
However, investigators in San Diego, California, noted that, as few HIV-positive individuals are diagnosed within the first year of infection, the value of resistance testing as part of routine clinical practice may be open to question.
They therefore conducted a study involving 103 individuals with HIV infection of unknown duration to determine the prevalence of drug resistance. The study was conducted in 2005 and the investigators conducted genotypic resistance tests on blood samples provided after the patients gave consent to participate in the study.
A total of 26 (25%) of patients had resistance to at least one class of antiretrovirals; 6% of individuals had resistance to two classes of anti-HIV drugs; and 1% had resistance to drugs from all the three main classes of antiretrovirals.
The most commonly detected resistance mutation was K103N which confers resistance to drugs in the NNRTI class. This was present in twelve patients, although analysis revealed that this was not due to a transmission cluster. The next most common mutation was M184V (associated with resistance to the nucleoside analogue 3TC) was present in six patients. The investigators note that this mutation is not readily transmitted between individuals. Two patients with M184V resistance also had NNRTI resistance and two had resistance to protease inhibitors.
Two patients had identical patterns of resistance. The investigators questioned these two individuals and established that they lived in the same household, and one the patients was in the habit of taking the other individual's antiretrovirals when he felt unwell.
“These investigations found an extremely high prevalence of drug-resistant HIV among antiretroviral-naïve patients receiving medical care”, comment the investigators. They add that it also demonstrated, “a higher rate of HIV drug resistance among antiretroviral-naïve individuals with unknown duration of HIV infection than previously described.”
The investigators attribute this high rate of resistance to three causes: transmission of primary resistance; failure of post-exposure prophylaxis; and, possibly, the sharing of anti-HIV drugs.
The investigators note that given the level of resistance indicated by this study, resistance testing would for all patients before beginning treatment would be cost effective “whether the duration of HIV infection is known or unknown.”
They recommend, “ongoing patient education regarding the mechanism of antiretroviral drug resistance and routine inquiries of patients by clinicians regarding any informal use of antiretroviral drugs.”
Smith D et al. Clinical utility of HIV standard genotyping among antiretroviral-naïve individuals of unknown duration of infection. J Infect Dis 44: 456 – 458, 2007.