Impact of HIV-1 pol diversity on drug resistance and its clinical implications

Current Opinion in Infectious Diseases

Volumn 19, Issue 6, 2006, Pages 594-606

  Kantor, Rami ^a,b  

^a MIRIAM HOSPITAL   (United States)

^b BROWN UNIVERSITY   (United States)

Author keywords

Diversity; Drug resistance; HIV; Subtypes

Indexed keywords

LAMIVUDINE; RNA DIRECTED DNA POLYMERASE INHIBITOR;

DISEASE COURSE; DRUG RESISTANCE; DRUG SENSITIVITY; GENE MUTATION; GENOTYPE; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; PATIENT CARE; REVIEW; SOUTH AFRICA; TREATMENT RESPONSE;

ALGORITHMS; ANTI-HIV AGENTS; DISEASE PROGRESSION; DRUG RESISTANCE, VIRAL; FEMALE; GENES, POL; GENOME, VIRAL; GENOTYPE; HIV INFECTIONS; HIV-1; HUMANS; MALE; VARIATION (GENETICS);

EID: 33750519867     PISSN: 09517375     EISSN: None     Source Type: Journal    
DOI: 10.1097/QCO.0b013e3280109122     Document Type: Review

References (112)

1. McCutchan FE. Global epidemiology of HIV. J Med Virol 2006; 78 (Suppl 1): S7-S12. This is an overview on HIV diversity, global geography and epidemiology: all essential as background for the current review. It summarizes viral origin, variation, classification, global distribution and relevance of variation to HIV diagnostics.
2. Osmanov S, Pattou C, Walker N, et al. Estimated global distribution and regional spread of HIV-1 genetic subtypes in the year 2000. J Acquir Immune Defic Syndr 2002; 29:184-190.
3. Ivers LC, Kendrick D, Doucette K. Efficacy of antiretroviral therapy programs in resource-poor settings: a meta-analysis of the published literature. Clin Infect Dis 2005; 41:217-224.
4. Kantor R, Katzenstein D, Efron B, et al. Impact of HIV-1 subtype and antiretroviral therapy on protease and reverse transcriptase genotypic evolution: results of a global collaboration. PLOS Medicine 2005; 2:e112.
5. Carpenter CC. Universal access to antiretroviral therapy: when, not if. Clin Infect Dis 2006; 42:260-261.
6. Kim JY, Gilks C. Scaling up treatment: why we can't wait. N Engl J Med 2005; 353:2392-2394.
7. Merson MH. The HIV-AIDS pandemic at 25: the global response. N Engl J Med 2006; 354:2414-2417. This historic overview summarizes the events in the past 20 years that led to the evolution of the global approach to the HIV pandemic and to the increase in funding and access to antiretroviral drugs.
8. Beck EJ, Vitoria M, Mandalia S, et al. National adult antiretroviral therapy guidelines in resource-limited countries: concordance with 2003 WHO guidelines? Aids 2006; 20:1497-1502. This is an aggregation of data from 43 resource limited HIV high burden countries, looking at existence of national ARV guidelines and their concordance to WHO recommendations, potentially providing insight on expected drug resistance.
9. Calmy A, Pinoges L, Szumilin E, et al. Generic fixed-dose combination antiretroviral treatment in resource-poor settings: multicentric observational cohort. Aids 2006; 20:1163-1169. This describes the largest study on treatment response in non-B infected patients in the review period, presenting data from nearly 7000 patients from 21 Medecins Sans Frontieres sites around the world, showing positive outcomes of treatment with fixed dosed ARV combinations.
10. Braitstein P, Brinkhof MW, Dabis F, et al. Mortality of HIV-1-infected patients in the first year of antiretroviral therapy: comparison between low-income and high-income countries. Lancet 2006; 367:817-824.
11. Wools-Kaloustian K, Kimaiyo S, Diero L, et al. Viability and effectiveness of large-scale HIV treatment initiatives in sub-Saharan Africa: experience from western Kenya. Aids 2006; 20:41-48. The largest one-site study on treatment outcome within the review period presents data from 2059 AMPATH (Academic Model for the Preventions and Treatment of HIV/AIDS) patients in Eldoret, Kenya. Treatment response data demonstrate the model's success and the viability and effectiveness of large-scale HIV treatment initiatives in resource-limited settings.
