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HIV Education > Clinical Cases in HIV Resistance > Case Study 1

Clinical Cases in HIV Resistance

Volume 1 Number 1
May 2009

Clinical Cases in Resistance is the first in a series of patient profiles that illustrate key practice points for clinicians on the use and interpretation of resistance tests in the overall care of HIV-infected patients.

Dr.Rafael E. Campo

Dr. Rafael E. Campo is Professor of Clinical Medicine in the Division of Infectious Diseases at the University of Miami School of Medicine in Miami, Florida. Dr. Campo’s current work focuses on therapy for HIV infection, resistance to antiretroviral agents, and salvage therapies for treatment experienced patients. Dr. Campo is a paid consultant for Virco Lab, Inc.


A 30-year-old African American mother presents to the clinic with viremia and declining CD4 cell count after a year of intermittent adherence to her HAART regimen

Medical History

The patient was diagnosed with HIV in 2002. Her screening HIV RNA level and CD4 cell count were 85,600 copies/mL and 312 cells/mm3, respectively. A screening genotype was not performed. The medical history was remarkable in that the patient had 2 unplanned pregnancies, both carried to full term, in the 3 years prior to her HIV diagnosis. She had a very chaotic lifestyle. Following the birth of her children, she remained sexually active and admitted to using birth control in a haphazard, intermittent fashion.

Treatment History

The patient initiated antiretroviral therapy in late 2002 with a regimen of lopinavir/ritonavir + zidovudine/lamivudine. An efavirenz-based regimen was not chosen because of a concern over another unplanned pregnancy.

Over the next year, the patient had intermittent adherence to the regimen due to adverse events (nausea and vomiting). The HIV RNA level decreased to a nadir of 1500 copies/mL and the CD4 cell count increased to 450 cells/mm3. A resistance test conducted in November 2003 showed no resistance mutations (see Practice Point 1). The patient’s hemoglobin and hematocrit were 10.5 g/dL and 31%, respectively.

Nelfinavir was substituted for lopinavir/ritonavir because of the patient’s gastrointestinal issues with lopinavir/ritonavir. The NRTI combination of zidovudine/lamivudine was continued. During the next year, the HIV RNA level fluctuated between 350 to 4800 copies/mL with the CD4 cell count remaining stable at 420 to 500 cells/mm3. The patient’s hemoglobin and hematocrit were 9.5 g/dL and 28%, respectively. However, the patient declined the option of receiving erythropoietin to improve her hemoglobin.

In December 2004, a genotype test showed the following mutations: PI: 10F, 30N; RT: 184V (see Practice Point 2). Based on these results, nelfinavir was stopped and no further use of lamivudine or emtricitabine was contemplated due to the presence of the 184V mutation. In addition, zidovudine was not considered an option anymore because of persistent anemia and her refusal to use erythropoietin.

Antiretroviral therapy was switched to didanosine + tenofovir DF, a commonly used combination at the time, plus the lopinavir/ritonavir she had received before. Over the next 2 years, the patient had better tolerance to the new regimen, 4 out of 6 HIV RNA levels were <50 copies/mL, and the CD4 cell count stabilized at approximately 500 cells/mm3. However, by late 2006 the patient became pregnant once more. Following successful delivery of her third child in June 2007, the patient underwent bilateral tubal ligation.

Current Evaluation

During a clinic visit in June 2008, approximately 1 year after the birth of her third child, the patient admitted poor adherence to her HAART regimen. During the preceding year, HIV RNA levels had ranged from 2300 to 12,500 copies/mL. The current CD4 cell count was 350 cells/mm3. A virco®TYPE was ordered.CLICK here to see the results

The virco®TYPE HIV-1 report showed selection of the K65R mutation and mutations to multiple PIs (see Practice Points 3 and 4). Based on these results, the newly prescribed regimen consisted of efavirenz + saquinavir + ritonavir + raltegravir. Over the next 9 months, the regimen was well tolerated, two HIV RNA measurements were <50 copies/mL, and the most recent CD4 cell count was 480 cells/mm3.

Practice Points

  1. In patients with extreme non-adherence, it is possible to see no selection of resistance-associated mutations irrespective of the regimen used. In patients with partial non-adherence, the emergence of primary PI resistance-associated mutations rarely occurs in treatment-naïve patients whose initial antiretroviral therapy regimen includes a boosted PI plus 2 NRTIs. Initial boost-PI-based regimens are also associated with a low frequency of emergence of NRTI resistance-associated mutations. 1-13
  2. Unboosted PIs have a lower barrier to resistance than boosted PIs. Because of this, the failure of unboosted PI regimens is often accompanied by selection of PI resistance and also selection of resistance to the NRTI components of the regimen.1
  3. A low frequency of selection of the K65R mutation has been observed during the major clinical trials for tenofovir DF (Studies 903 and 934).14,15 However, this mutation does emerge more frequently when tenofovir DF is combined with didanosine.16
  4. Selection of resistance to boosted-PI based regimens (including lopinavir/ritonavir) occurs when the patient is not naïve to PIs and some selection of PI resistance-associated mutations has already occurred. In this situation, the high genetic barrier of PIs no longer prevents emergence of resistance to boosted PIs.17

Not an actual patient. This case study is for educational purposes only and does not constitute professional medical advice. It should not be relied upon for making patient treatment decisions.


References

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  10. Smith KY, Weinberg WG, DeJesus E, et al. Fosamprenavir or atazanavir once daily boosted with ritonavir 100 mg, plus tenofovir/emtricitabine, for the initial treatment of HIV infection: 48-week results of ALERT. AIDS Res Ther. 2008;5:5.
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  13. Ortiz R, Dejesus E, Khanlou H, et al. Efficacy and safety of once-daily darunavir/ritonavir versus lopinavir/ritonavir in treatment-naive HIV-1-infected patients at week 48. AIDS. 2008;22:1389-1397.
  14. Gallant JE, Staszewski S, Pozniak AL, et al. Efficacy and safety of tenofovir DF vs stavudine in combination therapy in antiretroviral-naive patients: a 3-year randomized trial. JAMA. 2004;292:191-201.
  15. Arribas JR, Pozniak AL, Gallant JE, et al. Tenofovir disoproxil fumarate, emtricitabine, and efavirenz compared with zidovudine/lamivudine and efavirenz in treatment-naive patients: 144-week analysis. J Acquir Immune Defic Syndr. 2008;47:74-78.
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