Our study is one of few cohorts evaluating impact of DAA treatment in quality of life of HCV/HIV co-infected patients. Early on, improved HRQoL was shown to be associated with a SVR of IFN-based treatment that has high toxicity, more complexity and lower treatment uptake in many low-middle income countries [32]. In HCV/HIV co-infected patients, SVR rates are historically 20–30% lower than in HCV mono-infected patients [33]. The introduction of interferon-free DAA treatment has been a significant breakthrough since this combination is likely to close the gap of SVR between HCV/HIV co-infection and HCV mono-infection [8, 9].
Results from clinical trials of DAA treatments have shown improvements in the physical and psychological components of HRQoL, mostly in HCV mono-infected patients [16, 19, 34]. Many clinicians were concerned that clinical trial results cannot be generalized to real-world situations due to the studies’ strict selection criteria [35]. Several researchers have attempted to investigate the impact of DAA treatments on HR-QoL of HCV/HIV co-infected patients, with various treatment combinations and tools, with conflicting results [23, 34, 36, 37]. In studies comparing HCV mono-infected and HCV/HIV co-infected patients, HCV/HIV co-infected patients were associated with significantly lower HR-QoL and lower gain in the HR-QoL scores [21, 22]. Our study design aimed to inform real-world impact of sofosbuvir and daclatasvir combination treatment in a younger and mainly former IVDU population.
We found that the improvements were observed across most of HR-QoL domains in both WHOQOL-HIV BREF and SF-36. This finding provides additional evidence that DAA treatment has a positive influence on HCV/HIV co-infected patients on cART [13, 23, 34, 37, 38]. Improvements were not observed in some domains when comparing 12 weeks after treatment scores with baseline scores. Longer study duration and more follow-up timepoints could show potential benefits in more domains.
Using multivariate analyses, we determined several baseline predictors of several WHOQoL-HIV BREF domain changes 12 weeks after treatment completion. We found that male patients had improved their level of independence 4 times higher than female patients after DAA treatment, which is consistent with previous studies in male HIV patients [39–41]. Most female patients in our study were married and not working despite being highly educated. Tesfay, et al [42] showed that monthly income was an independent predictor of poor HR-QoL among female HIV patients. We also found that having normal BMI was associated with better improvement in level of independence compared to being overweight/obese. This result is aligned with a study in Southern Ethiopia that showed normal BMI significantly improved QoL score of HIV-infected patients. Protection from infectious diseases, improvement of health status, and the ability to live a productive life are promoted by better nutritional status.[43] Moreover, people with obesity have higher risk of having mobility disability, eventuating a higher risk of becoming unemployed [44, 45].
Lower improvement of overall perception of QoL was noticed in patients with higher baseline HCV-RNA. HCV viremia has been associated with depression and fatigue [46]. Younossi, et al [34]. found that in HCV/HIV co-infected patients, continuous viremia was associated with substantial impairment in QoL. However, we did not observe differences of any HR-QoL changes in SVR responders compared to non-responders. All patients were well-informed of the high success rate of these expensive but free drugs. Though the final questionnaires were delivered before HCV-RNA results came out, many patients were confident of their treatment success. Yeung, et al, demonstrated that those achieving an SVR had higher HR-QoL scores over time. Only 38% participants in that study achieved SVR, 30% did not respond, 13% had ongoing treatment, and 17% had unknown treatment response [38]. Our study had a much higher treatment response (95.5%), but the shorter period of HR-QoL evaluation might be insufficient. A longer duration of evaluation might be needed to see further impact of SVR as another study with high treatment response found modest immediate improvement following SVR, then continued thereafter [38].
Overall perception of health significantly improved after treatment in our study, and this effect was more prevalent in smokers. Our finding contradicted with Toghianifar, et al [47] study that showed overall QoL among current and past smokers was decreased relative to non-smokers. Some evidence of disparaging behaviour towards relative risk of lung cancer on smoker population might explain this finding [48]. We also observed a significant reduction on spiritual/religion belief domain compared to baseline, and this effect was higher in smokers. Highly successful treatment belief might influence our participants’ perception of health and spiritual, since patients did not know their HCV-RNA results when they filled in their final questionnaires. As they had used cART for a median of 9 years and knew their untreated HCV status for a long time, completing DAA treatment would be considered as morbidity risk reduction for these patients despite their smoking status. Evidence has shown that smoking behaviour was significantly related to religious involvement (religious attendance, importance, religious/spiritual comfort-seeking, and religious/spiritual decision-making). Higher religious involvement was linked with a lower risk of being persistent or ex-smoker [49]. Islam as a dominant religion among participants (78.6%) might also play a role in this finding as smoking is considered as a discouraged act (mukrooh) in Islamic law [50].
We proceeded to determine baseline predictors of several SF-36 domain changes 12 weeks after treatment completion in the studied population. Similar to other reports, we demonstrated a significant rise in the general health domain [34, 51]. Positive relationships between general health increase with male gender and stage F0-F1 fibrosis were also noticed. This gender association was in line with the level of independence domain in WHOQoL-HIV BREF. Younossi et al also confirmed a similar increase of general health among stage F0-F1 fibrosis in HCV mono-infected patients treated with sofosbuvir and ledipasvir [52].
Limitations
There are several limitations to our study. Firstly, the study was done in a tertiary center and the population size was not large enough to acquire conclusive results of certain subanalyses. However, we were able to evaluate 81% of the patients who received treatment during the study period. Since it was done in the early phase of free DAA treatment program in Indonesia, we believe that these encouraging results would endorse the expansion of the program. Secondly, we only used WHOQoL-HIV BREF and RAND SF-36 whereas many studies use multiple instruments [53–57]. Moreover, we did not evaluate depression and anxiety as other factors that could be potentially related to QoL.
Despite those limitations, our study could give a standing point for future research on QoL studies and health outcome improvement among HCV/HIV co-infected patient. These findings provide information about QoL and some influencing factors among HCV/HIV co-infected patients in Indonesia where studies in these cohorts are still limited.