12. Kabugo C, Bahendeka S, Mwebaze R, et al. Long-term experience providing antiretroviral drugs in a fee-for-service HIV clinic in Uganda: evidence of extended virologic and CD4+ cell count responses. J Acquir Immune Defic Syndr 2005; 38:578-583. This study on antiretroviral treatment response had the longest patient follow-up within the review period, up to 4 years between 1998 and 2002, in a fee-for-service program, demonstrating similar results to industrialized countries in patients who survived and remained on therapy, and discussing challenges and lessons learned.
13. Virological response to a triple nucleoside/nucleotide analogue regimen over 48 weeks in HIV-1-infected adults in Africa. Aids 2006; 20:1391-1399.
14. van Oosterhout JJ, Bodasing N, Kumwenda JJ, et al. Evaluation of antiretroviral therapy results in a resource-poor setting in Blantyre, Malawi. Trop Med Int Health 2005; 10:464-470.
15. Laurent C, Ngom Gueye NF, Ndour CT, et al. Long-term benefits of highly active antiretroviral therapy in Senegalese HIV-1-infected adults. J Acquir Immune Defic Syndr 2005; 38:14-17.
16. Wester CW, Kim S, Bussmann H, et al. Initial response to highly active antiretroviral therapy in HIV-1C-infected adults in a public sector treatment program in Botswana. J Acquir Immune Defic Syndr 2005; 40:336-343.
17. Spacek LA, Shihab HM, Kamya MR, et al. Response to antiretroviral therapy in HIV-infected patients attending a public, urban clinic in Kampala, Uganda. Clin Infect Dis 2006; 42:252-259.
18. Chaix ML, Rouet F, Kouakoussui KA, et al. Genotypic human immunodeficiency virus type 1 drug resistance in highly active antiretroviral therapy-treated children in Abidjan, Cote d'Ivoire. Pediatr Infect Dis J 2005; 24:1072-1076. The authors provide comprehensive data on treatment outcome as well as drug resistance, including suggestions for inter-subtype dissimilarities, in a pediatric cohort. Such data are not common from resource limited settings, and are thus of increased interest.
19. Jooste JP, Van Zyl AJ, Baker A, et al. Antiretroviral treatment in the Northern Cape. S Afr Med J 2005; 95:812.
20. Bourgeois A, Laurent C, Mougnutou R, et al. Field assessment of generic antiretroviral drugs: a prospective cohort study in Cameroon. Antivir Ther 2005; 10:335-341.
21. Idigbe EO, Adewole TA, Eisen G, et al. Management of HIV-1 infection with a combination of nevirapine, stavudine, and lamivudine: a preliminary report on the Nigerian antiretroviral program. J Acquir Immune Defic Syndr 2005; 40:65-69.
22. Kumarasamy N, Solomon S, Chaguturu SK, et al. The changing natural history of HIV disease: before and after the introduction of generic antiretroviral therapy in southern India. Clin Infect Dis 2005; 41:1525-1528.
23. Etard JF, Ndiaye I, Thierry-Mieg M, et al. Mortality and causes of death in adults receiving highly active antiretroviral therapy in Senegal: a 7-year cohort study. Aids 2006; 20:1181-1189.
24. Lawn SD, Myer L, Orrell C, et al. Early mortality among adults accessing a community-based antiretroviral service in South Africa: implications for programme design. Aids 2005; 19:2141-2148.
25. Bocket L, Cheret A, Deuffic-Burban S, et al. Impact of human immunodeficiency virus type 1 subtype on first-line antiretroviral therapy effectiveness. Antivir Ther 2005; 10:247-254.
26. Atlas A, Granath F, Lindstrom A, et al. Impact of HIV type 1 genetic subtype on the outcome of antiretroviral therapy. AIDS Res Hum Retroviruses 2005; 21:221-227.
