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      Trends of CD4 cell count levels at the initiation of antiretroviral therapy over time and factors associated with late initiation of antiretroviral therapy among Asian HIV-positive patients

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          Abstract

          Introduction

          Although antiretroviral therapy (ART) has been rapidly scaled up in Asia, most HIV-positive patients in the region still present with late-stage HIV disease. We aimed to determine trends of pre-ART CD4 levels over time in Asian HIV-positive patients and to determine factors associated with late ART initiation.

          Methods

          Data from two regional cohort observational databases were analyzed for trends in median CD4 cell counts at ART initiation and the proportion of late ART initiation (CD4 cell counts <200 cells/mm 3 or prior AIDS diagnosis). Predictors for late ART initiation and mortality were determined.

          Results

          A total of 2737 HIV-positive ART-naïve patients from 22 sites in 13 Asian countries and territories were eligible. The overall median (IQR) CD4 cell count at ART initiation was 150 (46–241) cells/mm 3. Median CD4 cell counts at ART initiation increased over time, from a low point of 115 cells/mm 3 in 2008 to a peak of 302 cells/mm 3 after 2011 ( p for trend 0.002). The proportion of patients with late ART initiation significantly decreased over time from 79.1% before 2007 to 36.3% after 2011 ( p for trend <0.001). Factors associated with late ART initiation were year of ART initiation (e.g. 2010 vs. before 2007; OR 0.40, 95% CI 0.27–0.59; p<0.001), sex (male vs. female; OR 1.51, 95% CI 1.18–1.93; p=0.001) and HIV exposure risk (heterosexual vs. homosexual; OR 1.66, 95% CI 1.24–2.23; p=0.001 and intravenous drug use vs. homosexual; OR 3.03, 95% CI 1.77–5.21; p<0.001). Factors associated with mortality after ART initiation were late ART initiation (HR 2.13, 95% CI 1.19–3.79; p=0.010), sex (male vs. female; HR 2.12, 95% CI 1.31–3.43; p=0.002), age (≥51 vs. ≤30 years; HR 3.91, 95% CI 2.18–7.04; p<0.001) and hepatitis C serostatus (positive vs. negative; HR 2.48, 95% CI 1.−4.36; p=0.035).

          Conclusions

          Median CD4 cell count at ART initiation among Asian patients significantly increases over time but the proportion of patients with late ART initiation is still significant. ART initiation at higher CD4 cell counts remains a challenge. Strategic interventions to increase earlier diagnosis of HIV infection and prompt more rapid linkage to ART must be implemented.

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          Most cited references27

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          Prevalence of intestinal parasitic infections and risk factors among schoolchildren at the University of Gondar Community School, Northwest Ethiopia: a cross-sectional study

          Background Intestinal parasitic infections are among the major public health problems in Sub-Saharan Africa. Their distribution is mainly associated with poor personal hygiene, environmental sanitation and limited access to clean water. Indeed, epidemiological information on the prevalence of various intestinal parasitic infections in different localities is a prerequisite to develop appropriate control measures. Therefore, the aim of this study was to assess the prevalence of intestinal parasitic infections and associated risk factors among schoolchildren. Method This school-based cross-sectional study was undertaken at the University of Gondar Community School from April 2012 to June 2012. Study subjects were selected using a systematic random sampling method. Data were gathered through direct interview by using a pretested questionnaire. The collected stool specimens were examined microscopically for the presence of eggs, cysts and trophozoites of intestinal parasites using direct saline smear and formol-ether concentration methods. Data entry and analysis were done using SPSS version 16 software. Result Out of 304 study subjects, 104 (34.2%) were infected with one or more intestinal parasites. The prevalence rate was 43 (32.1%) for male and 61 (35.9%) for female. The prevalence of intestinal parasites was high in age group of 10–12 years compared to other age groups. The predominant intestinal parasite was Hymenolepis nana, followed by Entamoeba histolytica/dispar and Ascaris lumbricoides with 42 (13.8%), 28 (9.2%), 18 (5.9%), respectively. Hand washing practice and ways of transportation were statistically associated with intestinal parasitic infections. Children in grades 1 to 3 had a higher prevalence of intestinal helminthic infection than those in grades 4 to 8 (p = 0.031). Conclusions Intestinal parasites were prevalent in varying magnitude among the schoolchildren. The prevalence of infections were higher for helminths compared to protozoa. Measures including education on personal hygiene, environmental sanitation, water supply and treatment should be taken into account to reduce the prevalence of intestinal parasites.
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            Long-term immunologic response to antiretroviral therapy in low-income countries: a collaborative analysis of prospective studies.

