Red Cross AIDS Research Centre Research Articles

Tracking coreceptor switch of the transmitted/founder HIV-1 identifies co-evolution of HIV-1 antigenicity, coreceptor usage and CD4 subset targeting: the RV217 acute infection cohort study

The CCR5 (R5) to CXCR4 (X4) coreceptor switch in natural HIV-1 infection is associated with faster progression to AIDS, but the mechanisms remain unclear. The difficulty in elucidating the evolutionary origin of the earliest X4 viruses limits our understanding of this phenomenon. We tracked the evolution of the transmitted/founder (T/F) HIV-1 in RV217 participants identified in acute infection. The origin of the X4 viruses was elucidated by single genome amplification, deep sequencing and coreceptor assay. Mutations responsible for coreceptor switch were confirmed by mutagenesis. Viral susceptibility to neutralization was determined by neutralization assay. Virus CD4 subset preference was demonstrated by sequencing HIV-1 RNA in sorted CD4 subsets. We demonstrated that the earliest X4 viruses evolved de novo from the T/F strains. Strong X4 usage can be conferred by a single mutation. The mutations responsible for coreceptor switch can confer escape to neutralization and drive the X4 variants to replicate mainly in the central memory (CM) and naïve CD4 subsets. Likely due to the smaller viral burst size of the CM and naïve subsets, the X4 variants existed at low frequency in plasma. The origin of the X4 viruses preceded accelerated CD4 decline. All except one X4 virus identified in the current study lost the conserved V3 N301 glycan site. The findings demonstrate co-evolution of HIV-1 antigenicity, coreceptor usage and CD4 subset targeting which have implications for HIV-1 therapeutics and functional cure. The observations provide evidence that coreceptor switch can function as an evolutionary mechanism of immune evasion. Institute of Human Virology, National Institutes of Health, Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc, Thai Red Cross AIDS Research Centre, Gilead Sciences, Merck, and ViiV Healthcare.

Characteristics of suboptimal immune response after initiating antiretroviral therapy among people living with HIV with a pre-treatment CD4 T cell count

BackgroundComplete recovery of the CD4 T cell count is uncommon among chronically HIV-infected individuals with very low pre-treatment CD4 count. We studied the prevalence of chronically immune recovery and its associated factors including immune characteristics chronic HIV-infected Thais. MethodsTreatment-naïve participants (n ​= ​375) from the HIV-NAT 006 cohort with a pre-treatment CD4 T cell count after initiating antiretroviral therapy (ART) and having achieved a suppressed viremia (HIV-RNA level ​< ​400 copies/mL) were retrospectively followed at the Thai Red Cross AIDS Research Centre, Bangkok, Thailand. Suboptimal immune recovery (SIR) was defined as having a CD4+ T cell count <200 ​cells/mm3 for 3 years after ART initiation. A case-control sub-study matched for age, sex and pre-ART CD4 T cell count was conducted to compare immunological characteristics between SIR (n ​= ​17) and non-SIR (n ​= ​24) participants. Immunological biomarkers such as interleukin-7 (IL-7) and soluble CD14 (sCD14) and other covariates including cytomegalovirus (CMV) DNA level, baseline hemoglobin level, hepatitis B and C co-infections, and T cell subsets associated with immune activation and exhaustion were evaluated. ResultsAmong 375 participants with pre-ART CD4 T cell counts < 200 ​cells/mm3, the prevalence of SIR was 39.7%, 19.7% and 7.7% at years 1, 2 and 3 after starting ART, respectively. In a multivariate analysis, a pre-ART CD4 T cell count ≤100 ​cells/mm3 (adjusted odds ratio [aOR] 9.45, 95% CI 2.92–30.61, p ​< ​0.001), older age (aOR 1.07, 95% CI 1.01–1.13, p ​= ​0.029) and baseline HIV-RNA level (aOR 0.36, 95% CI 0.21–0.59, p ​< ​0.001) were independently associated with SIR at year 3 after ART initiation. In the matched case-control sub-study (cases ​= ​17, controls ​= ​24), there was a higher prevalence of hepatitis C co-infection (18.8% vs. 0%, p ​= ​0.05), lower sCD14 levels (mean, 6.23 vs. 6.27 log10 ​pg/mL, p ​= ​0.04), lower CD8 T cell counts (mean, 514 vs. 876, p ​= ​0.0003), lower CD4/CD8 T cell ratio (mean, 0.27 vs. 0.41, p ​= ​0.01) and higher expression of PD1 on CD8+ T cells (74.2% vs. 65.1%, p ​= ​0.02) observed in SIR participants compared to their non-SIR counterparts at year 3 after ART initiation. ConclusionsNearly 10% of the study participants who had achieved virological suppression failed to recover a CD4 T cell count > 200 cells/mm3 after 3 years of ART which was with a very low pre-ART CD4 T cell count and older age. The long-term clinical outcomes of SIR participants need to be further explored.