27. Lawrence P, Lutz MF, Saoudin H, et al. Analysis of polymorphism in the protease and reverse transcriptase genes of HIV type 1 CRF02-AG subtypes from drug-naive patients from Saint-Etienne, France. J Acquir Immune Defic Syndr 2006; 42:396-404. Interesting analysis of inter-subtype differences in drug resistance identifying subtype-specific polymorphisms and subsequently analyzing their relevance to clinical outcome.
28. Cane PA, de Ruiter A, Rice PA, et al. Resistance-associated mutations in the human immunodeficiency virus type 1 subtype C protease gene from treated and untreated patients in the United Kingdom. J Clin Microbiol 2001; 39:2652-2654.
29. Grossman Z, Paxinos EE, Averbuch D, et al. Mutation D30N is not preferentially selected by human immunodeficiency virus type 1 subtype C in the development of resistance to nelfinavir. Antimicrob Agents Chemother 2004; 48:2159-2165.
30. Brenner B, Turner D, Oliveira M, et al. A V106M mutation in HIV-1 clade C viruses exposed to efavirenz confers cross-resistance to nonnucleoside reverse transcriptase inhibitors. AIDS 2003; 17:F1-F5.
31. Caride E, Brindeiro R, Hertogs K, et al. Drug-resistant reverse transcriptase genotyping and phenotyping of B and non-B subtypes (F and A) of human immunodeficiency virus type I found in Brazilian patients failing HAART. Virology 2000; 275:107-115.
32. Caride E, Hertogs K, Larder B, et al. Genotypic and phenotypic evidence of different drug-resistance mutation patterns between B and non-B subtype isolates of human immunodeficiency virus type 1 found in Brazilian patients failing HAART. Virus Genes 2001; 23:193-202.
33. Kantor R, Zijenah LS, Shafer RW, et al. HIV-1 subtype C reverse transcriptase and protease genotypes in Zimbabwean patients failing antiretroviral therapy. AIDS Res Hum Retroviruses 2002; 18:1407-1413.
34. Ariyoshi K, Matsuda M, Miura H, et al. Patterns of point mutations associated with antiretroviral drug treatment failure in CRF01_AE (subtype E) infection differ from subtype B infection. J Acquir Immune Defic Syndr 2003; 33:336-342.
35. Hsu LY, Subramaniam R, Bacheler L, Paton NI. Characterization of mutations in CRF01_AE virus isolates from antiretroviral treatment-naive and -experienced patients in Singapore. J Acquir Immune Defic Syndr 2005; 38:5-13.
36. Gupta RK, Chrystie IL, O'Shea S, et al. K65R and Y181C are less prevalent in HAART-experienced HIV-1 subtype A patients. AIDS 2005; 19:1916-1919. Comparison of drug resistance between different subtypes from drug-experienced patients in one geographic location, suggesting different mutation prevalence despite similar drug exposure.
37. Abecasis AB, Deforche K, Snoeck J, et al. Protease mutation M89I/V is linked to therapy failure in patients infected with the HIV-1 non-B subtypes C, F or G. AIDS 2005; 19:1799-1806. Inter-subtype analyses of drug resistance suggest new resistance mutations for certain subtypes, also introducing a new analysis method as a tool to study mutation interaction.
38. Fischer A, Karasi JC, Kibibi D, et al. Antiviral efficacy and resistance in patients on antiretroviral therapy in Kigali, Rwanda: the real-life situation in 2002. HIV Med 2006; 7:64-66.
39. Laurent C, Kouanfack C, Vergne L, et al. Antiretroviral drug resistance and routine therapy, Cameroon. Emerg Infect Dis 2006; 12:1001-1004.
40. Doualla-Bell F, Avalos A, Gaolathe T, et al. Impact of human immunodeficiency virus type 1 subtype C on drug resistance mutations in patients from Botswana failing a nelfinavir-containing regimen. Antimicrob Agents Chemother 2006; 50:2210-2213. Examination of drug resistance evolution to nelfinavir in subtype C isolates from Botswana, suggesting different resistance pathways than other subtype C isolates, augmented by in-vitro analyses and polymorphisms identification.
41. Yam WC, Chen JH, Wong KH, et al. Clinical utility of genotyping resistance test on determining the mutation patterns in HIV-1 CRF01_AE and subtype B patients receiving antiretroviral therapy in Hong Kong. J Clin Virol 2006; 35:454-457.
