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Oyomopito R.,University of New South Wales | Lee M.P.,Queen Elizabeth Hospital | Phanuphak P.,Red Cross | Lim P.L.,Tan Tock Seng Hospital | And 15 more authors.
HIV Medicine

Objectives: Surrogate markers of HIV disease progression are HIV RNA in plasma viral load (VL) and CD4 cell count (immune function). Despite improved international access to antiretrovirals, surrogate marker diagnostics are not routinely available in resource-limited settings. Therefore, the objective was to assess effects of economic and diagnostic resourcing on patient treatment outcomes. Methods: Analyses were based on 2333 patients initiating highly active antiretroviral therapy (HAART) from 2000 onwards. Sites were categorized by World Bank country income criteria (high/low) and annual frequency of VL (≥3, 1-2 or <1) or CD4 (≥3 or <3) testing. Endpoints were time to AIDS/death and change in CD4 cell count and VL suppression (<400 HIV-1 RNA copies/mL) at 12 months. Demographics, Centers for Disease Control and Prevention (CDC) classification, baseline VL/CD4 cell counts, hepatitis B/C coinfections and HAART regimen were covariates. Time to AIDS/death was analysed by proportional hazards models. CD4 and VL endpoints were analysed using linear and logistic regression, respectively. Results:Increased disease progression was associated with site-reported VL testing less than once per year [hazard ratio (HR)=1.4; P=0.032], severely symptomatic HIV infection (HR=1.4; P=0.003) and hepatitis C virus coinfection (HR=1.8; P=0.011). A total of 1120 patients (48.2%) had change in CD4 cell count data. Smaller increases were associated with older age (P<0.001) and 'Other' HIV source exposures, including injecting drug use and blood products (P=0.043). A total of 785 patients (33.7%) contributed to the VL suppression analyses. Patients from sites with VL testing less than once per year [odds ratio (OR)=0.30; P<0.001] and reporting 'Other' HIV exposures experienced reduced suppression (OR=0.28; P<0.001). Conclusion: Low measures of site resourcing were associated with less favourable patient outcomes, including a 35% increase in disease progression in patients from sites with VL testing less than once per year. © 2010 British HIV Association. Source

Sungkanuparph S.,Mahidol University | Oyomopito R.,University of New South Wales | Sirivichayakul S.,Chulalongkorn University | Sirisanthana T.,Research Institute for Health science | And 7 more authors.
Clinical Infectious Diseases

(See editorial commentary by Jordan on pages 1058-1060.)Of 682 antiretroviral-naïve patients initiating antiretroviral therapy in a prospective, multicenter human immunodeficiency virus type 1 (HIV-1) drug resistance monitoring study involving 8 sites in Hong Kong, Malaysia, and Thailand, the prevalence of patients with ≥1 drug resistance mutation was 13.8%. Primary HIV drug resistance is emerging after rapid scaling-up of antiretroviral therapy use in Asia. © 2011 The Author. Source

Ahn J.Y.,Yonsei University | Boettiger D.,University of New South Wales | Law M.,University of New South Wales | Kumarasamy N.,Chennai Antiviral Research and Treatment Clinical Research Site CART CRS | And 19 more authors.
Journal of Acquired Immune Deficiency Syndromes

Background: Current treatment guidelines for HIV infection recommend routine CD4+ lymphocyte (CD4) count monitoring in patients with viral suppression. This may have a limited impact on influencing care as clinically meaningful CD4 decline rarely occurs during viral suppression. Methods: In a regional HIV observational cohort in the Asia-Pacific region, patients with viral suppression (2 consecutive viral loads <400 copies/mL) and a CD4 count ≥200 cells per microliter who had CD4 testing 6 monthly were analyzed. Main study end points were occurrence of 1 CD4 count <200 cells per microliter (single CD4 <200) and 2 CD4 counts <200 cells per microliter within a 6-month period (confirmed CD4 <200). A comparison of time with single and confirmed CD4 <200 with biannual or annual CD4 assessment was performed by generating a hypothetical group comprising the same patients with annual CD4 testing by removing every second CD4 count. Results: Among 1538 patients, the rate of single CD4 <200 was 3.45/100 patient-years and of confirmed CD4 <200 was 0.77/100 patient-years. During 5 years of viral suppression, patients with baseline CD4 200-249 cells per microliter were significantly more likely to experience confirmed CD4 <200 compared with patients with higher baseline CD4 [hazard ratio, 55.47 (95% confidence interval: 7.36 to 418.20), P < 0.001 versus baseline CD4 ≥500 cells/μL]. Cumulative probabilities of confirmed CD4 <200 was also higher in patients with baseline CD4 200-249 cells per microliter compared with patients with higher baseline CD4. There was no significant difference in time to confirmed CD4 <200 between biannual and annual CD4 measurement (P = 0.336). Conclusions: Annual CD4 monitoring in virally suppressed HIV patients with a baseline CD4 ≥250 cells per microliter may be sufficient for clinical management. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. Source

