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
1. Hamers F, Devaux I, Alix J, Nardone A. HIV/AIDS in Europe: trends and EU-wide priorities. Eurosurveillance 2006; 11. E061123.1.
2. Sinka K, Mortimer J, Evans B, Morgan D. Impact of the HIV epidemic in sub-Saharan Africa on the pattern of HIV in the UK. Aids 2003; 17:1683–1690.
3. Institut de Veille Sanitaire. The fight against HIV/AIDS and sexually transmitted infections in France. 10 years of surveillance, 1996–2005
. Saint-Maurice: Institut de veille sanitaire; 2007:155.
4. Semaille C, Barin F, Cazein F, Pillonel J, Lot F, Brand D, et al
. Monitoring the dynamics of the HIV epidemic using assays for recent infection and serotyping among new HIV diagnoses: experience after 2 years in France. J Infect Dis 2007; 196:377–383.
5. Calvez M, Semaille C, Fierro F, Laporte A. Patients from sub-Saharan countries with late access to HIV care: results from the ‘Retard survey’, France, Nov. 2003–Aug. 2004. BEH 2006; 31:227–229.
6. Lot F, Larsen C, Valin N, Gouezel P, Blanchon T, Laporte A. Sociomedical access of HIV infected patients from sub-Saharan countries followed in hospitals of the Ile de-France region, 2002. BEH 2004; 5:17–20.
7. Connor EM, Sperling RS, Gelber R, Kiselev P, Scott G, O'Sullivan MJ, et al
. Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment. Pediatric AIDS Clinical Trials Group Protocol 076 Study Group. N Engl J Med 1994; 331:1173–1180.
8. Warszawski J, Tubiana R, Le Chenadec J, Blanche S, Teglas JP, Dollfus C, et al
. Mother-to-child HIV transmission despite antiretroviral therapy in the ANRS French Perinatal Cohort. AIDS 2008; 22:289–299.
9. Cooper ER, Charurat M, Mofenson L, Hanson IC, Pitt J, Diaz C, et al
. Combination antiretroviral strategies for the treatment of pregnant HIV-1-infected women and prevention of perinatal HIV-1 transmission. J Acquir Immune Defic Syndr 2002; 29:484–494.
10. Mandelbrot L, Landreau-Mascaro A, Rekacewicz C, Berrebi A, Benifla JL, Burgard M, et al
. Lamivudine-zidovudine combination for prevention of maternal-infant transmission of HIV-1. JAMA 2001; 285:2083–2093.
11. European Collaborative Study. Mother-to-child transmission of HIV infection in the era of highly active antiretroviral therapy
. Clin Infect Dis
12. Ioannidis JP, Abrams EJ, Ammann A, Bulterys M, Goedert JJ, Gray L, et al
. Perinatal transmission of human immunodeficiency virus type 1 by pregnant women with RNA virus loads <1000 copies/ml. J Infect Dis 2001; 183:539–545.
13. Newell ML, Huang S, Fiore S, Thorne C, Mandelbrot L, Sullivan JL, et al
. Characteristics and management of HIV-1-infected pregnant women enrolled in a randomised trial: differences between Europe and the USA. BMC Infect Dis 2007; 7:60.
14. Yeni P. Management of HIV-infected patients. Paris: Flammarion; 2006.
15. Wood E, Montaner J, Chan K, Tyndall M, Schechter M, Bangsberg D, et al
. Socioeconomic status, access to triple therapy, and survival from HIV-disease since 1996. AIDS Care 2002; 16:2065–2072.
16. Dray-Spira R, Lert F. Living and working with HIV in France in 2003: results from the ANRS-EN12-VESPA Study. Aids 2007; 21(Suppl 1):S29–S36.
17. Lert F, Obadia Y, VESPA E. How are living HIV-infected persons in France? Population et sociétés
18. Chee CC, Mortier E, Dupont C, Bloch M, Simonpoli AM, Rouveix E. Medical and social differences between French and migrant patients consulting for the first time for HIV infection. AIDS Care 2005; 17:516–520.
19. Sas Institute. SAS user's guide: basics
. 9th ed. Cary, NC: SAS Institute Inc. 2006.
20. Cunningham CK, Balasubramanian R, Delke I, Maupin R, Mofenson L, Dorenbaum A, et al
. The impact of race/ethnicity on mother-to-child HIV transmission in the United States in Pediatric AIDS Clinical Trials Group Protocol 316. J Acquir Immune Defic Syndr 2004; 36:800–807.
21. Manfredi R, Calza L, Chiodo F. HIV disease among immigrants coming to Italy from outside of the European Union: a case-control study of epidemiological and clinical features. Epidemiol Infect 2001; 127:527–533.
22. Dray-Spira R, Spire B, Heard I, Lert F. Heterogeneous response to HAART across a diverse population of people living with HIV: results from the ANRS-EN12-VESPA Study. AIDS 2007; 21(Suppl 1):S5–S12.
