Characterization of Genotypic Mutations and Antiretroviral Resistance among Viremic HIV-Infected Patients in a High HIV Prevalence Area: Treatment Challenge and Transmission Risk

AliAsad Arastu, Virginia Kan

.

DOI: 10.4236/wja.2011.13011                

Abstract

There have been few reports evaluating the prevalence of genotypic mutations and antiretroviral resistance among chronic HIV-infected Veterans within the United States. This retrospective cross-sectional study characterizes the rates and changes in HIV genotypic mutations and antiretroviral resistance among viremic patients from 2001 to 2006 at the VA Medical Center located in Washington, DC. The District of Columbia is the metropolitan area with the highest HIV prevalence within the United States. De-identified, linked HIV RNA, genotypic reverse transcriptase (RT) and protease (Pr) mutations and antiretroviral resistance results were assessed for changes during the 6-year period. Aggregated clinic and antiretroviral utilization, and HIV acquisition risk data were evaluated for patients in care during this time. Among 990 viremic samples, the rate of any detected RT or Pr mutation fell from 100% in 2001 to 95% in 2006. This was primarily attributable to the 15% - 20% decrease seen for RT gene mutations against nucleoside/nucleotide class and non-nucleoside class during this period. Resistance to didanosine, stavudine, zidovudine, nevirapine and efavirenz decreased, and tenofovir resistance increased. Despite stable rates of Pr gene mutations, atazanavir resistance increased by 22% from 2003 to 2006. Some but not all changes in genotypic mutations and resistance patterns reflected our patients’ antiretroviral drug utilization. As sexual contacts (77%) and injection drug use (22%) were the leading acquisition risks disclosed by our HIV-infected patients, the high prevalence and changing patterns of HIV genotypic mutations and drug resistance among these patients have had pivotal impacts not only on HIV treatment but potential transmission into our community.

Keywords

HIV Viremia, Antiretroviral Resistance, Genotypic Antiretroviral Mutations, Transmission, Nucleoside/Nucleotide Reverse Transcriptase Inhibitors, Non-Nucleoside Reverse Transcriptase Inhibitors, Protease Inhibitors

