In 50.5% of cases, mothers presented with AIDS before pregnancy, according to the Brazilian definition criteria; among them, only 32.8% were taking antiretroviral drugs during pregnancy.
Among 94.2% of pregnant women who took prophylaxis at some point, 38.5% did so before 14 weeks and 21.7% began after 27 weeks. The majority had cesarean section (73%) and a single birth (96.1%); antiretroviral use during labor was 91.2%. Maternal deaths occurred in 2.8% (22 women) of this population.
Table 3 presents the main characteristics of HIV-exposed children with an established diagnosis. The majority were given antiretroviral prophylaxis (98.3%), although 41.3% received it late (between 6 and 24 hours); 56.7% had prophylaxis in the first 6 hours (32.4% within 2 hours of birth and 24.3% between 2 and 6 hours). Ninety-eight percent did not breastfeed, and 99.7% did not receive donated breast milk. Duration of antiretroviral prophylaxis was 6 weeks in 91.5% of cases. Forty-nine children (7.0%) had siblings infected with HIV.
Variables related to mothers, such as divorced or separated, age <16 years, injection drug use, lack of antenatal care, diagnosis at delivery (with antenatal care as a protective factor), and progression to death, were more common in women whose children were HIV infected, although differences did not reach statistical significance.
In univariate analysis, children at greater risk for HIV infection had the following characteristics: mother exposed to HIV by blood transfusion, <6 antenatal visits, not receiving antiretroviral prophylaxis at any point (pregnancy, birth, or newborn), mother not using antiretrovirals at time of birth, child not taking prophylaxis or taking prophylaxis for <6 six weeks, and breastfeeding.
This study indicates a decreasing trend of HIV vertical transmission in Sao Paulo with levels approaching elimination, which seems to be associated with antiretroviral policy and interruption of breastfeeding. However, we still identified associated factors with this mode of transmission related to serious operational issues in implementation of these interventions.
The analysis of the epidemiological and operational profile of Sao Paulo state provides lessons for responding to vertical transmission in the country as a whole, despite epidemiological and operational differences. Considering the main national-level studies as a reference,5,10 the rate of vertical HIV transmission in the state has progressed to levels suggestive of control. According to the definition by the Pan American Health Organization, “elimination” corresponds to ≤2 HIV-positive children per 100 HIV-positive mothers.13
In Brazil, there was a decline from 1988-2003 of 16%10 to 2.7% in 2006, with a relative reduction of 83.1%. Internationally, this performance is inferior to many developed countries, some of which have reached levels <2%,1,14 but it is excellent in comparison with other developing countries.15,16 For example, from a transmission rate of 25% in 1991, the United States reached a transmission rate of <2% during 1999-20001; in 2004, it was estimated that <100 children were diagnosed annually as new cases of HIV infection.1
Reductions of varying proportions have also been reported by other studies in other Brazilian states, all in the southeastern region, highlighting the impact of interventions to prevent vertical HIV transmission.13,17-20 Brazil still presents major social, economic, and cultural inequalities, and there are multiple levels of quality of health services in terms of prenatal care and the adoption of measures to prevent vertical transmission of HIV.21 Attention should be given to continued surveillance and routine care, especially in places with social inequalities, even in Brazil's southeastern region and Sao Paulo state.
Concerning exposed children, lack of prophylaxis (or receipt for <6 weeks) and maternal breastfeeding are associated with increased vulnerability and are fundamental for vertical transmission.22 In our study, in 94% of cases, mothers of infected children received prenatal care, and the main variables associated with vertical transmission were related to operational issues. This situation demonstrates that, beyond access to prenatal care, it is necessary to expand the quality of health services.23 Besides these operational issues, factors such as urban poverty, race/color, and low educational level were identified as determinants of vertical transmission of HIV, even in more developed areas of the country.6,24 In our study, none of the demographic and socioeconomic variables were significantly associated with vertical transmission; although these variables did not present statistical significance, there is a suggestion of increased infection when the mother was divorced or separated, was of age <16 years, was an injection drug user, lacked antenatal care, was diagnosed at delivery, and progressed to death.
