Outcome Evaluation of Early Implementation of Option B+ in Cameroon: A Prospective Cohort Observational Survey in the Northwest and Southwest Regions

Background: Mother to child transmission (MTCT) of HIV constitutes a major source of new pediatric infections in Cameroon. Objective: The aim of this implementation research was to assess outcomes and effectiveness of providing life-long antiretroviral therapy (ART) for HIV-positive pregnant and breastfeeding women (Option B+). Methods: From October 2013 to July 2014, HIV-positive pregnant and breastfeeding women, not on antiretroviral (ARV) prophylaxis and ART, were recruited from 22 purposefully selected health facilities in the Northwest and Southwest regions for a prospective, observational cohort evaluation. Option B+ was offered to participants and outcome indicators were measured. Results: Out of 680 women eligible for this assessment, 669 (98%) were initiated on Option B+. Retention-in-care was 90% (95% CI, 87.85 92.61) and 79% (95% CI, 75.20 81.88), and loss to follow up (LTFU) was 7% (95% CI: 4.95 8.90) and 15% (95% CI: 12.06 17.56) at 6 and 12 months respectively. Maternal mortality at 12 months after ART initiation was 2% (13). As of March 2015, 538 HIV exposed infants (HEIs) were enrolled and received postpartum nevirapine prophylaxis within How to cite this paper: Muffih, P.T., Tshimwanga, E.K., Abutu, A., Abongwa, L.E., Awa, J.C., Atanga, P.N., Desembuin, F., Khan, E.M., Bonje, K.E., Emmanuel, N., Chimoun, E.F.T., Welty, T., Fosah, G.T., Lim, J., Duncan, D., Petit, L., Tene, G., Mosoko, J. and Bolu, O. (2018) Outcome Evaluation of Early Implementation of Option B+ in Cameroon: A Prospective Cohort Observational Survey in the Northwest and Southwest Regions. World Journal of AIDS, 8, 90-104. https://doi.org/10.4236/wja.2018.83008 Received: May 30, 2018 Accepted: September 18, 2018 Published: September 21, 2018 DOI: 10.4236/wja.2018.83008 Sep. 21, 2018 90 World Journal of AIDS


Introduction
With a population of 23. 3  of these HIV-positive women received antiretroviral therapy (ART) for PMTCT [3] [4]. Although the Cameroon HIV guidelines in 2011 specified that all HIV-positive exposed infants (HEIs) were eligible for immediate ART, at the time this implementation research was initiated in 2013, only 25% of HEIs were provided antiretroviral (ARV) prophylaxis at birth, 9.3% had an HIV deoxyribonucleic acid polymerase chain reaction (DNA PCR) test at 8 weeks of age (7.1% infants testing HIV-positive), and approximately 3% of those HIV infected were initiated on lifelong ART [4]. Consequently, HIV-related deaths have contributed to a decrease in life expectancy in Cameroon from 54 years in 1990 to 51.5 years in 2010, with 10.1% of maternal deaths estimated to be HIV-related [5] [6].
In support of the national HIV/AIDS program in Cameroon, the Cameroon Baptist Convention Health Services (CBCHS), in collaboration with the Elizabeth Glaser Pediatric AIDS Foundation (EGPAF), the Centers for Disease Control and Prevention (CDC), and the Cameroon Ministry of Public Health P. T. Muffih et al. feeding women in 2010 [7] [8]. For HIV-infected pregnant women who were not eligible for lifelong ART based on CD4 count or clinical staging, Option A consisted of antepartum twice-daily zidovudine (ZDV) to HIV-infected pregnant women starting at 14 weeks of gestation and continued throughout pregnancy.
At the onset of labor, sdNVP was administered with the initiation of twice daily ZDV and lamivudine (3TC) for seven days postpartum. HIV-exposed infant (HEI) prophylaxis involved neviparine (NVP) syrup from birth until one week after cessation of breastfeeding or for six weeks postpartum if not breastfeeding [9] [10]. In 2010, the government of Cameroon developed a national plan for the elimination of mother-to-child transmission of HIV (eMTCT) to align with the global eMTCT plan to reduce new pediatric HIV infections and decrease the MTCT rate to less than 5% by 2015 [11] [12].
In 2012, Cameroon's MOPH decided to implement Option B+ (life-long ART for pregnant and breastfeeding women regardless of CD4 count) nationwide using a phased approach to reach these goals [11]. With funding from the U.S. President's Emergency Plan For AIDS Relief (PEPFAR) through CDC, CBCHS piloted a rollout of PMTCT Option B+ in the Northwest and Southwest regions of the country. The aim of this study was to evaluate outcomes and effectiveness of PMTCT Option B+ service at 12 months postpartum in order to facilitate national scale-up by the MOPH. A second evaluation will describe 24 months postpartum outcomes. were not on ARV prophylaxis or antiretroviral therapy (ART). HIV positive breastfeeding women whose infants were greater than 18 months of age were excluded. As per Option B+ recommendations, clients were initiated on ART immediately after HIV diagnosis, and blood was drawn for baseline laboratory tests of CD4 cell count, full blood count, liver function test, serum creatinine, and fasting blood sugar. None of these tests delayed ART initiation. All costs associated with laboratory tests were absorbed by the project and study participants did not pay for any testing. All women who only accepted Option B received ongoing counseling throughout this period to continue ART for life. women attending ANC services in the 10 months enrolment period, facility-specific sampling targets were determined by sampling proportionally to three patient volume categories (low, medium, and high) based on ANC attendance, PMTCT services utilization rate, and geographical accessibility. Effort was made to enrol participants from all volume sites resulting in the enrolment of 100 mother-infant pairs from low and medium volume sites, and 400 from high volume sites.

