Testing for human immunodeficiency virus type 1 (HIV-1) infection in pregnancy

BACKGROUND

This statement replaces the Canadian Paediatric Society statement ID95-01 (1). Since the publication of statement ID95-01 in 1995, the evidence for the benefit of early detection of human immunodeficiency virus type 1 (HIV-1) infection has been strengthened. In particular, there is more information on the use of antiretroviral agents during pregnancy and the peripartum period to reduce mother-to-child transmission of HIV-1 (2–10).

Implementation of a strategy to reduce perinatal HIV transmission requires two steps. The first step is the identification of women who may benefit from the interventions. The second step involves collaborative efforts, on the part of health care workers (HCWs) and professionals, to allow women and children to have access to coordinated HIV care, as follows:

• obstetric care providers to identify HIV-positive pregnant women and to provide access for them to receive HIV care;

• HCWs who care for HIV-positive women to help with HIV management during pregnancy, including the selection of antiretroviral therapy;

• HCWs who provide the intrapartum care to provide intrapartum antiretroviral therapy and counselling on the risks of HIV transmission when selecting the mode of delivery of a baby; and

• HCWs who care for infants to provide the antiretroviral therapy for the newborn, and monitor both the short and long term outcomes of these HIV-exposed infants.

Five factors are of critical importance in a screening program. These five factors are:

• sensitivity and specificity of the diagnostic test;

• acceptability and feasibility of the diagnostic test;

• benefit of early detection;

• disadvantages of testing; and

• prevalence of disease.

In this statement, the above factors are reviewed, and the previous recommendations are revised, based on current information.

REVIEW OF FACTORS CRITICAL IN A SCREENING PROGRAM: APPLIED TO HIV TESTING IN PREGNANCY

Sensitivity and specificity of the test

The standard approach to diagnostic testing for HIV infection in adults and adolescents applies to HIV testing of pregnant women. This method, which detects antibodies to HIV, uses a two-step approach. The first step is a screening test for HIV antibody by using an enzyme immunoassay. If positive, the enzyme immunoassay is followed by a confirmatory test for HIV antibody by using a Western blot or immunofluorescence assay to confirm HIV positivity. This approach has both a sensitivity and specificity of 99% with the most common North American subtype of HIV-1, which is clade B (11). The test does distinguish HIV-1 from HIV-2, but the sensitivity and specificity may be lower for HIV-1 clades from other parts of the world.

Recently, rapid HIV tests have been developed (12) and one test (MedMira Rapid HIV Screen Test; MedMira Laboratories Inc, Canada) has been licensed for use in Canada. When performed in the laboratory by trained personnel, this system was found to perform on blood specimens from nonpregnant individuals, with a sensitivity and specificity of 99% to 100% and 100%, respectively (12). This is similar to the sensitivity and specificity of the standard ELISA screening test. This rapid HIV test may be considered as a screening test to be offered to a pregnant woman who presents for care during labour and is of unknown HIV status (13,14). Any positive test result using this technology must be confirmed. The availability of kits for rapid HIV testing is variable across the country and in different settings.

Acceptability and feasibility of the test

HIV testing includes not only the procedure of collecting the blood sample, but also counselling, obtaining informed consent and providing the results (15,16). The recommended practice for HIV testing in pregnancy varies among provinces and territories, as shown in Table 1 (17). Across Canada, many women may believe that they are being tested for HIV, even if there is no specific discussion of HIV testing. The testing rates vary across the country, ranging from testing rates of 97.6% in Alberta (B Larke, personal communication) to 50% in Ontario (18). A major determinant of acceptance by women is that the counsellor recommends the testing (19).

