ANTEPARTUM MANAGEMENT

should they fail to inform a patient of the availablity of testing, and if that woman gives birth to a child subsequently determined to be congenitally infected with HIV. As noted, the law of the land has been written, and it spells out penalties for states in which testing rates do not move dramatically upward and congenital infection rates do not follow the converse trajectory.

ANTEPARTUM MANAGEMENT

Since the early years of the epidemic, concerns have been raised about the possible interaction of HIV and pregnancy. Because pregnancy represents a time of dramatic hormonal and physiologic alteration and because immune status, in turn, may be altered by these effects, these concerns had a reasonable basis. Drs. Landers, Martinez de Tejada, and Coyne review the interactions between pregnancy and HIV disease. To date, the empiric data have not sustained the fears of an adverse interaction. Studies of immune status alterations during the pregnancy of HIV-infected women do not reveal a dramatic difference from changes among women who are not pregnant. Pregnancy outcomes also appear to be relatively unaffected by HIV serostatus, though women with advanced states of illness might be less insured to HIV’s effects. Although pregnancy does not seem to exert a markedly deleterious effect on the course of HIV disease, it is still important to ensure that the woman receives appropriate therapy. The keys to the optimal care of an HIV-infected woman during pregnancy are optimal care of the pregnancy, and optimal care of the HIV infection. The need to provide one of these services should not encroach on the clinician’s ability to provide fully for the other. Dr. Augenbraun’s article provides a thorough guide to the provision of HIV care in an era of rapidly evolving diagnostic modalities, therapeutic strategies, and as a direct consequence, clinical standards. Unquestionably, the last few years have been witness to dramatic advances in treatment, but these advances have carried some confusion in their wake. The rapidity with which drugs have been developed and approved has outpaced the clinical research community’s ability to complete large scale phase I11 trials that might have been able to more precisely guide choices and more fully document risks. The absence of defining information is particularly acute in the setting of pregnancy; however, in the presence of treatments that are obvious improvements over earlier interventions, there is a need to act, even in the absence of definitive information. A recent Public Health Service task force has codified this philosophy. With Dr. Augenbraun‘s article serving as a ”user’s manual,” the obstetrician’s principal responsibility is to ensure that pregnancy never be used as a reason to accept second tier standards of antiretroviral or prophylactic therapies. The paradigm of antiretroviral therapies in the late 1990s is, in sum, that ZDV monotherapy is no longer the standard of care for any patient whose clinical, immunologic, or virologic condition warrants antiretroviral therapy. The landmark studies of viral dynamics that outlined the explosive rate of viral replication from the onset of infection, and the concomitant risk of mutation to resistance, were in essence the death knell of monotherapy. Therefore, only if the woman’s immunologic and virologic circumstances are such that if she were not pregnant, she would not be given antiretroviral therapy, should the sole focus be on prevention of mother-to-child transmission. Undoubtedly, pregnant women deserve additional counseling regarding the use of these agents during gestation. Although follow-up of the children born to the mothers in the ACTG 076 study and other cohorts have been reassuring, animal data recently presented from the National Cancer Institute, PREFACE