Safety and efficacy of VRC01 broadly neutralising antibodies in adults with acutely treated HIV (RV397): a phase 2, randomised, double-blind, placebo-controlled trial

HIV-1-specific broadly neutralising antibodies such as VRC01 could promote HIV remission by halting viral replication and clearing infected cells. We investigated whether VRC01 could promote sustained viral control off antiretroviral therapy (ART) in adults who initiated ART during acute HIV infection. We did a randomised, double-blind, placebo-controlled trial at the Thai Red Cross AIDS Research Centre in Bangkok, Thailand. Eligible participants were aged 20-50 years, had initiated ART during acute infection (ie, Fiebig stages I-III), had been taking ART for more than 24 months, had fewer than 50 HIV-1 RNA copies per mL on three consecutive measurements, had more than 400 CD4 cells per μL, had fewer than ten copies of integrated HIV-1 DNA per 106 peripheral blood mononuclear cells, and were in generally good health. Eligible participants were randomly assigned (3:1) based on computer-generated lists with a blocking factor of 4 to receive VRC01 (40 mg/kg) or placebo (saline) intravenously every 3 weeks for up to 24 weeks during analytic interruption of ART, followed by continued observation off all therapies. Randomisation was stratified by Fiebig stage (I vs II vs III) at HIV diagnosis. Participants were monitored closely and resumed ART if 1000 or more HIV-1 RNA copies were detected per mL of plasma. The primary outcomes were the frequency of serious adverse events and the proportion of participants with fewer than 50 HIV-1 RNA copies per mL 24 weeks after treatment interruption. Efficacy analyses included all participants who received at least one full dose of study product, and safety analyses included all participants exposed to any study product. The trial was registered with ClinicalTrials.gov, number NCT02664415. This trial is completed. Between Aug 8, 2016, and Jan 9, 2017, 19 men were randomly assigned, 14 to the VRC01 group and five to the placebo group. One participant in the VRC01 group received a partial infusion without undergoing treatment interruption. The other 18 participants all received at least one full study infusion and underwent ART interruption. No serious adverse events were reported in either group. Only one participant in the VRC01 group achieved the primary efficacy endpoint of viral suppression 24 weeks after ART interruption. The other 17 restarted ART because of a confirmed recording of 1000 or more HIV-1 RNA copies per mL before 24 weeks. VRC01 monotherapy in individuals who initiated ART during acute HIV infection was well tolerated but did not significantly increase the number of participants with viral suppression 24 weeks after ART interruption. Further development of VRC01 and other immunotherapies for HIV will probably occur as part of combination regimens that include several treatments directed against unique therapeutic targets. US Department of the Army, US National Institutes of Health, and the Thai Red Cross AIDS Research Centre.

Oral manifestations, salivary flow rates and Candida species in Thai HIV-infected patients.

