South East Asia Research Collaboration with Hawaii

South East, Thailand

South East Asia Research Collaboration with Hawaii

South East, Thailand
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Shikuma C.M.,University of Hawaii at Manoa | Gerschenson M.,University of Hawaii at Manoa | Ananworanich J.,South East Asia Research Collaboration with Hawaii | Valcour V.G.,University of California at San Francisco | And 11 more authors.
HIV Medicine | Year: 2012

Objectives: Distal leg epidermal nerve fibre density (ENFD) is a validated predictor of small unmyelinated nerve fibre damage and neuropathy risk in HIV infection. As pre-existing damage may increase the risk of neuropathy following antiretroviral (ARV) therapy, particularly when the regimen contains stavudine (d4T), we assessed the relationship between ENFD and various parameters including mitochondrial factors in HIV-infected Thai individuals naïve to ARV therapy. Methods: Distal leg and proximal thigh ENFDs were quantified in HIV-infected Thai individuals without neuropathy prior to randomization to a HIV clinical trial that focused on mitochondrial toxicity issues. We assessed their association with various clinical and immunovirological parameters as well as with peripheral blood mononuclear cell (PBMC) mitochondrial (mt) DNA copies/cell, oxidative phosphorylation (OXPHOS) complex I (CI) and complex IV (CIV) enzyme activities, and mt 8-oxo-deoxyguanine (8-oxo-dG) break frequencies. Results: In 132 subjects, the median (interquartile range) ENFD (fibres/mm) values were 21.0 (16.2-26.6) for the distal leg and 31.7 (26.2-40.0) for the proximal thigh. By linear regression, lower CD4 count (P<0.01), older age (P<0.01), increased body mass index (BMI) (P=0.04), increased height (P=0.02), and higher PBMC OXPHOS activity as measured by CIV activity (P=0.02) were associated with lower distal leg ENFD. Conclusions: Older age, increased height, higher BMI, poorer immunological status and higher PBMC OXPHOS activity are associated with lower distal leg ENFD in HIV-infected subjects free of neuropathy prior to initiation of first-time ARV therapy. © 2012 British HIV Association.

Puthanakit T.,Thailand Research Collaboration HIV National | Puthanakit T.,Chulalongkorn University | Puthanakit T.,Chiang Mai University | Jourdain G.,Chiang Mai University | And 13 more authors.
HIV Medicine | Year: 2010

Objectives: The aim of the study was to assess the prevalence, predictors and patterns of genotypic resistance mutations in children after failure of World Health Organization-recommended initial nonnucleoside reverse transcriptase inhibitor (NNRTI)-based treatment regimens. Methods: We carried out a multicentre retrospective study of genotyping tests performed for all HIV-infected children at eight paediatric centres in Thailand who experienced failure of NNRTI therapy at a time when virological monitoring was not routinely available. Results: One hundred and twenty children were included in the study. Their median age (interquartile range) was 9.1 (6.8-11.0) years, the median duration of their NNRTI regimens was 23.7 (15.7-32.6) months, their median CD4 percentage was 12% (4-20%), and their median plasma HIV RNA at the time of genotype testing was 4.8 (4.3-5.2) log10 HIV-1 RNA copies/mL. The nucleoside reverse transcriptase inhibitor (NRTI) resistance mutations found were as follows: 85% of the children had M184V/I, 23% had at least four thymidine analogue mutations, 12% had the Q151M complex, 5% had K65R, and 1% had the 69 insertion. Ninety-eight per cent of the children had at least one NNRTI resistance mutation, and 48% had etravirine mutation-weighted scores ≥4. CD4 percentage <15% prior to switching regimens [odds ratio (OR) 5.49; 95% confidence interval (CI) 2.02-14.93] and plasma HIV RNA>5 log10 copies/mL (OR 2.46; 95% CI 1.04-5.82) were independent predictors of at least four thymidine analogue mutations, the Q151M complex or the 69 insertion. Conclusions: In settings without routine viral load monitoring, second-line antiretroviral therapy regimens should be designed assuming that clinical or immunological failure is associated with high rates of multi-NRTI resistance and NNRTI resistance, including resistance to etravirine. © 2010 British HIV Association.