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	“Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents,” 2011. http://aidsinfo.nih.gov/contentfiles/AdultandAdolescentGL.pdf
[2]	D. Costagliola, D. Descamps, L. Assoumou, L. Morand- Joubert, A. G. Marcelin, V. Brodard, C. Delaugerre, V. Mackiewicz, A. Ruffault, J. Izopet, J. C. Plantier, C. Tamalet, S. Yerly, S. Saidi, F. Brun-Vezinet, B. Masquelier and Agence Nationale de Recherches sur le SIDA et les Hepatites Virales (ANRS) AC11 Resistance Study Group, “Prevalence of HIV-1 Drug Resistance in Treated Patients: A French Nationwide Study,” Journal of Acquired Immune Deficiency Syndromes, Vol. 46, No. 1, 2007, pp. 12-18.
[3]	D. D. Richman, S. C. Morton, T. Wrin, N. Hellmann, S. Berry, M.F. Shapiro and S. A. Bozzette, “The Prevalence of Antiretroviral Drug Resistance in the United States,” AIDS, Vol. 18, No. 10, 2004, pp. 1393-1401. doi:10.1097/01.aids.0000131310.52526.c7
[4]	C. Tamalet, J. Fantini, C. Tourres and N. Yahi, “Resistance of HIV-1 to Multiple Antiretroviral Drugs in France: A 6-year Survey (1997-2002) Based on an Analysis of Over 7000 Genotypes,” AIDS, Vol. 17, No. 16, 2003, pp. 2383-2388. doi:10.1097/00002030-200311070-00014
[5]	R. Kagan, M. Winters, T. Merigan and P. Heseltine, “HIV Type 1 Genotypic Resistance in a Clinical Database Cor- relates with Antiretroviral Utilization,” AIDS Research Human Retroviruses, Vol. 20, No. 1, 2004, pp. 1-9. doi:10.1089/088922204322749440
[6]	P. Scott, E. Arnold, B. Evans, A. Pozniak, G. Moyle, M. Shahmenesh, D. White, J. Shirley, P. Cane and D. Pillay, “Surveillance of HIV Antiretroviral Drug Resistance in Treated Individuals in England: 1998-2000,” Journal of Antimicrobial Chemotherapy, Vol. 53, No. 3, 2004, pp. 469-473. doi:10.1093/jac/dkh102
[7]	C. Sukasem, V. Churdboonchart, S. Chasombat, S. Ko- hreanudom, C. Watitpun, W. Piroj, M. Tiensuwan and W. Chantratita, “Surveillance of Genotypic Resistance Mutations in Chronic HIV-1 Treated Individuals after Completion of the National Access to Antiretroviral Program in Thailand,” Infection, Vol. 35, No. 2, 2007, pp. 81-88. doi:10.1007/s15010-007-6169-x
[8]	O. Gallego, L. Ruiz, A. Vallejo, E. Ferrer, A. Rubio, B. Clotet, M. Leal, V. Soriano and ERASE-3 Group, “Changes in the Rate of Genotypic Resistance to Antiretroviral Drugs in Spain,” AIDS, Vol. 15, No. 14, 2001, pp. 1894-1896. doi:10.1097/00002030-200109280-00025
[9]	“The District of Columbia HIV/AIDS, Hepatitis, STD and TB [HAHSTA] Annual Report 2010,” published 15 June 2011, accessed on 22 June 2011. http://dchealth.dc.gov/doh/frames.asp?doc=/doh/lib/doh/services/administration_offices/hiv_aids/pdf/2010_Annual _Report_FINAL.pdf
[10]	H. B. Gale, V. L. Kan and R. C. Shinol, “Performance of the Tru-Gene Human Immunodeficiency Virus Type 1 Genotyping Kit and Open-Gene DNA Sequencing System on Clinical Samples Diluted to Aapproximately 100 Copies per Milliliter,” Clinical Vaccine Immunolology, Vol. 13, 2006, pp. 235-238. doi:10.1128/CVI.13.2.235-238.2006
[11]	V. L. Kan, H. B. Gale and R. C. Shinol, “Response to Waters et al. ‘Successful Use of Genotypic Resistance Testing in HIV-1-Infected Individuals with Detectable Viraemia’,” AIDS, Vol. 20, No. 15, 2006, pp. 1991-1992. doi:10.1097/01.aids.0000247129.65623.d1
[12]	V. A. Johnson, F. Brun-Vézinet, B. Clotet, H. F. Günthard, D. R. Kuritzkes, D. Pillay, J. M. Schapiro and D. D. Richman, “Update of the Drug Resistance Mutations in HIV-1: December 2010,” Topics in HIV Medicine, Vol. 18, 2010, pp. 156-163.
[13]	M. Holodniy, E. D. Charlebois, D. R. Bangsberg, A. R. Zolopa, M. Schulte and A. R. Moss, “Prevalence of Antiretroviral Drug Resistance in the HIV-1-Infected Urban Indigent Population in San Francisco: A Representative Study,” International Journal of STD and AIDS, Vol. 15, No. 8, 2004, pp. 543-551. doi:10.1258/0956462041558212
