In sub-Saharan Africa, short-course antiretroviral (ARV) prophylaxis programs are currently implemented to prevent mother-to-child transmission of HIV-1 infection (PMTCT). However, the uptake of these PMTCT interventions remains low, generally around 20%. 1,2 One explanation for this low uptake could be an association with maternal CD4 levels. Indeed, CD4+ T-cell count (CD4) is a strong predictor for HIV-1 disease progression, with increased morbidity in immunosuppressed individuals. 3,4 Our hypothesis in Abidjan, Côte d'Ivoire, was that women with less advanced HIV disease felt no interest in receiving PMTCT interventions and self-excluded themselves during antenatal follow-up. The stigmatization toward HIV-1–infected (HIV+) patients and the inappropriate attitude of some health workers described in this population could lead to this self-exclusion. 5 To explore this hypothesis, we described the CD4 counts, used as a marker of HIV-1–related symptoms, in all women diagnosed antenatally as HIV+ so as to study the relationship between maternal immune status and the uptake of a PMTCT ARV-based intervention.
POPULATION AND METHODS
Since March 2001, the Ditrame Plus French National AIDS Research Agency (ANRS) 1201/1202 project has provided a comprehensive PMTCT package, including zidovudine from 36 weeks of amenorrhea until delivery and intrapartum nevirapine, alternatives to prolonged and predominant breast-feeding (formula-feeding at birth or exclusive breast-feeding for 3 months, followed by rapid weaning), and mother and child cotrimoxazole prophylaxis in 5 antenatal clinics in Abidjan, Côte d'Ivoire. 6,7 In April 2002, a CD4 prevalence survey was conducted within this project. After individual pre-test counseling, HIV testing was systematically proposed to every pregnant woman attending these antenatal clinics. After having accepted HIV testing and signed an informed consent document, pregnant women were enrolled in the prevalence survey. Two venous blood samples were collected. The first sample was used for the serologic diagnosis of HIV-1 using an on-site rapid serial HIV testing algorithm (Determine and, if positive, Genie2). HIV test results were made available within 24 hours after blood collection. Women were considered as HIV+ if both tests were positive. The second specimen was shipped to a reference laboratory (CeDReS, Treichville University Hospital, Abidjan, Côte d'Ivoire) to perform the CD4 count in all HIV+ women by standard flow cytometry (FACS-can, Becton Dickinson). All HIV+ pregnant women were followed until delivery to determine the proportion receiving their HIV test result during individual posttest counseling and, among them, those who started the prophylactic ARV regimen.
Between April and June 2002, 2407 pregnant women received prenatal counseling and 2144 (89.1%) accepted HIV testing. The women who refused to be tested were comparable to those who accepted in terms of parity and gestational age but were older by 14 months on average (27.0 ± 5.3 years vs. 25.8 ± 5.6 years; P < 0.001). The prevalence of HIV-1 infection was 10.5% (n = 226; 95% confidence interval [9.2%–11.9%]). Among these 226 HIV+ pregnant women, 172 (76.1%) returned to the clinics to receive their HIV test result. A similar return rate for HIV test results was found among HIV-uninfected women (76.9%).
All but 5 HIV+ pregnant women diagnosed antenatally had a CD4 count measurement. Overall, their median CD4 count was 408 cells/mm3, with an interquartile range (IQR) of 304 to 570 cells/mm3 (Table 1). According to CD4 values (in absolute counts and in 4 distinct classes), no significant difference was found between the 50 (22.6%) HIV+ women who did not receive their HIV test result and those (n = 171) who received it (P = 0.19). Considering individual expected dates of delivery as the censoring time, 72 of 226 women (31.9%) received the PMTCT ARV regimen. In addition, no difference was found between the 99 HIV+ pregnant women who were informed of their serostatus but did not initiate the ARV PMTCT regimen and the 72 women initiating it (median: 425 cells/mm3 vs. 405 cells/mm3; P = 0.47).
