PCRS data confirmed that all cluster members were distinct individuals and elicited 5-40 partners in the year before HIV-1 diagnosis. Of these, no more than 5 partners were located for each cluster member. Identified sexual partners did not overlap between cases, although the anonymous nature of their sexual encounters precluded such identifications. Two were in primary nonmonogamous relationships with noncluster MSM. All sexual partners contacted through PCRS were either not infected with HIV-1 or had a non-MDR HIV-1 strain.
The clinical impact of primary drug resistance is not completely understood, with both more rapid and slower disease progression reported. Adverse clinical outcomes include a faster CD4 decline early in disease6-8 and, after ARV initiation, an increased time to viral suppression (<500 copies/mL) and a shorter period of sustained viral suppression.23 Still, drug resistance does not necessarily accelerate disease progression and may even slow disease progression if the viral fitness is compromised.24
Use of methamphetamine is associated with more sexual partners, high-risk behaviors, and acquisition of sexually transmitted infections, including HIV-1.25-27 Methamphetamine use has also been correlated with drug-resistant HIV-1 and with NNRTI drug resistance.28 Methamphetamine use together with erectile dysfunction agents increases high-risk sexual behavior.29
This MDR strain does not seem to be highly virulent (based on intermediate VL levels and RC), but may be persistent (transmissions being diagnosed for more than a minimum of 24 months), and given the number of individuals infected with this strain, may also be easily transmitted. Furthermore, although it would be difficult to prove without stored sera available for additional testing, 1 of the ARV-experienced individuals may have contracted this strain of HIV due to a superinfection despite being on ARV therapy at the time with good viral suppression, as measured by consistently undetectable VL.
1. Oette M, Kaiser R, Daumer M, et al. Primary HIV
drug resistance and efficacy of first-line antiretroviral therapy guided by resistance testing. J Acquir Immune Defic Syndr
2. Weinstock HS, Zaidi I, Heneine W, et al. The epidemiology of antiretroviral drug resistance among drug-naive HIV-1
-infected persons in 10 US cities. J Infect Dis
3. Shet A, Berry L, Mohri H, et al. Tracking the prevalence of transmitted antiretroviral drug-resistant HIV-1
: a decade of experience. J Acquir Immune Defic Syndr
4. Wheeler W, Mahle K, Bodnar U, et al. Antiretroviral drug-resistance mutations and subtypes in drug-naïve persons newly diagnosed with HIV-1
infection, US, March 2003 to October 2006. Presented at: Conference on Retroviruses and Opportunistic Infections; February 25-28; 2007; Los Angeles, CA. Poster # 648.
5. Ghosn J, Pellegrin I, Goujard C, et al. HIV-1
resistant strains acquired at the time of primary infection massively fuel the cellular reservoir and persist for lengthy periods of time. AIDS
6. CASCADE Virology Collaboration. The impact of transmitted drug resistance on the natural history of HIV
infection and response to first-line therapy. AIDS
7. Bhaskaran K, Pillay D, Walker AS, et al. Do patients who are infected with drug-resistant HIV
have a different CD4 cell decline after seroconversion? An exploratory analysis in the UK Register of HIV
8. Pillay D, Bhaskaran K, Jurriaans S, et al. The impact of transmitted drug resistance on the natural history of HIV
infection and response to first-line therapy. AIDS
9. Hammer SM, Saag MS, Schechter M, et al. Treatment for adult HIV
infection: 2006 recommendations of the International AIDS Society-USA panel. JAMA
10. DHHS Panel on Antiretroviral Guidelines for Adult and Adolescents. Guidelines for the Use of Antiretroviral Agents in HIV
-Infected Adults and Adolescents. Department of Health and Human Services; December 1, 2007:1-136. Available at: http://aidsinfo.nih.gov/contentfiles/AdultandAdolescentGL.pdf
. Accessed December 26, 2007.
11. Operskalski EA, Busch MP, Mosley JW, et al. Comparative rates of disease progression among persons infected with the same or different HIV-1
strains. J Acquir Immune Defic Syndr Hum Retrovirol
12. Smith DM, Richman DD, Little SJ. HIV
superinfection. J Infect Dis
13. Johnson VA, Brun-Vezinet F, Clotet B, et al. Update of the drug resistance mutations in HIV-1
: Fall 2006. Top HIV Med
14. Shafer RW, Rhee SY, Pillay D, et al. HIV-1
protease and reverse transcriptase mutations for drug resistance surveillance. AIDS
15. Thompson JD, Gibson TJ, Plewniak F, et al. The CLUSTAL_X windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools. Nucleic Acids Res
16. Swofford DL. PAUP*. Phylogenetic Analysis Using Parsimony (*and Other Methods)
. Version 4. Sunderland, MA: Sinauer Associates; 2002.
17. Pieniazek D, Wheeler W, Mahle K, et al. Frequency and mutation patterns of phylogenetically linked drug resistant strains among drug-naïve Ppersons newly diagnosed with HIV1-infection, United States, March 2003-October 2006 [B14 - 4]. Presented at: National HIV
Prevention Conference; December 2-5 2007; Atlanta, GA.
18. Lindstrom A, Ohlis A, Huigen M, et al. HIV-1
transmission cluster with M41L ‘singleton’ mutation and decreased transmission of resistance in newly diagnosed Swedish homosexual men. Antivir Ther
19. Drumright LN, Little SJ, Richman DD, et al. Age discordance and drug resistance predict clustering of HIV
among recently-infected MSM in San Diego CA. Presented at: 14th Conference on Retroviruses and Opportunistic Infections (CROI); February 25-28, 2007; Los Angeles, CA. Abstract 654.
20. Leigh Brown AJ, Frost SD, Mathews WC, et al. Transmission fitness of drug-resistant human immunodeficiency virus and the prevalence of resistance in the antiretroviral-treated population. J Infect Dis
21. de Mendoza C, Rodriguez C, Corral A, et al. Evidence for differences in the sexual transmission efficiency of HIV
strains with distinct drug resistance genotypes. Clin Infect Dis
22. Simon V, Padte N, Murray D, et al. Infectivity and replication capacity of drug-resistant human immunodeficiency virus type 1 variants isolated during primary infection. J Virol
23. Little S, Frost S, Smith D, et al. Transmission of HIV
drug resistance and treatment response. Presented at: Conference on Retroviruses and Opportunistic Infections; February 25-28, 2007, Los Angeles, CA. Abstract 60.
24. Zaccarelli M, Tozzi V, Perno CF, et al. The challenge of antiretroviral-drug-resistant HIV
: is there any possible clinical advantage. Curr HIV Res
25. Taylor MM, Aynalem G, Smith LV, et al. Methamphetamine use and sexual risk behaviours among men who have sex with men diagnosed with early syphilis in Los Angeles County. Int J STD AIDS
26. Plankey MW, Ostrow DG, Stall R, et al. The relationship between methamphetamine and popper use and risk of HIV
seroconversion in the Multicenter AIDS Cohort Study. J Acquir Immune Defic Syndr
27. Gorbach PM, Drumright LN, Javanbakht M, et al. Antiretroviral drug resistance and risk behavior among recently HIV
-infected men who have sex with men. J Acquir Immune Defic Syndr Hum Retrovirol
28. Colfax GN, Vittinghoff E, Grant R, et al. Frequent methamphetamine use is associated with primary non-nucleoside reverse transcriptase inhibitor resistance. AIDS
29. Mansergh G, Shouse RL, Marks G, et al. Methamphetamine and sildenafil (Viagra) use are linked to unprotected receptive and insertive anal sex, respectively, in a sample of men who have sex with men. Sex Transm Infect