42. Tee KK, Kamarulzaman A, Ng KP. Prevalence and pattern of drug resistance mutations among antiretroviral-treated HIV-1 patients with suboptimal virological response in Malaysia. Med Microbiol Immunol (Berl) 2006; 195:107-112.
43. Lolekha R, Sirivichayakul S, Siangphoe U, et al. Resistance to dual nucleoside reverse-transcriptase inhibitors in children infected with HIV clade A/E. Clin Infect Dis 2005; 40:309-312.
44. Couto-Fernandez JC, Silva-de-Jesus C, Veloso VG, et al. Human immunodeficiency virus type 1 (HIV-1) genotyping in Rio de Janeiro, Brazil: assessing subtype and drug-resistance associated mutations in HIV-1 infected individuals failing highly active antiretroviral therapy. Mem Inst Oswaldo Cruz 2005; 100:73-78.
45. Calazans A, Brindeiro R, Brindeiro P, et al. Low accumulation of L90M in protease from subtype F HIV-1 with resistance to protease inhibitors is caused by the L89M polymorphism. J Infect Dis 2005; 191:1961-1970.
46. Grossman Z, Paxinos E, Auerbuch D, et al. D30N is not the preferred resistance pathway in subtype C patients treated with nelfinavir. Antivir Ther 2002; 7:S30-S34.
47. Shanmugam V, Switzer WM, Nkengasong JN, et al. Lower HIV-2 plasma viral loads may explain differences between the natural histories of HIV-1 and HIV-2 infections. J Acquir Immune Defic Syndr 2000; 24:257-263.
48. Guay LA, Musoke P, Fleming T, et al. Intrapartum and neonatal single-dose nevirapine compared with zidovudine for prevention of mother-to-child transmission of HIV-1 in Kampala, Uganda: HIVNET 012 randomised trial. Lancet 1999; 354:795-802.
49. Eshleman SH, Guay LA, Wang J, et al. Distinct patterns of emergence and fading of K103N and Y181C in women with subtype A vs. D after single-dose nevirapine: HIVNET 012. J Acquir Immune Defic Syndr 2005; 40:24-29.
50. Eshleman SH, Hoover DR, Chen S, et al. Nevirapine (NVP) resistance in women with HIV-1 subtype C, compared with subtypes A and D, after the administration of single-dose NVP. J Infect Dis 2005; 192:30-36.
51. Eshleman SH, Jones D, Galovich J, et al. Phenotypic drug resistance patterns in subtype A HIV-1 clones with nonnucleoside reverse transcriptase resistance mutations. AIDS Res Hum Retroviruses 2006; 22:289-293. Phenotypic analyses of subtype A clones, 7-days after nevirapine exposure for mother-to-child-transmission prevention, demonstrated unexpected drug susceptibility, possibly related to unique polymorphisms, demonstrating potential intersubtype diversity influence.
52. Flys TS, Chen S, Jones DC, et al. Quantitative analysis of HIV-1 variants with the K103N resistance mutation after single-dose nevirapine in women with HIV-1 subtypes A, C, and D. J Acquir Immune Defic Syndr 2006; 42:610-613. The authors describe detection of inter-subtype difference in drug resistance occurrence and in levels of drug resistance mutations after single-dose nevirapine exposure for mother to child HIV transmission, using sensitive detection and quantitative methods.
53. Flys T, Nissley DV, Claasen CW, et al. Sensitive drug-resistance assays reveal long-term persistence of HIV-1 variants with the K103N nevirapine (NVP) resistance mutation in some women and infants after the administration of single-dose NVP: HIVNET 012. J Infect Dis 2005; 192:24-29. The importance of this study is in the use of sensitive methods for drug resistance detection, which may provide new insight into the impact of drug exposure on resistance evolution and treatment outcome.
54. Johnson JA, Li JF, Morris L, et al. Emergence of drug-resistant HIV-1 after intrapartum administration of single-dose nevirapine is substantially underestimated. J Infect Dis 2005; 192:16-23. The importance of this study is in the use of sensitive methods for drug resistance detection, which may provide new insight into the impact of drug exposure on resistance evolution and treatment outcome.
