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Decreasing incidence of pregnancy by decreasing CD4 cell count in HIV-infected women in Côte d'Ivoire: a 7-year cohort study

Loko, Marc-Arthura,b; Toure, Siakab; Dakoury-Dogbo, Nicoleb; Gabillard, Delphinea; Leroy, Valérianea; Anglaret, Xaviera

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aINSERM U.593, Université Victor Segalen, Bordeaux 2, Bordeaux, France

bProgramme PAC-CI, Abidjan, Côte d'Ivoire

Received 6 December, 2004

Accepted 5 January, 2005

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Abstract

In a cohort study of women of childbearing age in Abidjan, Côte d'Ivoire, we followed 473 HIV-infected women for 1551 person-years, and found that the incidence of pregnancy and livebirth decreased with decreasing CD4 cell counts. This has consequences in terms of scaling-up strategies for highly active antiretroviral therapy (HAART). Women who need HAART will be less likely than those who do not to be recruited into prenatal care facilities.

In sub-Saharan Africa, 14 million women of childbearing age are living with HIV/AIDS, and the risk of mother-to-child transmission (MTCT) of HIV during pregnancy, labour, delivery or breastfeeding is 15–45% [1].

Antiretroviral drugs play an important part in the interventions aimed at reducing the risk of HIV MTCT. At present, the type and number of antiretroviral drugs needed, together with the foreseeable antiretroviral treatment duration partly depend on the mother's CD4 cell count [1]. On the one hand, the MTCT risk increases with the increasing immunosuppression of the mother [2]. On the other hand, whether a pregnant woman meets the criteria for receiving highly active antiretroviral therapy (HAART) largely depends on her immunological status [1].

We report here the incidence of pregnancy and livebirth by baseline CD4 cell count in a cohort study of women of childbearing age in Abidjan, Côte d'Ivoire.

The ANRS 1203 cohort has been described previously [3]. In summary, from 23 April 1996 to 31 August 2003, HIV-infected adults were followed up in a medical centre through standardized procedures, including monthly visits, free access to the centre at any time and procedures for tracing participants lost to follow-up. Pregnancy incidence was defined as the number of women having at least one pregnancy per 100 woman-years of at-risk follow-up in the cohort. The at-risk follow-up began on the day of inclusion and continued to 31 August 2003 or the date of the pregnancy, death or default if before that date. For pregnant women, the date of the pregnancy was the date of the last menstrual period. Default was the date of HAART initiation if before 31 August 2003, or the date of the last contact with the study team for women not receiving HAART whose last contact was before 31 August 2003 and who were not found to be deceased. Groups of baseline CD4 cell counts and CD4 cell percentages were compared for the pregnancy outcomes using Fisher's exact test, and for the incidence of pregnancy and the incidence of livebirth using Poisson regression, adjusting for age, number of children alive and marital status.

A total of 473 women of childbearing age were included in the cohort. At baseline, 50% were living in a couple, 47% had a remunerative activity and 71% had not gone beyond primary school level education. Their median age was 29 years [interquartile range (IQR) 25–34], their number of children alive was two (IQR 1–4) and their median CD4 cell count was 387 cell/mm3 (IQR 183–573). The women were followed up for 1551 person-years, a median of 3.0 years per person (IQR 1.7–4.9). As of 31 August 2003, 175 women were deceased, 124 had initiated HAART, and 174 were alive with no HAART.

None of the women were pregnant at baseline. During follow-up, 100 women had 116 pregnancies. The overall incidence of pregnancy was 7.9 per 100 person-years [95% confidence interval (CI) 6.3–9.4]. Of the 100 first pregnancies, 55% led to a livebirth, 31% ended with a voluntary induced abortion, 7% with a spontaneous abortion and 3% with the death of the mother and the fetus before the end of the pregnancy. In 4% of pregnancies, the outcome was unknown to the study team. In women with baseline CD4 cell counts less than 200 cells/mm3, 200–349 cells/mm3, 350–499 cells/mm3 and over 500 cells/mm3, the percentage of fetal loss was 22, 12, 0 and 7% and the percentage of livebirths was 22, 69, 62 and 53%, respectively (P = 0.01). The overall incidence of livebirth was 3.8 per 100 person-years (95% CI 2.8–4.8). Table 1 details the incidence of pregnancy and the incidence of livebirth by baseline CD4 cell count and CD4 cell percentage strata.

