Sex difference in survival status among antiretroviral therapy users in Yirgalem general hospital, Sidama zone, south nations nationalities and peoples’ region (SNNPR), Ethiopia: retrospective cohort study

Antiretroviral treatment (ART) has been shown to enhance the survival of people living with HIV (PLWHIV) worldwide. The goal of ART initiation has also expanded to include not only prevention of Acquired Immuno Deficiency Syndrome (AIDS)-related morbidity and mortality but also prevention of HIV transmission. However, despite the ongoing ART scale up, HIV transmission and AIDS-related mortality remain high in many parts of the world [1].

Globally, in 2017, about 21.7 million PLWHIV were accessing ART and of all adults living with HIV, 59% were accessing ART. Similarly, over the past decade, ART programs have been scaled up dramatically in the sub Saharan region and the number of ART users has increased dramatically from about 100,000 in 2004 to 15.4 million in 2017, making the ART coverage of 60% [2] However, the existing evidences show that the survival probability in this region is shorter [3, 4]. For instance in 2013, the estimated 1 year and 5 years survival of ART users in this region was about 87% (95% CI: 72, 94%) and 70% (95% CI: 36, 86%), respectively [4].

Ethiopia launched its ART initiative in 2003 based on a subsidized fee based approach. With the assistance of global and national programs, ART became available free of charge in 2005. As a result, there has been a continuous increase in the number of PLWHIV accessing life-saving ART from about 47,422 in 2005, 535,069 in 2015 to about 703,516 in 2017. As a result the ART coverage increased from 53% in 2015 to 71% in 2017 [5]. However, lost to follow up and early mortality remain significant challenges for the success of the national ART program [6‐8]. In 2014, ART services were available in 1047 health facilities in Ethiopia and ART coverage for adults of 15 years and above reached 79.6% in same period [9]. In 2013, about 70.3% of individuals who ever started ART were on treatment indicating challenges of adherence [10].

The possible difference in disease spectrum and prognosis of HIV infection in men and women is a major concern with conflicting reports about the effect of sex-related differences on mortality. The progression rates might differ between women and men because of biological and socioeconomic factors [11]. It is assumed that females appear not to access HIV services as often as males and also have worse treatment outcomes, including mortality, because they have less time to keep HIV outpatient appointments due to family commitments, or socioeconomic circumstances [12]. Existing data in Ethiopia also show that the proportion of males enrolled in ART programs is lower than females [13].

Mortality is one of the main reasons for PLWHIV’s attrition from ART programs. Mortality rates also vary based on sex difference. According to a study conducted in Tikur Anbesa Specialized Hospital, Ethiopia, female ART users had about two times higher rates of dying as compared to males [14]. In contrast, a study done in Goba hospital, Ethiopia, revealed that males had three times higher rate of dying within 5 years of ART initiation as compared to females [15].

Despite the availability of a large body of research evidence that addresses issues around HIV/AIDS treatment in Ethiopia, the level of understanding about survival status and differences based on sex as a result of HIV infection is low and inconsistent across studies. In the country, the survival probability of ART users is low and early mortality as a result of HIV/AIDS remains a major public health problem. Thus, improving understanding around survival status of males versus females is critical for progress towards reducing mortality and attaining universal health for all stated under the Sustainable Development Goal (SDG)-3, particularly target 3.7 which aims at ensuring universal access to sexual and reproductive health care service. To realize this, it is crucial to estimate mortality rates and identify predictors that affect the survival rate of ART users with a particular emphasis on sex difference.

This study highlights sex differences in survival status and its determinants among ART users in Yirgalem General Hospital, Ethiopia. Accordingly, probability of surviving for the first 5 years after ART initiation among females was 80.10%, which is significantly lower than that of males, 91.18%. This indicates that the risk of dying within 5 years of treatment follow up was nearly two times among females as compared to males. This finding is consistent with a study conducted in Tikur Anbesa Specialized hospital, Addis Ababa, Ethiopia in 2012 [14]. This might be due to the reason that females bear more work burden, including domestic work, child care and community management roles, which limit their time for rest and self-care as well as taking medications appropriately leading to early death.

