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How to care for the HIV-infected pregnant patient
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Caring for an expectant mother who is HIV-positive may be complex; but with adequate information and expert help, it can also be quite rewarding.
With continued progress in understanding the pathogenesis of HIV infection and advances in antiretroviral therapy, countless numbers of HIV-infected patients can now live relatively normal lives.
Upon completion of this article, participants will be able to:
These developments have also resulted in improved outcomes for pregnant women and their infants, at least in industrialized nations. With these advances in mind, obstetrician/gynecologists cannot only play a role in preventing women from acquiring HIV infection, they can take the lead in diagnosing the disease and ensuring that the most up-to-date medical care is available.
Unfortunately, these same impressive advances in diagnosis and treatment have made the care of infected patients quite complex. The purpose of this review is to help unravel these complexities and outline current treatment guidelines.
Ideally, women should know their HIV status before conceiving so they can make informed reproductive choices. In fact, a discussion of HIV testing should be a part of all preconceptual counseling sessions. With the exception of women known to be at low risk, HIV testing should be offered during the course of routine gynecologic carebut bear in mind that very few women are definitely known to be at low risk. Certainly you should encourage any woman who requires diagnosis or treatment of any sexually transmitted disease to be tested for HIV infection as well.
Testing should be repeated at least every 6 months in women who are engaged in high-risk behavior, including unprotected sexual activity. (The one possible exception to this rule is among partners who are known to be mutually monogamous.) When recommending HIV testing, also keep in mind that alcohol and drug useeven if it doesn't result in percutaneous exposureplace a woman at high risk for HIV infection by making her more likely to engage in risky sexual behavior.
The Institute of Medicine and the American College of Obstetricians and Gynecologists have recommended that HIV testing be routinely performed on all pregnant patients, recognizing, of course, that patients have the right to refuse it.1,2 The impetus for this recommendation includes the fact that many women who are ultimately found to be HIV-positive deny any risk factors. It is estimated that performing HIV testing only when risk factors are identified will fail to detect up to 50% of HIV-positive women.1
As with the nonpregnant patient, you should provide individualized, practice-specific counseling prior to testing and be prepared to arrange care for those women who test positive. Report all test results in person, both to maintain confidentiality and to allow the patient to ask questions. Women who are felt to be at high risk for acquiring HIV infection should be counseled about ways to reduce their risk and be retested every 6 months, including during their pregnancy.
With regard to the testing procedure itself, there are several options: Rapid HIV testing has recently become available, with results generally produced in 10 to 20 minutes. These tests have a sensitivity of 99.9% and a specificity of 99.6%, which is comparable to the standard ELISA with Western blot confirmation.3 Although their negative predictive value is high, positive predictive value is much lower, particularly in populations with a low seroprevalence. As a result, these rapid tests are of limited usefulness in many obstetrical offices or clinic practices.
In settings where the prevalence of HIV is high and the number of deliveries with no prenatal care is high, however, rapid testing may allow intrapartum diagnosis with subsequent intrapartum and neonatal antiretroviral chemoprophylaxis. In these settings, consider making the test available to patients. A cost-benefit analysis has shown that rapid HIV testing is cost effective in those situations in which HIV prevalence is higher than 0.97%, treatment reduces transmission by over 5.8%, and the lifetime cost of pediatric HIV infection is greater than $33,625.4 Given that the second and third assumptions are true in most areas, rapid testing may be a cost-saving option in most areas in which HIV seroprevalence in pregnancy is 9 per 1,000 or higher.
Patients who are diagnosed with HIV during their pregnancy, as well as those who are aware of their HIV status prior to pregnancy, should be counseled about the impact of HIV on pregnancy and about any im-pact of the pregnancy on HIV. Fortunately, pregnancy itself does not appear to adversely alter the course or natural history of HIV infection. Although CD4 counts may decrease during pregnancy, they return to baseline postpartum.5 In addition, plasma viral load does not change significantly during pregnancy.6
In the absence of any other complicating factors, such as drug use or chronic medical conditions, the incidence of most pregnancy-related complications does not seem to increase in women who are HIV-positive. The risks of spontaneous abortion, low birthweight, preterm birth, and intrauterine fetal death, for instance, are not increased. However, in women with significantly compromised immune systemsas evidenced by a CD4 count below 300 mg/dLthere does appear to be an increased risk of infectious complications.7 Patients should also be counseled about the risk of perinatal transmission, the factors that may increase this risk, and interventions that may decrease the danger (Table 1).