Although this is a cross-sectional study based on secondary data, the search for information from different sources, together with a better national database (SINAN), allowed for more and higher quality data than previous studies in Brazil. Additionally, the present study defines the transmission rate based on HIV-infected mothers and their exposed children in the health services of all of São Paulo state, instead of only selected reference centers, better approximating the actual situation.
Interestingly, if we define HIV-exposed children with only 1 undetectable viral load and subsequently lost to follow-up as actually noninfected, the total noninfected would be 803 (81.8%). The initial result indicating noninfection in children, when reported to family members as an undetectable viral load result, may have created a presumption of safety, and this may have been why they did not return for additional follow-up. This reinforces the need to contextualize posttest counseling in these situations and to strengthen active case identification.
Our study has limitations besides those related to database quality and quality of medical registries. Pregnant women with HIV not captured by the current reporting system may be influencing the results, biasing the observed rate of transmission; however, considering the structural network of health services in São Paulo state, infected children who progress to AIDS had a high probability to be identified by the health system. We were not able to examine other potential factors that might be associated with vertical transmission, including sociodemographic, behavioral, and economic factors. For example, sexual transmission may be associated with injecting drug use behavior of a partner that may be strongly underreported. Nevertheless, our results suggest that women who use drugs or whose partners use drugs should be the focus of greater attention for HIV testing services, family planning, and prenatal care. This issue is one of the main challenges for Brazil, especially in less developed regions.25 Another challenge is to improve procedures to assure that prenatal services receive timely laboratory results, including new technologies such as the use of rapid HIV diagnostic tests in maternity hospitals.
Our data reveal program shortcomings and also reveal areas of significant improvement, such as substantial (albeit not perfect) incorporation of prevention strategies in health services. This new scenario indicates other new challenges to include in the policy agenda and in national strategic planning: the large number of noninfected children exposed to antiretrovirals, HIV resistance to antiretrovirals used, and the increased survival of infected children, which demands new forms of care by health professionals.1,12
In conclusion, the study reinforces previous findings of advances toward elimination of HIV vertical transmission in São Paulo state. This trend is a result of different strategies used in the past 25 years, especially the introduction of antiretroviral treatment and nonuse of breastfeeding. Data on HIV vertical transmission in São Paulo state are comparable with those of many developed countries. Although serious operational issues remain, conditions exist to respond effectively. São Paulo state demonstrates that it is possible to achieve advanced levels of control for this preventable mode of HIV transmission.
