Estimating mother-to-child HIV transmission rates in Cameroon in 2011: A computer simulation approach

Background: Despite the progress in the Prevention of the Mother-to-Child Transmission of HIV (PMTCT), the paediatric HIV epidemic remains worrying in Cameroon. HIV prevalence rate for the population of pregnant women was 7.6 % in 2010 in Cameroon. The extent of the paediatric HIV epidemic is needed to inform policymakers. We developed a stochastic simulation model to estimate the number of new paediatric HIV infections through MTCT based on the observed uptake of services during the different steps of the PMTCT cascade in Cameroon in 2011. Different levels of PMTCT uptake was also assessed. Methods: A discrete events computer simulation-based approach with stochastic structure was proposed to generate a cohort of pregnant women followed-up until 6 weeks post-partum, and optionally until complete breastfeeding cessation in both prevalent and incident lactating HIV-infected women. The different parameters of the simulation model were fixed using data sources available from the 2011 national registry surveys, and from external cohorts in Cameroon. Different PMTCT coverages were simulated to assess their impact on MTCT. Available data show a low coverage of PMTCT services in Cameroon in 2011. Results: Based on a simulation approach on a population of 995, 533 pregnant women, the overall residual MTCT rate in 2011 was estimated to be 22.1 % (95 % CI: 18.6 %-25.2 %), the 6-week perinatal MTCT rate among prevalent HIV-infected mothers at delivery is estimated at 12.1 % (95 % CI: 8.1 %-15.1 %), with an additional postnatal MTCT rate estimated at 13.3 % (95 % CI: 9.3 %-17.8 %). The MTCT rate among children whose mothers seroconverted during breastfeeding was estimated at 20.8 % (95 % CI: 14.1 %-26.9 %). Overall, we estimated the number of new HIV infections in children in Cameroon to be 10, 403 (95 % CI: 9, 054-13, 345) in 2011. When PMTCT uptake have been fixed at 100 %, 90 % and 80 %, global MTCT rate failed to 0.9 % (95 % CI: 0.5 %-1.7 %), 2.0 % (95 % CI: 0.9 %-3.2 %) and 4.3 % (95 % CI: 2.4 %-6.7 %) respectively. Conclusions: This model is helpful to provide MTCT estimates to guide the national HIV policy in Cameroon. Increasing supply and uptake of PMTCT services among prevalent HIV infected pregnant women, as well as HIV-prevention interventions including the offer and acceptance of HIV testing and counselling in lactating women could reduce significantly the residual HIV MTCT in Cameroon. A public health effort should be made to encourage health care workers and pregnant women to use PMTCT services until complete breastfeeding cessation. We developed a discrete event computer simulation-based approach with a stochastic structure to generate a hypothetical cohort of pregnant women followed-up through different states during pregnancy until 6-weeks postnatally (perinatal transmission, which refers to all infections detected prior to 6 weeks postpartum), and optionally until complete weaning (prevalent and incident postnatal transmission). Briefly there were 3 main health states: No HIV infection, HIV-infection, and death. The HIV-infection state were then subdivided into two sub-states :chronic HIV infection (CD4 count ≥ 350 cells/mm3), acute HIV infection (CD4 count < 350 cells/mm3 who themselves were divided into sub-states according to breastfeeding, ART treatment and/or PMTCT intervention. The fundamental unit of time in the simulation was a month. Transition probabilities from one state to another were constant over time and based on observed data in Cameroon: the prevalence of HIV, access to antenatal care, coverage of maternal HIV testing, coverage of maternal CD4 cell count assessment and live birth rate. The MTCT HIV transmission probabilities depended on the timing of the mother’s infection (prior/during pregnancy or lactation), CD4 cell count at different stages, the ART regimen and duration and the breastfeeding practices, thus the duration spent in each health state (see Additional file 1 for detailed calculations). Baseline inputs used to characterize our hypothetical cohort of pregnant and lactating women were derived from different data sources: current national surveys from National AIDS Control Committee and Cameroon’s National Institute of Statistics [18, 19], clinical trials and cohort studies conducted in Cameroon or other resource-limited settings in the absence of national data [20–23]. All data used are summarised in Table 1. We also assumed that HIV infection is associated with a lower fertility among HIV-infected women [24, 25]. The proportion of live births issued from an HIV-infected woman was estimated taking this fact into account, as well as the fact that woman may die during pregnancy. Pregnant women population groups and model key parameters according to the observed data in the different age groups ANC antenatal care, ART antiretroviral therapy, ARV antiretroviral, MTCT mother-to-child transmission; aPediacam is a multisite cohort study started in Cameroon in November 2007 with two main objectives: to study the feasibility and effectiveness, of early antiretroviral multi-therapy offered systematically to HIV-infected infants before 7 months of age; and to evaluate the humoral response of these children to vaccines of the Expanded Program of Immunization; bUnpublished Early Infant Diagnosis of HIV data located at CIRCB Mother-to-child-transmission (MTCT) of HIV can mainly occur during the second and third trimester of pregnancy, during delivery or breastfeeding [1]. Indeed, HIV transmission through breastfeeding has emerged as a substantial mode of MTCT among African breastfeeding populations and can occur in two different