[14]	S. Vora S, A. G. Marcelin, H. F. Günthard, P. Flandre, H. H. Hirsch, B. Masquelier, A. Zinkernagel, G. Peytavin, V. Calvez, L. Perrin L, S. Yerly and Swiss HIV Cohort Study, “Clinical Validation of Atazanavir/Ritonavir Genotypic Resistance Score in Protease Inhibitor-Ex- perienced Patients,” AIDS, Vol. 20, No. 1, 2006, pp. 35-40. doi:10.1258/0956462041558212
[15]	M. M. Santoro, A. Bertoli, P. Lorenzini, F. Ceccherini- Silberstein, N. Gianotti, C. Mussini, C. Torti, G. Di Perri, G. Barbarini, T. Bini, S. Melzi, P. Caramello, R. Maserati, P. Narciso, V. Micheli, A. Antinori, C. F. Perno and CARe Study Group, “Two Different Patterns of Mutations Are Involved in the Genotypic Resistance Scores of Atazanavir Boosted Versus Unboosted by Ritonavir in Multiple Failing Patients,” Infection, Vol. 37, No. 3, 2009, pp. 233-243.
[16]	B. Dau, D. Ayers, J. Singer, P. R. Harrigan, S. Brown, T. Kyriakides, D. W. Cameron, B. Angus and M. Holodniy, “Connection Domain Mutations in Treatment-Experi- enced Patients in the OPTIMA Trial,” Journal of Acquired Immune Deficiency Syndromes, Vol. 54, No. 2, 2010, pp. 160-166.
[17]	P. R. Harrigan, B. Wynhoven, Z. L. Brumme, C. J. Brumme, B. Sattha, J. C. Major, R. de la Rosa and J. S. Montaner, “HIV-1 Drug Resistance: Degree of Underestimation by a Cross-sectional Versus a Longitudinal Testing Approach,” Journal of Infectious Diseases, Vol. 191, No. 8, 2005, pp. 1325-1330. doi:10.1086/428852
[18]	UK Collaborative Group on HIV Drug Resistance, UK Collaborative HIV Cohort Study, and UK Register of HIV Seroconverters, “Evidence of a Decline in Transmitted HIV-1Drug Resistance in the United Kingdom,” AIDS, Vol. 21, No. 8, 2007, pp. 1035-1039. doi:10.1097/QAD.0b013e3280b07761
[19]	O. Turriziani, M. Bucci, A. Stano, C. Scagnolari, F. Bellomi, C. Fimiani, I. Mezzaroma, G. D’Ettorre, A. Brogi, V. Vullo and G. Antonelli, “Genotypic Resistance of Archived and Circulating Viral Stains in the Blood of Treated HIV-Infected Individuals,” Journal of Acquired Immune Deficiency Syndromes, Vol. 44, 2007, pp. 518-524. doi:10.1097/QAI.0b013e3180315515
[20]	C. Diamond, J. L. Richardson, J. Milam, S. Stoyanoff, J. A. McCutchan, C. Kemper, R. A. Larsen, H. Hollander, P. Weismuller, R. Bolan and California Collaborative Trials Group, “Use of and Adherence to Antiretroviral Therapy Is Associated with Decreased Sexual Risk Behavior in HIV Clinic Patients,” Journal of Acquired Immune Deficiency Syndromes, Vol. 39, 2005, pp. 211-218.
[21]	S. C. Kalichman and D. Rompa, “HIV Treatment Adherence and Unprotected Sex Practices in People Receiving Antiretroviral Therapy,” Sexually Transmitted Infection, Vol. 79, No. 1, 2003, pp. 59-61. doi:10.1136/sti.79.1.59
[22]	W. C. Holmes and J. L. Pace, “HIV-seropositive Individuals’ Optimistic Beliefs about Prognosis and Relation to Medication and Safe Sex Adherence,” Journal of General Internal Medicine, Vol. 17, No. 9, 2002, pp. 677- 683. doi:10.1046/j.1525-1497.2002.00746.x
[23]	N. Crepaz, C. M. Lyles, R. J. Wolitski, W. F. Passin, S. M. Rama, J. H. Herbst, D. W. Purcell, R. M. Malow, R. Stall and HIV/AIDS Prevention Research Synthesis (PRS) Team, “Do Prevention Interventions Reduce HIV Risk Behaviors among People Living with HIV? A Meta-analytic Review of Controlled Trials,” AIDS, Vol. 20, No. 2, 2006, pp. 143-157. doi:10.1097/01.aids.0000196166.48518.a0
[24]	G. K. Robbins, K. L. Johnson, Y. Chang, K. E. Jackson, P. E. Sax, J. B. Meigs and K. A. Freedberg, “Predicting Virologic Failure in an HIV Clinic,” Clinical Infectious Diseases, Vol. 50, No. 5, 2010, pp. 779-786.
[25]	P. Roux, M. P. Carrieri, V. Villes, P. Dellamonica, I. Poizot-Martin, I. Ravaux, B. Spire and MANIF2000 Cohort Study Group, “The Impact of Methadone or Buprenorphine Treatment and Ongoing Injection on Highly Active Antiretroviral Therapy (HAART) Adherence: Evidence from the MANIF2000 Cohort Study,” Addiction, Vol. 103, No. 11, 2008, pp. 1828-1836. doi:10.1111/j.1360-0443.2008.02323.x