Option B+ Implementation Support
Task shifting with nurses and midwives, a defaulter tracking system and a laboratory sample transport system were implemented in all 22 study sites. CBCHS

Data Collection and Analysis
Nursing and midwifery staff in each health facility filled out PMTCT longitudinal maternal ART and HEIs registers following each visit. The registers were reviewed monthly by monitoring and evaluation officers who extracted data into an Epi Info database. Data were cleaned and analyzed using Epi Info version 3.5.4 and Stata/SE-13 software. Data analysis was performed on a monthly basis from October 2013 to October 2015, and results were reviewed during coordination meetings by the project implementation team to identify challenges and improve implementation.

Outcomes and Definitions
Outcomes of interest among pregnant and breastfeeding women initiating Option B+ were ART uptake, ART retention, stoppage of ART, loss to follow-up Transferred out was defined as women who were referred and/or transferred to other facilities due to either miscarriage, stillbirth, infant death, or relocation, or an HIV DNA PCR positive infant. HIV infected infants were transferred to ART clinics for ART initiation but were also included in the MTCT rate computation for this evaluation. The ART retention denominator was the number of clients on ART excluding the number who transferred out for each cohort at 6 and 12 months.

Ethical Considerations
This study was approved as a public health program evaluation by the CBCHS Institutional Review Board in August 2013 and the CDC in July 2013. All participants were counseled in line with national protocols and were asked to give verbal consent before enrollment in the evaluation. Option B+; this included three clients who initially accepted ART only during pregnancy but later changed to lifelong ART during the course of the pregnancy.

Results
All 669 participants who initiated Option B+ were enrolled in the study.

Maternal Demographic Characteristics
The median age at enrollment was 27 years (IQR: 24 -31 years
At six months after ART initiation, 6 women (1%) had died and 9 (1%) had stopped ART. At twelve months after ART initiation, a total of 10 women (2%) had died; 17 (3%) had a still birth, and 15 (2%) had a miscarriage. Of the 10 women who died, 2 died of HIV-related disease, 3 died of obstetrical complications, and the cause of death of five was unknown. An additional 12 women stopped their ART after six months for a total of 21 (3%) women who stopped ART at 12 months (Table 2).

ARV and Cotrimoxazole Uptake, Retention and Mortality, among Enrolled HEIs
Of the 669 women enrolled in the study, 120 women either died, had miscarriage, stillbirth or withdrew from care before delivery. The remaining 549 women gave birth to 568 HEIs; of these, 538 enrolled in the study. All 538 enrolled

