The nephrologist as a consultant

As with treatment of any acute or chronic infection, resistance patterns have emerged with HIV-1 in both treatment experienced pa-tients as well as treatment naïve. While frequency of resistance mutations reportedly vary based on risk behavior for acquisition, they have been reportedly as high as 15.2%.34-36

 


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Routine HIV resistance testing prior to initiation of ART, should be done in all patients with HIV RNA levels greater than 1,000 copies/mL. Virologic “blips” refer to intermittent periods of “detectable viremia” with loads greater than 50 copies/mL. Blips do not appear to demonstrate evolution of resistance mutations and do not require intervention unless the increase in load is sustained.37,38

 

Sustained increases, however, usually indicate the emergence of a resistance mutation and the potential loss in efficacy of certain antiretrovirals or classes of antiretrovirals. The analogy of the finite number of positions for potential arteriovenous access in a dialysis patient and the preservation of the limited therapeutic options is certainly valid.

 

The recognition that the “therapy” for a potential medication-related toxicity in some circumstances is more complex than simply discontinuing the potential offender is an important one. Stated another way, the need to discontinue a regimen that is currently successful in suppressing viral replication for a potential toxicity brings with it the concurrent and necessary decision to substitute a hopefully equally-as-effective regimen.

 

Where the toxicity is major or the relationship between the toxicity is clear and indisputable, the decision on simple withdrawal of the most obvious cause (i.e., the antiretroviral) is straightforward. Where toxicity is minor and the relationship is more “possible” than “likely,” the consideration of more definitive diagnostic testing to avoid potentially unneeded changes in successful regimens should be considered. 

 

Summary

The arsenal of medications available to prolong survival and enhance quality of life in persons infected with HIV continues to expand. The nephrologist, as a consultant participating in the care of persons with comorbidities or toxicities, needs to find reliable, efficient, and effective resources to understand the complexities of HIV care so that he can provide the best possible advice to patients and infectious disease colleagues.

 

Dr. Szczech is associate professor of nephrology at the Duke University School of Medicine in Durham, N.C., and a member of the Renal & Urology News editorial advisory board.

 