            Few data are available on the long-term immunologic response to antiretroviral therapy (ART) in resource-limited settings, where ART is being rapidly scaled up using a public health approach, with a limited repertoire of drugs. To describe immunologic response to ART among ART patients in a network of cohorts from sub-Saharan Africa, Latin America, and Asia. STUDY POPULATION/METHODS: Treatment-naive patients aged 15 and older from 27 treatment programs were eligible. Multilevel, linear mixed models were used to assess associations between predictor variables and CD4 cell count trajectories following ART initiation. Of 29 175 patients initiating ART, 8933 (31%) were excluded due to insufficient follow-up time and early lost to follow-up or death. The remaining 19 967 patients contributed 39 200 person-years on ART and 71 067 CD4 cell count measurements. The median baseline CD4 cell count was 114 cells/microl, with 35% having less than 100 cells/microl. Substantial intersite variation in baseline CD4 cell count was observed (range 61-181 cells/microl). Women had higher median baseline CD4 cell counts than men (121 vs. 104 cells/microl). The median CD4 cell count increased from 114 cells/microl at ART initiation to 230 [interquartile range (IQR) 144-338] at 6 months, 263 (IQR 175-376) at 1 year, 336 (IQR 224-472) at 2 years, 372 (IQR 242-537) at 3 years, 377 (IQR 221-561) at 4 years, and 395 (IQR 240-592) at 5 years. In multivariable models, baseline CD4 cell count was the most important determinant of subsequent CD4 cell count trajectories. These data demonstrate robust and sustained CD4 response to ART among patients remaining on therapy. Public health and programmatic interventions leading to earlier HIV diagnosis and initiation of ART could substantially improve patient outcomes in resource-limited settings.
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              Antiretroviral therapy in resource-limited settings 1996 to 2006: patient characteristics, treatment regimens and monitoring in sub-Saharan Africa, Asia and Latin America.

              To describe temporal trends in baseline clinical characteristics, initial treatment regimens and monitoring of patients starting antiretroviral therapy (ART) in resource-limited settings. We analysed data from 17 ART programmes in 12 countries in sub-Saharan Africa, South America and Asia. Patients aged 16 years or older with documented date of start of highly active ART (HAART) were included. Data were analysed by calculating medians, interquartile ranges (IQR) and percentages by regions and time periods. Not all centres provided data for 2006 and 2005 and 2006 were therefore combined. A total of 36,715 patients who started ART 1996-2006 were included in the analysis. Patient numbers increased substantially in sub-Saharan Africa and Asia, and the number of initial regimens declined, to four and five, respectively, in 2005-2006. In South America 20 regimes were used in 2005-2006. A combination of 3TC/D4T/NVP was used for 56% of African patients and 42% of Asian patients; AZT/3TC/EFV was used in 33% of patients in South America. The median baseline CD4 count increased in recent years, to 122 cells/microl (IQR 53-194) in 2005-2006 in Africa, 134 cells/microl (IQR 72-191) in Asia, and 197 cells/microl (IQR 61-277) in South America, but 77%, 78% and 51%, respectively, started with <200 cells/microl in 2005-2006. In all regions baseline CD4 cell counts were higher in women than men: differences were 22cells/microl in Africa, 65 cells/microl in Asia and 10 cells/microl in South America. In 2005-2006 a viral load at 6 months was available in 21% of patients Africa, 8% of Asian patients and 73% of patients in South America. Corresponding figures for 6-month CD4 cell counts were 74%, 77% and 81%. The public health approach to providing ART proposed by the World Health Organization has been implemented in sub-Saharan Africa and Asia. Although CD4 cell counts at the start of ART have increased in recent years, most patients continue to start with counts well below the recommended threshold. Particular attention should be paid to more timely initiation of ART in HIV-infected men.
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                Author and article information

