Abstract
In many developing countries, mothers’ awareness remains a challenge despite the scaling up of antenatal care and programs preventing mother-to-child (MTC) HIV transmission. The present study was done in Libreville, Gabon where all antenatal care (delivery included) is free of charge. Here we assessed the timing of antenatal antiretroviral (ARV) prophylaxis initiation, HIV-exposed infants’ age at their first postnatal HIV check visit and investigated the association between mothers’ awareness or knowledge on their ARV therapy and infants’ HIV infection. We interviewed HIV-positive mothers on their first and subsequent laboratory visits to investigate infants’ HIV status and tested infants for HIV RNA and antibody between 2012 and 2014. We established that (1) of 718 HIV-positive mothers, only 6% were fully aware and knew what ARV treatment they were on during pregnancy; (2) half of the women (54%) start their antenatal ARV prophylaxis initiation during the second trimester of pregnancy; (3) 64% of HIV-exposed infants had their first HIV infection screening between birth and three months of age; (4) the overall prevalence of HIV infection in infants born from infected mothers was 8.9%; and (5) infants born from mothers uncertain about taking prophylactic ARV therapy were 13.3 times more likely to be infected by HIV than infants born from mothers certain about taking prophylactic ARV therapy. In conclusion, the study showed that despite free antenatal care, early access and adherence to components of MTC, HIV transmission preventive care remains unsatisfactory.
Introduction
To paraphrase Evans et al., 1 in sub-Saharan Africa mother-to-child (MTC) transmission is one of the tragedies of the HIV epidemic. The likelihood of HIV transmission from MTC in the pre-antiretroviral therapy (ART) era was 15–45%. 2 There has been progress in the prevention of mother-to-child transmission (PMTCT) of HIV. 3 The implementation of ART during pregnancy has reduced considerably the rate of MTC HIV transmission to less than 5% in breastfeeding women and less than 2% in non-breastfeeding women. 4 In 2014, an estimated 220,000 children were newly infected with HIV worldwide, with 86% of new infections occurring in Africa. 5 A study done in Nigeria showed that if both the mother and child received ARVs, the rate of HIV transmission from MTC was 1.3%. 6 The reduction of HIV vertical transmission rates to 1% or below is therefore achievable in Africa. However, to virtually eliminate MTC HIV transmission in Africa, it is crucial to identify and understand specifics of PMTCT bottlenecks in Africa.
In Gabon, ARV prophylaxis for the PMTCT follows the World Health Organization 2009 PMTCT guidelines, which consist of triple therapy combining two nucleoside reverse-transcriptase inhibitors (tenofovir, emtricitabine, or zidovudine [AZT]) and one non-nucleoside inhibitor of reverse transcriptase (efavirenz or nevirapine) for the pregnant woman. For the newborn, the prophylaxis consists of six weeks of nevirapine or AZT (when the infant is not breastfed).
In this study we investigated the moment or period during the pregnancy when women were put on ART. We also assessed the association between mothers’ awareness of their ART and MTC transmission.
Methods
The National Laboratory of Public Health in Libreville (Gabon) is one of the government facilities monitoring HIV-exposed infants during their first 18 months of life. We compiled and analyzed routinely collected data from February 2012 to April 2014. We received for that period of time 900 HIV-1-infected mothers referred by the Gabonese PMTCT program. The mothers were questioned on the dates of HIV diagnosis, the first antenatal care visit and ARV prophylaxis initiation. Others questions included awareness of the therapy given: type of therapy and treatment given (women’s oral declarations were associated with their health book records: a woman was uncertain about taking prophylactic ARV therapy if she could not provide a health book and could remember taking ARVs). We also recorded infants’ ages at their first visit for laboratory assessment of their HIV status. To establish HIV perinatal infection, a sample of peripheral blood was taken during the infants’ first visit (usually at six weeks after delivery) and during the two or three subsequent visits until the age of nine months, and tested for HIV-RNA using the NucliSENS easyQ assay from Biomerieux, France. The test allows the detection and quantification of viral RNA. At 18 months, an additional sample was taken to determine anti-HIV-1 antibodies. All infants’ laboratory tests were done by our laboratory services.
