Factors associated with primary HIV drug resistance by duration of HIV infection - univariate logistic regression.

<p><b>Abbreviations:</b> HBsAg – hepatitis B surface antigen, anti-HCV – antibody to hepatitis C virus.</p>*<p>p-value is for test for trend (excluding missing values) for age groups, CDC category, and HIV RNA.</p

Distribution of reverse transcriptase resistance-associated mutations among 1,798 antiretroviral-naive HIV-infected patients.

<p>Abbreviations: NRTI; nucleoside reverse transcriptase inhibitor, NNRTI; non-nucleoside reverse transcriptase inhibitor.</p

Distribution of protease resistance-associated mutations among 1,798 antiretroviral-naive HIV-infected patients.

<p>Distribution of protease resistance-associated mutations among 1,798 antiretroviral-naive HIV-infected patients.</p

Baseline characteristics of 1,798 HIV-infected antiretroviral therapy-naïve patients stratified by duration of HIV infection.

<p><b>Abbreviations:</b> HBsAg – hepatitis B surface antigen, anti-HCV – antibody to hepatitis C virus.</p>*<p>p-value calculated for categorical data that did not include missing values, using Chi-square test or Fisher's exact test.</p

Regional distribution of HIV-1 subtypes and recombinants.

<p>The relative proportion of each subtype/recombinant is shown in the pie chart for each country. The data on Figure 1 are from the former studies in the region and estimates made by AVAN Task Force members of the manuscript based on the unpublished data of their own research projects.</p

AIDS Vaccine Trials across Asia to Date.

<p>CDC, Center for Disease Control and Prevention; DoD, Department of Defense; EU, European Union.</p

Renal Dysfunction during Tenofovir Use in a Regional Cohort of HIV-Infected Individuals in the Asia-Pacific

<div><p>Background</p><p>In resource-limited settings, routine monitoring of renal function during antiretroviral therapy (ART) has not been recommended. However, concerns for tenofovir disoproxil fumarate (TDF)-related nephrotoxicity persist with increased use.</p><p>Methods</p><p>We investigated serum creatinine (S-Cr) monitoring rates before and during ART and the incidence and prevalence of renal dysfunction after starting TDF by using data from a regional cohort of HIV-infected individuals in the Asia-Pacific. Time to renal dysfunction was defined as time from TDF initiation to the decline in estimated glomerular filtration rate (eGFR) to <60 ml/min/1.73m² with >30% reduction from baseline using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation or the decision to stop TDF for reported TDF-nephrotoxicity. Predictors of S-Cr monitoring rates were assessed by Poisson regression and risk factors for developing renal dysfunction were assessed by Cox regression.</p><p>Results</p><p>Among 2,425 patients who received TDF, S-Cr monitoring rates increased from 1.01 to 1.84 per person per year after starting TDF (incidence rate ratio 1.68, 95%CI 1.62–1.74, p <0.001). Renal dysfunction on TDF occurred in 103 patients over 5,368 person-years of TDF use (4.2%; incidence 1.75 per 100 person-years). Risk factors for developing renal dysfunction included older age (>50 vs. ≤30, hazard ratio [HR] 5.39, 95%CI 2.52–11.50, p <0.001; and using PI-based regimen (HR 1.93, 95%CI 1.22–3.07, p = 0.005). Having an eGFR prior to TDF (pre-TDF eGFR) of ≥60 ml/min/1.73m² showed a protective effect (HR 0.38, 95%CI, 0.17–0.85, p = 0.018).</p><p>Conclusions</p><p>Renal dysfunction on commencing TDF use was not common, however, older age, lower baseline eGFR and PI-based ART were associated with higher risk of renal dysfunction during TDF use in adult HIV-infected individuals in the Asia-Pacific region.</p></div

Trends in First-Line Antiretroviral Therapy in Asia: Results from the TREAT Asia HIV Observational Database

<div><p>Background</p><p>Antiretroviral therapy (ART) has evolved rapidly since its beginnings. This analysis describes trends in first-line ART use in Asia and their impact on treatment outcomes.</p><p>Methods</p><p>Patients in the TREAT Asia HIV Observational Database receiving first-line ART for ≥6 months were included. Predictors of treatment failure and treatment modification were assessed.</p><p>Results</p><p>Data from 4662 eligible patients was analysed. Patients started ART in 2003–2006 (n = 1419), 2007–2010 (n = 2690) and 2011–2013 (n = 553). During the observation period, tenofovir, zidovudine and abacavir use largely replaced stavudine. Stavudine was prescribed to 5.8% of ART starters in 2012/13. Efavirenz use increased at the expense of nevirapine, although both continue to be used extensively (47.5% and 34.5% of patients in 2012/13, respectively). Protease inhibitor use dropped after 2004. The rate of treatment failure or modification declined over time (22.1 [95%CI 20.7–23.5] events per 100 patient/years in 2003–2006, 15.8 [14.9–16.8] in 2007–2010, and 11.6 [9.4–14.2] in 2011–2013). Adjustment for ART regimen had little impact on the temporal decline in treatment failure rates but substantially attenuated the temporal decline in rates of modification due to adverse event. In the final multivariate model, treatment modification due to adverse event was significantly predicted by earlier period of ART initiation (hazard ratio 0.52 [95%CI 0.33–0.81], p = 0.004 for 2011–2013 versus 2003–2006), older age (1.56 [1.19–2.04], p = 0.001 for ≥50 years versus <30years), female sex (1.29 [1.11–1.50], p = 0.001 versus male), positive hepatitis C status (1.33 [1.06–1.66], p = 0.013 versus negative), and ART regimen (11.36 [6.28–20.54], p<0.001 for stavudine-based regimens versus tenofovir-based).</p><p>Conclusions</p><p>The observed trends in first-line ART use in Asia reflect changes in drug availability, global treatment recommendations and prescriber preferences over the past decade. These changes have contributed to a declining rate of treatment modification due to adverse event, but not to reductions in treatment failure.</p></div

Factors associated with rates of serum creatinine monitoring after ART initiation.

<p>Factors associated with rates of serum creatinine monitoring after ART initiation.</p

First-line ART use by year of initiation (n = 4662).

<p>a) Drug classes. NRTIs not represented as there was a single patient that initiated a regimen without an NRTI; b) NRTI. Not represented are didanosine (2.9% of patients overall) and zalcitabine (0.02%); c) NNRTI. Not represented is rilpivirine (0.13%); d) PI. Not represented are indinavir (0.66%), nelfinavir (0.39%), tipranavir (0.39%), saquinavir (0.17%), fosamprenavir (0.17%) and full-dose ritonavir (0.11%). ART = antiretroviral therapy; NRTI = nucleoside reverse transcriptase inhibitor; NNRTI = non-NRTI; PI = protease inhibitor; 3TC/FTC = lamivudine/emtricitabine; d4T = stavudine; AZT = zidovudine; TDF = tenofovir; ABC = abacavir; EFV = efavirenz; NVP = nevirapine; LPV = lopinavir; ATV = atazanavir; DRV = darunavir.</p