Research team: Alberto Novaes Ramos, Jr (Federal University of Ceará), Ângela Tayra (STD/AIDS State Program, São Paulo), Arachu Castro (Harvard University); Carmen Silvia Bruniera Domingues (STD/AIDS State Program, São Paulo), Cristina Possas (Department of STD, AIDS and Viral Hepatitis), Ivone Aparecida de Paula (STD/AIDS State Program, São Paulo), Luiza Harunari Matida (research coordinator, STD/AIDS State Program, São Paulo), Maria Clara Gianna (coordinator of STD/AIDS State Program, São Paulo), Mariliza Henrique da Silva (STD/AIDS State Program, São Paulo), Marina Aragão Wahlbuhl Gonçalves (STD/AIDS Municipality Program, São Paulo), Marizélia Moreira (National Agency of Health), Naila Janilde Seabra Santos (STD/AIDS State Program, São Paulo), Paulo Roberto Teixeira (Secretary of Health, São Paulo State), Sandra Regina de Souza (Secretary of Health, São Paulo State); Arachu Castro (Harvard University, EUA); and the Department of STD, AIDS and Viral Hepatitis, Data collection and supervision team: Adélia Araujo Bispo, Ana Maria Rodrigues, Ana Silvia da Paixão Gibbons, Analice de Oliveira, Angela Mattos Marchesini, Aparecida Massako Nakae, Beatriz Scanavelli, Benedita Maria de Castro, Cândida Maria dos Santos, Carlos Roberto de Oliveira, Carmenm Silvia Bruniera Domingues, Celsis de Jesus Pereira, Clara Alice Franco de Almeida Carvalho, Dagmar Maia Kistemann, Eliana Mara Pessoa, Eliane Monteiro, Filomena Maria do Carmo Nicoletti Chudek, Francisco Vanin Pascalicchio, Gisele Gutierres Carvalho Ciciliato, Ione Aquemi Guibu, Ivone Aparecida de Paula, Kezia Paiva Martins, Kimie Therezinha Nishimura Turuta, Laura Brzeski, Lilian Andrade Grimm, Lucia Aparecida Dourado Shiguematsu, Lucille Mary Loureiro Soares, Luiza Harunari Matida, Marcia Polon do Carmo, Marcia Regina Pacola, Marco Antonio Ribas, Maria Angela Silva Landroni, Maria Aparecida da Silva, Maria Aparecida Ferreira Fernandes, Maria Cecilia Rossi de Almeida, Maria Clara Neves da Costa, Maria Cristina Covolan Bachiega, Maria da Conceição Pinto, Maria de Fatima Jorge, Maria do Carmo Ferreira, Marina Aragão Wahlbuhl Gonçalves, Marisdalva Viegas Stump, Mariza Vono Tancredi, Marli Prado, Monica de Arruda Rocha, Naila Janilde Seabra Santos, Nivania Fuin Zavith, Olinda Keiko Mizuta, Patricia Helena Vaquero Marques, Rejane Alves Fraissat, Rosa Maria Alves Seixas, Ruth Nogueira Cordeiro de Moraes Jardim, Saloa Abdelnour Hoeppner, Sheila Maria Figueira Jacintho da Cruz, Silvia Karina Favinha Campassi Falzoni, Sonia Aparecida Fioratti, Sueli Bellini Garcia, Teresa Maria Isaac Nishimoto, Viviane da Rocha Sousa, Wedja Sparinger, and finally, the Grupo de Estudo de Transmissão Vertical do HIV e da Sífilis do Estado de São Paulo.
1. Hazra R, Siberry GK, Mofenson LM. Growing up with HIV: children, adolescents, and young adults with perinatally acquired HIV infection. Annu Rev Med
3. Mofenson LM, Brady MT, Danner SP, et al. Guidelines for the prevention and treatment of opportunistic infections among HIV-exposed and HIV-infected children: recommendations from CDC, the National Institutes of Health, the HIV Medicine Association of the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the American Academy of Pediatrics. MMWR Recomm Rep
4. Matida LH, da Silva MH, Tayra A, et al. Prevention of mother-to-child transmission of HIV in Sao Paulo State, Brazil: an update. AIDS
. 2005;19(Suppl 4):S37-S41.
5. Menezes Succi RC. Mother-to-child transmission of HIV in Brazil during the years 2000 and 2001: results of a multi-centric study. Cad Saude Publica
. 2007;23(Suppl 3):S379-S389.
6. Ramos AN Jr, Matida LH, Hearst N, et al. AIDS in Brazilian children: history, surveillance, antiretroviral therapy, and epidemiologic transition, 1984-2008. AIDS Pat Care STDS
7. Hacker MA, Kaida A, Hogg RS, et al. The first ten years: achievements and challenges of the Brazilian program of universal access to HIV/AIDS comprehensive management and care, 1996-2006. Cad Saude Publica
. 2007;23(Suppl 3):S345-S359.
8. Nunn AS, da Fonseca EM, Bastos FI, et al. AIDS treatment in Brazil: impacts and challenges. Health Aff (Millwood)
9. Ministério da Saúde, Brasil. Boletim Epidemiológico Aids e DST. Ano VI, n. 1. 2009. Available at: http://www.aids.gov.br/data/documents/storedDocuments/
%7BB8EF5DAF-23AE-4891-AD36-1903553A3174%7D/%7BAECBBB9D-25EF-4846-8DFA-44FFFFC17713%7D/Boletim2010.pdf. Accessed June 5, 2010.
