Abstract
The World Health Organization guidelines recommend lopinavir/ritonavir (LPV/r) as a second-line antiretroviral therapy (ART) for HIV-infected adults in middle-income and low-income countries as a protease inhibitor boost based on clinical trials; however, the real-world safety and efficacy remain unknown. Therefore, we conducted a large-scale, multicenter retrospective cohort study to evaluate the efficacy and safety of LPV/r-based ART among HIV-infected adults in China in whom first-line therapy failed. The data were obtained from a national database covering 17 clinics in China for six years of follow-up from 2009 to 2016. Failure of first-line treatment was determined according to a viral load at least 400 copies/ml at week 48, non-completers at week 48 for any reason, and those who switched ART before week 48 for any reason such as side effects. Treatment effectiveness was assessed by the rate of CD4+T cell recovery, defined as >500 cells/mm3, and the proportion of patients achieving viral suppression, defined as <400 or <50 copies/ml according to the methods used during treatment. Safety was assessed by rates of LPV/r-related adverse events (AEs), including lipid disorder, severe abnormal liver function, myelosuppression, and renal function. Between 2009 and 2016, 1196 participants (median, 36 years old; IQR, 30–43 years) were ultimately enrolled. All patients had been on LPV/r-based second-line ART treatment for more than one year after failure of any first-line ART regimen. Overall CD4+T cell counts increased from 138 cells/mm3 to 475 cells/mm3 and 37.2% of all participants reached CD4 recovery. Viral suppression rates dramatically increased at the end of the first year (<400 copies/ml, 88.8%; <50 copies/ml, 76.7%) and gradually increased during follow-up (<400 copies/ml, 95.8%; <50 copies/ml, 94.4%). The most frequently reported AEs were LPV/r-induced lipid disorders with no obvious increase on LDL-C at follow-up visits. This is the first real-world LPV/r-based second-line treatment study to cover such a large population in China. These results provide strong clinical evidence that LPV/r-based second-line ART is effective in increasing CD4+T cell counts and viral suppression rates with tolerable side effects in HIV-infected adults in China in whom first-line treatment had failed.
Highlights
Over two thirds of new cases of HIV diagnosed globally in 2017 were estimated to have occurred in resource-limited areas, including eastern and southern Africa, western and central Africa, and Latin America (UNAIDS, 2018)
2078 patients with a viral load below 400 copies/ml at baseline were excluded from the study, leaving a total of 1928 patients in the first-line treatment failure group
A further 53 patients below 18 years of age, 556 patients who were undergoing the second-line treatment for less than 1 year, and 23 duplicate records were excluded, resulting in a total 1196 participants who failed any first-line antiretroviral therapy (ART) regimen and switched to Lopinavir/ ritonavir (LPV/r)-based second-line ART enrolled in the study
Summary
Over two thirds of new cases of HIV diagnosed globally in 2017 were estimated to have occurred in resource-limited areas, including eastern and southern Africa, western and central Africa, and Latin America (UNAIDS, 2018). A recent study presented at the 25th Conference on Retroviruses and Opportunistic Infections (CROI 2018) demonstrated that more than half of all HIV-infected adults in low- and middleincome countries may not achieve and maintain continuous viral suppression under second-line ART. The WHO guidelines recommend second-line combination ART with a ritonavir-boosted protease inhibitor (PI; either lopinavir or atazanavir) combined with at least two nucleoside/ nucleotide reverse transcriptase inhibitors (NRTIs). Boosted PI options are recommended as part of second-line regimens because of their safety and efficacy as indicated by systematic reviews and meta-analyses (Hermes et al, 2012; Huang et al, 2018). There is still no solid real-world evidence for the long-term safety and efficacy of LPV/r as second-line therapy in resource-limited settings
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
