Effectiveness of dolutegravir-based antiretroviral treatment for HIV-2 infection: retrospective observational study from Western India.

BACKGROUND: Data on the use of dolutegravir for treatment of HIV-2 infection are limited. OBJECTIVES: To assess the effectiveness of dolutegravir in people living with HIV-2 (PLHIV-2). METHODS: A retrospective chart review was performed in two clinics in Western India. PLHIV-2 initiated on dolutegravir-based regimens were included. Response to treatment in both treatment-naive (TN) and treatment-experienced (TE; substitution and not in the context of failure) was assessed by CD4 counts and HIV-2 viral load (VL) in a proportion of individuals. The primary objective was to assess immunological effectiveness (absence of a drop in absolute CD4 counts by more than 30% of baseline). Change in absolute CD4 counts was assessed by fitting a mixed-effects model. RESULTS: Sixty-two PLHIV-2 treated with dolutegravir were included. The immunological effectiveness rates (95% CI) were 91.9% (82.4%-96.5%), 92% (81.1%-96.8%) and 91.6% (64.6%-98.5%) amongst all, TE and TN individuals, respectively. Median change in absolute CD4 counts at 6, 12 and 18 months were +29 cells/mm3, +101 cells/mm3 and +72 cells/mm3, respectively. The virological effectiveness rates (HIV-2 VL <100 copies/mL) (95% CI) for all, TE and TN individuals were 88.8% (74.6%-95%), 89.6% (73.6%-96.4%) and 85.7% (48.6%-97.4%), respectively. Three clinical events were documented: spinal tuberculosis, relapsed non-Hodgkin's lymphoma and herpes simplex virus retinitis. One individual reported self-limiting somnolence. CONCLUSIONS: Dolutegravir was well tolerated and associated with immunological, virological and clinical effectiveness in both TN and TE PLHIV-2 in a large cohort from Western India. Dolutegravir-based ART is an excellent option for treatment of individuals with HIV-2 infection.

Changes in renal function with long-term exposure to antiretroviral therapy in HIV-infected adults in Asia.

PURPOSE: Renal disease is common among people living with human immunodeficiency virus (HIV). However, there is limited information on the incidence and risk factors associated with renal dysfunction among this population in Asia. METHODS: We used data from the TREAT Asia HIV Observational Database. Patients were included if they started antiretroviral therapy during or after 2003, had a serum creatinine measurement at antiretroviral therapy initiation (baseline), and had at least 2 follow-up creatinine measurements taken ≥3 months apart. Patients with a baseline estimated glomerular filtration rate (eGFR) ≤60 mL/min/1.73 m2 were excluded. Chronic kidney disease was defined as 2 consecutive eGFR values ≤60 mL/min/1.73 m2 taken ≥3 months apart. Generalized estimating equations were used to identify factors associated with eGFR change. Competing risk regression adjusted for study site, age and sex, and cumulative incidence plots were used to evaluate factors associated with chronic kidney disease (CKD). RESULTS: Of 2547 patients eligible for this analysis, tenofovir was being used by 703 (27.6%) at baseline. Tenofovir use, high baseline eGFR, advanced HIV disease stage, and low nadir CD4 were associated with a decrease in eGFR during follow-up. Chronic kidney disease occurred at a rate of 3.4 per 1000 patient/years. Factors associated with CKD were tenofovir use, old age, low baseline eGFR, low nadir CD4, and protease inhibitor use. CONCLUSIONS: There is an urgent need to enhance renal monitoring and management capacity among at-risk groups in Asia and improve access to less nephrotoxic antiretrovirals.

Higher risk of renal impairment associated with tenofovir use amongst people living with HIV in India: a comparative cohort analysis between Western India and United Kingdom.

BACKGROUND: Data on the renal safety of Tenofovir (TDF) in Low and Middle Income Countries (LMICs) is scarce. We compared development of various forms of renal impairment with use of TDF-containing antiretroviral therapy (ART) between a cohort from the Institute of Infectious Diseases (IID) Pune, Western India and the Royal Free Hospital (RFH) London, UK. METHODS: This is a retrospective analysis of change in estimated glomerular filtration rates (eGFRs) at 6, 12 and 24 months post TDF initiation using the Modification of Diet in Renal Disease (MDRD) equation. In people living with Human Immunodeficiency virus (PLHIV) with pre-TDF eGFR > 90 ml/min/1.73 m2 time to development of and factors associated with progression to eGFR < 60 ml/min/1.73 m2 were calculated using standard survival methods. RESULTS: A total of 574 (59% Caucasian) at the RFH, and 708 (100% Indian ethnicity) PLHIV from IID were included. Baseline median eGFR were similar; RFH 102 (IQR 89, 117), IID 100 (82, 119). At 24 months, mean (SD) decline in eGFR was -7(21) at RFH (p < 0.0001) and -7(40) at IID (p = 0.001). Amongst those with pre-TDF eGFR > 90 ml/min/1.73 m2 PLHIV at IID were more likely to develop an eGFR < 60 ml/min/1.73 m2 (aHR = 7.6 [95% CI 3.4, 17.4] p < 0.0001) and had a faster rate of progression estimated using Kaplan Meier methods. Risk factors included age (per 10 years older: aHR = 2.21 [1.6, 3.0] p < 0.0001) and receiving concomitant ritonavir boosted Protease Inhibitor (PI/r) (aHR = 2.4 [1.2, 4.8] p = 0.01). CONCLUSIONS: There is higher frequency of treatment limiting renal impairment events amongst PLHIV receiving TDF in Western India. As TDF scale up progresses, programs need to develop capacity for monitoring and treatment of renal impairment associated with TDF.