The -1Year Survival In Hiv-Infected People Receiving Antiretroviral Therapy Varies Across Location Of Health Care Facilities In Benin
C. Sossa Jerome*1,2, Mt Agonnoudé3, Ge. Sopoh1, Ai Bah-Chabi1, A.De Souza1, M. Bachabi1, G. Gbetowenonmon1, V. Agueh2, Em Ouendo2, Lt Ouedraogo2
1Programme National de Lutte contre le Sida et les IST(PNLS), 01 BP 882 Cotonou, Bénin
2Institut Régional de Santé publique, BP 384, Ouidah, Bénin
3ENATSE, Université de Parakou, BP123, Tél./Fax : (229)23 61 07 12; Fax : (229) Parakou, Bénin
*Corresponding author: Dr. Sossa Jerome Charles, University of Abomey-Calavi, Regional Institute of Public Health, Route des esclaves,
Submitted: 12-15-2016 Accepted: 08-01-2016 Published: 08-11-2017
Keywords: Pwlha; Survival; Arv Therapy; Predictors; Benin
Mortality reduction and improved quality of life due to the benefit of antiretroviral treatment (ART) for acquired immunodeficiency syndrome (AIDS) patients is well known. The efficacy of ART, as reflected by viral suppression. Cluster of differentiation 4 (CD4) lymphocyte repletion and durable reductions in AIDS related opportunistic diseases and death is similar among patients treated in high-income as well in low income countries [1, 2]. However, high early mortality after starting ART has been observed in the resource limited countries[ 2]. The impact of ART programs in resource poor setting[ 2] is, therefore, unlikely to be related to questions of drug efficacy, but rather to health system issues and programme effectiveness .
Factors that limit the success of ART include poor therapy adherence, regimen complexity, viral resistance, drug tolerance and toxicity, therapy costs, and presence of comorbid conditions such as substance abuse and addiction.
It is well established that survival among patients on antiretroviral (ARV) therapy is associated with good adherence [4-6], a high CD4 cell count at baseline, young age [4, 5, 7, 8], world health organization (WHO) classification of HIV infection stages [5,7]. Studies reported that coinfection or comorbidity (especially tuberculosis), the marital status [5,7], ARV combination, occupation and body mass index (BMI) were predictor of death . Another influence of sex was uncovered at Dar es Salam in Tanzania, where researchers reported that oneyear after ART initiation, women have a better immunologic response with high rate of undetectable virus load .
In Benin the estimated prevalence of HIV/AIDS was 1.2 % in 2012 (1.6 % in urban setting and 0.9 % in rural area) , ART began in Benin since February 2002 in three sites. In scaling up according to 3 by 5 initiative, National Programme for Fight against HIV/AIDS (PNLS) opted for decentralized health centers for HIV/AIDS care . Two 1-year survival after stating ART were performed and the rate varied from 88.5% (2006- 2007) to 93.4% (2008-2009). In order to assess changes in the performance of ART caregivers and to improve program’s quality of services to persons living with HIV/AIDS (PLWHA), PNLS needed to assess 1-year in 2014. Furthermore, PNLS needed to identify regions where the likelihood of death during the first year of ART initiation is high in order to improve the quality of services in these area. Comparing the survival of patients treated in health facilities across health regions can inform HIV/AIDS program managers for actions. The objective of this study was to assess 1-year survival in PLWHA receiving ART in Benin in 2014, to compare it with survival rate reported from 2006-2007 and 2008-2009 studies and explore its association with health regions.
Material and Methods
We conducted a retrospective study in PLWHA under ART in the National HIV/AIDS program. Patients were enrolled from 46 HIV/AIDS care sites in all parts of Benin. Forty two ART centers with more than 100 patients were randomly selected out of all 86 centers available in Benin in 2014. In order to take into account representativeness of sites, four complementary sites with fewer than 100 patients were randomly selected. PLWHA whose medical records include complete information on 1-year survival after ART initiation participated in the study.
The study population was HIV/AIDS patients aged 15 and over receiving ART according to 2006 WHO guidelines for antiretroviral therapy (ART for all HIV-positive patients with CD4 counts <350 cells / mm3, regardless of clinical symptoms) . The criteria for inclusion were: - being HIV positive; - starting antiretroviral therapy from July, 1st 2011 to June, 30th 2012. The exclusion criterion was being pregnant receiving ART for preventing mother to child HIV transmission.
