Lack of ART was strongly associated with gestational age at HIV diagnosis and booking at the obstetrical center. During the period 1997–2004, the proportion of mothers who did not receive ART was 29.1% when HIV was diagnosed in the third trimester, 7.9% when it was diagnosed earlier but booking occurred in the third trimester, and 1% among women whose HIV diagnosis and booking took place in the first or second trimester. After adjustment in bivariate models (Table 3), African and French women did not differ for lack of ART (aOR 0.8, 95% CI 0.5–1.3) and for late initiation of ART (aOR 1.0, 95% CI 0.8–1.5). Adjustment for additional variables did not change the odds ratios.
Zidovudine monotherapy and vaginal delivery despite poor viral control
Among women whose last viral load before delivery was at least 10 000 copies/ml, the proportion receiving zidovudine monotherapy decreased from 20.6% in 1997 to 10% in 2004 (P < 0.001), with no difference between African and French women. This situation involved fewer than 2% of the study population. The proportion of mothers who delivered vaginally despite a viral load equal to or above 400 copies/ml was also similar in both groups (7.5%) (Table 3).
ORs adjusted for birth period, maternal age, parity, time at booking, time at ART initiation, and CD4 cell counts were similar to crude ORs, not significantly different from one.
Highly active antiretroviral therapy use and virologic success at delivery
The proportion of mothers who received HAART during pregnancy increased from 1.6% in 1997 to 74.1% in 2004 (P < 0.001). During this period, it was higher in African than in French women (52.8 vs. 43.9%, OR 1.4, 95% CI 1.3–1.6). This association was explained by the increase in enrollment of African mothers over time. Stratifying by each period of delivery, the proportion receiving HAART was similar in African and French women. The aOR declined to 1.0 (0.8–1.1), after adjustment for year of delivery. The proportion with an undetectable viral load (<400 copies/ml) was the same in African and French women (65.0 vs. 66.6%; aOR 0.9, 95% CI 0.7–1.0, P = 0.5). However, the CD4 cell counts at delivery were lower in African compared with French women, even after adjusting for gestational age at ART initiation and viral load at delivery (aOR 2.5, 95% CI 1.9–3.3, P < 0.001) (Table 3).
Perpartum and neonatal prophylaxis, breastfeeding and infant follow-up
African and French mothers did not differ according to lack of intrapartum zidovudine (5.8%), lack of neonatal prophylaxis (1.5%), nor for the proportion of breastfeeding (0.4%), both in univariate and multivariate analyses (Table 3).
Among mothers who received ART during pregnancy, the overall MTCT rate was 1.5% in the period 1997–2004. It was higher in African women 1.8% (43/2348) than in French women 0.8% (10/1232) (P = 0.016), with a crude OR of 2.3 (95% CI 1.1–4.6). The overall difference remained for mothers with CD4 cell counts above 350 cells/μl: 1.5 vs. 0.7%, crude OR 2.4 (95% CI 1.0–5.8); P = 0.06. The difference was no longer significant after adjusting for parity, maternal age, CD4 cell count, viral load, gestational age at delivery, antepartum, intrapartum and neonatal prophylaxis (OR 1.7; 95% CI 0.8–3.7, P = 0.17). There was no difference between African and French women among the 2110 mothers who had full-term deliveries (≥37 weeks) with a viral load less than 400 copies/ml (0.8 vs. 0.6%, respectively; P = 0.5).
The proportion of pregnancies in mothers from sub-Saharan Africa increased from 12% in 1984–1986 to 64% in 2003–2004 in the EPF cohort. We found that, in comparison with French-born mothers, immigrants from sub-Saharan African countries had more delayed access to HIV testing and care, whatever period was considered. The proportion of women who were unaware of their HIV status before becoming pregnant was higher in African than in French women. Moreover, among women who discovered their HIV status during the pregnancy, screening was done later in African mothers. Furthermore, after HIV diagnosis, the booking visit in the maternity occurred later in African than in French women. Late access to diagnosis or to care accounted for the higher rate of late initiation of ART during pregnancy in African than in French women. The relation between delays in screening and treatment initiation has also been reported in an American survey . A higher rate of late diagnosis has been observed in contexts other than pregnancy among immigrants in several European countries [2,3,5,21]. We could not study whether this was related to the time since arrival in France, as this date was not recorded.
Precarious housing, poverty and poor literacy are more frequent among HIV-infected immigrants than French natives [17,18,22]. We found that despite these obstacles, once women from sub-Saharan Africa accessed obstetrical care and HIV diagnosis, they benefited from the same prevention strategies as French women and were no more likely to be undertreated. Follow-up and care for children were similar in both groups. Contrary to widespread beliefs, and in contrast with practices in Africa, African women delivering in France did not have a lower rate of elective cesarean section than French women, and cases of breastfeeding were exceptional. We previously showed that geographic origin was not associated with lack of antiretroviral prophylaxis in the period 1996–1999 . Only one other report investigated the relationship between geographical origin and MTCT and found no association between race/ethnicity and use of antiretroviral prophylaxis or elective cesarean section when indicated . In nonpregnant patients, some European studies reported that access to ART following HIV diagnosis was equivalent in immigrant and natives [21,24].