Table 1
Table 1
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These data confirm the association between the incidence of pregnancy and CD4 cell count recently reported in Uganda [4]. Previously, only a few studies had estimated the global incidence of pregnancy in sub-Saharan African HIV-infected women, and none of them had estimated the incidence of pregnancy by CD4 cell count [5–7]. In our study, the incidence of pregnancy was approximately twice and three times as high in women with CD4 cell counts of more than 350 cells/mm3 than in those with CD4 cell counts of 200–350 cells/mm3 and less than 200 cells/mm3, respectively. The incidence of livebirth was globally half the incidence of pregnancy, while remaining significantly associated with the CD4 cell count. The most frequent cause of pregnancy interruption was voluntary induced abortion; fetal loss was the second cause and was more frequent in women with a low CD4 cell count. As a consequence, the incidence of livebirth was five times as high in women with CD4 cell counts of more than 350 cells/mm3 than in women with less than 200 cells/mm3.

Our study focused on the central importance of the CD4 cell count when reporting the incidence of pregnancy in sub-Saharan African HIV-infected women. It did not aim to explore the other risk factors for pregnancy in these women, such as the willingness to be pregnant, the attitude of the partner, a pre-existing subfertility as a risk-factor for multiplying sexual acts and therefore becoming HIV infected, the presence of clinical HIV manifestations, the level of education and a history of stillbirth or death of a child [4–7]. In addition, the incidence that we observed in each CD4 cell count stratum was in a given population with its own frequency of contraceptive use and sexual intercourse [4]. To estimate the incident rate of pregnancy for each of these risk factors, larger studies would be needed.

The decreasing incidence of pregnancy and livebirths by decreasing CD4 cell counts has two consequences. First, in terms of projections of the need for prevention of MTCT interventions and other HIV care for pregnant women and their children, acknowledging the fact that WHO experts now recommend specific antiretroviral regimens according to different clinical situations [1]. Second, in terms of strategies for scaling-up HIV care. If women with advanced immunosuppression are less likely to become pregnant, then women who need HAART and their families will be less likely to be recruited into prenatal care facilities than women who do not need HAART.

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Acknowledgements

Informed consent was obtained from patients, and the protocol was approved by the ethics committee of the PNLS/MST/TUB and the institutional review board of the ANRS.

Sponsorship: This study was supported by the Agence Nationale de Recherches sur le SIDA (ANRS, France) and the Programme National de Lutte contre le SIDA, les maladies sexuellement transmissibles et la tuberculose (PNLS/MST/TUB, Côte d'Ivoire) within the collaborative Programme PAC-CI.

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References

1. World Health Organization. Antiretroviral drugs for treating pregnant women and preventing HIV infection in infants. Guidelines on care, treatment and support for women living with HIV/AIDS and their children in resource-constrained settings. Available at: http://www.who.int/hiv/pub/mtct/en/arvdrugswomenguidelinesfinal.pdf. Accessed 28 October 2004.

2. Leroy V, Karon JM, Alioum A, Ekpini ER, Meda N, Greenberg AE, et al. Twenty-four month efficacy of a maternal short-course zidovudine regimen to prevent mother-to-child transmission of HIV-1 in West Africa. AIDS 2002; 16:631–641.

3. Anglaret X, Messou E, Ouassa T, Toure S, Dakoury-Dogbo N, Combe P, et al. Pattern of bacterial diseases in a cohort of HIV-1 infected adults receiving cotrimoxazole prophylaxis in Abidjan, Cote d'Ivoire. AIDS 2003; 17:575–584.

4. Ross A, Van der Paal L, Lubega R, Mayanja BN, Shafer LA, Whitworth J. HIV-1 disease progression and fertility: the incidence of recognized pregnancy and pregnancy outcome in Uganda. AIDS 2004; 18:799–804.

5. Desgrees-du-Lou A, Msellati P, Viho I, Yao A, Yapi D, Kassi P, et al. Incidence of pregnancies among African HIV-infected women, Abidjan, 1995–2000. AIDS 2001; 15:2327–2330.

6. Gray RH, Wawer MJ, Serwadda D, Sewankambo N, Li C, Wabwire-Mangen F, et al. Population-based study of fertility in women with HIV-1 infection in Uganda. Lancet 1998; 351:98–103.

7. Ryder RW, Batter VL, Nsuami M, Badi N, Mundele L, Matela B, et al. Fertility rates in 238 HIV-1-seropositive women in Zaire followed for 3 years post-partum. AIDS 1991; 5:1521–1527.

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© 2005 Lippincott Williams & Wilkins, Inc.

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