However, the finding of this study were inconsistent with similar studies conducted in Goba, South East Ethiopia in 2015, in Aksum, North Ethiopia in 2014 and in Southeast Uganda in 2011 [15, 17, 18], in which males had low chance of 5 years’ survival as compared to females. This difference may be due to the reasons that males in those regions might have been engaged in risky behaviors like alcohol consumption, smoking and poor ART adherence than women.

In our study, we found that marital status had statistically significant association with the survival status of ART users. Divorced individuals were two times more at risk of dying within 5 years treatment follow up as compared to married ART users. This is in agreement with a study done in the United States in 2013 [19]. This may indicate that divorced people in the study area and in the United States may have limited social/family support and less social integration leading to poor survival as compared to those who are in a stable marital union. The existence of partner may also increase adherence and appropriate use of drugs by reminding each other.

Our study also revealed that a greater educational status increases the probability of survival for the first 5 years of ART initiation. This finding is consistent with a previous study done in Aksum Hospital Northern Ethiopia in 2014 [18]. This may be due to the reason that educated individuals have exposure to better sources of information like the internet, written materials and better understanding about the disease and the importance of ART adherence, leading to better survival.

Not disclosing HIV sero-status was also found to reduce the 5 years’ survival in this study. This finding is consistent with a study done in Jinka, South Omo, Ethiopia in 2016 [16]. Disclosing HIV status to others may reduce the risk of depression and the fear of stigma and discrimination. Individuals who disclosed their HIV status may also have better acceptance, supportive care and reminder from others about their drug schedule leading to better quality of life and survival.

In our study, we found that those who were bedridden at baseline were nearly three times more likely to die in the 5 year treatment follow up period compared to those with working functional status. This finding is consistent with similar studies conducted in Ethiopia, including the Armed Forces General Teaching Hospital (2012), Debre Marcos Referral Hospital (2014), Tikur Anbessa Specialized Hospital (2012), Hadiya and Kembata zone public health facility (2015), Jinka South Omo (2016), as well as similar analyses conducted in India [14, 16, 20‐24].

Additionally, we found that individuals with TB-HIV co-infection at baseline had more than two times higher risk of dying within the 5 year treatment follow up period. This finding is consistent with studies done in other parts of the country and abroad [15‐17, 24‐26]. Co-infection may lead to faster deterioration of the immune system, further exacerbating patients’ clinical conditions and lead to early death [27]. The burden of drug side effects of both diseases, drug-drug interactions and adverse drug reactions might have also led to early death.

In terms of program implications, findings of this study support the current WHO and Ethiopian guidelines regarding ART initiation at early clinical stage, which is test and treat approach regardless of any criteria [28, 29]. HIV counseling and testing (HCT) is a gateway for treatment provision. Though HCT services are aimed at reaching groups at higher risk of HIV acquisition, patients are often diagnosed late in the course of HIV disease. This can result in poor quality of life and early mortality, as well as delays in achieving the Sustainable Development Goal-3, aimed at ensuring healthy live and well-being for all. This also needs improving the survival of female ART users at least as that of males by addressing the gender related social determinants.

This study is not without limitations. For example, mortality might have been overestimated since real causes of death were not ascertained so that all deaths were considered as AIDS-related. Further, lost-to-follow up and drop-outs were censored; however, ART users may have died after changing their residence or even at home. This might have under-estimated the true level of non-survival. As the data were extracted from ART monitoring and follow-up charts, some variables like body mass index (BMI) at the baseline, socio-economic status, levels of alcohol consumption, and substance use were not assessed which might have confounded the findings.

This study found that female had a lower 5 years survival probably as compared to males following ART initiation in Yirgalem hospital, Ethiopia. Overall, drop-outs contributed to a higher attrition rate of ART users during the 5 year treatment follow up period. Marital status, educational level, disclosure of HIV status, functional status and TB co-infection at baseline were found to be independent predictors of 5 years’ survival.

Empowering women through gender interventions and mobilizing mass media on social behavioral change communication on benefit of ART adherence, disclosure of HIV status and negative impact of treatment interruptions are recommended. Strengthening counseling at initiation and ART users’ retention mechanism using reminders and follow up to trace at home when lost to follow up are also crucial. Strengthening TB prevention and control strategy, and information dissemination on treatment and its impact are also very important to reduce co-infection and improve survival.