Correspondence
Human Immunodeficiency Virus in Pregnancy
N Engl J Med 2002; 347:1208-1209October 10, 2002
- Article
To the Editor:
In her review of the management of human immunodeficiency virus (HIV) infection during pregnancy (June 13 issue),1 Watts recommends addressing coexisting herpes simplex virus (HSV) infection as one would for a nonpregnant patient. However, it may be rational to prescribe daily suppressive doses of acyclovir during the last trimester — certainly for those with a history of genital HSV disease, and perhaps empirically for all HIV-infected women, lest an inopportune outbreak of HSV during labor and delivery increase the risk of vertical transmission of HIV. HIV is expressed in high titers in herpetic ulcers — disproportionately more than in concurrent plasma samples.2 Acyclovir has a long history of safe use during pregnancy.
2 ReferencesSteven Leiner, N.P., P.A.-C.
Mission Neighborhood Health Center, San Francisco, CA 94110
sleiner@itsa.ucsf. edu 1
Watts DH . Management of human immunodeficiency virus infection in pregnancy. N Engl J Med 2002;346:1879-1891
Full Text | Web of Science | Medline2
Schacker T ,Ryncarz AJ ,Goddard J ,Diem K ,Shaughnessy M ,Corey L . Frequent recovery of HIV-1 from genital herpes simplex virus lesions in HIV-1-infected men. JAMA 1998;280:261-266
CrossRef | Web of Science
To the Editor:
The review by Watts advocates that “midazolam . . . should not be used in women receiving protease inhibitors, efavirenz, or delavirdine, because their metabolism may be delayed by such antiretroviral drugs.” In such patients, we urge caution, rather than avoidance, in the use of this and other agents (e.g., barbiturates, benzodiazepines, and propofol) that modulate the interaction of γ-aminobutyric acid at its receptor.
Although concern about the interaction between antiretroviral agents and γ-aminobutyric acid modulators has focused on their shared hydroxylation through the cytochrome P-450 system, the resulting pharmacokinetic and pharmacodynamic expression remains variable. In the case of the short-term administration of these agents, this clinical effect is due predominantly to the influence of redistribution rather than metabolism.
In reference to the hydroxylation by the cytochrome P-450 system, the protease inhibitor saquinavir has been noted to reduce the metabolism of midazolam, resulting in a 50 percent increase in bioavailability.1 By contrast, lower bioavailability would be expected with nevirapine, the reverse-transcriptase inhibitor (like efavirenz and delavirdine) that induces cytochrome P-450 metabolism.2 These conflicting effects on cytochrome P-450 may suggest that temazepam and lorazepam, which are minimally affected by this hepatic enzyme, and oxazepam, which is metabolized by plasma esterases, are preferable options.3
Patients with HIV frequently undergo procedures that may be performed more comfortably, and even more safely, with the use of sedative or anesthetic agents. Clinical and experimental data regarding the use of such agents during labor in women with HIV are limited.4 We encourage further investigation into this area of critical and growing importance.
4 ReferencesJohn P.R. Loughrey, M.D.
Lawrence C. Tsen, M.D.
Brigham and Women's Hospital, Boston, MA 02115
ltsen@zeus.bwh. harvard. edu 1
Palkama VJ ,Ahonen J ,Neuvonen PJ ,Olkkola KT . Effect of saquinavir on the pharmacokinetics and pharmacodynamics of oral and intravenous midazolam. Clin Pharmacol Ther 1999;66:33-39
CrossRef | Web of Science | Medline2
Mirochnick M ,Clarke DF ,Dorenbaum A . Nevirapine: pharmacokinetic considerations in children and pregnant women. Clin Pharmacokinet 2000;39:281-293
CrossRef | Web of Science | Medline3
Greenblatt DJ ,Divoll M ,Abernethy DR ,Ochs HR ,Shader RI . Clinical pharmacokinetics of the newer benzodiazepines. Clin Pharmacokinet 1983;8:233-252
CrossRef | Web of Science | Medline4
Tsen LC. Anesthesia for the parturient with HIV infection. In: Nedeljkovic SS, ed. Pain management, anesthesia, and HIV/AIDS. Boston: Butterworth–Heinemann, 2002:257-67.
Author/Editor Response
Dr. Watts replies:
To the Editor: Leiner raises an interesting issue regarding the use of antiviral agents for the prevention of recurrent outbreaks of HSV at delivery, given the potential for an increased rate of HIV type 1 (HIV-1) transmission with the detection of HIV-1 in herpetic ulcers.1 The current recommendation is that cesarean delivery be used in women with herpetic lesions at the onset of labor, regardless of their HIV-1 serologic status, in order to prevent neonatal HSV infection2; this course of action should reduce exposure to HIV-1 as well.3 The use of antiviral agents in late pregnancy to prevent the reactivation of HSV and the transmission of HIV-1, although it seems logical, must still be considered experimental, since data are unavailable on the efficacy of antiviral drugs in preventing both symptomatic and asymptomatic shedding of HSV by HIV-1–infected pregnant women. Data for HIV-1–negative pregnant women suggest that suppression is incomplete.4 Current recommendations for the management of HSV in pregnant, HIV-infected women are to use antiviral agents as in nonpregnant persons, primarily for symptomatic outbreaks or suppression of frequent recurrences.5 Clearly, further investigation into the optimal management of concomitant HSV and HIV-1 infections in pregnant women is warranted.
Loughrey and Tsen discuss an important point regarding the use of midazolam and other γ-aminobutyric acid agonists in women who are receiving protease inhibitors, efavirenz, or delavirdine. With careful monitoring, short-term use of midazolam or similar drugs for invasive procedures, as opposed to total avoidance of these agents, may be appropriate. I agree that further investigation of interactions between antiretroviral agents and other commonly used drugs is critically important.
5 ReferencesD. Heather Watts, M.D.
National Institutes of Health, Bethesda, MD 20892
hw59i@nih.gov 1
Schacker T ,Ryncarz AJ ,Goddard J ,Diem K ,Shaughnessy M ,Corey L . Frequent recovery of HIV-1 from genital herpes simplex virus lesions in HIV-1-infected men. JAMA 1998;280:261-266
CrossRef | Web of Science2
Management of herpes in pregnancy. ACOG practice bulletin no. 8. Washington, D.C.: American College of Obstetricians and Gynecologists, October 1999.
3
The European Mode of Delivery Collaboration
CrossRef | Web of Science | Medline4
Watts DH ,Brown ZA ,Money D , et al. A double-blind, randomized, placebo-controlled trial of acyclovir in late pregnancy for reduction of herpes simplex (HSV) shedding and cesarean section. Infect Dis Obstet Gynecol 2001;9:165-166 abstract.5
Guidelines for preventing opportunistic infection among HIV-infected persons -- 2002: recommendations of the U