TABLE 1:

Provincial and territorial recommendations for human immunodeficiency virus (HIV) testing in pregnancy

Newfoundland: In 1997, the Newfoundland and Labrador Advisory Committee on Infectious Diseases recommended that HIV testing be added to the existing prenatal screening program. HIV testing is done as part of the routine prenatal screen, unless the woman declines

Prince Edward Island: In June 1999, the Prince Edward Island Department of Health and Social Services formally adopted a policy of supporting HIV testing for all pregnant women and recommended that physicians offer HIV testing at the first prenatal visit

Nova Scotia: The Reproductive Care Program recommends that HIV testing should be offered to all pregnant women, together with other prenatal tests in the first trimester. Women who decline testing in the first trimester or who are known to engage in high risk activities should be offered testing again during the latter stages of their pregnancy

New Brunswick: The New Brunswick Medical Society's Subcommittee on Perinatal Health Care recommended, in July 1999, that physicians should routinely encourage all pregnant women to be tested for HIV, with appropriate pre- and post-test counselling and informed consent

Quebec: Since 1997, as part of an intervention program on HIV infection and pregnancy, the Ministry of Health and Social Services, in accordance with the College of Physicians, initiated a program recommending that all pregnant women and women contemplating pregnancy be offered an HIV test

Ontario: On December 1, 1998, the Minister of Health announced that the prenatal screening program would be expanded to include HIV testing. Through this expanded program, all pregnant women are offered an HIV test as part of their prenatal care. The HIV test is performed only after counselling is provided and informed consent is given. Health providers must complete the laboratory requisition to confirm that these two provisions have been met

Manitoba: The College of Physicians has issued “Guidelines to Practice”, which include approval of a policy, adopted in 1994, that all physicians offer pre-test counselling and HIV testing, with informed consent, to all pregnant women

Saskatchewan: The College of Physicians issued guidelines for physicians to assess a woman's risk and inform her that testing is available

Alberta: On September 1, 1998, HIV screening was added to the routine prenatal blood tests for all women in Alberta. HIV screening is performed unless the woman declines to be tested

British Columbia: In June 1994, the British Columbia Ministry of Health recommended that HIV testing be offered as a routine prenatal component, with informed consent and pre- and post-test counselling

Northwest Territories and Nunavut: In 1993, the Northwest Territories Maternal and Perinatal Committee, which has representation from the Department of Health and Social Services and the Northwest Territories Medical Association, recommended that all pregnant women be tested for HIV. In 1998, screening for HIV became fully integrated with routine prenatal care, although women are provided the opportunity to opt out

Yukon: In 1994, the Chief Medical Officer of Health, in conjunction with Yukon Communicable Disease Control, “strongly recommended” the testing of all pregnant women. Women who present for testing are also encouraged to recommend that their partner be tested as well

Data from reference 17

Benefit of early detection

The earlier that a woman is aware of her HIV status, the greater the number of options that are available to her and the better the chance of optimizing HIV care for both her and her infant(s). However, identification late in pregnancy or during labour still allows for the use of interventions that reduce perinatal HIV transmission, although they may not be as effective.

The benefits of zidovudine monotherapy for the prevention of mother-to-child transmission of HIV were shown in a randomized, placebo controlled trials (3). In that study, the transmission rate was reduced by two-thirds, from 25% to 8%, with a three-phase intervention. Since then, a number of studies have shown that maternal viral load is a critical determinant of the risk of perinatal transmission and that women with nondetectable viral loads rarely transmit HIV (20,21). In the early 1990s, highly active antiretroviral therapy became available and became the standard treatment for infected adults (22). Preliminary data indicate that the use of such regimens during pregnancy has been associated with a further reduction in perinatal transmission to 2% or lower (10,23,24). The choice of antiretroviral therapy for a pregnant woman must be individualized, taking into consideration such factors as her current HIV status, side effects (especially those of greater importance in pregnancy), information on the effects of specific drugs on pregnancy outcome, her previous therapy, the expected interval from start of therapy to delivery and, if known, antiretroviral susceptibility of the viral strains (23,25).

