HIV resistance mutations common but CXCR4 rare among untreated US gay men

A study of 195 men who have sex with men (MSM) in the United States, all of whom seroconverted between 1999 and 2003, found drug-resistance mutations in nearly 16% shortly after their seroconversion. All were found to have HIV subtype B; a small percentage (3.2%) had virus that was tropic for (i.e., able to bind to) the CXCR4 as well as the CCR5 co-receptor. The study was published in the May 31^st issue of AIDS.

A significant number of new HIV infections are known to involve drug-resistant virus. There have also been reports of suspected transmissions of CXCR4-tropic virus, which is usually associated with late-stage, rapidly progressing HIV disease, as opposed to the CCR5-tropic virus more commonly found in recent infection and early disease.

This study analysed blood samples from 195 recently HIV-infected men who have sex with men (MSM) to identify drug resistance mutations and HIV tropisms and subtypes.

This resistance study subsample was drawn from the larger EXPLORE study (an investigation of an HIV-preventive behavioural intervention). EXPLORE participants were enrolled at six study sites in major US cities (Boston, Chicago, Denver, New York, San Francisco and Seattle) between 1999 and 2001, and followed for a maximum of 48 months. From this cohort, 259 men were identified who had recently seroconverted (six months previously or less); blood samples were available from 220 of these. Most were infected in 2001 and 2002; just over half were over 31 years old; ethnicity was 65% non-Hispanic white, 19% Hispanic, 10% black, 5% other.

HIV viral load was measured using Roche AMPLICOR version 1.5; the samples were genotyped using the ViroSeq HIV-1 Genotyping System. The samples were also analysed for HIV subtype (clade) and for tropism (CCR5, CXCR4, or dual/mixed). Genotypic results were available for 195 of the samples; the researchers found no significant demographic or behavioural differences between the 195 and the original larger sample.

Viral subtype and tropism

All 195 of the men were found to be infected with HIV subtype B. Data for tropism were available for 126 of the samples; again, no significant demographic differences were introduced by this reduced sample size. All samples showed the expected CCR5 tropism; however, four (3%) were dual/mixed tropic (i.e., able to bind to CXCR4 as well as CCR5). One of these four also displayed class resistance to NNRTIs.

The authors conclude that the “frequent detection of antiretroviral drug resistant HIV-1 strains in recently infected MSM emphasizes the importance of antiretroviral drug resistance testing in similar patient populations”, and that there is a “need for further studies defining the prevalence of mixed or dual tropic HIV strains in individuals with recent HIV-1 infection”.

Antiretroviral drug resistance

Of the 195 samples with genotypic results available, 31 (16%) showed resistance to at least one antiretroviral. Resistance to nevirapine (Viramune), delavirdine (Rescriptor), stavudine (Zerit), efavirenz (Sustiva), zidovudine (Retrovir), and nelfinavir (Viracept) were most common (in the order listed). Resistance to at least one NRTI was seen in 13 samples (9%), to at least one NNRTI in 13 (7%), to at least one PI in 11 (6%), to two drug classes in 4 (2%), and three drug classes in 3 (2%).

No significant association was found between drug resistance and any demographic factors, sexual behaviour, or use of recreational drugs or post-exposure prophylaxis (PEP).