Statistical analysis
All statistical analyses were done using the software GraphPad Prism version 6. Features and antenatal care-seeking behaviors of the mothers were analyzed using column statistics and D’Agostino & Pearson omnibus, Shapiro–Wilk, and the KS normality tests. The association between mothers’ ARV prophylaxis and HIV-exposed infant status was assessed using the contingency table.
Ethics statement
Informed consent was obtained from parents of all study participants. The Gabonese National Laboratory of Public Health Ethics Review Board approved the protocol. We adhered to the World Medical Association’s Declaration of Helsinki and Good Clinical Practice guidelines during the treatment of all participants and handling of their personal data.
Results
Out of 900 HIV-1-infected mothers and infants we received, 718 HIV-1-infected mothers and their infants were included in the study (182 HIV-infected mothers and their infants were excluded because information collected was deemed insufficient). The women’s average age was 29 years old (range 18 to 43 years). Three hundred and sixty-eight (51.2%) of the infants were female and 350 (48.8%) were male.
ARV prophylaxis during pregnancy
Of the 718 women were included in the study, 14 were on ARVs before pregnancy (2%), 27 had not taken ARV prophylaxis during pregnancy (4%), and 64 indicated they were on therapy during pregnancy (9%). Of the women who reported being on therapy during pregnancy, 44 out of 64 (69% [6% of all women]) were fully aware and knew what treatment they were on. Six hundred and thirteen of the 718 women (85%) could not inform us of the treatment they were on (uncertain about taking prophylactic ARV therapy) (Figure 1).
Distribution of HIV-positive mothers based on antiretroviral (ARV) prophylaxis. Eighty-five percent of mothers were uncertain about taking ARV treatment during pregnancy. Four percent of mothers were not on ARV treatment and, 2% and 9% of mothers were on ARV treatment before and during pregnancy, respectively. ART: antiretroviral therapy.
Timing of antenatal ARV prophylaxis initiation
The 25% percentile of antenatal ARV prophylaxis initiation was set at three months of pregnancy, with 54% of women starting their antenatal ARV prophylaxis during the second trimester of pregnancy (Figure 2). The average gestational age at the beginning of antenatal ARV prophylaxis initiation was four months (95% CI: 3.4–4.6).
Gestational age of ARV prophylaxis initiation. The gestational age at which women started ARV therapy ranged from one month to nine months, with 92% of women starting therapy between the first month and the fifth month of pregnancy. ARV: antiretroviral.
HIV-exposed infants’ age at their first postnatal HIV check
The age of infants’ first postnatal HIV check was highly heterogeneous (P < 0.0001 for all, D’Agostino & Pearson omnibus, Shapiro–Wilk, and the KS normality test). Sixty-four percent of HIV-exposed infants had their first HIV-screening within the first trimester of life, 14% during their second semester of life, and 23% between seven and 27 months (Figure 3).
Infants’ age at the first HIV screening. Sixty-four percent of infants had their first HIV screening (viral RNA screening) between birth and 12 weeks of age (first trimester of life), 14% were tested between 13 and 24 weeks of age ([3–6] months of age) and 23% of infants were screened between 28 and 108 weeks of age ([7–27] months of age).
HIV infection rate in HIV-exposed infants
The overall prevalence of HIV infection in infants born from infected mothers was 8.9%. All HIV-positive infants were either from mothers uncertain about taking prophylactic ARV therapy or from mothers who were not on ARV prophylaxis during pregnancy.
Association between mothers’ ARV prophylaxis and exposed infant HIV status
Infants born from women who were uncertain about taking prophylactic ARV therapy were 13.3 times more likely to be infected by HIV than infants born from mothers certain about taking prophylactic ARV therapy. The association between mothers’ uncertainties about taking prophylactic ARV therapy and infants’ HIV status was significant (p < 0.005) (Figure 4). The rate of HIV infection in infants born from mothers uncertain about taking ARV prophylaxis was 10%. None of the HIV-exposed infants born from mothers certain about taking prophylactic ARV therapy were infected.
