February 26, 2007
Wheeler and colleagues1 presented antiretroviral data from newly diagnosed HIV-infected people. The data is part of the HIV/AIDS Reporting System (HARS), which is sponsored by the U.S. Centers for Disease Control and Prevention. In 2004, the U.S. Variant, Atypical, and Resistant HIV Surveillance (VARHS) system was established to supplement the epidemiology data already being collected in HARS by collecting blood samples to look for resistance mutations and determine subtypes of HIV-1. Sequencing was performed at four reference labs and antiretroviral-associated mutations were defined by International AIDS Society-USA guidelines.2
The researchers collected 3,130 sequences from newly diagnosed patients between March 2003 and October 2006 in 11 states from STD (sexually transmitted disease) clinics (33%), testing sites (25%), private physicians (8%), hospitals (7%) and other sites.
Of those patients for whom information was available, 680 (24%) were female, 2,073 (72%) were male, 498 (20%) were less than 25 years old, 1,516 (61%) were 25 to 44 years old, and 486 (19%) were more than 44 years old. Forty-seven percent were black, 22% were white and 9% were Hispanic.
The results showed that subtype B virus accounted for 94.9% of the samples and non-B subtypes accounted for 5.1%. Non-subtype B strains included subtypes such as A, G, F, and circulating recombinant forms. Cases of non-B subtypes were significantly higher in blacks than whites, and in females, males with heterosexual contact as opposed to men who have sex with men (MSM) contact and cases of non-U.S. origin.
Antiretroviral drug mutations were found in 10.4% of the samples (3.6% nucleoside/nucleotide reverse transcriptase inhibitor [NRTI], 6.9% non-nucleoside reverse transcriptase inhibitor [NNRTI] and 2.4% protease inhibitor [PI] mutations). Multidrug resistance was found in 1.9% of the samples. Antiretroviral mutations were found in 8.2% of those with non-subtype B compared to 10.6% of those with subtype B. The prevalence of PI and multidrug resistance was higher in whites. The mutation that occurred with the most frequency by antiretroviral class was K103N (70%) for NNRTIs, M41L (45%) for NRTIs, and L90M (40%) for PIs.
The authors point out several limitations to their study: It was limited to only a few states, STD clinics (and therefore possible risk factors) were over represented, and there is the possibility that there was duplication of some of the samples based on the process the investigators used for sample collection.
Their results, however, are consistent with the prevalence of antiretroviral resistance in newly diagnosed patients that has been found in past studies. Their data also suggest that there are links between non-U.S. exposure and non-B subtype infection, and that there may be associations between race and the prevalence of more mutations in whites.
We don't know how recently these patients were infected. It is important to note that these are newly diagnosed patients and not necessarily newly infected patients. Although over half of the patients were seen at STD clinics and testing centers, we do not know the reasons why many of the other patients sought testing. This data could underestimate the number of mutations in very acute infection as some mutations tend to fade away as the dominant wild-type virus emerges over time.
As seen in this study, it is important to recognize that more than 10% of the patients with either newly or recently acquired HIV infection may harbor resistant virus. Therefore resistance testing is recommended in all recently infected patients for both primary workup and when contemplating antiretroviral initiation.
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