International studies (4–7) and observational studies in the United States (8,9) have shown that shorter courses of zidovudine, peripartum zidovudine or neonatal zidovudine started within 24 h provide some reduction in perinatal HIV transmission, although to a lesser extent than longer three-phase regimens (5). Nevirapine use during the peripartum period was more effective than short-course zidovudine monotherapy in the peripartum period (6). These strategies are of particular benefit in resource-poor settings, but are also of potential benefit for HIV-positive women whose HIV status is not recognized until late in pregnancy or at delivery.

Transmission of HIV is known to occur through breastfeeding (2). In a randomized clinical trial of the effect of breastfeeding and formula feeding on the transmission of HIV, the frequency of breast milk transmission of HIV was 16% (26). Therefore, in Canada, where formula feeding is a safe and available alternative to breastfeeding, avoidance of HIV exposure from breast milk, regardless of the mother's viral load or antiretroviral therapy, is an additional measure for the prevention of HIV transmission from mother to child.

Elective cesarean delivery performed before the onset of labour and rupture of membranes has also been shown to reduce perinatal transmission for HIV-infected women who are not receiving antiretroviral drugs or who are receiving only zidovudine (27,28). There are insufficient data to determine the point at which the maternal viral load is low enough that the risks of cesarean delivery outweigh the benefits. By consensus, The American College of Obstetricians and Gynecologists has taken a ‘cut-off’ of a viral load measured by HIV ribonucleic acid of 1000 copies/mL, below which the risks of a cesarean delivery are considered to outweigh the benefits of prevention of HIV transmission (29). In contrast, the Canadian consensus is that an elective cesarean section should be offered to women whose viral load is incompletely suppressed (24).

Disadvantages of testing

There are many personal, familial and societal stresses for a woman when she learns that she is HIV-positive (30). In addition, now that there are more options available, the HIV-positive pregnant woman has many difficult decisions to make in choosing the strategy best for her and her offspring. Some resources that may be helpful are listed in Table 2.

TABLE 2:

Resources for pregnant women with human immunodeficiency virus (HIV)^*

National
Motherisk HIV Healthline – an HIV counsellor answers questions on HIV and pregnancy from women or care providers	1-888-246-5840, <www.motherisk.org>
Positive Women's Network – based in Vancouver, British Columbia, it is an agency providing support, information, community education and advocacy for women with HIV	1-604-692-3000, 1-866-692-3001
Voices of Positive Women – Toronto, Ontario agency providing support, information and advocacy for women with HIV	1-416-324-8703, <www.webhome.idirect.com/~vopw>
Canadian AIDS Society – includes a list of AIDS Service organizations across Canada. To access, under “contacts” choose “members”	<www.cdnaids.ca>
Canadian HIV/AIDS Clearinghouse – provides information on HIV/AIDS prevention	<www.clearinghouse.cpha.ca> (bilingual)
Community AIDS Treatment Information Exchange (CATIE) – based in Canada, provides up-to-date information, including a toll-free telephone line with confidential counselling and access to resources	<www.catie.ca> (bilingual)
HIV/AIDS Treatment Information Service – based in the United States, provides information on American treatment guidelines for HIV and AIDS	<www.hivatis.org>
Managing Your Health, 1999. This publication is jointly produced by CATIE and the Toronto People with AIDS foundation, and contains an extensive list of telephone numbers of AIDS resources across Canada	To order free copies (English or French) contact: Canadian HIV Clearinghouse, 400-1565 Carling Avenue, Ottawa, Ontario K1Z 8R1, 1-613-725-3434
Oak Tree Clinic – Vancouver HIV clinic for women and children	1-604-875-2212, <www.cw.bc.ca/bcw/oak_tree.asp>
St Justine's HIV Clinic – Montreal, Quebec HIV clinic for women and children	1-514-345-4836, <www.hsj.qc.ca>
The Hospital for Sick Children's HIV Clinic – Toronto clinic for children and families with HIV program	1-416-813-6268, <www.sickkids.on.ca>
National HIV/AIDS Network for Children, Youth and Families	<www.resnat.ca/e/resources_clinics.html>
Le réseau national VIH/SIDA pour les Enfants, Jeunes, et Familles	<www.resnat.ca/f/ressources_cliniques.html>
Project Inform – an American HIV/AIDS Treatment Information Service for people living with HIV/AIDS	1-800-833-7422
British Columbia Persons with AIDS Society	1-604-681-2122, <www.bcpwa.org>
The Centre for AIDS Services of Montreal (Women) – based in Quebec, Montreal link to AIDS services for women	<www.netrover.com/~casm> (bilingual)
The Teresa Group Child and Family Aid – based in Ontario, Toronto link to AIDS services for women and children. The Teresa Group is a contact agency for Ontario's free formula program	1-416-596-7703, <www.teresagroup.org>
Provincial hotlines and major AIDS organizations
Alberta AIDS Information Line	1-800-772-2437
British Columbia AIDS Information Line	1-800-661-4337
Manitoba AIDS Information Line	1-800-782-2437
Newfoundland and Labrador AIDS Committee Hotline	1-800-563-1575
New Brunswick AIDS Hotline	1-800-561-4009
Northwest Territories AIDS Information Line	1-800-661-0795
AIDS Coalition of Nova Scotia	1-800-566-2437
AIDS PEI	1-800-314-2437
Ontario AIDS Information Line	1-800-668-2437
Quebec AIDS Information Line	1-800-463-5656
Saskatchewan AIDS Information Line	1-800-667-6876
Yukon AIDS information Line	1-800-661-0507