BackgroundEffects of various Highly Active Antiretroviral Therapy (HAART) regimens on oral heath are unclear. Objectives: We aimed to evaluate effects of HAART on oral manifestations, salivary flow rates (SFR) and Candida species in HIV-infected patients who took mostly non-protease inhibitor-based HAART regimens.Material and MethodsA cross-sectional study was performed on HIV-infected patients taking and never taken HAART who attended Thai Red Cross AIDS Research Centre (n = 48). Non-HIV subjects were recruited as control (n = 20). Oral conditions and salivary flow rates were evaluated using oral examination and measurement of unstimulated and stimulated saliva. In addition, Candida colonization counts (colony forming units; CFUs) and Candida species from the collected saliva were evaluated using CHROMagar.ResultsThe most common oral manifestation in HIV-infected subjects taking HAART was hyperpigmentation. Unstimulated and stimulated SFR among the three groups were not statistically significant. Candida colonization was detected in 64%, 65% and 35% of HIV-infected subjects taking HAART, HAART-naïve, and non-HIV subjects, respectively. While 20% and 35% of HIV-infected subjects with and without HAART, respectively, had Candida CFUs higher than 500/ml, all non-HIV carriers had Candida CFUs lower than 500/ml. The most common Candida colonization species was C. albicans in HAART and non-HIV groups. Interestingly, HAART-naïve group was colonized more by non-albicans species.ConclusionsHAART has minimal effects on oral health. While HAART may not prevent Candida colonization, it might lead to reduction of non-albicans species. Because maintaining low Candida counts is important, HAART administration and antifungal sensitivity test should be considered in HIV-infected patients. Key words:HIV, Candida, HAART, Oral manifestation, Salivary flow rates.

Same-Day Antiretroviral Therapy Initiation Hub Model at the Thai Red Cross Anonymous Clinic in Bangkok, Thailand: High Levels of Acceptability, Long-Term Retention, and Viral Load Suppression

Background: WHO has recommended rapid antiretroviral therapy (ART) initiation, including same-day ART (SDART). However, data on the feasibility in real-world settings are limited. We implemented a cohort study at a stand-alone HIV testing center using initiation hub model to examine its applicability and effectiveness. Methods: We collected data from the Thai Red Cross Anonymous Clinic in Bangkok, Thailand, from clients who were ART-naive and could return for follow-up visits (logistical criteria). Baseline laboratory tests and chest x-ray were performed according to national guidelines, and clinical eligibility was determined based only on physical examination and chest x-ray finding. Acceptability and care linkage were assessed, as well as viral load (VL) suppression and retention in care three, six, and 12 months after ART initiation. Historical data from clients at the same venue between February 2015 to June 2017 were used to compare ART initiation after HIV diagnosis and VL suppression with SDART clients by using Cox proportional-hazards model. Findings: Between July 2017 and July 2018, 2,427 people tested HIV-positive at the clinic, and 2,107 met logistical criteria. Of these, 1,904 (90·4%) agreed to SDART. 1,624 (85·3%) were placed on ART, and 77·4% (1,251/1,624) received same-day initiation. 92·8% (1,198/1,291) were successfully referred to sustained ART sites. Retention at month three, six, and 12 was 93·3% (1,211/1,289), 89·0% (757/851), and 92·1% (70/76), respectively. When compared to historical data, the hazard ratios to ART initiation after HIV diagnosis and viral load suppression among SDART clients were 3·6 (95%CI:3·4-3·8;p<0·001), and 2·1 (95%CI:1·8- 2·3;p<0·001), respectively. Interpretation: Same-Day ART at a stand-alone HIV testing center in an urban setting in Bangkok, Thailand, is highly feasible, and improves ART uptake and viral load suppression. Funding Statement: The United States Agency for International Development (USAID), the U.S. President's Emergency Plan for AIDS Relief (PEPFAR), and the Thai Red Cross AIDS Research Centre. Declaration of Interests: All authors declare no competing interests related to this work. Ethics Approval Statement: This study was approved by the Institutional Review Board of Chulalongkorn University.

Noncirrhotic Portal Hypertension in Perinatally HIV-infected Adolescents Treated With Didanosine-containing Antiretroviral Regimens in Childhood.