ARV prophylaxis and exposed infant HIV status. None of the mothers certain about their ARV treatment gave birth to HIV-infected infants. The rate of HIV infection in infants born from mothers uncertain about taking ARV prophylaxis was 10% (64 out of 657). ARV: antiretroviral.
Discussion
The majority of children living with HIV are infected via MTC transmission, during pregnancy, childbirth, or breastfeeding. 7 Therefore, adhering to proper ARV drug prophylaxis for themselves and their exposed infants is the key to virtually eliminate vertical transmission of HIV.2,6,8
In our setting, the majority of women started antenatal ARV prophylaxis at the mid-term of their pregnancies. This observation reveals a weakness in our PMTCT program. The delay in ARV prophylaxis initiation in HIV-positive pregnant women seems to characterize African countries. Wettstein et al. 9 highlighted in her systematic review that in selected African settings, antenatal HIV tests and ARV prophylaxis were often done in the late second or third trimesters during pregnancy.
The other weakness of the Gabonese PMTCT program could be its inability to give proper counseling to pregnant women. Indeed, with 85% of mothers uncertain about taking prophylactic ARV prophylaxis therapy, we believe that between the PMTCT program and the women ‘something was maybe lost in translation.’ Data suggest that the use of ART or it benefits seemed to be confusing to many women. Experience showed that patients who do not understand the treatment they were prescribed have poorer adherence.10,11 Also important is the patients’ ability to remember the recommendations made to them. It has been shown that forgetting recommendations is a factor leading to nonadherence. 12 HIV-exposed infants born from women who were uncertain about taking prophylactic ARV therapy were 13.3 times more likely to be infected with HIV than infants born from mothers who knew about their ARV therapy. None of the mothers who were aware or provided evidence of their ARV treatment gave birth to HIV-infected infants. In addition, the 8.9% infection rate in HIV-exposed infants, all linked to mothers' understanding and adherence to their ARV therapy, made it clear that the education of pregnant HIV-positive women on ARV prophylaxis is crucial for preventing MTC HIV transmission. The study revealed that the level of mothers’ awareness or conscientiousness about ARV prophylaxis and its importance was unsatisfactory. We should look at the way counseling is done in our setting and if need be, adapt it to the socioeconomic status, mental, and psychological state of the woman. 13
The PMTCT program should make the transition from simple and generic information to comprehensive prevention taking into consideration psychological, socioeconomic, and sociocultural determinants. 14 The fact that infants from the small number of mothers aware and knowing of their ARV therapy were all free of HIV infection suggests that a comprehensive approach to MTC prevention that leads to mothers’ conscientiousness is the key. Again we believe that personalized counseling of the mother is required. 11 Because ARV therapy adherence is challenging, the counselor should, for example, be able to identify suboptimal literacy and should also, while respecting their privacy, ask the mothers to indicate a trusted family mentor to help with psychological support and therapy adherence.2,11,12
The Gabonese setting offers an interesting study setting. The country has universal healthcare insurance, which provides free antenatal care (medical consultation, biomedical examination, and even delivery) to all pregnant women. This shows us that beyond gratuity, there are other factors, which are very important in granting access and adherence to care.
Although the present study is the first of its kind in Gabon, it has some limitations. First, the study did not evaluate the part played by literacy, socioeconomic, and sociocultural status in the observed awareness of the women. Second, the study did not directly assess women’s adherence to ARV therapy; and finally, because few of the mothers breastfed their infants it was difficult to investigate the impact of breastfeeding in MTC HIV transmission in our setting.
Conclusion
The present study showed that even in an African setting where antenatal care is free, the PMTCT program is still unsatisfactory. Although free antenatal care contributes to the reduction of MTC HIV transmission, it is not sufficient to guarantee early access and adherence to the PMTCT program. Mothers’ awareness or conscientiousness about ARV prophylaxis is crucial in preventing MTC transmission.
Footnotes
Acknowledgments
We are grateful to all mothers who participated in the study.
Declaration of conflicting interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Many thanks to ‘la Direction Générale de la Prévention du SIDA, Agence Française de Developpement, UNICEF that supports the Gabonese National laboratory of Public Health (Laboratoire National de Santé Publique) in its actions to improve HIV diagnosis.
