Tenofovir disoproxil fumarate co-administered with lopinavir/ritonavir is strongly associated with tubular damage and chronic kidney disease.

BACKGROUD: With expanding antiretroviral therapy (ART) in a resource-limited setting, the use of second line ART with ritonavir boosted lopinavir (LPV/r) is increasing. However, little is known regarding the renal safety of tenofovir (TDF) co-administered with LPV/r. METHODS: In total 1382 HIV-infected patients were enrolled and data were recorded twice (October 2014 and 2015) in Vietnam. Tubular dysfunction (TD) was defined as urinary beta 2 microglobulin (ß2MG) > 1000 µg/L at both timepoints or increase in ß2MG by > 2000 µg/L. Chronic kidney disease (CKD) was defined as creatinine clearance ≤60 ml/min or urinary protein/creatinine ratio ≥ 0.15 g/gCre at both timepoints. RESULTS: The patients'mean weight and age were 55.9 kg and 38.4 years, respectively, and 41.5% were female. Additionally, 98.2% were on ART, 76.3% were on TDF (mean exposure duration was 35.4 months), and 22.4% had never TDF exposure. TD and CKD were diagnosed in 13% and 8.3% of all patients, respectively. In multivariate analyses, age (OR = 1.057; 95%CI, 1.034-1.081), being female (OR = 0.377; 95%CI, 0.221-0.645), HBsAg positive (OR = 1.812; 95%CI, 1.134-2.894), HCVAb positive (OR = 1.703; 95%CI, 1.100-2.635), TDF exposure (OR = 9.226; 95%CI, 2.847-29.901) and LPV/r exposure (OR = 5.548; 95%CI, 3.313-9.293) were significantly associated with TD. Moreover, age (OR = 1.093; 95%CI, 1.068-1.119), being female (OR = 0.510; 95%CI, 0.295-0.880), weight (OR = 0.909; 95%CI, 0.879-0.939), hypertension (OR = 3.027; 95%CI, 1.714-5.347), TDF exposure (OR = 1.963; 95%CI, 1.027-3.7 53) and LPV/r exposure (OR = 3.122; 95%CI, 1.710-5.699) were significantly associated with CKD. CONCLUSIONS: TDF and LPV/r exposure were strongly associated with TD and CKD, in addition to their known risks. Therefore, attention to renal safety for patients on second line ART is necessary.

Incidence of AIDS-Defining Opportunistic Infections and Mortality during Antiretroviral Therapy in a Cohort of Adult HIV-Infected Individuals in Hanoi, 2007-2014.

BACKGROUND: Although the prognosis for HIV-infected individuals has improved after antiretroviral therapy (ART) scale-up, limited data exist on the incidence of AIDS-defining opportunistic infections (ADIs) and mortality during ART in resource-limited settings. METHODS: HIV-infected adults in two large hospitals in urban Hanoi were enrolled to the prospective cohort, from October 2007 through December 2013. Those who started ART less than one year before enrollment were assigned to the survival analysis. Data on ART history and ADIs were collected retrospectively at enrollment and followed-up prospectively until April 2014. RESULTS: Of 2,070 cohort participants, 1,197 were eligible for analysis and provided 3,446 person-years (PYs) of being on ART. Overall, 161 ADIs episodes were noted at a median of 3.20 months after ART initiation (range 0.03-75.8) with an incidence 46.7/1,000 PYs (95% confidence interval [CI] 39.8-54.5). The most common ADI was tuberculosis with an incidence of 29.9/1,000 PYs. Mortality after ART initiation was 8.68/1,000 PYs and 45% (19/45) died of AIDS-related illnesses. Age over 50 years at ART initiation was significantly associated with shorter survival after controlling for baseline CD4 count, but neither having injection drug use (IDU) history nor previous ADIs were associated with poor survival. Semi-competing risks analysis in 951 patients without ADIs history prior to ART showed those who developed ADIs after starting ART were at higher risk of death in the first six months than after six months. CONCLUSION: ADIs were not rare in spite of being on effective ART. Age over 50 years, but not IDU history, was associated with shorter survival in the cohort. This study provides in-depth data on the prognosis of patients on ART in Vietnam during the first decade of ART scale-up.