In the past few years there has been increasing concern about the transmission of antiretroviral-resistant HIV-1. A recent study by Shet et al.  reported a 24.1% transmitted resistance in New York City in 2003–2004. Other recent studies have reported resistance rates between 8 and 23% [2–5]. Individuals infected with resistant HIV often have limited options for antiretroviral therapy and may also have an attenuated response to therapy .
Little is known as to whether different modes of HIV transmission are associated with an increased risk of primary drug resistance. One study of over 1000 participants found a higher prevalence of reverse transcriptase (RT) or protease inhibitor resistance in men who had sex with men (MSM) than in women or in heterosexual men . The same study also found an increased rate of resistance in white than in African-American or Hispanic individuals . However, the overall prevalence of mutations in that study associated with reduced antiretroviral drug susceptibility was only 8.3% .
In our clinic population, previous work demonstrated a 4% prevalence in drug-resistant virus in the period from 1996 to 1998 and a 17% prevalence in drug-resistant virus in the period from 1999 to 2001 in chronically infected patients (excluding acute HIV infection and long-term non-progressors) . Our clinic population is a racially and gender diverse group, probably representative of the ongoing HIV epidemic within the larger US population. We thus wanted to assess whether there has been further progression or stabilization in drug resistance and resistance patterns in drug-naive patients in our clinic population.
We conducted a retrospective cohort study at the Washington University HIV Outpatient Care Clinic. Institutional review board approval was obtained before the initiation of research. All Washington University Infectious Diseases Clinic patients naive to antiretroviral therapy with genotypes performed between 1 January 2003 and 1 January 2005 were included. The first available sample was used. Genotypic resistance was defined as the presence of viral mutations associated with impaired drug susceptibility or virological response as specified by the International AIDS Society USA mutations panel March/April 2005 revision . Also included were T215A/C/D/E/G/H/I/L/N/S/V, T69N/A/I and K103S.
The Student's t-test was used to compare continuous variables, and the χ2 test was used for dichotomous variables. For purposes of analysis, plasma HIV-RNA values of more than 100 000 and more than 750 000 copies/ml were treated as 100 000 and 750 000 copies/ml, respectively. HIV-RNA levels were log-transformed for analysis. All P values are two tailed and P < 0.05 is considered significant.
A total of 82 women (43%) and 110 men (57%) were identified; 67% were African-American, 28% were white, 4% were latino and 2% were other ethnicities. Reported or probable transmission was 37% MSM, 59% heterosexual sex and 4% intravenous drug users. The mean age was 35 ± 9.7 years. The mean CD4 T-lymphocyte count was 290 ± 208; the mean log viral load was 4.7 ± 0.9. The overall prevalence of resistance with either an RT or major protease mutation was 18%. Fifteen per cent of patients demonstrated at least one RT resistance mutation [4% with thymidine analog mutations (TAM), 7% with non-nucleoside reverse transcription inhibitor (NNRTI) mutations]. Four per cent demonstrated major protease mutations. Two patients demonstrated both NNRTI and major protease mutations. Neither the CD4 T-lymphocyte count, log HIV viral load, nor age was associated with an increased prevalence of patients with or without a RT, major protease inhibitor, TAM or NNRTI mutation. There was no significant difference by transmission risk (heterosexual versus MSM) or sex for RT, NNRTI, protease or TAM mutations. White individuals had a significantly increased risk of TAM mutations compared with African-Americans (P < 0.01) but no significant difference in the risk of RT, NNRTI or protease mutations.
Within our diverse clinic population, we continue to see a high rate of genotypic mutations in a cohort of antiretroviral-naive HIV-1-infected individuals. As reported in other studies, we noted primary resistance in some patients to each of the three major classes of antiretroviral drugs tested. Also as reported in other recent studies, RT mutations conferring resistance to nucleoside analogues were the most frequently encountered mutations.
Although not directly comparable with earlier work at our clinic, as we did not exclude patients with CD4 cell counts of less than 300 cells/μl or viral loads less than 1000 copies/ml, our recent results suggest that in a similar diverse clinic population, the rate of primary mutations remains high.
There does not appear to be a significant difference in primary resistance patterns between different modes of HIV transmission (heterosexual versus MSM), gender or between white and African-American individuals. Our sample was relatively small, however, and a larger prospective trial might answer this question better. Until then, it seems prudent to conduct genotype testing on all chronically infected HIV-1 individuals before the initiation of antiretroviral therapy as suggested in the recently revised Department of Health and Human Services guidelines  (Table 1).
1. Shet A, Berry L, Mohri H, Mehandru S, Chung C, Kim A, et al
. Tracking the prevalence of transmitted antiretroviral drug-resistant HIV-1: a decade of experience. J Acquir Immune Defic Syndr 2006; 41:439–446.
2. Oette M, Kaiser R, Daumer M, Petch R, Fatkenheuer G, Carls H, et al
. Primary drug resistance and efficacy of first-line antiretroviral therapy guided by resistance testing. J Acquir Immune Defic Syndr 2006; 41:573–581.
3. Grant RM, Hecht FM, Warmerdam M, Liu L, Liegler T, Petropoulos CJ, et al
. Time trends in primary HIV-1 drug resistance among recently infected persons. JAMA 2002; 288:181–188.
4. Weinstock HS, Zaidi I, Heneine W, Bennett D, Gerardo Garcia-Lewis J, Douglas JM Jr, et al
. The epidemiology of antiretroviral drug resistance among drug-naive HIV-1-infected persons in 10 US cities. J Infect Dis 2004; 189:2174–2180.
5. Masquelier B, Bhaskaran K, Pillay D, Gifford R, Balestre E, Jorgensen LB, et al
. Prevalence of transmitted HIV-1 drug resistance and the role of resistance algorithms: data from seroconverters in the cascade collaboration from 1987 to 2003. J Acquir Immune Defic Syndr 2005; 40:505–511.
6. Ristig MB, Arens MQ, Kennedy M, Powderly W, Tebas P. Increasing prevalence of resistance mutations in antiretroviral-naive individuals with established HIV-1 infection from 1996–2001 in St Louis. HIV Clin Trials 2002; 3:155–160.
7. Johnson VA, Brun-Vezinet F, Clotet B, Conway B, Kuritzkes DR, Pillay D, et al
. Update of the drug resistance mutations in HIV-1: 2005. Top HIV Med 2005; 13:51–57.