Mulligan K.,University of California at San Francisco | Glidden D.V.,University of California at San Francisco | Anderson P.L.,University of Colorado at Denver | Liu A.,University of California at San Francisco | And 15 more authors.
Clinical Infectious Diseases

Background. Daily preexposure prophylaxis (PrEP) with oral emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) decreases the risk of human immunodeficiency virus (HIV) acquisition. Initiation of TDF decreases bone mineral density (BMD) in HIV-infected people. We report the effect of FTC/TDF on BMD in HIV-seronegative men who have sex with men and in transgender women. Methods. Dual-energy X-ray absorptiometry was performed at baseline and 24-week intervals in a substudy of iPrEx, a randomized, double-blind, placebo-controlled trial of FTC/TDF PrEP. Plasma and intracellular tenofovir concentrations were measured in participants randomized to FTC/TDF. Results. In 498 participants (247 FTC/TDF, 251 placebo), BMD in those randomized to FTC/TDF decreased modestly but statistically significantly by 24 weeks in the spine (net difference, -0.91% [95% confidence interval {CI}, -1.44% to -.38%]; P =. 001) and hip (-0.61% [95% CI, -.96% to -.27%], P =. 001). Changes within each subsequent 24-week interval were not statistically significant. Changes in BMD by week 24 correlated inversely with intracellular tenofovir diphosphate (TFV-DP), which was detected in 53% of those randomized to FTC/TDF. Net BMD loss by week 24 in participants with TFV-DP levels indicative of consistent dosing averaged -1.42% ± 29% and -0.85% ± 19% in the spine and hip, respectively (P <. 001 vs placebo). Spine BMD tended to rebound following discontinuation of FTC/TDF. There were no differences in fractures (P =. 62) or incidence of low BMD. Conclusions. In HIV-uninfected persons, FTC/TDF PrEP was associated with small but statistically significant decreases in BMD by week 24 that inversely correlated with TFV-DP, with more stable BMD thereafter. © 2015 The Author 2015. Source

Prybylski D.,Thailand MOPH U.S. CDC Collaboration | Prybylski D.,Centers for Disease Control and Prevention | Manopaiboon C.,Thailand MOPH U.S. CDC Collaboration | Visavakum P.,Thailand MOPH U.S. CDC Collaboration | And 10 more authors.
Drug and Alcohol Dependence

Background: Thailand's long-standing HIV sero-sentinel surveillance system for people who inject drugs (PWID) is confined to those in methadone-based drug treatment clinics and representative data are scarce, especially outside of Bangkok. Methods: We conducted probability-based respondent-driven sampling (RDS) surveys in Bangkok (n = 738) and Chiang Mai (n = 309) to increase understanding of local HIV epidemics and to better inform the planning of evidence-based interventions. Results: PWID had different epidemiological profiles in these two cities. Overall HIV prevalence was higher in Bangkok (23.6% vs. 10.9%, p < 0.001) but PWID in Bangkok are older and appear to have long-standing HIV infections. In Chiang Mai, HIV infections appear to be more recently acquired and PWID were younger and had higher levels of recent injecting and sexual risk behaviors with lower levels of intervention exposure. Methamphetamine was the predominant drug injected in both sites and polydrug use was common although levels and patterns of the specific drugs injected varied significantly between the sites. In multivariate analysis, recent midazolam injection was significantly associated with HIV infection in Chiang Mai (adjusted odds ratio = 8.1; 95% confidence interval: 1.2-54.5) whereas in Bangkok HIV status was not associated with recent risk behaviors as infections had likely been acquired in the past. Conclusion: PWID epidemics in Thailand are heterogeneous and driven by local factors. There is a need to customize intervention strategies for PWID in different settings and to integrate population-based survey methods such as RDS into routine surveillance to monitor the national response. © 2015. Source

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