Uncontrolled viral load is the major risk factor for MTCT [8,9,25–33]. In our study, African origin was not associated with a higher viral load at delivery during the period 1997–2004. This contrasts with findings from the United States where black or Hispanic mothers had higher viral loads at delivery than white mothers . The CD4 cell count at delivery was lower in African compared with French mothers in EPF, and the difference remained significant after adjustment for delay in starting ART and for viral load at delivery. Lower CD4 counts at diagnosis or treatment initiation in HIV-infected patients originating from Africa was found in several European cohorts [22,24,34–38]. The reason for the difference of CD4 level according to the geographical origin and its impact on virological response to treatment is unclear [22,34,38–40]. Although the overall MTCT rate was higher in African than French women enrolled in EPF, lower CD4 cell counts did not account for this difference, the transmission rate remained higher in African than in French mothers who delivered with more than 350 cells/μl. The association was no longer statistically significant, however, when adjusting for delay at starting ART, gestational age, plasma viral load and CD4 cell count at delivery. Moreover, the MTCT rate was under 2% in both treated populations in the 1997–2004 period, and did not differ between French and African women who term delivered with a viral load less than 400 copies/ml, as we reported previously . Thus, our findings do not support the hypothesis that genetic susceptibility or HIV subtypes, associated with geographical origin may play a major role in MTCT when the viral load at delivery is controlled. However, we cannot exclude that, among mothers with uncontrolled viral load, differences in viral resistances or subtypes, not collected routinely in the EPF cohort, may partly explain the higher transmission rate in mothers originating from sub-Saharan Africa.
Our results are encouraging as, once HIV diagnosis is made, MTCT prevention is similar in French and sub-Saharan Africa women delivering in France. Such results are likely owing to our universal free access to care for HIV infection and antenatal care, also offered to immigrants with nonregular status until recently. It thus appears important to maintain such access in a context of illegal immigration. Further efforts should be made to extend timely access to HIV screening and obstetrical care for all women, including recent immigrants.
C.J. realized the statistical analysis and contributed to conception, interpretation of data and drafting the article. L.M. and R.T. contributed to conception, design and drafting the paper. J.L.C. and J.-P.T. contributed to acquisition of data, analysis and interpretation. A.F., C.D., C.R. and S.B. contributed to conception, design and interpretation. J.W. is the principal investigator of the EPF and was responsible for the whole scientific process of this study. All authors revised the paper and approved the final version.
This study was supported by the French National Agency for AIDS Research (ANRS), Paris, France. We thank Valerie Benhammou, Karima Hamrene, Yassine Benmebarek, Aziz Diop, Nancy Zeller, Corinne Laurent, Elisa Ramos, Marlène Peres, Thierry Wack, Leila Boufassa, Paulette Huynh and Robert Murphy.
The following persons and institutions participated in the ANRS French Perinatal Cohort:
Hôpital d'Aix en Provence* (Tadrist B.); Hôpital Nord, Amiens (Schmit J.L., Horlé B.); Hôpital d'Angers (Fournié A.); Hôpital Victor Dupouy, Argenteuil (Brault D.); Hôpital Paris La Roseraie*, Aubervilliers (Rozan M.A.); Hôpital Robert Ballanger, Aulnay (Zakaria A.); Hôpital Saint Claude, Basse-Terre* (Sibille G.); Hôpital de Bastia (Pincemaille O.); Hôpital de la Côte Basque, Bayonne (Cayla C.); Clinique du Blanc Mesnil* (Balde P.); Hôpital Saint Jacques, Besançon (Estavoyer J.M.); Hôpital Avicenne, Bobigny (Bentata M.); Hôpital Jean Verdier, Bondy (Lachassine E., Rodrigues A.); Hôpital Pellegrin, Bordeaux (Roux D., Douard D.); Hôpital Ambroise