Viraemic-time predicts mortality among people living with HIV on second-line antiretroviral treatment in Myanmar: A retrospective cohort study

Abstract

Introduction Despite HIV viral load (VL) monitoring being serial, most studies use a cross-sectional design to evaluate the virological status of a cohort. The objective of our study was to use a simplified approach to calculate viraemic-time: the proportion of follow-up time with unsuppressed VL above the limit of detection. We estimated risk factors for higher viraemic-time and whether viraemic-time predicted mortality in a second-line antiretroviral treatment (ART) cohort in Myanmar. Methods We conducted a retrospective cohort analysis of people living with HIV (PLHIV) who received second-line ART for a period >6 months and who had at least two HIV VL test results between 01 January 2014 and 30 April 2018. Fractional logistic regression assessed risk factors for having higher viraemic-time and Cox proportional hazards regression assessed the association between viraemic-time and mortality. Kaplan-Meier curves were plotted to illustrate survival probability for different viraemic-time categories. Results Among 1,352 participants, 815 (60.3%) never experienced viraemia, and 172 (12.7%), 214 (15.8%), and 80 (5.9%) participants were viraemic <20%, 20–49%, and 50–79% of their total follow-up time, respectively. Few (71; 5.3%) participants were ≥80% of their total follow-up time viraemic. The odds for having higher viraemic-time were higher among people with a history of injecting drug use (aOR 2.01, 95% CI 1.30–3.10, p = 0.002), sex workers (aOR 2.10, 95% CI 1.11–4.00, p = 0.02) and patients treated with lopinavir/ritonavir (vs. atazanavir; aOR 1.53, 95% CI 1.12–2.10, p = 0.008). Viraemic-time was strongly associated with mortality hazard among those with 50–79% and ≥80% viraemic-time (aHR 2.92, 95% CI 1.21–7.10, p = 0.02 and aHR 2.71, 95% CI 1.22–6.01, p = 0.01). This association was not observed in those with viraemic-time <50%. Conclusions Key populations were at risk for having a higher viraemic-time on second-line ART. Viraemic-time predicts clinical outcomes. Differentiated services should target subgroups at risk for a higher viraemic-time to control both HIV transmission and mortality.

Systematic review on cumulative HIV viraemia among people living with HIV receiving antiretroviral treatment and its association with mortality and morbidity

“…A study from Myanmar reported that among PLHIV with viraemic time of 50–79% or >80%, mortality hazard was almost threefold higher compared with those who were not viraemic during their follow-up time (aHR 2.92 [95% CI 1.21 to 7.10], p=0.02; aHR 2.71 [95% CI 1.22 to 6.01], p=0.01, respectively). 29 In the same study, mortality hazard was not increased in participants with a viraemic time <50% of their follow-up. Similarly, Quiros-Roldan et al.…”

“…Cumulative viraemia was defined as the proportion of the follow-up time on ART under or over a certain VL threshold 16 , 17 , 26 , 27 , 29 , 35–37 , 43 or both 16 , 17 , 26 , 27 , 36 , 37 or as viraemia copy-years (VCY; or a variation of this definition), which estimates the area under a patient's VL curve 23 , 24 , 28 , 32 , 33 , 35 , 38–42 , 44–46 (Table 1 ). The method was first presented by Cole et al.…”

“… 16 , 27–29 , 32 , 33 , 35 , 37–39 , 41 , 42 , 45 Various approaches were used to deal with values below the lower limit of detection (LLD): those were either considered equal to the LLD, 36 , 38 , 40 half the LLD 35 , 39 , 46 or set to zero. 17 , 29 , 32 , 37 , 41 , 42 , 45 …”

“…Studies that used the proportion of time under or over a given VL threshold defined this VL threshold either as the LLD (20–500 copies/ml) 16 , 17 , 26 , 27 , 29 , 36 , 37 or as 1500 copies/ml when transmission risk was studied. 43 …”

Treatment Outcomes After Switching to Second-Line Anti-Retroviral Therapy: Results From the Thai National Treatment Program

“…However, protracted periods of poor adherence with longer viremic time will result in virological and immunological failure and ultimately death. 17 Adjusted Cox regression analyses found the relative mortality risk was elevated by 49% to 75% in people with 1, 2, or ≥2 VL tests >1000 copies/mL during secondline treatment, respectively. The highest proportion of deaths and losses were in the group who had not been taking second-line regimens for long enough to quality for VL testing, or perhaps had disengaged from care, and in this group without a VL test, the adjusted HR for death was 6.40 (95% CI 5.91-6.93).…”