|Risk factor||Possible preventive intervention|
|Advanced HIV disease - low CD4 count - high plasma viral load||Antiretroviral therapy|
|Prolonged rupture of the membranes Vaginal delivery Increased exposure to maternal blood||Scheduled C/S, avoiding artificial rupture of membranes Scheduled C/S Scheduled C/S, avoiding scalp electrodes scalp sampling, and episiotomy|
Without treatment, about one in four women will pass on the infection during the perinatal period. This may occur in the antepartum, intrapartum, or postpartum period, with 75% to 80% of transmissions thought to occur in the intrapartum period. Experts believe that the vast majority of cases of vertical transmission occur late in the third trimester and in the intrapartum period. With current obstetric and medical practices, the risk of vertical transmission in the United States is approximately 5% or less.8
If your patient is HIV-positive, thoroughly evaluate her health at the initial visit. The work-up should include a complete history and physical examination, with particular attention given to signs and symptoms of opportunistic infections. Also assess immune and infection status by performing a CD4 count and quantitative plasma viral load, using PCR technology (Table 2). Current recommendations by the Department of Health and Human Services and the Public Health Service are to repeat the CD4 count and viral load every 3 to 4 months.9,10 The tests should also be repeated approximately 4 to 6 weeks following the initiation or following any change in antiretroviral therapy, or if treatment failure is suspected. The US Panel of the International AIDS Society recommends monitoring every 2 to 3 months.11
Also evaluate the patient for other STDs and for associated infections, including gonorrhea and chlamydia, hepatitis B and hepatitis C, tuberculosis (PPD), cytomegalovirus, and toxoplasmosis (serology). In general, an HIV-positive pregnant patient is at increased risk for STDs, although this may result from her life-style rather than any effect of the HIV infection. As with other pregnant patients, syphilis serology should be obtained. Assuming there are no other risk factors like drug use, there is no evidence that the fetus is at increased risk for growth abnormalities or for perinatal morbidityother than the transmission of HIV, of course. As a result, ultrasound and other fetal assessment should be performed for the usual obstetric indications.
Also keep in mind that the virus may be transmitted to the fetus during invasive procedures such as chorionic villus sampling, amniocentesis, and percutaneous umbilical blood sampling, although the relative risk is unknown. Advise any HIV-positive patient requiring prenatal diagnosis or other invasive procedures of this risk. Unfortunately there is currently no prenatal test available to determine which infants will ultimately be HIV-infected.
As in the nonpregnant patient, the goals of antiretroviral therapy in pregnancy are to reduce serum viral load to below detectable limits while keeping adverse effects to a minimum. In pregnancy, an additional goal is to reduce vertical transmission to the neonate while minimizing potential adverse effects on the developing fetus and the neonate. In some cases, these two goals will conflict.
As we go to press, there are currently 14 antiretroviral drugs available (Table 3). Therapy should be individualized, using guidelines established for the nonpregnant patient, including those published by the CDC, the Department of Health and Human Services, the Public Health Service, and by the International AIDS Society.9-11 The choice of therapy should be based on the patient's prior exposure to antivirals and current compliance history, current viral load and CD4 count, and her motivation and wishes. It has been recommended that, if possible, the regimen include zidovudine as outlined in the AIDS Clinical Trials Group Protocol 076 (ACTG 076), because until recently this was the only agent proven to reduce transmission (Table 4).12 Newer studies have shown, however, that other antiretroviral regimens are effective in reducing vertical transmission.9,10
|Generic name||Trade name||FDA pregnancy category|
|Lamivudine + zidovudine||Combivir||C|
|Zidovudine (ZDV, AZT)||Retrovir||C|
|Generic||Trade Name||FDA Pregnancy Category|
|Generic||Trade Name||FDA Pregnancy Category|
|Saquinavir||Fortovase (soft gel capsule) Invirase (hard gel capsule)||B|
Initiate zidovudine (ZDV) at 14 to 34 weeks gestation; continue throughout pregnancy
a) ZDV 100 mg p.o. 5 times a day (q4h while awake)
ZDV 200 mg p.o. q8h
ZDV 300 mg p.o. q12h
ZDV 2 mg/kg IV over 1 hour, followed by continuous infusion of 1 mg/kg IV until delivery
Neonatal treatment with p.o. ZDV syrup 2 mg/kg every 6 hours for first 6 weeks of life, beginning 8 to 12 hours following birth
In some cases, prior antiviral therapy and the development of resistant strains of HIV may limit one's therapeutic options. To avoid the potential risk of teratogenesis, you will usually want to avoid starting drug therapy in antiviral-naive patients until after the first trimester. For patients already on these drugs, the benefits of continuing them, and avoiding drug resistance, outweigh the potential teratogenic effects in most cases.