Paré*, Boulogne Billancourt (Zenaty D.); Hôpital Clémenceau, Caen (Brouard J.); Hôpital André Rosemon, Cayenne (Elenga N.); Hôpital Beaujon*, Clichy (De Curtis A.); Hôpital de Creil (Kingue-Ekollo C.); Hôpital Intercommunal, Créteil (Garrait V., Lemerle S., Pichon C.); Hôpital Béclère, Clamart (Chambrin V., Labrune P., Clech L.); Hôpital Louis Mourier, Colombes (Crenn-Hebert C., Floch-Tudal C.); Hôpital de Compiègne* (Lagrue A.); Hôpital d'enfants, Dijon (Reynaud I.; Martha S.); Hôpital de Dourdan* (Ercoli V.); Hôpital de Dreux* (Denavit M.F.); Hôpital des Feugrais*, Elbeuf (Lahsinat K.); Hôpital Intercommunal, Evreux (Touré K.); Hôpital Francilien Sud, Evry-Corbeil (Devidas A., May A., Granier M.); Hôpital de Fontainebleau (Routier C.); Hôpital Victor Fouche, Fort de France (Hatchuel Y.); Hôpital de Gonesse* (Balde P.); Hôpital Jean Rostand, Ivry (Jault T.); Hôpital de Lagny (Chalvon Demersay A.); Hôpital du Lamentin* (Monlouis M.); Hôpital Les Oudairies, La Roche sur Yon (Perré P); Hôpital de La Seyne sur Mer (Chamouilli J.M.); Hôpital Louis Domergue, La Trinité* (Hugon N.); Hôpital André Mignot, Le Chesnay (Hentgen V., Messaoudi F.); Hôpital de Bicêtre, Le Kremlin-Bicêtre (Peretti D., Fridman S); Hôpital Jeanne de Flandres, Lille (Mazingue F., Hammou Y.); Hôpital Dupuytren*, Limoges (De Lumley L.); Hôpital de Longjumeau (Seaume H.); Hôpital Hôtel Dieu-Hôpital Debrousse, Lyon (Cotte L., Kebaïli K.); Hôpital François Quesnay, Mantes La Jolie (Doumet A.); Hôpital la Conception, Marseille (Cravello L., Thuret I.); Hôpital de Meaux (Karaoui L.); Hôpital de Meulan* (Seguy D.); Hôpital Marc Jacquet, Melun (Le Lorier B.); Hôpital Intercommunal, Montfermeil (Talon P.); Hôpital Arnaud de Villeneuve, Montpellier (Benos P., Lalande M.); Hôpital Intercommunal, Montreuil (Heller-Roussin B.); Maternité Régionale A. Pinard, Nancy (Hubert C.); Hôpital de Nanterre* (Karoubi P.); Hôpital de Nantes (Reliquet, V., Brunet-François C.); Hôpital de Neuilly sur Seine* (Berterottiere D.); Hôpital l'Archet-Fondation Lenval, Nice (Monpoux F., Bongain A., Deville A.); Hôpital Caremeau, Nîmes (Dendale J.); Hôpital Orléans (Arsac P.); Hôpital d'Orsay (De Gennes C.); Hôpital Bichat, Paris (Matheron S., Batallan A.); Hôpital Boucicaut*, Paris (Lafay Pillet M.C.); Hôpital Cochin-Port Royal, Paris (Firtion G., Pannier A); Hôpital Lariboisière, Paris (Ciraru-Vigneron N.); Hôpital des Métallurgistes*, Paris (Rami M.); Institut Mutualiste Montsouris*, Paris (Carlus Moncomble C.); Hôpital Necker, Paris (Parat S., Blanche S., Rouzioux C.); Hôpital Notre Dame du Bon Secours, Paris (Ayral D.); Hôpital Pitié Salpêtrière, Paris (Tubiana R.); Hôpital Robert Debré, Paris (Levine M., Faye A., Ottenwalter A.); Hôpital Rothschild, Paris (Wallet A.); Hôpital Saint-Antoine, Paris (Carbonne B.); Hôpital Hôpital Saint Michel, Paris (Aufrant C.); Hôpital Tenon, Paris (Lebrette M.G.); Hôpital Trousseau, Paris (Dollfus C.); Hôpital Marechal Joffre, Perpignan (Medus M.); Hôpital Les Abymes, Pointe-à-Pitre (Bataille H.); Hôpital de Poissy-Saint-Germain en Laye* (Rousset M.C.); Hôpital René Dubos, Pontoise (Mouchnino G.); Hôpital Américain, Reims (Munzer M.); Hôpital Charles Nicolle, Rouen (Brossard V.); Hôpital de Saint-Denis (Allemon M.C., Ekoukou D., Khuong M.A.); Hôpital Nord, Saint Etienne (Billiemaz K.); Hôpital de Saint Martin (Bissuel F.); Hôpital Esquirol*, Saint-Maurice (Robin M.); Hôpital de Sèvres* (Segard L.); Hôpital de Haute Pierre-Hôpital Civil, Strasbourg (Partisani M., Favreau, J. J, Entz-Werle N.); C.M.C. Foch, Suresnes* (Botto C.); Hôpital Chalucet,Toulon (Hittinger G.); Hôpital La Grave, Toulouse (Berrebi A., Tricoire J.); Hôpital Bretonneau, Tours (Besnier J.M.); Hôpital Brabois, Vandoeuvre les Nancy (Neimann L.); Hôpital Paul Brousse*,Villejuif (Dussaix E.); Hôpital de Villeneuve Saint Georges (Guillot F., Chacé A.).
* sites not active currently
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Keywords:© 2008 Lippincott Williams & Wilkins, Inc.
access to care; Africans; epidemiology; HIV/AIDS; prevention of mother-to-child transmission; public health