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suggesting a risk of transplacental carcinogenesis, served to chasten those who would be cavalier about the use of new medications with nucleoside potential. Prevention of opportunistic infections is also a critical goal for the obstetrician. As CD4 counts decline and viral loads climb, the patient becomes susceptible to an array of infections that, if acquired, would augur poorly for the patient and her pregnancy. At the current time, critical landmarks for the introduction of prophylaxis include CD4 counts of 5200 mm/3 (Pneumocytis carinii pneumonia), 5100 mm/3 (Toxoplasma gondii) and 150 mm/3 (MAC and perhaps CMV conjuntivitis). Obstetricians must vigilantly guard against these infections by monitoring CD4 counts and viral loads on a regular basis and modifying antiretroviral and prophylactic therapies as appropriate. Obstetric management (i.e., decisions regarding monitoring obstetric problems) and choosing candidates for, or timing of, induced delivery are uninfluenced by a woman’s serostatus; however, aspects of management that are unique to the infected patient are pharmacologic strategies that minimize the rate of mother-to-child transmission of HIV. Since February of 1994, the core strategy has been based on the results of the remarkably successful ACTG 076 trial. More than any other factor, the dramatic reduction in transmission rates attributable to ZDV has underpinned national efforts to identify and treat pregnant women. AZI HIV-infected pregnant women should be offered ZDV during the antepartum and intrapartum periods, and their neonates should receive ZDV syrup. As noted, the recent reports from the National Cancer Institute suggesting carcinogenic risk for the offspring of exposed mice, using the same animal model in which DES acts as a transplacental carcinogen, remind us to be wary of any new drug’s long-term effects and of the need to discuss all aspects of therapy with mothers. The contrasting data in other animal models, the reassurance offered by the hundreds of births to date with no documented tumors, and the overwhelming number of children saved by AZT, put that data in appropriate perspective. Further research regarding the carcinogenic potential of these agents is ongoing. In the interim, according to a blue ribbon panel charged with assessing the animal data, pregnant HIV-infected women should be informed of potential risks, but the demonstrated benefits of ZDV should be stressed and its use should stand as the level of care to which all women are entitled. Additionally, efforts should be made to assure long-term follow-up of all exposed infants. Undoubtedly, results of ongoing research will soon inform modifications of that therapy, either pointing out equally effective, potentially safer, abbreviated regimens or more effective alternative strategies. Data from several sources, including the recently ended ACTG 185, reinforce the importance of ZDV. In ACTG 185, ZDV (combined with either HIViG or NiG) was given to women with low CD4 counts and prior ZDV use-groups who had been excluded from the ACTG 076 trial. Transmission in women in both arms of the trial was under 5%. Treatment efficacy was uninfluenced by prior drug exposure. These results speak to the broader generality of ACTG 076‘s findings and reinforce the critical importance of this approach to care. A few controversies regarding management remain, one of which is the issue of vaccination. There is some evidence that there is a viremia associated with vaccinations. Although it might be argued that the disease against which the vaccination protects would likely cause an equal or greater viremia, one would not choose to induce any viremia, even a putatively more subtle one, during pregnancy. Viremia during pregnancy poses the theoretic risk of increasing the rate of antepartum transmission of HIV. The clinician must, therefore, perform the delicate task of balancing two risks: the risk of increased transmission associated with viremia and the risk of a patient acquiring a preventable disease during pregnancy because she did not receive a vaccine until the postxiv

PREFACE

partum period. Unfortunately, the magnitude of these risks is unclear, owing to an absence of empiric data. INTRAPARTUM MANAGEMENT

As detailed in articles by Tuomala and Mofenson, a great deal has been learned about the determinants of mother-to-child transmission of HIV (particularly those transmissions occurring in the intraparturn period) and potential obstetric practices that may influence them. In deciding how to alter intraparturn management in response to this information, one must consider the strength of the data and the potential consequence of the intervention. For example, if the data supporting a change in the usual pattern of practice are weak and the proposed intervention is associated with serious risk to the mother, then it would be inappropriate, at present, to modify standard management protocols. On the one hand, however, because the evidence tying duration of ruptured membranes to transmission is fairly consistent and strong, and the risks from avoiding routine amniotomy are not substantive, it would be appropriate to maintain the integrity of the membranes for as long as possible. Elective amniotomy should not be performed in the setting of HIV infection. Alternatively, data suggesting that cesarean section is protective are a bit more nebulous. Although obstetricians can clearly vouchsafe the membranes with elective operative delivery, the evidence that this approach will spare the child from infection with HIV is less secure, and the risk of routinely performing surgery, particularly in those countries with limited access to antibiotics, blood supplies, and anesthesia, are not insignificant. If ZDV is unavailable, however, or if new data document a benefit, even in the setting of peripartum ZDV use, providers may need to exercise their clinical judgement in determining whether to discuss operative delivery as a reasonable clinical choice with the mother. Ultimately, it is hoped that results of ongoing randomized trials of cesarean section will provide clearer guidance. A bit of "good news" associated with the advent of antiretroviral agents recently reported, and with the direct relevance for clinicians providing care in the intraparturn period, is evidence that postexposure prophylaxis reduces the risk of iatrogenic infection with HIV. Case-control studies have demonstrated a reduction in the rate of seroconversion after needle-stick injuries associated with the use of antiretroviral prophylaxis.2As a result of these reports and the array of newly available treatments, several proposals have been published for the care of the injured health care worker.', Although subtle differences in recommended regimens exist, there is an apparent consensus that therapy should be instituted as soon as possible after the offending event, that combination therapy might have an advantage over monotherapy, and that drugs to which the source patient has not been exposed are preferable. In general, the exposed individual should use two nucleoside reverse transcriptase inhibitors. If, however, the exposure is particularly high risk (e.g., deep needle-stick injury from a source patient with end stage disease), then a protease inhibitor should be added. Protocols should be established at each institution in anticipation of, not in response to, a needle-stick exposure. It may also be appropriate to consider the same sort of protocols for individuals whose exposure is sexual (e.g., rape). POSTPARTUM MANAGEMENT

Ongoing care of the HIV-infected woman through the puerperal period and beyond requires an understanding of the gynecologic manifestations of PREFACE

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