The most recent recommendations of the Department of Health and Human Services say that antiviral therapy should be offered to all patients with symptomatic HIV infection. Those patients who are asymptomatic and have a CD4 count below 500 cells/dL or a plasma viral load greater than 10,000 (bDNA) or greater than 20,000 (RT-PCR) should also be offered therapy. It should initially consist of two nucleoside reverse-transcriptase inhibitors (NRTI) plus one protease inhibitor (PI) or ritonavir plus saquinavir plus an NRTI. Of course, agents known or suspected to be teratogenic should be avoided (Table 3). Treatment of patients with a CD4 count above 500 and a viral load of less than 10,000 (bDNA) or 20,000 (RT-PCR) is controversial.9
As noted above, zidovudine should be incorporated into the drug regimen if possible. Even in those cases in which the drug was not given antepartum, it should still be offered to patients during the intrapartum period and as postnatal therapy to protect the neonate, unless the patient can't tolerate the drug or carries a viral strain that is resistant to it (Table 5). Neonatal zidovudine should also be offered, even for those HIV-positive women who did not receive the drug in the antepartum period because abbreviated courses also reduce transmission, although not to the degree of the 076 regimen.16
|Medication||Drug regimen||Comparison group||Transmission rate|
|Zidovudine||Given antepartum, intrapartum,and postpartum||Placebo||Reduced mother-to-childtransmission by 66%(from 22.6% to 7.6%)|
|Zidovudine||Given antepartum from week 36 and intrapartum||Placebo||Reduced transmission by 50%(from 19% to 9%)|
|Zidovudine and lamivudine||Given intrapartum and postpartum for 1 week for motherand neonate||Placebo||Reduced transmission by 38%(from 17% to 10%)|
|Nevirapine||200 mg at onset of labor, one dose to neonate*||Zidovudine intrapartum and to neonate||Reduced transmission by 50%(25% to 13%)|
Because of the complex nature of medical therapy and the rapid changes in therapeutic options for HIV-infected pregnant women, obstetric care should be provided by an obstetric specialist with experience in the care of HIV-affected pregnancies, if at all possible. If this is not possible, the obstetrician caring for such patients should do so in conjunction with an HIV specialist. In practices where specialists are not readily available, one should be consulted at least once during the pregnancy.
Some research suggests that a scheduled, elective C/S, performed prior to rupture of membranes and labor, can reduce vertical HIV transmission.17-20 But these studies were done when many patients were not on antiretroviral therapy and essentially predate combination antiretroviral therapy in pregnancy, as well as the routine use of plasma viral loads to monitor therapy. In addition, studies conflict in terms of the benefits of scheduled C/S in patients on antiretroviral therapy.
Several randomized clinical trials have evaluated the value of zidovudine in the prevention of mother-to-child transmission of human immunodeficiency virus. The latest Cochrane Library analysis included four RCTs that compared the drug to placebo in 1,585 patients. The antiretroviral reduced the risk of transmission almost in half (RR=0.54, 95% CI 0.42-0.69). The analysis was not able to detect any clinical differences between short-and long-term therapy regimens.1 Since the Cochrane review was published, however, a new clinical trial has concluded that abbreviated courses of maternal zidovudine are less effective than longer courses.2
Another clinical trial, this one comparing intrapartum and postnatal nevirapine with intrapartum and postpartum zidovudine, concluded that the former drug was more effective, reducing the risk of transmission by about 40% (RR=0.58, 95% CI 0.40-0.83). Most of the women in the trial were breastfeeding.