55. Loubser S, Balfe P, Sherman G, et al. Decay of K103N mutants in cellular DNA and plasma RNA after single-dose nevirapine to reduce mother-to-child HIV transmission. Aids 2006; 20:995-1002. The importance of this study is in the use of sensitive methods for drug resistance detection, which may provide new insight into the impact of drug exposure on resistance evolution and treatment outcome.
56. Eshleman SH, Hoover DR, Chen S, et al. Resistance after single-dose nevirapine prophylaxis emerges in a high proportion of Malawian newborns. Aids 2005; 19:2167-2169.
57. Lee EJ, Kantor R, Zijenah L, et al. Breast-milk shedding of drug-resistant HIV-1 subtype C in women exposed to single-dose nevirapine. J Infect Dis 2005; 192:1260-1264. This provides an important look at differences in resistance evolution after exposure to single-dose nevirapine between plasma and breast-milk, demonstrating inter-compartmental variability in resistance prevalence with differential mutation patterns.
58. Kuhn L, Sinkala M, Kankasa MP, et al. Nevirapine resistance viral mutations after repeat use of nevirapine for prevention of perinatal HIV transmission. J Acquir Immune Defic Syndr 2006; 42:260-262. This is an important look at the use of nevirapine for mother to child transmission prevention in second pregnancy, and the evolution of drug resistance, demonstrating no increase in resistance.
59. Toni TD, Masquelier B, Lazaro E, et al. Characterization of nevirapine (NVP) resistance mutations and HIV type 1 subtype in women from Abidjan (Cote d'Ivoire) after NVP single-dose prophylaxis of HIV type 1 mother-to-child transmission. AIDS Res Hum Retroviruses 2005; 21:1031-1034.
60. Kantor R, Lee E, Johnston E, et al. Rapid flux in nonnucleoside reverse transcriptase inhibitor resistance mutations among subtype C HIV-1 infected women after single dose nevirapine. Antivir Ther 2003; 8:85.
61. Palmer S, Kearney M, Maldarelli F, et al. Multiple, linked human immunodeficiency virus type 1 drug resistance mutations in treatment-experienced patients are missed by standard genotype analysis. J Clin Microbiol 2005; 43:406-413.
62. Rhee SY, Kantor R, Katzenstein DA, et al. HIV-1 pol mutation frequency by subtype and treatment experience: extension of the HIVseq program to seven non-B subtypes. Aids 2006; 20:643-651. This important extension of the tools on the Stanford Database website also incorporates data from non-B infected sequences, allowing inter-subtype comparisons.
63. Agwale SM, Zeh C, Paxinos E, et al. Genotypic and phenotypic analyses of human immunodeficiency virus type 1 in antiretroviral drug-naive Nigerian patients. AIDS Res Hum Retroviruses 2006; 22:22-26. Genotypic-phenotypic comparisons of drug resistance mutations, showing good correlation with potential discordances, demonstrating the needed information for further inter-subtype difference analyses.
64. Kinomoto M, Appiah-Opong R, Brandful JA, et al. HIV-1 proteases from drug-naive West African patients are differentially less susceptible to protease inhibitors. Clin Infect Dis 2005; 41:243-251. Phenotypic analyses of drug resistance mutations suggest protease inhibitor resistance in sequences from drug-naïve persons, accompanied by structural and energy binding analyses, adding information on potential effects of intersubtype diversity.
65. Fleury HJ, Toni T, Lan NT, et al. Susceptibility to antiretroviral drugs of CRF01_AE, CRF02_AG, and subtype C viruses from untreated patients of Africa and Asia: comparative genotypic and phenotypic data. AIDS Res Hum Retroviruses 2006; 22:357-366. Phenotypic analyses of multiple subtypes from different locations, looking at all drug classes, identify similarities and potential differences with genotypic correlations.
66. Vergne L, Stuyver L, Van Houtte M, et al. Natural polymorphism in protease and reverse transcriptase genes and in vitro antiretroviral drug susceptibilities of non-B HIV-1 strains from treatment-naive patients. J Clin Virol 2006; 36:43-49. Examination of the association of nonsubtype B minor mutations with decreased invitro ARV susceptibility detects some resistance against each of the three drug classes.