Noncirrhotic portal hypertension (NCPH) has been reported in HIV-infected adults. Antiretroviral drugs, as well as genetic and thrombophilic predisposition, have been suggested as possible etiologic factors. Clinical data were collected from 6 HIV-infected patients attending the Infectious Diseases Departments at respectively Emma Children's Hospital Academic Medical Centre in Amsterdam, The Thai Red Cross AIDS Research Centre, Bangkok, Imperial College Healthcare NHS Trust, London who were diagnosed with NCPH. All underwent extensive blood analysis, liver ultrasound, liver elastography, esophagogastroduodenoscopy and percutaneous needle liver biopsy for histological evaluation. We describe 6 perinatally HIV-infected adolescents, all female, who developed NCPH after prolonged exposure during childhood to a didanosine-containing antiretroviral regimen. Histology and electron microscopy showed periportal fibrosis and mitochondrial damage as key findings in their liver biopsies. One of these 6 patients required surgical intervention, the remainder have been managed conservatively to date. Thus, symptomatic NCPH may present in adolescence after perinatally acquired HIV-1 infection. In this case series, risk factors included female sex and prolonged exposure to antiretroviral regimens that included the nucleoside-analogue didanosine in childhood.

A qualitative assessment of barriers and facilitators to antiretroviral adherence in Thai patients

ObjectivesExcellent adherence to combination antiretroviral therapy can suppress HIV replication and produce life expectancies nearing those of individuals without HIV infection. This qualitative study sought to identify the barriers and facilitators to good antiretroviral medication adherence in Thai patients living with HIV. MethodsSemi-structured interviews were conducted with a convenience sample (n=21) of patients attending routine clinic visits at Srinagarind Hospital in Khon Kaen, or HIV-NAT, the Thai Red Cross AIDS Research Centre in Bangkok. ResultsMedian informant age was 43 years (range 27–60 years) and 43% were female. We identified key facilitators and barriers to adherence among HIV-infected Thai patients along three major themes (patient-related, health system-related and medication-related). Stigma was a primary concern for most informants, operating throughout Thai society to induce feelings of shame for Thai people living with HIV. Determination to stay healthy and incorporate taking cART into their daily routine were key components of good adherence. Supportive and trusting relationships, particularly with the clinic team, empowered patients to maintain good medication adherence. ConclusionsChanging public perceptions about HIV, and training of HIV clinic staff on the importance of trusting and supportive provider–patient relationships in promoting good health outcomes, will help Thailand achieve its aim of having zero new HIV infections, zero discrimination and zero AIDS-related deaths by 2030.

Innovative strategies using communications technologies to engage gay men and other men who have sex with men into early HIV testing and treatment in Thailand

ObjectivesOne-in-three men who have sex with men (MSM) surveyed between 2007 and 2010 in Bangkok were HIV infected; 54% of new infections in Thailand are expected to be among MSM. Although MSM are the top internet-accessing population in Thailand, it has not been optimally used to scale up early HIV testing and counselling (HTC) and linkage to treatment. Thailand needs innovative technology-based strategies to help address the exploding epidemic of HIV among gay men and other MSM. MethodsAdam's Love, an innovative web-based communications strategy, was launched in 2011 by the Thai Red Cross AIDS Research Centre. It includes a dedicated website, integrated social media and web message boards for online counselling, recruitment and appointment making, a club membership programme offering non-financial incentives for HTC, targeted marketing and promotions, and collaboration with MSM-friendly clinics and private hospitals to improve accessibility of HTC services. ResultsBetween September 2011 and January 2015, the website engaged 1.69 million viewers, and gained more than 8 million page views. An estimated 11,120 gay men and other MSM received online counselling; 8,288 MSM were referred to HTC services; 1,223 to STI testing services; and 1,112 MSM living with HIV were advised regarding HIV treatment. In total, 1,181 MSM recruited online were enrolled in the club membership programme, and 15.5% were diagnosed with HIV. ConclusionsThe Adam's Love programme has successfully demonstrated the potential for utilising ‘online-to-offline’ recruitment models in Thailand, and has attracted national and regional recognition as a trusted resource on HIV and referral to testing and care.