DISCUSSION AND CONCLUSION
To our knowledge, this study is the first to describe the immune status of all HIV+ women diagnosed antenatally in an African setting of high HIV-1 prevalence in relation to their uptake of a PMTCT intervention. We found a lack of difference in CD4 count between those HIV+ women who did not return for their test result and those who were informed of their serostatus. In addition, no difference was found in HIV+ pregnant women who did not accept the PMTCT ARV prophylaxis and those who received the PMTCT package. In our experience, CD4 levels in women who accepted the PMTCT intervention were representative of the HIV disease stage of HIV+ pregnant women. Thus, the low uptake of the Ditrame Plus program cannot be explained by the self-exclusion of pregnant women in relation to advanced HIV disease measured per CD4+ count. One possible reason for this lack of difference is that among severely immunosuppressed women as a whole, some of them may be more stigmatized (and then did not accept the intervention), but some of them, on the contrary, were more motivated to seek help for their unborn children (and then accepted ARVs more frequently than disease-free women). In our study, we used CD4 counts as markers of the presence of HIV-associated symptoms. The lack of simultaneous clinical data is clearly a limitation of our study. We believe that CD4 counts permitted the identification of all women with advanced HIV disease. In our population, stigmatization could well be the main factor limiting the uptake of the PMTCT program. Population-specific research could be required to understand better the different factors influencing the low uptake of the PMTCT interventions in the various populations of sub-Saharan Africa.
Zidovudine (Retrovir) is kindly provided to the Ditrame Plus programme by Glaxo Smith Kline–France.
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2. Ekouevi DK, Leroy V, Viho I, et al. Acceptability and uptake of a package to prevent mother-to-child transmission (PMTCT) using rapid HIV testing in Abidjan, Côte d'Ivoire. AIDS
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5. Horo A, Bequet L, Viho I, et al. Knowledge and attitudes about HIV infection amongst health professionals working in prevention of mother-to-child transmission of HIV. Abidjan, Cote d'Ivoire [10BT5-2]. Presented at the XIIth International Conference on AIDS and STDs in Africa, Ouagadougou, Burkina Faso, 2001.
6. Dabis F, Ekouevi D, Bequet L, et al. A short course of zidovudine + peripartum nevirapine is highly efficacious in preventing mother-to-child transmission of HIV-1: the ANRS 1201 Ditrame Plus Study, Abidjan, Côte d'Ivoire [poster 854]. Presented at the Xth Conference on Retroviruses and Opportunistic Infections, Boston, 2003.
7. Leroy V, Bequet L, Ekouevi D. Uptake of infant feeding interventions to reduce postnatal transmission of HIV-1 in Abidjan, Cote d'Ivoire. The Ditrame Plus ANRS 1202 project [MoPeD3677]. Presented at the XIV International AIDS conference, Barcelona, 2002.
The composition of the ANRS 1201/1202 Ditrame Plus Study Group is as follows: Principal Investigators: François Dabis, Valériane Leroy, Marguerite Timité-Konan, and Christiane Welffens-Ekra; Coordination in Abidjan: Laurence Bequet, Didier Koumavi Ekouévi, Besigin Towne-Gold, and Ida Viho; Clinical Team: Clarisse Amani-Bosse, Ignace Ayekoe, Gédé on Bédikou, Nacoumba Coulibaly, Christine Danel, Patricia Fassinou, Appolinaire Horo, Ruffin Likikouët, and Hassan Touré; Laboratory Team: Dominique Bonard, André Inwoley, Crépin Montcho, and François Rouet; Biostatistics and Data Management: Renaud Becquet, Laurence Dequae-Merchadou, Gérard Allou, Charlotte Sakarovitch, and Dominique Touchard; Psychosocial Team: Hortense AkaDogo, Annabel Desgrées du Loû, Alphonse Sihé, and Benjamin Zanou; and Scientific Committee: Stéphane Blanche, Jean-François Delfraissy, Philippe Lepage, Laurent Mandelbrot, Christine Rouzioux, and Roger Salamon.