A total of 3080 patient’s records enrolled from July, 1st 2011 to June 30th 2012 were reviewed.
The independent variables studied were patients sociodemographic (sex and age) ART care site (size of attendance) and on region in which ART care sites were located. The main dependent variable was the time of death.
Investigators were divided in teams of two; each team was responsible for one or more centres of HIV/AIDS management according to the number of patients receiving ART in the centres and the distance between sites. Data were collected through a documentary review of the medical records of patients and the periodic reports from the centres of HIV/AIDS management. At each centre, data collectors extracted information regarding the variables from these documents. Investigators were enrolled for two days training to be familiar with study procedure. National supervision of data collection was also set. Deaths were verified by professional or site mediator information, if possible, and were otherwise verified by a death certificate in the patient file, by a death record in the death register, or by a phone call using the phone number in the patient file. National supervision of the data collection was set up by the principal investigator and PNLS’s monitoring evaluation representatives.
Data was collected from regular patients’ medical records in each site and were analyzed using SPSS version 20.0 (SPSS Inc, Chicago, IL, USA). Univariate analyses were performed to describe patients’ baseline characteristics.
For survival analysis, patient lost of follow up for three months were censored unless it was verified that patient was died. Verification was done by professional or site mediator information, or by a phone call using the phone number in the patient file. Kaplan Meier estimation was used to estimate survival function with two main principles [12, 13]: -survival function was hypothesized to be stable between two death time intervals; - survival function is estimated at each observed death time. Cox proportional hazards regression models  were used to investigate associations between regions associated with survival takin Ouémé-Plateau as reference (the capital of Benin is located in this region). Interactions between factors were also explored. The level of significance was fixed at p < 0.05.
The study was approved by Benin National Health Research
Ethics Committee before the operational stage beginning.
Confidence and anonymity were ensured regarding collected
A total of 3080 patient’s records enrolled from July, 1st 2011 to June 30th 2012 were reviewed.
Among 3080 patient’s records reviewed, 2176 (70.67%) had all data complete with possibility of survival estimation. We don’t find any difference between social demographic characteristics (sex an age) of patients with incomplete data and those with complete ones. The mean age at initiation of ART was 36.9 ± 10.4 years and the mean hemoglobin level was 10.3±2.7g/dl. Table I shows that 68.9% of the patients were female, 42.2% of subjects lived in Atlantic-littoral region and 95.5% had CD4 cells count less than 500 per mm3. The mean of CD4 cells count was 196.4±176.8 cells/mm3.
Table 1. Participants’ characteristics: socio sociodemographic and region of residence, PLWHA aged 15 and over on HART, Benin 2014.
1-year survival of PLWHA
The mortality rate was estimated at 2% at 12 months among 2176 PLWHA included in the study (Figure 1). The total patient- time contributed was 32253 patient-months. The maximum observed exit time was approximately 38 months, and the last death was observed at 25 months. During the first year follow up, 42 patients (1.9%) died and the estimated mortality rate were 2% at 12 months.
Figure 1. Overall crude survival curve in PLWHA aged 15 and over under HART, Benin 2014, n=2176
1-year survival and ART care site location
Log survival curves using Kaplan-Meier technique showed differences between regions. Khi-Square of Log Rank (Mantel- Cox) was 47.9 with p<0.001. Using Cox regression model, location (department or health region) of ART providing facilities was associated with 1-year survival in PLWHIV after ART initiation. Likelihood of 1-year death was higher in men [OR=1.93 95%CI = (1.07 - 3.48)] than in women and in PLWHA treated in Zou-Collines ART providing facilities [OR=2.89, 95% CI = (1.25-6.70)] compared to Ouémé-Plateau ones. Likelihood of 1-year death was lower in PLWHA under HART in Atlantique – littoral ART providing facilities [OR=0.270 95% CI = (0.09 - 0.783)] compared to Ouémé-Plateau ones.
Legend: AB=Alibori-Borgou, AD=Atacora-Donga, AL=Atlantique-Littoral, ZC=Zou-Collines, MC=Mono-Couffo, OP=Ouémé- Plateau
Figure 2. Log survival crude functions by regions in PLWHA under HART in Benin, 2014.