10. Tess BH, Rodrigues LC, Newell ML, et al. Breastfeeding, genetic, obstetric and other risk factors associated with mother-to-child transmission of HIV-1 in Sao Paulo State, Brazil. Sao Paulo Collaborative Study for Vertical Transmission of HIV-1. AIDS
11. Connor EM, Mofenson LM. Zidovudine for the reduction of perinatal human immunodeficiency virus transmission: pediatric AIDS Clinical Trials Group Protocol 076—results and treatment recommendations. Pediatr Infect Dis J
12. Brazilian Ministry of Health, Health Surveillance Secretariat, STD, AIDS and Viral Hepatitis Department. Targets and Commitments Made by Member-States at the United Nations General Assembly Special Session on HIV/AIDS UNGASS—HIV/AIDS: Brazilian Response. 2008-2009. Country Progress Report
. Brasília, Brazil: MS; 2010. Available at: http://data.unaids.org/pub/Report/2010/brazil_2010_country_progress_report_en.pdf
. Accessed November 15, 2010.
13. Organización Panamericana de la Salud. Iniciativa regional para la eliminación de la transmisión materno-infantil de VIH y de la sífilis congénita en América Latina y el Caribe: documento conceptual
. Montevideo: CLAP/SMR; 2009.
14. Birkhead GS, Pulver WP, Warren BL, et al. Acquiring human immunodeficiency virus during pregnancy and mother-to-child transmission in New York: 2002-2006. Obstet Gynecol
15. Viani RM, Ruiz-Calderon J, Lopez G, et al. Mother-to-child HIV transmission in a cohort of pregnant women diagnosed by rapid HIV testing at Tijuana General Hospital, Baja California, Mexico. J Int Assoc Physicians AIDS Care (Chic)
16. Zhou Z, Meyers K, Li X, et al. Prevention of mother-to-child transmission of HIV-1 using highly active antiretroviral therapy in rural Yunnan, China. J Acquir Immune Defic Syndr
. 2010;53(Suppl 1):S15-S22.
17. Kakehasi FM, Pinto JA, Romanelli RM, et al. Determinants and trends in perinatal human immunodeficiency virus type 1 (HIV-1) transmission in the metropolitan area of Belo Horizonte, Brazil: 1998-2005. Mem Inst Oswaldo Cruz
18. Tornatore M, Goncalves CV, Mendoza-Sassi RA, et al. HIV-1 vertical transmission in Rio Grande, Southern Brazil. Int J STD AIDS
19. Matida LH, Ramos AN Jr, Heukelbach J, et al. Improving survival in children with AIDS in Brazil: results of the second national study, 1999-2002. Cad Saude Publica
20. Matida LH, Ramos AN Jr, Heukelbach J, et al. Continuing improvement in survival for children with acquired immunodeficiency syndrome in Brazil. Pediatr Infect Dis J
21. Nemes MI, Melchior R, Basso CR, et al. The variability and predictors of quality of AIDS care services in Brazil. BMC Health Serv Res
22. Havens PL, Mofenson LM. Evaluation and management of the infant exposed to HIV-1 in the United States. Pediatrics
23. McIntyre J, Lallemant M. The prevention of mother-to-child transmission of HIV: are we translating scientific success into programmatic failure? Curr Opin HIV AIDS
24. Veloso VG, Portela MC, Vasconcellos MT, et al. HIV testing among pregnant women in Brazil: rates and predictors. Rev Saude Publica
25. Szwarcwald CL, Barbosa Junior A, Souza-Junior PR, et al. HIV testing during pregnancy: use of secondary data to estimate 2006 test coverage and prevalence in Brazil. Braz J Infect Dis
Keywords:Copyright © 2011 Wolters Kluwer Health, Inc. All rights reserved.
vertical transmission of HIV; epidemiology; HIV infection; antiretroviral; Brazil