PubMed | Red Cross, Queen Savang Vadhana Memorial Hospital, University of Hawaii at Manoa, South East Asia Research Collaboration with Hawaii and 2 more.
Type: Journal Article | Journal: Journal of neurovirology | Year: 2015

Distal leg epidermal nerve fiber density (ENFD) is a validated predictor of HIV sensory neuropathy (SN) risk. We assessed how ENFD is impacted by initiation of first-time antiretroviral therapy (ART) in subjects free of neuropathy and how it is altered when mitochondrial toxic nucleoside medications are used as part of ART. Serial changes in proximal thigh and distal leg ENFD were examined over 72 weeks in 150 Thai subjects randomized to a regimen of stavudine (d4T) switching to zidovudine (ZDV) at 24 weeks vs ZDV vs tenofovir (TDF) for the entire duration of study, all given in combination with nevirapine. We found individual variations in ENFD change, with almost equal number of subjects who decreased or increased their distal leg ENFD over 72 weeks and no relationship to nucleoside backbone or to development of neuropathic signs or symptoms. Lower baseline distal leg ENFD and greater increases in mitochondrial oxidative phosphorylation complex I (CI) activity were associated with larger increases in distal leg ENFD over 72 weeks. Distal leg ENFD correlated with body composition parameters (body surface area, body mass index, height) as well as with blood pressure measurements. Assessed together with a companion cross-sectional study, we found that mean distal leg ENFD in all HIV+ subjects was lower than in HIV- subjects but similar among HIV+ groups whether ART-nave or on d4T with/without neuropathy/neuropathic symptoms. The utility of ENFD as a useful predictor of small unmyelinated nerve fiber damage and neuropathy risk in HIV may be limited in certain populations.

Hulgan T.,Vanderbilt University | Levinson R.T.,Vanderbilt University | Gerschenson M.,University of Hawaii at Manoa | Phanuphak N.,South East Asia Research Collaboration with Hawaii | And 14 more authors.
AIDS | Year: 2014

Objective: We explored associations between mitochondrial DNA (mtDNA) haplogroups, epidermal nerve fiber density (ENFD), and HIV-associated sensory neuropathy (HIV-SN) in a randomized trial of Thai patients initiating antiretroviral therapy (ART). Design: The South East Asia Research Collaboration with Hawaii 003 study evaluated toxicity of nucleoside reverse transcriptase inhibitors (stavudine vs. zidovudine vs. tenofovir). We present secondary analyses of mtDNA haplogroups and ENFD changes. Methods: ENFD, peripheral blood mononuclear cell mitochondrial complex I and IV, and 8-oxo-deoxyguanine (8-oxo-dG) were quantified. Peripheral blood mononuclear cell mtDNA sequences were obtained for haplogroup determination. Multivariate regression of ENFD change was performed. Results: Paired ENFD was available from 118 patients. Median age, CD4+ cell count, and height at entry were 34 years, 172 cells/μl, and 162 cm, respectively. Major haplogroups included M (42%), F (21%), and B (16%). Baseline ENFD, CD4+ cell count, randomized ART, and biomarkers did not differ by haplogroup. Haplogroup B patients were older (P=0.02) at baseline, and had an increase in median ENFD (+1.5 vs. 2.9 fibers/mm; P=0.03) and 8-oxo-dG break frequency (+0.05 vs. 0.00; P=0.05) compared to other haplogroups. In a multivariate model, haplogroup B was associated with increased ENFD (β=3.5, P=0.009) at week 24, whereas older age (P=0.02), higher baseline CD4+ cell count, (P=0.03), higher complex I level (P=0.03), and higher ENFD (P<0.001) at baseline were all associated with decreased ENFD. Three of the six HIV-SN cases were haplogroup B (P=0.05). Conclusions: Thai persons belonging to mtDNA haplogroup B had increased ENFD and 8-oxo-dG on ART, and were more likely to develop HIV-SN. These results suggest that mtDNA variation influences early oxidative damage and ENFD changes. © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Ananworanich J.,South East Asia Research Collaboration with Hawaii | Ananworanich J.,Red Cross | Ananworanich J.,Chulalongkorn University | Ananworanich J.,Armed Forces Research Institute of Medical science United States Component | And 33 more authors.
PLoS ONE | Year: 2012