23. Mayaux MJ, Teglas JP, Blanche S. Characteristics of HIV-infected women who do not receive preventive antiretroviral therapy in the French Perinatal Cohort. J Acquir Immune Defic Syndr 2003; 34:338–343.
24. Staehelin C, Rickenbach M, Low N, Egger M, Ledergerber B, Hirschel B, et al
. Migrants from Sub-Saharan Africa in the Swiss HIV Cohort Study: access to antiretroviral therapy, disease progression and survival. AIDS 2003; 17:2237–2244.
25. Mayaux MJ, Dussaix E, Isopet J, Rekacewicz C, Mandelbrot L, Ciraru-Vigneron N, et al
. Maternal virus load during pregnancy and mother-to-child transmission of human immunodeficiency virus type 1: the French perinatal cohort studies. SEROGEST Cohort Group. J Infect Dis 1997; 175:172–175.
26. Recommendations PHSTF. Use of antiretroviral drugs in pregnant HIV-1-infected women for maternal health and interventions to reduce perinatal hiv-1 transmission in the United States
. 2005. http://aidsinfo.nih.gov/
27. Sperling RS, Shapiro DE, Coombs RW, Todd JA, Herman SA, McSherry GD, et al
. Maternal viral load, zidovudine treatment, and the risk of transmission of human immunodeficiency virus type 1 from mother to infant. Pediatric AIDS Clinical Trials Group Protocol 076 Study Group. N Engl J Med 1996; 335:1621–1629.
28. Lallemant M, Jourdain G, Le Coeur S, Mary JY, Ngo-Giang-Huong N, Koetsawang S, et al
. Single-dose perinatal nevirapine plus standard zidovudine to prevent mother-to-child transmission of HIV-1 in Thailand. N Engl J Med 2004; 351:217–228.
29. Cao Y, Krogstad P, Korber BT, Koup RA, Muldoon M, Macken C, et al
. Maternal HIV-1 viral load and vertical transmission of infection: the Ariel Project for the prevention of HIV transmission from mother to infant. Nat Med 1997; 3:549–552.
30. Dickover RE, Garratty EM, Herman SA, Sim MS, Plaeger S, Boyer PJ, et al
. Identification of levels of maternal HIV-1 RNA associated with risk of perinatal transmission. Effect of maternal zidovudine treatment on viral load. JAMA 1996; 275:599–605.
31. Garcia PM, Kalish LA, Pitt J, Minkoff H, Quinn TC, Burchett SK, 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.
32. The European Collaborative Study. Maternal viral load and vertical transmission of HIV-1: an important factor but not the only one
33. Mofenson LM, Lambert JS, Stiehm ER, Bethel J, Meyer WA 3rd, Whitehouse J, et al
. Risk factors for perinatal transmission of human immunodeficiency virus type 1 in women treated with zidovudine. Pediatric AIDS Clinical Trials Group Study 185 Team. N Engl J Med 1999; 341:385–393.
34. Meyer L, Chaix ML, Deveau C, Venet A, Pacanowski J, Nagy S, et al
. Low CD4 T cell counts in sub-Saharan African patients with primary HIV-1 infection enrolled in the ANRS PRIMO Cohort
. 4th IAS Conference
. Sydney 2007.
35. Nellen J, Wit F, De Wolf F, Jurriaans S, Lange J, Prins J. Virologic and immunologic response to highly active antiretroviral therapy in indigenous and nonindigenous HIV-1-infected patients in the Netherlands. J Acquir Immune Defic Syndr 2004; 36:943–950.
36. Jensen-Fangel S, Pedersen L, Pedersen C, Larsen C, Tauris P, Moller A, et al
. The effect of race/ethnicity on the outcome of highly active antiretroviral therapy for human immunodeficiency virus type 1-infected patients. Clin Infect Dis 2002; 35:1541–1548.
37. Bunders M, Thorne C, Newell ML. Maternal and infant factors and lymphocyte, CD4 and CD8 cell counts in uninfected children of HIV-1-infected mothers. AIDS 2005; 19:1071–1079.
38. Frater A, Dunn D, Beardall A, Ariyoshi K, Clarke J, McClure M, Weber J. Comparative response of African HIV-1-infected individuals to highly active antiretroviral therapy. AIDS 2002; 16:1139–1146.
39. Kassu A, Tsegaye A, Petros B, Wolday D, Hailu E, Tilahun T, et al
. Distribution of lymphocyte subsets in healthy human immunodeficiency virus-negative adult Ethiopians from two geographic locales. Clin Diagn Lab Immunol 2001; 8:1171–1176.
40. Smith C, Sabin C, Youle M, Kinloch-de Loes S, Lampe F, Madge S, et al
. Factors influencing increases in CD4 cell counts of HIV-positive persons receiving long-term highly active antiretroviral therapy. J Infect Dis 2004; 190:1860–1868.
Keywords:© 2008 Lippincott Williams & Wilkins, Inc.
access to care; Africans; epidemiology; HIV/AIDS; prevention of mother-to-child transmission; public health