Abstract and Introduction
Abstract
Background: Current guidelines for the use of antiretroviral (ARV) therapy during pregnancy recommend that women be offered treatment with combination ARV therapy used in nonpregnant HIV-infected individuals. It is unclear whether the risk of ARV-related adverse drug reactions (ADRs) is increased during pregnancy.
Objective: To evaluate the frequency and severity of ADRs likely caused by ARV therapy in pregnant women who are HIV-positive.
Methods: A retrospective analysis of HIV-infected women who received ARV therapy during pregnancy and delivered between January 1997 and February 2006 was conducted. Incidence of maternal ADRs was determined through evaluation of laboratory findings, documented physical examinations, and patient self-reports. An AIDS Clinical Trials Group severity grading scale was applied to the ADRs. Cause-effect relationship was adjudicated based on the Naranjo probability scale and, if causality was found, that information was included.
Results: There were 103 women who accounted for 133 pregnancies that resulted in deliveries. Of the 111 pregnancies in which treatment was received, regimens included 26 nucleoside reverse transcriptase inhibitor monotherapy, 40 nonnucleoside reverse transcriptase inhibitor (NNRTI)-based, 44 protease inhibitor (PI)-based, and 1 PI/NNRTI combination therapy. Ninety-eight ADRs were documented in 49 pregnancies. The most common ADRs were gastrointestinal (n = 48), followed by central nervous system symptoms (n = 15), anemia (n = 15), elevated liver/pancreatic enzyme levels (n = 11), and cutaneous reactions (n = 8). Severe ADRs included elevations in liver/pancreatic enzymes (n = 3), nausea and vomiting (n = 3), and anemia (n = 2). Seven women required a change in therapy due to an ADR.
Conclusions: Approximately 7 ADRs were reported for every 10 pregnancies in this cohort. Most ADRs were mild to moderate. Short exposure times in most women (second and third trimester) may have accounted for the lack of long-term toxicities. Although ADRs did not pose a major barrier to use of ARVs in pregnancy, close monitoring of pregnant women receiving ARV therapy continues to be warranted.
Introduction
The selection of antiretroviral (ARV) therapy during pregnancy requires consideration of various factors: physiologic changes during pregnancy, risk of maternal adverse drug reactions (ADRs), ARV potency, placental passage, and potential for teratogenicity. Currently, guidelines for the use of ARV therapy during pregnancy recommend that women be offered treatment with combination ARV therapy used in nonpregnant HIV-infected individuals, with the exception of efavirenz because of concern over teratogenicity. It is not clear whether the risk of ARV-related ADRs is increased during pregnancy; however, close monitoring is recommended due to observed adverse events with the use of ARVs in other settings. In the HIV-infected general population, protease inhibitors (PIs), particularly the older agents, have been associated with insulin resistance, hyperglycemia, and new-onset diabetes mellitus. Hepatotoxicity associated with nevirapine is 12-fold higher in women with CD4 cell counts greater than 250 cells/µL. Although it is unclear whether pregnancy increases these risks, it is recommended that nevirapine be used with caution in pregnant women with higher CD4 cell counts. Fatal lactic acidosis has been reported in pregnant women receiving combined didanosine/stavudine; thus, current guidelines recommend avoiding this combination.
The purpose of this study was to evaluate the frequency and severity of ADRs likely caused by ARVs in HIV-positive pregnant women. Results of ARV efficacy in this cohort have been published elsewhere.