Correction: HIV DNA Reservoir Increases Risk for Cognitive Disorders in cART-Naïve Patients

There were errors in multiple affiliations for multiple authors. Please see the following correct list of authors and affiliations: Victor G. Valcour 1,2*,Jintanat Ananworanich, 3,4,5,6, Melissa Agsalda 6, Napapon Sailasuta 7, Thep Chalermchai 3, Alexandra Schuetz 8, Cecilia Shikuma 6, Chin-Yuan Liang 6, Supunee Jirajariyavej 9, Pasiri Sithinamsuwan 10, Somporn Tipsuk 3, David B. Clifford 11, Robert Paul 12, James L. K. Fletcher 3, Mary A. Marovich 13, Bonnie M. Slike 14, Victor DeGruttola 15, Bruce Shiramizu 6 1. Memory and Aging Center, Department of Neurology, University of California, San Francisco, CA USA 2. Division of Geriatric Medicine, Department of Medicine, University of California, San Francisco CA, USA 3. SEARCH, Thai Red Cross AIDS Research Centre, Bangkok, Thailand 4. HIV-NAT, Thai Red Cross AIDS Research Center, Bangkok, Thailand 5. Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand 6. Hawaii Center for AIDS, University of Hawaii, Honolulu HI USA 7. Huntington Medical Research Institutes, Pasadena CA USA 8. Department of Retrovirology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand 9. Taksin Hospital, Bangkok, Thailand 10. Division of Neurology, Department of Medicine, Phramongkutklao Hospital, Bangkok, Thailand 11. Department of Neurology, Washington University, St. Louis MO USA 12. Department of Psychology, University of Missouri, St. Louis MO, USA 13. Division of AIDS, National Institute of Allergy and Infection Diseases of the National Institutes of Health, Bethesda MD, USA 14. US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring MD, USA 15. Department of Biostatistics, Harvard School of Public Health, Boston MA, USA

Anal Human Papillomavirus Infection Among Thai Men Who Have Sex With Men With and Without HIV Infection

HIV-positive men who have sex with men (MSM) have a higher prevalence of anal human papillomavirus (HPV) infection and anal cancer incidence than HIV-negative MSM. High-risk HPV persistence is an important risk factor for the development of anal cancer. A total of 123 HIV-positive and 123 HIV-negative MSM were enrolled from the Thai Red Cross AIDS Research Centre in Bangkok, Thailand, and followed for 12 months. Anal sample collection for HPV genotyping was performed at every visit. HPV prevalence, incidence, clearance, and persistence were calculated. A logistic regression model was used to study factors associated with high-risk HPV persistence. The prevalence of any anal HPV infection was 85% in HIV-positive and 58.5% in HIV-negative MSM (P < 0.0001). The prevalence of high-risk HPV infection was 57.5% in HIV-positive and 36.6% in HIV-negative MSM (P = 0.001). HPV 16 was the most common high-risk HPV type. HIV-positive MSM had a higher prevalence (22.5% vs. 9.8%, P = 0.008) and persistence (16.7% vs. 1.3%, P < 0.001) of HPV 16 than HIV-negative MSM and a trend for higher incidence (16.1 vs. 6.1 episodes/1000 person-months, incidence rate ratio 2.6, P = 0.058). HIV infection (odds ratio: 4.45, 95% confidence interval: 2.11 to 9.4, P < 0.001) and smoking in HIV-positive MSM (odds ratio: 2.3, 95% confidence interval: 1.17 to 4.5, P = 0.015) were independently associated with high-risk HPV persistence in multivariate models. In addition to targeting HIV-positive MSM who are at higher risk for anal, high-risk HPV persistence, anal cancer prevention programs should also integrate behavioral interventions such as smoking cessation to modify risk for high-risk HPV persistence.