Table 2. Cox regression 1-year survival of PLWHA aged 15 and over with socio-demographic, ART care site attendance and location, Benin 2014, n=2176
This 1-year survival study in PLWHA receiving ART showed an estimated survival rate at 98% at 12 months, meaning a continuous improvement of survival rate among PLWHA under HART in Benin since 2006 (88.5 % in 2006, 93.4% in 2009, and 98% in the present study). Using sex an age adjusted Cox regression HR, we found that location of ART providing facilities influenced and patients’ 1-year survival.
Continuous improvement of 1-year survival
Findings in this study were in accordance with those worldwide who reported that the introduction of ART has significantly reduced morbidity and mortality in HIV-infected patients in various developed and developing countries [13,15]. In contrast, Chakravarty et al. reported in India that , the mortality in patients on ART was 14/100 person-years which was higher than results from in a study from eastern India  but similar to another study from western part of the country . Indeed, the goal of universal access to ART adopted at the June 2006 General Assembly High-Level Meeting on HIV/ AIDS, has a positive impact on survival in PLWHA . Mahy and al.  in a study on estimating the impact of antiretroviral therapy: regional and global estimates of life-years gained among adults reported that 14.4 million life-years have been gained among adults globally between 1995 and 2009 as a result of ART. According to authors, 54 % of these years were gained in Western Europe and North America, where ART has been available for over 10 years. In recent years the growth in life-years has occurred more rapidly in sub-Saharan Africa and Asia . The benefits of highly active antiretroviral therapy in the treatment of HIV infection have been well described including viral suppression, CD4 lymphocyte repletion, and durable reductions in AIDS related opportunistic diseases and death [21,22].
In organizational context, the large size of ARV site (ART site attendance) was associated with decreased mortality rate in PLWHA, but we didn’t point out this link. This may be due to low number of ART sites with high attendance included in the study, reflecting the general characteristics of ART sites attendance in Benin. According to Megerso et al.  the antiretroviral treatment outcome among ART naïve adult patients was not significantly different among patients treated at the primary health care centers and from those treated at hospital. In the study we didn’t explore survival differences between PLWHA receiving ART in primary health care centers versus those treated in hospitals.
Location of ART providing facilities was associated with mortality. In Benin context, according to household consumption surveys, the evolution of poverty by department between 2006 and 2011 shows that poverty has decreased in Ouémé-Plateau region, increased in Zou-Collines, Mono-Couffo and remained virtually unchanged in Atlantic-Littoral . House hold food insecurity prevalence ranged from 3-6% in Oueme Plateau, 1-5% in Atlantique Littoral, 7-10% in Zou-Collines and 28- 29% in Mono-Couffo . These information may explain, partly these findings. Ensuring food security in Zou Collines departments may help in reducing mortality in PLWHA in Zou Collines. In contrast, mortality did not increase in Mono-Couffo where it was expected (due to poverty and food insecurity rate) to be worsened compared to Oueme-Plateau. High early mortality after starting ART has been observed in the resource poor setting by Braitstein et al. . The impact of ART programmes in low-income countries is, therefore, unlikely to be related to questions of drug efficacy, but rather to health system issues and programme effectiveness  that needs to be take into account by AIDS programme manager.
This study of survival in PLWHIV receiving ART had some limitation including incomplete patients’ medical record.
The study shows that one-year survival of patients initiated to ART is in a continuous improvement in Benin since 2006. This improvement reflects efforts made by the national Aids Control Programme of Benin in ART has positive impact on patients. The 1-year survival in HIV-infected people receiving antiretroviral therapy varies across location of health care facilities. Efforts are needed to strength health system in regions were survival in PLWHA was low.
We thank all ARV cares sites managers and Benin Information and PLWHA cares centers (CIPEC) managers for their contributions to data collect in this study.
Funding: We thank Global fund for Malaria, HIV/AIDS and tuberculosis Representative in Benin and its partner PNLS for funding this study as periodic evaluation of ART care for PLWHA.
Cite this article: C. Sossa Jerome. The 1-Year Survival In Hiv-Infected People Receiving Antiretroviral Therapy Varies Across Location Of Health Care Facilities In Benin.
J J Epidemiol Prevent. 2017, 3(1): 033.