circumstances: among HIV prevalent mothers HIV-infected at delivery and among incident mothers HIV-infected while lactating. The risk of transmission through breastfeeding is cumulative according to the duration of breastfeeding and the longer the duration of breastfeeding, the greater the transmission risks [26–29]. Thus, we estimated three MTCT probabilities, using data from MTCT studies among pregnant and breastfeeding populations in Africa: 1/ the perinatal transmission probability at 6-week, 2/ the postnatal transmission probability and 3/ the postnatal transmission probability in those born to incident HIV-mothers who seroconverted while lactating. Additionally, we hypothesized that each of these three MTCT probabilities varied according to the maternal age group and CD4 count. Infants HIV status was computed using these estimated MTCT probabilities. Details regarding the calculation of live births rate among HIV infected woman and the calculation of MTCT probabilities are available in an additional text file (see Additional file 1, which describes models used for the calculation of MTCT probabilities and live birth rate among HIV infected women). Using our model we simulated 1, 000 cohorts of the population size of pregnant women expected in Cameroon in 2011, through each state of the PMTCT cascade described in Fig. 1. PMTCT cascade. This figure shows the different state between pregnancy and delivery, then delivery and breastfeeding cessation, including PMTCT services offering: gray colour highlights the missed opportunities in the PMTCT process. Each oval represents a maternal health state, rounded rectangle represents child health state and rectangle represents clinical events and breastfeeding practices We calculated, using a Monte Carlo approach simulation, the MTCT rates including perinatal and postnatal transmission rates among prevalent HIV-infected mothers at birth and the postnatal transmission rate among incident mothers for these 1000 cohorts. We first modelled the probability for a mother to infect her infant, used that probability to estimate a number of HIV-infected infants born to mothers in the simulated cohort and divided that number by the number of children at risk of being HIV-infected in that cohort. Specifically, the final MTCT risks were calculated as follows: Perinatal transmission rate is equal to the average number of HIV-infected children at 6-weeks born alive to prevalent HIV-infected mothers divided by the total average number of live births from prevalent HIV-infected mothers. Postnatal transmission rate is equal to the average number of children HIV-uninfected at 6-weeks who become infected beyond through breastfeeding, divided by the total average number of children born alive to prevalent and incident HIV-infected mothers. Postnatal t ransmission rate due to incident infection among lactating mothers: this rate is equal to the average number of breastfed HIV-infected children born alive to mothers HIV-uninfected at delivery but who seroconverted during breastfeeding, divided by the total average number of breastfed children born alive to incident HIV-infected mothers. Population size of new paediatric HIV infections is equal to the total average number of live born children from an HIV-infected prevalent mother at birth who become HIV-infected perinatally or during the breastfeeding period and the number of children HIV-infected through breastmilk from an incident HIV-infected lactating mother. Finally, we examined the impact of different levels of uptake of PMTCT services on the MTCT rates and the number of new paediatric infections. Three scenarios were considered. First, we considered 100 % uptake and with a 100 % retention on treatment during the whole breastfeeding period. This meant that all pregnant women had access to antenatal care (ANC), HIV testing and counselling, disclosure of their HIV results; those who were infected had a CD4 assessment and were initiated on ART prophylaxis during pregnancy until the end of breastfeeding, as well for their child. In the second scenario, we considered a 90 % uptake of PMTCT services, described as 100 % access to ANC, 90 % HIV testing and counselling, a 100 % of HIV testing result disclosure and a 90 % rate of ART prophylaxis during pregnancy. The third scenario meant 80 % uptake of PMTCT services, described as 100 % access to ANC, 80 % HIV testing and counselling, a 100 % of HIV testing result disclosure and an 80 % rate of ART prophylaxis during pregnancy. 95 % confidence intervals of perinatal, postnatal and postnatal due to maternal incident infection rates, as well as the population size of new paediatric infections were derived from the 0.025 and 0.975 quintiles of 1000 subpopulation generated by bootstraps. Sensitivity analyses of the results of the simulation model were conducted by varying in suitable intervals some key parameters in the prevention of MTCT of HIV, as described in Table 2. Sensitivity analyses were performed by varying these parameters in specific intervals based on the lowest and highest published values. For each key parameter 1000 values were randomly drew within the corresponding range. For each of these 1000 sets of randomly drawn parameter we simulated one cohort of the population size of pregnant women expected in Cameroon in 2011 and the associated MTCT rates were calculated. Range of Model parameters for sensitivity analyses (results expressed in %) ANC antenatal care, ART antiretroviral therapy, ARV antiretroviral treatment, MTCT mother-to-child transmission In this work, all results were performed using R statistical software (R Core Team (2013). R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. URL http://www.R-project.org/.).