67. Vessiere A, Nerrienet E, Kfutwah A, et al. HIV-1 pol gene polymorphism and antiretroviral resistance mutations in drug-naive pregnant women in Yaounde, Cameroon. J Acquir Immune Defic Syndr 2006; 42:256-258.
68. Bussmann H, Novitsky V, Wester W, et al. HIV-1 subtype C drug-resistance background among ARV-naive adults in Botswana. Antivir Chem Chemother 2005; 16:103-115.
69. Vidal N, Mulanga C, Bazepeo SE, et al. HIV type 1 pol gene diversity and antiretroviral drug resistance mutations in the Democratic Republic of Congo (DRC). AIDS Res Hum Retroviruses 2006; 22:202-206.
70. Bellocchi MC, Forbici F, Palombi L, et al. Subtype analysis and mutations to antiviral drugs in HIV-1-infected patients from Mozambique before initiation of antiretroviral therapy: results from the DREAM programme. J Med Virol 2005; 76:452-458.
71. Maslin J, Rogier C, Caron M, et al. Short communication. Antiretroviral drug resistance among drug-naive HIV-1-infected individuals in Djibouti (Horn of Africa). Antivir Ther 2005; 10:855-859.
72. Bessong PO, Larry Obi C, Cilliers T, et al. Characterization of human immunodeficiency virus type 1 from a previously unexplored region of South Africa with a high HIV prevalence. AIDS Res Hum Retroviruses 2005; 21:103-109.
73. Petch LA, Hoffman IF, Jere CS, et al. Genotypic analysis of the protease and reverse transcriptase of HIV type 1 subtype C isolates from antiretroviral drug-naive adults in Malawi. AIDS Res Hum Retroviruses 2005; 21:799-805.
74. Ly N, Recordon-Pinson P, Phoung V, et al. Characterization of mutations in HIV type 1 isolates from 144 Cambodian recently infected patients and pregnant women naive to antiretroviral drugs. AIDS Res Hum Retroviruses 2005; 21:971-976.
75. Grossman Z, Lorber M, Maayan S, et al. Drug-resistant HIV infection among drug-naive patients in Israel. Clin Infect Dis 2005; 40:294-302. This is an important analysis of drug resistance among different HIV subtypes from one location, thus potentially reducing multiple confounding variables and identifying resistance differences according to time and place of infection.
76. Tee KK, Kamarulzaman A, Ng KP. Short communication: low prevalence of genotypic drug resistance mutations among antiretroviral-naive HIV type 1 patients in Malaysia. AIDS Res Hum Retroviruses 2006; 22:121-124.
77. Balakrishnan P, Kumarasamy N, Kantor R, et al. HIV type 1 genotypic variation in an antiretroviral treatment-naive population in southern India. AIDS Res Hum Retroviruses 2005; 21:301-305.
78. Zarandia M, Tsertsvadze T, Carr JK, et al. HIV-1 genetic diversity and genotypic drug susceptibility in the Republic of Georgia. AIDS Res Hum Retroviruses 2006; 22:470-476.
79. Rodrigues R, Scherer LC, Oliveira CM, et al. Low prevalence of primary antiretroviral resistance mutations and predominance of HIV-1 clade C at polymerase gene in newly diagnosed individuals from south Brazil. Virus Res 2006; 116:201-207.
80. Vazquez de Parga E, Rakhmanova A, Perez-Alvarez L, et al. Analysis of drug resistance-associated mutations in treatment-naive individuals infected with different genetic forms of HIV-1 circulating in countries of the former Soviet Union. J Med Virol 2005; 77:337-344.
81. Paraschiv S, Otelea D, Dinu M, et al. Polymorphisms and resistance mutations in the protease and reverse transcriptase genes of HIV-1 F subtype Romanian strains. Int J Infect Dis 2006; Jun 6 [Epub ahead of print].
82. Kilby JM, Hopkins S, Venetta TM, et al. Potent suppression of HIV-1 replication in humans by T-20, a peptide inhibitor of gp41-mediated virus entry. Nat Med 1998; 4:1302-1307.