Background: Limited knowledge exists on early HIV events that may inform preventive and therapeutic strategies. This study aims to characterize the earliest immunologic and virologic HIV events following infection and investigates the usage of a novel therapeutic strategy. Methods and Findings: We prospectively screened 24,430 subjects in Bangkok and identified 40 AHI individuals. Thirty Thais were enrolled (8 Fiebig I, 5 Fiebig II, 15 Fiebig III, 2 Fiebig IV) of whom 15 completed 24 weeks of megaHAART (tenofovir/emtricitabine/efavirenz/raltegravir/maraviroc). Sigmoid biopsies were completed in 24/30 at baseline and 13/15 at week 24. At baseline, the median age was 29 years and 83% were MSM. Most were symptomatic (87%), and were infected with R5-tropic (77%) CRF01_AE (70%). Median CD4 was 406 cells/mm3. HIV RNA was 5.5 log10 copies/ml. Median total blood HIV DNA was higher in Fiebig III (550 copy/106 PBMC) vs. Fiebig I (8 copy/106 PBMC) (p = 0.01) while the median %CD4+CCR5+ gut T cells was lower in Fiebig III (19%) vs. Fiebig I (59%) (p = 0.0008). After 24 weeks of megaHAART, HIV RNA levels of &50 copies were achieved in 14/15 in blood and 13/13 in gut. Total blood HIV DNA at week 0 predicted reservoir size at week 24 (p&0.001). Total HIV DNA declined significantly and was undetectable in 3 of 15 in blood and 3 of 7 in gut. Frequency of CD4+CCR5+ gut T cells increased from 41% at baseline to 64% at week 24 (p>0.050); subjects with less than 40% at baseline had a significant increase in CD4+CCR5+ T cells from baseline to week 24 (14% vs. 71%, p = 0.02). Conclusions: Gut T cell depletion and HIV reservoir seeding increases with progression of AHI. MegaHAART was associated with immune restoration and reduced reservoir size. Our findings could inform research on strategies to achieve HIV drug-free remission. © 2012 Ananworanich et al. 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 author and source are credited.

Edwards-Jackson N.,Columbia University | Kerr S.J.,Red Cross | Kerr S.J.,University of New South Wales | Tieu H.V.,Columbia University | And 11 more authors.
HIV Medicine | Year: 2011

Objective: There is growing concern regarding cardiovascular disease in HIV-infected individuals in developing countries such as Thailand. We evaluated the 10-year risk of coronary heart disease (CHD) in a Thai HIV-infected cohort using three cardiovascular risk equations, and assessed the level of agreement among their predictions. Methods: We carried out a cross-sectional analysis of data on 785 Thai subjects followed prospectively in the HIV Netherlands Australia Thailand Collaboration (HIV-NAT) cohort study from 1996 to 2009. Cardiovascular risk factor history, along with relevant laboratory and clinical data, was collected at follow-up clinic visits. Ten-year risks of CHD were calculated using the Framingham, Ramathibodi-Electricity Generating Authority of Thailand (Rama-EGAT) and Data Collection on Adverse Effects of Anti-HIV Drugs (D:A:D) risk equations. Results: The mean age of the patients was 41.0 years; 55% of the subjects were male. The mean duration of antiretroviral therapy was 7.7 years. The prevalence of cardiovascular risk factors was low, with the most common risk factor being low high-density lipoprotein (HDL) (36.3%). The prevalence of high cardiovascular risk scores (defined as 10-year risk of CHD≥10%) was also low: 9.9, 2.1 and 0.8%, by the Framingham, Rama-EGAT and D:A:D scoring systems, respectively. Only eight subjects (1.0%) had a history of CHD. Bland-Altman plots showed that the Framingham equation predicted a higher risk of CVD compared with the Rama-EGAT and D:A:D equations, which agreed relatively well. Conclusion: The predicted cardiovascular risk in this HIV-infected Thai cohort was relatively low. The agreement among the Rama-EGAT and D:A:D risk scores suggests that both equations may be appropriate estimators of cardiovascular risk in this population. © 2011 British HIV Association.