^*This is not an exhaustive list of available resources. AIDS Acquired immune deficiency syndrome

Toxicity due to in utero exposure to any of the antiretroviral agents is a potential disadvantage. Information on the short and long term toxicities of intrauterine exposure to antiretroviral agents is minimal and controversial (31–33).

Prevalence of disease

Of Canadians who are HIV-positive, the proportion of women increased from 9.6% in 1995 to 23.9% in 1999 (34). Almost all of these women are of childbearing age. The seroprevalence in pregnant women in Canada varies by region, and also varies within regions between city and rural areas. For example, in Quebec, when the provincial rate was 5.2/10,000, the rate on Montreal island was 15.3/10,000, and in British Colombia, when the provincial rate was 1.9/10,000, the rate in Vancouver was 5.1/10,000 (35).

CONCLUSIONS

The information that is available strengthens the recommendation for routine offering of HIV testing to all pregnant women. There is incontrovertible evidence that transmission of HIV from mother to infant can be reduced, and almost eliminated by HIV testing during pregnancy, the use of perinatal antiretroviral therapy, reduction of HIV exposure during delivery and avoidance of breastfeeding.

RECOMMENDATIONS

The Canadian Paediatric Society recommends the following.

• HIV testing should be offered routinely to all women as early as possible during each pregnancy, with testing repeated later in pregnancy if there is suspected ongoing exposure to HIV infection.

• All HIV testing of women and children should be voluntary, and accompanied by appropriate confidentiality, counselling and informed consent.

• Testing in the perinatal period must be part of a program that includes post-test counselling, retesting of the HIV-exposed infant, and medical care for the mother and child (36).

• If the mother has not been tested during pregnancy, then every effort should be made for expedited testing of the mother and newborn.

• If the mother refuses testing, this should be documented, and testing offered again, with consideration of a referral to a counsellor experienced in HIV counselling. The infant should be followed as an infant of unknown HIV status.

• HIV-positive pregnant women should be given information on factors that reduce perinatal HIV transmission, which includes offering antiretroviral therapy, obstetrical options and resources for formula feeding.

• Management of the HIV-positive pregnant woman and her infant should be done in consultation with an HIV specialist(s).

• The provinces and territories should ensure that there are comprehensive, accessible programs for HIV testing in pregnancy with appropriate follow-up and care for women and infants. These programs must be evaluated for their effectiveness in preventing perinatal HIV, and amended to achieve a goal of HIV testing of 95% of women receiving prenatal care and 100% follow-up of HIV-exposed infants.