                Journal
                J Int AIDS Soc
                J Int AIDS Soc
                JIAS
                Journal of the International AIDS Society
                International AIDS Society
                1758-2652
                14 March 2014
                2014
                : 17
                : 1
                : 18804
                Affiliations
                [1 ]Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
                [2 ]The Kirby Institute, University of New South Wales, Kensington, NSW, Australia
                [3 ]Queen Elizabeth Hospital, Hong Kong, China SAR
                [4 ]University of Malaya Medical Centre, Kuala Lumpur, Malaysia
                [5 ]National Center for Global Health and Medicine, Toyama Shinjuku-ku, Tokyo, Japan
                [6 ]Tan Tock Seng Hospital, Singapore
                [7 ]TREAT Asia, amfAR – The Foundation for AIDS Research, Bangkok, Thailand
                [8 ]HIV-NAT/Thai Red Cross AIDS Research Centre, Bangkok, Thailand
                [9 ]Research Institute for Tropical Medicine, Manila, Philippines
                [10 ]Research Institute for Health Sciences, Chiang Mai University, Chiang Mai, Thailand
                [11 ]Chiang Rai Prachanukroh Hospital, Chiang Rai, Thailand
                [12 ]Hospital Sungai Buloh, Sungai Buloh, Malaysia
                [13 ]Hospital Raja Perempuan Zainab II, Kota Bharu, Malaysia
                [14 ]National Center for HIV/AIDS, Dermatology & STDs, Phnom Penh, Cambodia
                [15 ]Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
                [16 ]Faculty of Medicine, Udayana University & Sanglah Hospital, Bali, Indonesia
                [17 ]YRG Centre for AIDS Research and Education, Chennai, India
                [18 ]Taipei Veterans General Hospital and AIDS Prevention and Research Centre, National Yang-Ming University, Taipei, Taiwan
                [19 ]Beijing Ditan Hospital, Beijing, China
                [20 ]Bach Mai Hospital, Hanoi, Vietnam
                [21 ]Institute of Infectious Diseases, Pune, India
                [22 ]Division of Infectious Diseases, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
                [23 ]Working Group on AIDS Faculty of Medicine, University of Indonesia, Cipto Mangunkusumo Hospital, Jakarta, Indonesia
                Author notes
                [§ ] Corresponding author: Sasisopin Kiertiburanakul, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, 270 Rama 6 Road, Bangkok 10400, Thailand. Tel: +66 2 201 1581. Fax: +66 2 201 2232. ( sasisopin.kie@ 123456mahidol.ac.th )

                Presented in part at the 20th Conference on Retroviruses and Opportunistic Infections (CROI), 3–6 March 2013, Atlanta (Abstract 1089).

                Article
                18804
                10.7448/IAS.17.1.18804
                3944639
                24598459
                df921c0e-b947-4ca3-9ed5-8bb452eae4dd
                © 2014 Kiertiburanakul S et al; licensee International AIDS Society

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 23 July 2013
                : 06 January 2014
                : 12 February 2014
                Categories
                Research Article

                Infectious disease & Microbiology
                aids,antiretroviral therapy,asia,cd4,hiv,trends
                Infectious disease & Microbiology
                aids, antiretroviral therapy, asia, cd4, hiv, trends

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