Schneider K.,University of New South Wales | Puthanakit T.,Red Cross | Puthanakit T.,Chulalongkorn University | Kerr S.,University of New South Wales | And 13 more authors.
AIDS | Year: 2011

Objective: Antiretroviral therapy (ART) management for HIV-infected children is critical in many resource-constrained countries. We investigated the cost-effectiveness and cost-utility of different frequencies of monitoring plasma viral load among HIV-positive children initiating ART in a resource-limited setting. Design/Methods: A stochastic agent-based simulation model was built and directly informed by a cohort of 304 HIV-infected children starting ART in Thailand between 2001 and 2009. The model simulated the expected costs and clinical outcomes over time according to different viral load monitoring frequencies and initiation of second-line therapies when appropriate. Results: The optimal frequency of viral load monitoring was found to be annual, after a single screening at 6 months. Associated costs of viral load monitoring and appropriate ART would approximately triple current treatment costs. Compared with current conditions, a single screening during the first year of ART led to a 58.4% reduction in the total person-years of virological failure with annual monitoring leading to a 76.6% reduction. The incremental cost per quality adjusted life year gained from the optimal monitoring frequency was estimated as US$ 68 084 when including costs of ART and US$ 7224 without ART costs. The estimated cost attributed to preventing 1 year of virological failure was US$ 3393 with ART costs and US$ 359 without ART costs. Conclusion: Even infrequent viral load monitoring is likely to provide substantial clinical benefit to HIV-infected children on ART. Viral load monitoring can be considered cost-effective in many resource-limited settings. However, the costs associated with second-line therapies could be a barrier to its economic feasibility. © 2011 Wolters Kluwer Health - Lippincott Williams & Wilkins.

Tieu H.-V.,Columbia University | Phanuphak N.,Red Cross | Phanuphak N.,South East Asia Research Collaboration with Hawaii | Ananworanich J.,South East Asia Research Collaboration with Hawaii | And 12 more authors.
Sexually Transmitted Diseases | Year: 2010

Limited data are available on circumcision prevalence and acceptability among Thai men to prevent human immunodeficiency virus. Of 408 high-risk heterosexual men, 12.3% were circumcised. 14.2% and 24.9% expressed willingness to be circumcised before and after circumcision education, respectively. Neonatal circumcision acceptability was relatively high. One participant underwent circumcision at 3-month follow-up. Copyright © 2010 American Sexually Transmitted Diseases Association.

Landolt N.K.,HIV Netherlands Australia Thailand Research Collaboration HIV National | Phanuphak N.,Red Cross | Phanuphak N.,South East Asia Research Collaboration with Hawaii | Teeratakulpisarn N.,Red Cross | And 8 more authors.
AIDS Care - Psychological and Socio-Medical Aspects of AIDS/HIV | Year: 2013

Copper intrauterine device (IUD) is not commonly used in many countries, though it provides effective reversible contraception with no or minimal primary systemic side effects. We assessed its uptake and continuation of use among HIV-positive Thai women. Sixty-six of 322 women of reproductive age, whom we approached for the study, met the eligibility criteria. Sterilization (62%) was the main reason for failure to enroll. Twenty-nine of them (44%) underwent IUD insertion. Considering condom use sufficient for pregnancy prevention (12%) was the main reason among eligible women for the refusal to participate in the study. At six months, 54% of enrolled participants reported one or more side effects such as increased menstrual flow (43%), spotting (21%) and dysmenorrhea (11%). The continuation rate of IUD use was high (93%), in spite of the persistent non-systemic side effects. The study showed that copper IUD could be an acceptable contraceptive choice for Thai HIVpositive women. Easy access to the method in a setting linked with the HIV service, and education on IUD risks and benefits is needed to promote the use of IUD in addition to condoms as an effective contraceptive option in HIV-infected women. © 2013 Taylor & Francis.

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