Discussion
Historically, PMTCT coverage and ART retention along the PMTCT cascade have been poor in Cameroon [4]. UNAIDS reported a 6 weeks MTCT rate of 5.2% in Cameroon, which is higher than the global eMTCT targets of less than 2% and 5% at 6 weeks and after cessation of breastfeeding respectively [13]. To achieve these targets, ART uptake and maternal retention on ART are essential.
Early implementers of Option B+ have reported high ART uptake, yet many countries have struggled with maternal retention [14] [15]. In this evaluation, early retention at 6 months after ART initiation was high at 90% and then declined at 12 months after ART initiation to 79%. The 12 months ART retention rate was high when compared to 60% from a nationwide survey of Cameroon's adult ART program in 2014 [16]. Among women in Option B+ programs, the 6 months retention rate in Cameroon was higher than the rate seen in Uganda and the Democratic Republic of Congo (DRC), while the 12 months retention was similar to data from Malawi Option B+ program [14] [17] [18]. To identify effective strategies to improve maternal retention, it was important to first understand which patients were at highest risk of LTFU. Similar to results from Malawi [17] and Ethiopia [15], this study found that clients with higher transport cost to the facility were twice as likely to become LTFU at 12 months compared to those with lower transport cost. To minimize LTFU after ART initiation and after delivery, we used appointment diaries and peer educators throughout the Figure 3. Enrollment and outcome of HIV exposed infants selected for Option B+ evaluation.
duration of the study, to closely monitor clients with missed appointments and to re-engage defaulters and patients with more than one month since the last ART refills. We did not experience high LTFU immediately after ART initiation and among women who initiated Option B+ while breastfeeding. Compared to the Cameroon adult ART retention data, our study suggested that women involved in the Option B+ program had a better 12 months ART retention, and this may be due to the interventions in place. However, this evaluation was limited to only 2 regions of Cameroon and was not nationwide as the Cameroon adult ART retention data.
In Malawi, 6 months retention data demonstrated that women initiating ART during pregnancy were five times more likely not to return to the clinic after they initiated ART compared to non-pregnant women (OR: 5.0, 95% CI 4.2 -6.1) and those who started Option B+ while breastfeeding were twice as likely to miss their first follow up visit compared to women who initiated during ANC [17].
During this evaluation, CD4 testing was used since the Cameroon national guidelines on management of HIV recommended CD4 testing at baseline and every 6 months while on ART. Despite cost subsidies and laboratory sample transportation systems to improve uptake of laboratory tests, we noted a drop in P. T. Muffih et al.
CD4 testing uptake greater than 50% at 6 months and almost 90% at 12 months after ART initiation. Reliance on ongoing CD4 monitoring for PMTCT Option B+ for a test and start approach may not be feasible in the Cameroon setting. Some of the challenges noted in this evaluation included systemic barriers (such as long waiting times for sample collection, stock out of reagents, frequent break down of equipment) and distance to testing site; these have been described in other countries as well [9] [10]. The results of this study stressed the importance of addressing programmatic challenges related to laboratory equipment and supply chain system of reagents and other commodities to ensure high uptake of routine laboratory testing.
In Cameroon, HIV is a large contributor to maternal mortality rates. A 2012 study attributed 10% of pregnancy-related deaths to HIV [6]. However, in this current study which took place in an Option B+ setting, a mortality rate of 2% was found among enrolled women at 12 months post-ART initiation; this is similar to 1.7% found in a study in Malawi [17] and 2.6% found 6 months after initiation of Option B in the Cameroon DREAM study [19].
Rates of infant NVP uptake after birth, HIV DNA PCR testing at 6 to 8 weeks of life, and MTCT at 6 weeks captured by PCR were similar to those found in Malawi, where 95% of HEIs received ARV prophylaxis (NVP) after birth, 82% received a DNA PCR test at 6 to 8 weeks of life, and 2.6% tested positive [20]. We put systems in place to track defaulters and improve retention along the PMTCT cascade and early infant diagnosis (EID) uptake using community workers.
The uptake of EID of 95.7% and the HIV transmission rate among infants tested at 8 weeks of 2.4% reported in this study are 3 times better than the 2014 overall country EID uptake of 24% and MTCT rate at 6 weeks of 7%, identified shortly before Option B+ was implemented nationwide in Cameroon [21] The 2015 estimated uptake of EID at 8 weeks was 30% while the HIV transmission rate among infants tested at 6 weeks was 5% [22].

Strengths and Limitations
This evaluation follows a large prospective cohort of mother-infant pairs across 22 busy PMTCT sites predominantly in semi-urban and rural areas of Cameroon. The descriptive evaluation of the outcomes of mother-infant pairs was not designed as an experimental study that would allow causal inferences to be made. The selection strategy of participating health facilities and eligibility of participants may limit the generalizability of findings and the ability to be a model for a complete Option B+ policy. Because many HEIs were still breastfeeding at the time of the 6 weeks HIV DNA PCR testing, our results may underestimate final HIV rates in this cohort after cessation of breastfeeding. Additionally, we only know the HIV status of HEIs who were retained during the reporting period; HEIs who were not retained might have been more likely to become HIV infected or to have died. Final outcomes of enrolled HEIs are not included since many had not yet reached 18 months of age at the time of analysis.