Elevated plasma concentrations of protease inhibitors and nonnucleoside reverse transcriptase inhibitors in patients coinfected with human immunodeficiency virus and hepatitis B OR C: Case series and literature review

Sarah M. Robertson, Kimberly K. Scarsi, Michael J. Postelnick, Patrick Lynch

Research output: Contribution to journalReview article

12 Citations (Scopus)

Abstract

Study Objective. To evaluate antiretroviral pharmacokinetics in patients who are coinfected with human immunodeficiency virus (HIV) and hepatitis B and/or C virus. Specifically, we sought to determine whether coinfection results in higher than expected concentrations of protease inhibitors and nonnucleoside reverse transcriptase inhibitors (NNRTIs). Design. Case series. Setting. Human immunodeficiency virus clinic. Patients. Twenty-six patients infected with HIV and hepatitis B and/or C virus. Measurements and Main Results. Patients' plasma trough concentrations (Cmeasured) of protease inhibitors and NNRTIs were compared with population average trough concentrations reported in the literature (Cpredicted). Trough concentrations were obtained irrespective of the patients' liver function. A concentration ratio of C measured:Cpredicted was determined for each patient. The mean concentration ratio of the 26 patients was 1.43 (95% confidence interval 1.08-1.78). For the six patients taking nelfinavir, the ratio of nelfinavir's active metabolite (M8):parent drug was calculated. The median M8:nelfinavir ratio for these six patients was 69% lower than what has been reported in a general HIV population. Conclusion. These preliminary findings suggest that trough concentrations of protease inhibitors and NNRTIs may be elevated in patients with HIV infection who are coinfected with hepatitis B and/or C, compared with a general population of patients with HIV infection. Until further investigation defines the relationship between coinfection, metabolic dysfunction, and increased antiretroviral exposure, therapeutic drug monitoring may be helpful to identify coinfected patients at risk for antiretroviral toxicity secondary to elevated plasma drug concentrations.

Original languageEnglish (US)
Pages (from-to)1068-1072
Number of pages5
JournalPharmacotherapy
Volume25
Issue number8
DOIs
StatePublished - Aug 1 2005

Fingerprint

Reverse Transcriptase Inhibitors
Hepatitis C
Protease Inhibitors
Hepatitis B
HIV
Nelfinavir
Virus Diseases
Coinfection
Hepatitis B virus
Hepacivirus
Population
Drug Monitoring
Pharmaceutical Preparations
Pharmacokinetics
Parents

Keywords

  • Antiretroviral therapy
  • Coinfection
  • HIV
  • Hepatitis B
  • Hepatitis C
  • Protease inhibitors
  • Reverse transcriptase inhibitors

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

Elevated plasma concentrations of protease inhibitors and nonnucleoside reverse transcriptase inhibitors in patients coinfected with human immunodeficiency virus and hepatitis B OR C : Case series and literature review. / Robertson, Sarah M.; Scarsi, Kimberly K.; Postelnick, Michael J.; Lynch, Patrick.

In: Pharmacotherapy, Vol. 25, No. 8, 01.08.2005, p. 1068-1072.

Research output: Contribution to journalReview article

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abstract = "Study Objective. To evaluate antiretroviral pharmacokinetics in patients who are coinfected with human immunodeficiency virus (HIV) and hepatitis B and/or C virus. Specifically, we sought to determine whether coinfection results in higher than expected concentrations of protease inhibitors and nonnucleoside reverse transcriptase inhibitors (NNRTIs). Design. Case series. Setting. Human immunodeficiency virus clinic. Patients. Twenty-six patients infected with HIV and hepatitis B and/or C virus. Measurements and Main Results. Patients' plasma trough concentrations (Cmeasured) of protease inhibitors and NNRTIs were compared with population average trough concentrations reported in the literature (Cpredicted). Trough concentrations were obtained irrespective of the patients' liver function. A concentration ratio of C measured:Cpredicted was determined for each patient. The mean concentration ratio of the 26 patients was 1.43 (95{\%} confidence interval 1.08-1.78). For the six patients taking nelfinavir, the ratio of nelfinavir's active metabolite (M8):parent drug was calculated. The median M8:nelfinavir ratio for these six patients was 69{\%} lower than what has been reported in a general HIV population. Conclusion. These preliminary findings suggest that trough concentrations of protease inhibitors and NNRTIs may be elevated in patients with HIV infection who are coinfected with hepatitis B and/or C, compared with a general population of patients with HIV infection. Until further investigation defines the relationship between coinfection, metabolic dysfunction, and increased antiretroviral exposure, therapeutic drug monitoring may be helpful to identify coinfected patients at risk for antiretroviral toxicity secondary to elevated plasma drug concentrations.",
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