High prevalence and incidence of high-grade anal intraepithelial neoplasia among young Thai men who have sex with men with and without HIV

Men who have sex with men (MSM) are at elevated risk of having anal cancer. However, the prevalence and incidence among MSM of high-grade anal intraepithelial neoplasia (HGAIN), the putative precursor of anal cancer, is understudied, particularly in Asians. A total of 123 HIV-positive and 123 HIV-negative MSM were enrolled at the Thai Red Cross AIDS Research Centre in Bangkok, Thailand, and followed for 12 months. Anal sample collection for human papillomavirus (HPV) genotyping and high-resolution anoscopy (HRA) with biopsies were performed at every visit. Mean age at enrollment was 28.9 years. HIV-positive MSM were more commonly infected with high-risk HPV types in the anus than HIV-negative MSM (57.5 vs. 36.6%; P = 0.001). The prevalence of HGAIN was 18.9% in HIV-positive and 11.4% in HIV-negative MSM (P = 0.1). The incidence of HGAIN at 12 months was 29% in HIV-positive and 8% in HIV-negative MSM (P = 0.001). The hazard ratios for incident HGAIN in multivariate models were 5.16 [95% confidence interval (CI) 1.89-14.08, P < 0.001] in MSM with persistent HPV 16 and/or 18 infection and 2.62 (95% CI 1.04-6.61, P = 0.042) in HIV-positive MSM. Approximately one-third of HIV-positive MSM developed incident HGAIN within 12 months. Given the relative increased prevalence of HIV among MSM worldwide, local HGAIN data are needed to guide practitioners, policy makers, and communities in planning for strategies to screen for and treat HGAIN in this population.

Impaired neurocognitive function among HIV‐infected Thais on stable antiretroviral therapy for more than 7 years

BackgroundThere are limited data on HIV‐associated neurocognitive disorders (HANDs) from resource‐constraint region and few studies have firm documentation of duration of treatment and suppression of plasma virus. This study aimed to estimate the prevalence of HIV‐related cognitive deterioration among HIV‐infected patients who were on stable ART and to describe the pattern of neurocognitive impairment (NCI), daily life disturbance and associated factors.MethodsThis was a cross‐sectional evaluation of cognition in a sample of HIV adults at HIV‐NAT, the Thai Red Cross AIDS Research Centre with data captured over a 6‐month period. The Montreal Cognitive Assessment (MoCA), International HIV Dementia Scale (IHDS) and Activities of Daily Living Questionnaire (ADLQ) scale were administered. NCI was defined as a score of ≤10 on the IHDS or &lt;26 on the MoCA. The HIV‐NAT Cohort Database was explored to retrieve sociodemographic data and clinical factors.ResultsAmong the 162 patients evaluated, the mean (±SD) age was 42.8 (±7.3) years and 56.8% were male. HBV and HCV co‐infection frequencies were 11.7% and 7.4%, respectively. The mean (±SD) duration of ART was 9.03 (±3.12) years. Of all, 59.3% were concurrently on protease inhibitor (PI) based regimens. 97.5% had virologic success with HIV‐RNA load of less 200 copies/mL. The prevalence of NCI was 68.5% by MoCA and 75.8% by IHDS. Tests on visuospatial cognition, language and abstraction were most commonly poor scores (81.5%, 89.5% and 74.1%, respectively). Among these, 54.9% and 61.3%, respectively, were asymptomatic without overt daily functioning interference. Daily self‐care and household care were the most commonly endorsed daily activity defects (16.7% and 12.3%, respectively). Remaining as a couple (p=0.001), duration of education &lt;12 years (p&lt;0.001) and heterosexual risk (p=0.001) were associated with NCI. The MoCA and IHDS scales correlated to each other (r2=0.177, p=0.024). Logistic regression demonstrated fewer years of education and remaining as a couple were associated with impaired MoCA scale (P=0.001 and 0.008, respectively).ConclusionImpaired cognitive function is commonly detected among HIV‐infected Thais on stable ART for over 7 years. The frequency of NCI is higher than that reported in other settings. However the performance characteristics of our screens have not been firmly established in this setting and the cut‐off levels used may over‐estimate NCI.