References

  1. Lucas GM, Eustace JA, Sozio S, et al. Highly active antiretroviral therapy and the incidence of HIV-1-associated nephropathy: a 12-year cohort study. AIDS. 2004;18:541-546.
  2. Herman ES, KlotmanPE. HIV-associated nephropathy: Epidemiology, pathogenesis, and treatment. Semin Nephrol. 2003;23:200-208.
  3. Shah SN, He CJ, Klotman P. Update on HIV-associated nephropathy. Curr Opin Nephrol Hypertens. 2006;15:450-455.
  4. Gupta SK, Eustace JA, Winston JA, et al. Guidelines for the management of chronic kidney disease in HIV-infected patients: Recommendations of the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis. 2005;40:1559-1585.
  5. http://www.selzentry.com/ accessed on 8/23/07.
  6. Chan DC, Fass D, Berger JM, Kim PS. Core structure of gp41 from the HIV envelope glycoprotein. Cell. 1997;89:263–273. 
  7. Coakley E, Petropoulos CJ, Whitcomb JM. Assessing chemokine co-receptor usage in HIV. Curr Opin Infect Dis. 2005;18: 9-15.
  8. Selik RM, Byers RH Jr, Dworkin MS. Trends in diseases reported on U.S. death certificates than mentioned HIV infection, 1987-1999. J Acquir Immune Defic Syndr. 2002;29:378-387.
  9. Riddler SA, Smit E, Cole SR, et al. Impact of HIV infection and HAART on serum lipids in men. JAMA. 2003;289:2978-2982.
  10. Kotler DP. HIV infection and lipodystrophy. Prog Cardiovasc Dis. 2003;45:269-284.
  11. Koster JC, Remedi MS, Qiu H, et al. HIV protease inhibitors acutely impair glucose-stimulated insulin release. Diabetes. 2003;52:1695-1700.
  12. Behrens G, Dejam A, Schmidt H, et al. Impaired glucose tolerance, beta cell function and lipid metabolism in HIV patients under treatment with protease inhibitors. AIDS. 1999;13:F63-F70.
  13. Behrens GM, BoernerAR, Weber K, et al. Impaired glucose phosphorylation and transport in skeletal muscle cause insulin resistance in HIV-1-infected patients with lipodystrophy. J Clin Invest. 2002;110:1319-1327.
  14. Hadigan C, Borgonha S, Rabe J, et al. Increased rates of lipolysis among human immunodeficiency virus-infected men receiving highly active antiretroviral therapy. Metabolism. 2002;51:1143-1147.
  15. Engelson ES, Glesby MJ, Mendez D, et al. Effect of recombinant human growth hormone in the treatment of visceral fat accumulation in HIV infection. J Acquir Immune Defic Syndr. 2002;30:379-391.
  16. Tabib A, Leroux C, Mornex JF, Loire R. Accelerated coronary atherosclerosis and arteriosclerosis in young human-immunodeficiency-virus-positive patients. Coron Artery Dis. 2000;11:41-46.
  17. Holmberg SD, Moorman AC, Williamson JM, et al. Protease inhibitors and cardiovascular outcomes in patients with HIV-1. Lancet. 2002;360:1747-1748.
  18. Mary-Krause M, Cotte L, Simon A, et al. Increased risk of myocardial infarction with duration of protease inhibitor therapy in HIV-infected men. AIDS. 2003;17:2479-2486.
  19. Friis-Moller N, Sabin CA, Weber R, et al. Combination antiretroviral therapy and the risk of myocardial infarction. N Engl J Med. 2003;349:1993-2003.
  20. Bozzette SA, Ake CF, Tam HK, et al. Cardiovascular and cerebrovascular events in patients treated for human immunodeficiency virus infection. N Engl J Med. 2003;348:702-710.
  21. Klein D, Hurley LB, Quesenberry CP Jr, Sidney S. Do protease inhibitors increase the risk for coronary heart disease in patients with HIV-1 infection? J Acquir Immune Defic Syndr. 2002;30:471-477.
  22. Verhelst D, Monge M, Meynard JL, et al. Fanconi syndrome and renal failure induced by tenofovir: a first case report. Am J Kidney Dis. 2002;40:1331-1333.
  23. Coca S, Perazella MA. Rapid communication: acute renal failure associated with tenofovir: evidence of drug-induced nephrotoxicity. Am J Med Sci. 2002;324:342-344.
  24. Peyriere H, Reynes J, Rouanet I, et al. Renal tubular dysfunction associated with tenofovir therapy: report of 7 cases. J Acquir Immune Defic Syndr. 2004;35:269-273.
  25. Karras A, Lafaurie M, Furco A, et al. Tenofovir-related nephrotoxicity in human immunodeficiency virus-infected patients: three cases of renal failure, Fanconi syndrome, and nephrogenic diabetes insipidus. Clin Infect Dis. 2003;36:1070-1073.
  26. Creput C, Gonzalez-Canali G, Hill G, et al. Renal lesions in HIV-1-positive patient treated with tenofovir. AIDS. 2003;17:935-937.
  27. Gallant JE, Parish MA, Keruly JC, Moore RD. Changes in renal function associated with tenofovir disoproxil fuma-rate treatment, compared with nucleoside reverse-transcriptase inhibitor treatment. Clin Infect Dis. 2005;40:1194-1198.
  28. Zimmermann AE, Pizzoferrato T, Bedford J, et al. Tenofovir-associated acute and chronic kidney disease: A case of multiple drug interactions. Clin Infect Dis. 2006;42:283-290.
  29. Synovate Healthcare US HIV Monitor Q1 2007.
  30. Franceschini N, Napravnik S, Finn WF, et al. Immunosuppression, hepatitis
  31. C infection and acute renal failure in HIV-infected patients. J Acquir Immune Defic Syndr. 2006;42:368-372.
  32. Brewster UC, Perazella MA. Acute interstitial nephritis associated with atazanavir, a new protease inhibitor. Am J Kidney Dis. 2004;44:e81-e84.
  33. Krishnan M, Nair R, Haas M, Atta MG. Acute renal failure in an HIV-positive 50-year-old man. Am J Kidney Dis. 2000;36:1075-1078.
  34. Angel-Moreno-Maroto A, Suarez-Castellano L, Hernandez-Cabrera M, Perez-Arellano JL. Severe efavirenz-induced hypersensitivity syndrome (not-DRESS) with acute renal failure. J Infect. 2006;52:e39-40.
  35. Weinstock HS, Zaidi I, Heneine W, et al. The epidemiology of antiretroviral drug resistance among drug-naïve HIV-1-infected persons in 10 US cities. J Infect Dis. 2004;189:2174-2180.
  36. Novak RM, Chen L, MacArthur, RD, et al. Prevalence of antiretroviral drug resistance mutations in chronically HIV-infected, treatment-naïve patients: implications for routine resistance screening before initiation of antiretroviral therapy. Clin Infect Dis. 2005;40:468-474.
  37. Wensing AM, van de Vijver DA, Angar-ano G, et al. Prevalence of drug-resistant HIV-1 variants in untreated individuals in Europe: Implications for clinical management. J Infect Dis. 2005;192:958-966.
  38. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents.www.aidsinfo.nih.gov/guidelines/adult/AA_040705.pdf (accessed on August 22, 2007).
  39. Hammer SM, Saag MS, Schecter M, et al. Treatment for adult HIV infection: 2006 recommendations of the International AIDS Society-USA panel. JAMA. 2006;296:827-843.