83. Lalezari JP, Henry K, O'Hearn M, et al. Enfuvirtide, an HIV-1 fusion inhibitor, for drug-resistant HIV infection in North and South America. N Engl J Med 2003; 348:2175-2185.
84. Lazzarin A, Clotet B, Cooper D, et al. Efficacy of enfuvirtide in patients infected with drug-resistant HIV-1 in Europe and Australia. N Engl J Med 2003; 348:2186-2195.
85. Cilliers T, Moore P, Coetzer M, Morris L. In vitro generation of HIV type 1 subtype C isolates resistant to enfuvirtide. AIDS Res Hum Retroviruses 2005; 21:776-783.
86. Holguin A, Sune C, Hamy F, et al. Natural polymorphisms in the protease gene modulate the replicative capacity of non-B HIV-1 variants in the absence of drug pressure. J Clin Virol 2006; 36:264-271. Study of the influence of non-B polymorphisms on viral replicative capacity and drug susceptibility, both highly important and relevant for resistance evolution, demonstrating some similarities and potential differences, and highlighting the need for further look into this important issue. Because these polymorphisms are abundant, yet some are subtype-specific, these types of analysis could have multiple implications on treatment.
87. Gonzalez LM, Aguiar RS, Afonso A, et al. Biological characterization of human immunodeficiency virus type 1 subtype C protease carrying indinavir drug-resistance mutations. J Gen Virol 2006; 87:1303-1309. This look at differences in the impact of protease drug-resistance mutations on different subtypes uses a subtype-B-based subtype C construct and identifies potential differences.
88. Brenner BG, Oliveira M, Doualla-Bell F, et al. HIV-1 subtype C viruses rapidly develop K65R resistance to tenofovir in cell culture. Aids 2006; 20:F9-F13. This notable study looked at differences among subtypes in the selection of resistance mutations upon drug exposure, reporting more rapid selection of K65R with tenofovir exposure. The methods used as well as the implication of the results are important.
89. Wainberg MA. Generic HIV drugs: enlightened policy for global health. N Engl J Med 2005; 352:747-750.
90. Guidelines for the use of antiretroviral agents in HIV-1 infected adults and adolescents. Department of Health and Human Services; 4 May 4 2006. http://aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf. [Accessed August 18, 2006].
91. Clemente JC, Coman RM, Thiaville MM, et al. Analysis of HIV-1 CRF_01 A/E protease inhibitor resistance: structural determinants for maintaining sensitivity and developing resistance to atazanavir. Biochemistry 2006; 45:5468-5477. This almost unique study within the review period compared biochemical properties of different subtypes, predicting potential faster resistance selection in certain circumstances, suggesting inter-subtype differences.
92. van de Vijver DA, Wensing AM, Angarano G, et al. The calculated genetic barrier for antiretroviral drug resistance substitutions is largely similar for different HIV-1 subtypes. J Acquir Immune Defic Syndr 2006; 41:352-360.
93. Kijak GH, Rubio AE, Pampuro SE, et al. Discrepant results in the interpretation of HIV-1 drug-resistance genotypic data among widely used algorithms. HIV Med 2003; 4:72-78.
94. Ravela J, Betts BJ, Brun-Vezinet F, et al. HIV-1 protease and reverse transcriptase mutation patterns responsible for discordances between genotypic drug resistance interpretation algorithms. J Acquir Immune Defic Syndr 2003; 33:8-14.
95. Sturmer M, Doerr HW, Preiser W. Variety of interpretation systems for human immunodeficiency virus type 1 genotyping: confirmatory information or additional confusion? Curr Drug Targets Infect Disord 2003; 3:373-382.
96. Kantor R, Katzenstein D. Drug resistance in nonsubtype B HIV-1. J Clin Virol 2004; 29:152-159.
97. Snoeck J, Kantor R, Shafer RW, et al. Discordances between interpretation algorithms for genotypic resistance to protease and reverse transcriptase inhibitors of human immunodeficiency virus are subtype dependent. Antimicrob Agents Chemother 2006; 50:694-701.