Association of fibroblast growth factor 23 and hypophosphatemia in well‐suppressed HIV‐infected patients receiving antiretroviral therapy

IntroductionProlong hypophosphatemia may result in future bone loss which will have effect on patient's quality of life. Hypophosphatemia is observed in 4–31% of HIV‐infected patients receiving highly active antiretroviral therapy (HAART). Fibroblast growth factor 23 (FGF‐23), a potent phosphaturic hormone, has not been well studied in HIV‐infected Thai patients. We aimed to investigate whether FGF‐23 is involved in the etiology of hypophosphatemia in our HIV‐positive patients on HAART.MethodThis study was a case‐controlled study at HIV‐NAT, Thai Red Cross AIDS Research Centre, Bangkok, Thailand during June 2011‐May 2012. Serum and urine phosphate was studied in 696 well‐suppressed HIV‐infected patients. Hypophosphatemia was defined as a serum phosphate level &lt;2.5 mg/dl. All fasting blood and urine samples were taken between 7.00 and 10.00 hr to measure serum phosphate, calcium, 1,25 OHD, parathyroid hormone (PTH), FGF‐23 and urinary phosphate excretion. The renal phosphate threshold tubular maximum phosphate reabsorption per glomerular filtration rate (TmP/GFR) was calculated. eGFR was calculated using the MDRD.ResultsTotally 65 (9.3%) subjects were identified for hypophosphatemia. The prevalence of hypophosphatemia was not difference between TDF exposure [(46/544: 8.5%) and TDF unexposure (19/154: 12.5%), p=0.13]. However, only 56 subjects for a case group (hypophosphatemia group) and 65 subjects with normal phosphate (normophosphatemia group were included in this analysis. In the hypophosphatemia group, they were more likely younger, less female, and lower CD4 cell counts than the control group. About 80% and 74% of the case and control group had TDF exposure, respectively. The renal phosphate reabsorption threshold was significantly lower in hypophosphatemia group than in the control [43 (2.19–2.6) vs 3.16 (2.92–3.61) mg/dl, p&lt;0.001]. FGF‐23 was significantly higher in hypophosphatemia group [31.9 (24.7–40.0) vs 26.2 (19.3–34.1) pg/dl, p&lt;0.017]. TmP/GFR was strongly related to FGF‐23 levels (p&lt;0.04), but not for PTH (p&lt;0.06), and urine calcium (p&lt;0.07).ConclusionFGF‐23 is involved in pathogenesis of hypophosphatemia in our HIV‐positive patients on HAART.

Feasibility and Efficacy of Isoniazid Prophylaxis for Latent Tuberculosis in HIV-Infected Clients Patients in Thailand

A prospective study was conducted in 4339 HIV-positive clients at the Thai Red Cross AIDS Research Centre (TRC-ARC) Anonymous clinic, Bangkok, Thailand between January 2003 and April 2008. A tuberculin skin test (TST) was done for all patients without a previous history of tuberculosis (TB). Nine months of isoniazid (INH) was given for all positive TST/no active TB. TST-negative clients were asked to repeat the TST annually. The study aim was to evaluate the feasibility and efficacy of INH prophylaxis for preventing TB in HIV-positive Thai patients. Of those patients, 4111 (94.7%) had a TST done; 1157 (28.1%) were TST positive and 799 patients started INH prophylaxis. In all, 551 (69%) and 633 (79.2%) patients completed 9 months and 6 months of INH, respectively; 176 (20.2%) patients had a negative TST at baseline and subsequently converted to positive. Only patients with a baseline CD4 >200 cells/μL (p=0.000) and currently on antiretroviral (ARV) treatment (p=0.000) were related to having a positive TST. This baseline CD4 level was also significantly related to higher INH completion rates at 6 months (p=0.000). Interestingly, none of INH completion patients developed active TB. The feasibility of INH prophylaxis in TST-positive patients in this setting is possible. However, the long-term advantage of INH prophylaxis in terms of TB prevention, especially in HIV-1-infected patients on highly active antiretroviral therapy (HAART), is still an issue that needs more research.

Efficacy and Tolerability of Zidovudine 200 mg Twice a Day as Part of Combination Antiretroviral Therapy for 96 Weeks

Efficacy and Tolerability of Zidovudine 200 mg Twice a Day as Part of Combination Antiretroviral Therapy for 96 Weeks

Prevalence of anal squamous intraepithelial lesions in HIV-positive and HIV-negative men who have sex with men in Thailand.