A separate trial that met the reviewers' inclusion criteria for evaluation compared elective C/S with vaginal delivery, concluding that the surgery reduced the risk of vertical transmission by 83% (RR=0.17, 95% CI 0.05-0.55).
1. Brocklehurst P. Interventions aimed at decreasing the risk of mother-to-child transmission of HIV infection. Cochrane Database Syst Rev. 2000;(2):CD000102.
2. Lallemant M, Jourdain G, LeCoeur S, et al. A trial of shortened zidovudine regimens to prevent mother-to-child trnsmission of human immunodeficiency virus type 1. N Engl J Med. 2000;343:982-991.
Following their publication, ACOG recommended that scheduled C/S be offered to all patients, but they also note that the data are insufficient to demonstrate a benefit for women with HIV RNA viral loads of below 1,000 copies/mL.21 In addition, the rate of vertical transmission in patients on combination therapy and/or with undetectable viral loads appears to be extremely low (less than 1%), so it is unclear whether C/S will offer significant additional benefit to these patients.8,22
At present, there does not seem to be a significant reduction in HIV transmission if the C/S is performed following rupture of membranes and/or the onset of labor. As a result, it has been recommended that if the surgery is planned, it be performed at 38 weeks to reduce the risk of spontaneous labor and rupture of membranes.21 Because performing an amniocentesis to determine pulmonary maturity may increase the risk of vertical transmission, in those patients with uncertain dating, the physician and the patient must balance the risks of possible preterm delivery against those of spontaneous labor and rupture of the membranes as a result of delaying or forgoing scheduled cesarean delivery.
Although data on operative complication rates in HIV-infected women are sparse, they may be at increased risk for complications following C/S, particularly if they are significantly immunosuppressed. Following an analysis of the patients in one European randomized trial, Semprini and colleagues reported that there was an increased risk of major morbidity in women who underwent C/S, although it did not reach statistical significance.23 The only factor associated with an increased risk for complications was a CD4 count below 200 cells/mm3. In other cohorts, complication rates did not significantly increase.24,25
By Emily Hill, PA-C, Consultant on Coding and Compliance, Hill & Associates, Wilmington, N.C.
To be reimbursed for caring for HIV infected pregnant patients, one has to carefully select ICD-9 codes. Screening tests should be reported using V73.89, which denotes special screening for specified viral disease. If the patient has been exposed to HIV, then V01.7, exposure to other viral diseases, can be used to justify the testing. High-risk sexual behavior is identified by V69.2 and can be reported in addition to the screening or exposure codes.
There are several codes to identify the presence of the AIDS virus as well. 042 is used when signs and symptoms of HIV infection are present. Asymptomatic HIV infection status is reported using V08 and should not be used if signs and symptoms are present. When a test finding is reported as nonspecific, use codes 795.71 (nonspecific serologic evidence). Of course, opportunistic infections will have to be reported using the specific ICD-9 codes for each disease.
Prior to the onset of labor, clinicians should discuss the current state of knowledge concerning the relationship between delivery route and the risk of vertical transmission and complications with each HIV-positive pregnant patient. A consensus on the planned route of delivery should then be reached. Individualize the discussion, factoring in such variables as the patient's current viral load and antiretroviral therapy, her obstetric historyfor example, any prior C/Sand the presence of coexisting disorders like thrombocytopenia.
The most common complications following operative delivery are infection and anemia.22 Possible interventions that may reduce morbidity, particularly from operative delivery, include diagnosing and treating bacterial vaginosis and other cervicovaginal infections prior to delivery, treating pre-existing anemia, and perioperative antibiotic prophylaxis. Unfortunately, none of these interventions has yet to be studied in a prospective fashion.
In those patients who undergo labor and vaginal delivery, avoid invasive procedures such as fetal scalp electrode monitoring and scalp pH sampling, if possible. Although the risk of vertical transmission as a result of these procedures is unknown, significant fetal exposure to maternal HIV may occur during these procedures as a result of the disruption of the fetal epithelial barrier. Preliminary studies of intrapartum vaginal lavage with microbicidal solutions have not been able to demonstrate any significant reductions in vertical HIV transmission. The risk of transmission appears to increase with increasing duration of rupture of membranes. For this reason, avoid artificial rupture of membranes. Episiotomy should also be avoided, if possible. There are data to suggest that increased exposure to maternal blood during labor and deliveryincluding blood from the episiotomyincreases the risk of vertical transmission.