98. Vergne L, Snoeck J, Aghokeng A, et al. Genotypic drug resistance interpretation algorithms display high levels of discordance when applied to non-B strains from HIV-1 naive and treated patients. FEMS Immunol Med Microbiol 2006; 46:53-62.
99. Gianotti N, Galli L, Boeri E, et al. The 118I reverse transcriptase mutation is the only independent genotypic predictor of virologic failure to a stavudine-containing salvage therapy in HIV-1-infected patients. J Acquir Immune Defic Syndr 2006; 41:447-452.
100. Clark SA, Shulman NS, Bosch RJ, Mellors JW. Reverse transcriptase mutations 118I, 208Y, and 215Y cause HIV-1 hypersusceptibility to non-nucleoside reverse transcriptase inhibitors. Aids 2006; 20:981-984.
101. Saracino A, Monno L, Scudeller L, et al. Impact of unreported HIV-1 reverse transcriptase mutations on phenotypic resistance to nucleoside and non-nucleoside inhibitors. J Med Virol 2006; 78:9-17. Genotypic and phenotypic analyses of sequences from naïve and treated persons identifying unknown positions that may be related to drug resistance augment the concept that inter-subtype diversity may be related to unknown pathways to drug resistance.
102. Harrigan PR, Mo T, Wynhoven B, et al. Rare mutations at codon 103 of HIV-1 reverse transcriptase can confer resistance to nonnucleoside reverse transcriptase inhibitors. Aids 2005; 19:549-554.
103. Berkhout B, Back NK, de Ronde A, et al. Identification of alternative amino acid substitutions in drug-resistant variants of the HIV-1 reverse transcriptase. Aids 2006; 20:1515-1520.
104. Ode H, Neya S, Hata M, et al. Computational simulations of HIV-1 proteases-multidrug resistance due to nonactive site mutation L90M. J Am Chem Soc 2006; 128:7887-7895. This is an important look at structural pathogenic mechanisms for L90M, a major protease mutation. This insight provides additional understanding on how remote mutations and interactions between mutations at different positions can have an impact on drug resistance and drug binding.
105. Vasan A, Renjifo B, Hertzmark E, et al. Different rates of disease progression of HIV type 1 infection in Tanzania based on infecting subtype. Clin Infect Dis 2006; 42:843-852. This important study, not directly related to drug resistance, highlighted potential inter-subtype heterogeneity in the progression of HIV infection, adding insight to this ongoing debate, and emphasizing the importance of HIV diversity.
106. Laeyendecker O, Li X, Arroyo M, et al. The effect of HIV subtype on rapid disease progression in Rakai, Uganda. In: 13th Conference on Retroviruses and Opportunistic Infections; 5-8 February 2006; Denver. AlexandriaL Conference on Retroviruses and Opportunistic Infections; 2006. Abstract 44LB.
107. Costello C, Nelson KE, Suriyanon V, et al. HIV-1 subtype E progression among northern Thai couples: traditional and nontraditional predictors of survival. Int J Epidemiol 2005; 34:577-584.
108. Kantor R, Shafer RW, Katzenstein D. The HIV-1 Nonsubtype B Workgroup: an international collaboration for the collection and analysis of HIV-1 non-subtype B data. MedGenMed 2005; 7:71.
109. Abbas UL, Anderson RM, Mellors JW. Potential impact of antiretroviral therapy on HIV-1 transmission and AIDS mortality in resource-limited settings. J Acquir Immune Defic Syndr 2006; 41:632-641.
110. Akileswaran C, Lurie MN, Flanigan TP, Mayer KH. Lessons learned from use of highly active antiretroviral therapy in Africa. Clin Infect Dis 2005; 41:376-385.
111. Bautista-Arredondo S, Mane A, Bertozzi SM. Economic impact of antiretroviral therapy prescription decisions in the context of rapid scaling-up of access to treatment: lessons from Mexico. Aids 2006; 20:101-109.
112. Badri M, Cleary S, Maartens G, et al. When to initiate highly active antiretroviral therapy in sub-Saharan Africa? A South African cost-effectiveness study. Antivir Ther 2006; 11:63-72.