WBR0564

Author	[[PageAuthor::Serge Korjian M.D. (Reviewed by Serge Korjian)]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Microbiology
Sub Category	SubCategory::Infectious Disease
Prompt	[[Prompt::A 37-year-old woman diagnosed with HIV three months ago is started on highly-active antiretroviral therapy (HAART) therapy consisting of ritonavir, emtricitabine, and tenofovir. Two months later, the patient presents for a follow-up appointment having stopped two of her medications because of severe nausea. The patient continued taking ritonavir alone because she felt she was tolerating it well. You order follow-up labs that reveal an absolute increase in viral load and a drop in her CD4 count from 423 cells/mL to 144 cells/mL. Which of the following genes would you expect to be mutated in this patient?]]
Answer A	AnswerA::Gag gene
Answer A Explanation	AnswerAExp::The gag gene usually codes for the capsid protein which is not a target for protease inhibitors.
Answer B	AnswerB::Pol gene
Answer B Explanation	AnswerBExp::The Pol gene codes for HIV protease and mutations usually lead to resistance to certain protease inhibitors.
Answer C	AnswerC::Env gene
Answer C Explanation	AnswerCExp::The Env gene codes for gp160, which is cleaved by HIV protease into gp120 and gp41 both integral parts of the HIV envelope requires for docking and fusion into the cell respectively. Mutations are not associated with the HIV protease.
Answer D	AnswerD::Rev gene
Answer D Explanation	AnswerDExp::The Rev gene is a viral replication regulator requires for proper viral synthesis. Mutations do not affect HIV protease.
Answer E	AnswerE::Tat gene
Answer E Explanation	AnswerEExp::The Tat gene product is important for regulating reverse transcription and release of the virions from the infected cells. Mutations do not cause protease inhibitor resistance.
Right Answer	RightAnswer::B
Explanation	[[Explanation::HIV protease, a product of the HIV Pol gene is an important component of the HIV life-cycle that cleaves synthesized polyproteins into structural and functional protein products. Without HIV protease, virions would be unable to mature. HIV protease inhibitors (PI) act by inhibiting this enzyme and stopping peptide cleavage. HAART therapy usually consists of a triple regimen including at least 2 nucleoside reverse transcriptase inhibitors (NRTIs) combined with one of the following: PI, integrase inhibitor, or non-nucleoside reverse transcriptase inhibitors (NNRTI). PI monotherapy is associated with mutations in the HIV genome leading to resistance to the medication. The mutation should occur in the Pol gene in order to create an HIV protease resistant to PI. Educational Objective: HIV protease is targeted by protease inhibitors with resistance conferred by mutation in the Pol gene coding for a new HIV protease. References: Molla A, Korneyeva M, Gao Q, et al. Ordered accumulation of mutations in HIV protease confers resistance to ritonavir. Nat Med. 1996;2(7):760-6.]]
Approved	Approved::Yes
Keyword	WBRKeyword::HIV, WBRKeyword::AIDS, WBRKeyword::Pol gene, WBRKeyword::Protease inhibitors, WBRKeyword::Ritonavir, WBRKeyword::HIV resistance, WBRKeyword::Resistance
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