Patients with no prenatal care and those who did not receive antepartum antiretrovirals should be offered one of the treatment options shown to reduce vertical transmission. This would include IV intrapartum and oral neonatal ZDV, oral intrapartum and neonatal zidovudine and 3TC (Combivir) and oral intrapartum and neonatal nevirapine.
Start all exposed neonates on zidovudine prophylaxis, as there are data to suggest that even isolated postpartum antiretroviral therapy will reduce transmission to the neonate.16 Breastfeeding should be discouraged, though, because it doubles the risk of vertical transmission. Clinicians should ensure that both the patient and the neonate have adequate postpartum follow-up scheduled with care providers experienced in managing HIV infection in adults and children, respectively.
You should discuss contraceptive options with the patient before hospital discharge and ideally prior to delivery. Offer sterilization to all HIV-infected women; it can be performed at the time of a scheduled C/S. Barrier contraception, including foam, condoms, and the diaphragm, appears to be safe and reasonably effective. Hormonal contraception, including injectable depot medroxyprogesterone (Depo-Provera) and sustained release levonorgestrel (Norplant) are also safe and effective.
There are some data to suggest, however, that depot medroxyprogesterone and oral contraceptives increase cervical/vaginal shedding of HIV, which could potentially increase the risk of transmission. There are also some preliminary data suggesting that certain protease inhibitors reduce the bioavailability of ethinyl estradiol, which means that OCs may be less effective in women taking these antiretroviral agents.
The intrauterine device (IUD) is somewhat problematic, given the increased incidence of STD and pelvic inflammatory disease in HIV-positive patients. There are also theoretical concerns that the increased menstrual bleeding, as well as microtrauma to the penis, caused by the IUD string may increase the risk of HIV transmission from the patient to her partner.
In summary, caring for HIV-infected pregnant women can be complex, and staying abreast of advances in the field of antiretroviral therapy can be difficult for the practicing obstetrician. However, with appropriate medical therapy, most patients will deliver uninfected infants and can survive for a number of years to enjoy their child's progress and development. These successes are the rewards that await those who care for these challenging patients.
1. Stoto MA, Almario DA, McCormick MC, eds. Reducing the odds: preventing perinatal transmission of HIV in the United States. National Academy Press, 1999.
2. American College of Obstetricians and Gynecologists. Joint statement of ACOG/AAP on human immunodeficiency virus screening. Issued by the Executive Boards of ACOG and AAP. May, 1999.
3. Balano K, Beckerman K, Ng V. Rapid HIV screening during labor. JAMA. 1998;280:1664.
4. Stringer JS, Rouse DJ. Rapid testing and zidovudine treatment to prevent vertical transmission of human immunodeficiency virus in unregistered parturients: a cost-effectiveness analysis. Obstet Gynecol. 1999;94:34-40.
5. Burns DN, Nourjah P, Minkoff H, et al. Changes in CD4+ and CD8+ cell levels during pregnancy and postpartum in women seropositive and seronegative for human immunodeficiency virus-1. Am J Obstet Gynecol. 1996;174:1461-1468.
6. Burns DN, Landesman S, Minkoff H, et al. The influence of pregnancy on human immunodeficiency virus type I infection: antepartum and postpartum changes in human immunodeficiency virus type I viral load. Am J Obstet Gynecol. 1998;178:355-359.
7. Minkoff HL, Willoughby A, Mendez H, et al. Serious infections during pregnancy among women with advanced human immunodeficiency virus infection. Am J Obstet Gynecol. 1990;162:30-34.
8. Mofenson LM, Lambert JS, Stichin ER, et al. Risk factors for perinatal transmission of human immunodeficiency virus type I in women treated with zidovudine. Pediatric AIDS Clinical Trials Group Study 185 Team. N Engl J Med. 1999;341:385-393.
