A 24-year-old pregnant woman comes to the emergency department in active labor at full term. The patient has a history of HIV from injection drug use. She is not adherent with antiretroviral therapy and has had no recent testing of CD4 count or plasma viral load. Physical examination shows regular uterine contractions, ruptured amniotic membranes, and a fully dilated cervix. A decision is made to continue with the vaginal delivery due to advanced labor. Intravenous zidovudine is administered to the patient during the delivery and to the infant immediately after birth. This medication helps decrease the risk of perinatal transmission by inhibiting which of the following components of viral genome replication?

Question

A 24-year-old pregnant woman comes to the emergency department in active labor at full term.  The patient has a history of HIV from injection drug use.  She is not adherent with antiretroviral therapy and has had no recent testing of CD4 count or plasma viral load.  Physical examination shows regular uterine contractions, ruptured amniotic membranes, and a fully dilated cervix.  A decision is made to continue with the vaginal delivery due to advanced labor.  Intravenous zidovudine is administered to the patient during the delivery and to the infant immediately after birth.  This medication helps decrease the risk of perinatal transmission by inhibiting which of the following components of viral genome replication?

Quizplus · Accepted Answer

HIV is a single-stranded RNA virus that is converted into cDNA by the HIV enzyme reverse transcriptase. This enzyme grows DNA by adding nucleotides to the terminal 3′-hydroxyl group using a 3′-5′ phosphodiester bond. Nucleoside reverse transcriptase inhibitors (NRTIs) such as zidovudine block this step in viral replication. This class of medications is composed of nucleoside/nucleotide analogues that do not have a 3′-hydroxyl group. When reverse transcriptase incorporates an NRTI into a growing DNA strand, it results in chain termination because no 3′-hydroxyl group is available to add additional base pairs. Zidovudine (ZDT) was the first approved HIV medication but is now used primarily to prevent maternal to fetal transmission of HIV during labor and delivery. It is a thymidine analogue that contains an azido group in place of the hydroxyl group usually found at the 3′ end of thymidine. (Choice A) The enzyme thymidylate synthase catalyzes the conversion of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP). N5, N10-methylene tetrahydrofolate is the methyl donor in this reaction and is converted to dihydrofolate (DHF) in the process. Tetrahydrofolate is then regenerated from DHF by dihydrofolate reductase. Methotrexate is a chemotherapeutic agent that inhibits DNA synthesis by inhibiting dihydrofolate reductase. (Choice B) Integration of viral DNA into the host genome is mediated by integrase, an HIV enzyme that is inhibited by integrase strand transfer inhibitors (eg, raltegravir). (Choice C) Inhibition of nucleoside phosphorylation is not an effect of ZDT. In fact, nucleoside reverse transcriptase inhibitors (including ZDT) must be phosphorylated within the host cell to form the functional triphosphate moiety. Non-nucleoside reverse transcriptase inhibitors can bind directly to (and inactivate) reverse transcriptase without being phosphorylated. (Choice E) In double-stranded DNA, A always pairs with T, and G always pairs with C. These bases bind via hydrogen bonds. Some chemotherapeutic agents, such as the anthracyclines daunorubicin and doxorubicin, intercalate between the bases, causing defective base pairing and splitting of the DNA strands. Transcription and replication failure and mutagenesis ultimately result. Educational objective: Zidovudine (ZDT) is a nucleoside reverse transcriptase inhibitor used to prevent maternal to fetal transmission of HIV during labor (when the mother is not virally suppressed). It is a thymidine analogue that does not have the normal 3′-hydroxyl group found on thymidine. Because new nucleotides are added to growing DNA chains only at the 3′-hydroxyl group, the addition of ZDT into DNA results in chain termination.

A 24-Year-Old Pregnant Woman Comes to the Emergency Department in Active