9. Department of Health and Human Services and the Henry J. Kaiser Family Foundation, Panel on Clinical Practices for Treatment of HIV Infection. Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents. HIV Clinical Trials 2000;1:60-110. (For updates: http://www.hivatis.org )
10. Public Health Service Task Force recommendations for the use of antiretroviral drugs in pregnant women infected with HIV-1 for maternal health and for reducing perinatal HIV-1 transmission in the United States. MMWR Morb Mortal Wkly Rep. 1998;47(RR-2):1-30.
11. Carpenter CC, Cooper DA, Fischl MA, et al. Antiretroviral therapy in adults: updated recommendations of the international AIDS Society-USA Panel. JAMA. 2000;283:381-390.
12. Connor EM, Sperling RS, Gelber R, et al. Reduction of maternal-infant transmission of human immunodeficiency virus type I with zidovudine treatment. Pediatric AIDS Clinical Trials Group Protocol 076 Study Group. N Engl J Med. 1994;331:1173-1180.
13. Shaffer N, Chuachoowong R, Mock PA, et al. Short-course zidovudine for perinatal HIV I transmission in Bangkok, Thailand: a randomised controlled trial. Bangkok Collaborative Perinatal HIV Transmission Study Group. Lancet. 1999;353:773-780.
14. Saba J and the PETRA Trial Study Team. Interim analysis of early efficacy of three short ZDV/3TC combination regimens to prevent mother-to-child transmission of HIV-1: the PETRA trial. Sixth Conference on Retroviruses and Opportunistic Infections. Chicago, Ill, January 1999. (Abstract S-7).
15. Guay LA, Musoke P, Fleming T, et al. Intrapartum and neonatal single-dose nevirapine compared with zidovudine for prevention of mother-to-child transmission of HIV-1 in Kampala, Uganda: HIVNET 012 randomised trial. Lancet. 1999;354:795-802.
16. Wade NA, Birkhead GS, Warren BL, et al. Abbreviated regimens of zidovudine prophylaxis and perinatal transmission of the human immunodeficiency virus. N Engl J Med. 1998;339:1409-1414.
17. Elective caesarean-section versus vaginal delivery in prevention of vertical HIV-1 transmission: a randomised clinical trial. Published erratum appears in Lancet 1999 May 15;353(9165):1714. The European Mode of Delivery Collaboration. Lancet. 1999;353:1035-1039.
18. Mandelbrot L, Le Chenadec J, Berrebi A, et al. Perinatal HIV-1 transmission: interaction between zidovudine prophylaxis and mode of delivery in the French Perinatal Cohort. JAMA. 1998;280:55-60.
19 The International Perinatal HIV Group. The mode of delivery and the risk of vertical transmission of human immunodeficiency virus type Ia meta-analysis of 15 prospective cohort studies. The International Perinatal HIV Group. N Engl J Med. 1999;340:977-987.
20. Kind C, Rudin C, Siegrist CA, et al. Prevention of vertical HIV transmission: additive protective effect of elective cesarean section and zidovudine prophylaxis. Swiss Neonatal HIV Study Group. AIDS. 1998;12:205-210.
21. American College of Obstetricians and Gynecologists. Committee on Obstetric Practice. Scheduled cesarean delivery and the prevention of vertical transmission of HIV infection. Committee Opinion #234; May 2000.
22. Garcia PM, Kalish LA, Pitt J, et al. Maternal levels of plasma human immunodeficiency virus type 1 RNA and the risk of perinatal transmission. Women and Infants Transmission Study Group. N Engl J Med. 1999;341: 394-402.
23. Semprini AE, Castagna C, Ravizza M, et al. The incidence of complications after cesarean section in 156 HIV-positive women. AIDS. 1995;9:913-917.
24. Read J, Kpamegan E, Tuomala R, et al. Mode of delivery and postpartum morbidity among HIV-infected women: The Women and Infants Transmission Study (WITS). Sixth Conference on Retroviruses and Opportunistic Infections, Chicago, Ill, January 1999. (Abstract #683).
25. Watts H, Mofenson L, Whitehouse J, et al. Complications according to mode of delivery among HIV-positive women with CD4 counts < 500. Sixth Conference on Retroviruses and Opportunistic Infections, Chicago, Ill, January 1999. (Abstract #684).
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Mara Dinsmoor. CME: Managing the HIV-infected pregnant patient. Contemporary Ob/Gyn 2000;12:52-64.