1598 Background: Men who have sex with men (MSM) are at increased risk for high-grade squamous intraepithelial lesions (SIL), the putative precursor to anal cancer. Since 2006, the Thai Red Cross AIDS Research Centre (TRCARC) in Bangkok has offered anal cytology screening to MSM clients. Methods: Demographics, CD4+ T cell count, viral load, and anal cytologic (pap smear) and histologic (biopsy) specimens were collected as available from MSM who attended the TRCARC between February 1, 2008 and November 30, 2009. Chi-square analysis and Student's t-test were used to evaluate risk factors and SIL prevalence. Results: A total of 912 Thai MSM received anal cytology screening. Mean age was 31 years, and 65.8% (n = 600) were HIV-positive. Prevalence of abnormal anal cytology was 18.4%. HIV–positive MSM had higher prevalence of SIL than HIV-negative MSM (23.7% versus 8.3%, p < 0.001). Anal condyloma by clinical examination was detected in 11.2% of HIV-positive and 9.7% of HIV-negative patients (p = 0.496). Among HIV-positive MSM, 15.3% had atypical cells of undetermined significance (ASC- US), 8.2% had low-grade SIL (LSIL), and 0.2% had high-grade SIL (HSIL). Those with SIL were younger (29.9 vs. 32.2 years, p = 0.002) and had lower CD4+ T cell counts (283.9 vs. 372.2 cells/mm3, p < 0.001) than those with normal cytology. Among HIV-negative MSM, the prevalence of ASC-US, LSIL, and HSIL were 5.8%, 1.9%, and 0.6%. In follow-up, 91 MSM underwent a second pap smear, of these 11.0% progressed in cytologic grade, 28.6% regressed, and 60.4% were unchanged. The proportion of MSM with regression or progression of cytology did not differ by HIV infection (p = 0.905). Thirty-six men with SIL had high resolution anoscopy, and 35 underwent biopsy. Histology results were normal (14.3%), or were consistent with HPV infection (17.1%), AIN I (14.3%), AIN II (8.6%), AIN III (8.6%) and condyloma (31.4%). Conclusions: Prevalence of SIL is high among MSM in Thailand. Abnormal cytology was associated with lower CD4+ T-cell count and younger age among HIV-positive MSM. Histology confirmed high prevalence of AIN but did not correspond to pap cytology. Improved detection methods for pre-cancerous anal lesions are needed. No significant financial relationships to disclose.

Factors associated with positive tuberculin skin test results in HIV-1 infected Thai patients

Methods We performed standardized interviews, physical examinations, TST, and laboratory testing on HIV-1 infected Thai patients between September 2006 and January 2008 at the Anonymous Clinic of the Thai Red Cross AIDS Research Centre. All patients had sputum, blood, urine, stool, and, if enlarged, peripheral lymph nodes cultured for TB. A positive TST was defined as ≥5 mm of induration. We analyzed clinical, immunological, and microbiological characteristics associated with positive TST in multivariable logistic regression.

Predictive factors for immunological and virological endpoints in Thai patients receiving combination antiretroviral treatment

Routine CD4 count and HIV viral load monitoring is a financial barrier in developing countries. We assessed factors associated with CD4 counts < or =200 cells/microL and detectable viral load in Thai HIV-infected patients receiving antiretroviral therapy (ART) at the HIV Netherlands Australia Thailand Research Collaboration and the Thai Red Cross AIDS Research Centre (HIV-NAT). Univariate and multivariate Cox proportional hazards models for multiple treatment failures were used to determine factors related to CD4 counts < or =200 cells/microL and detectable viral load. Multivariate Cox proportional hazards models for CD4 counts < or =200 cells/microL were developed with and without viral load in order to build models applicable to contexts in which viral load is not available. Four hundred and seventeen patients were included in the study. Fifty-four per cent were male, and the median CD4 count and log(10) viral load at baseline were 283 cells/microL and 4.3 log(10) HIV-1 RNA copies/mL, respectively. Independent factors related to CD4 count < or =200 cells/microL were CD4 count at baseline [hazards ratio (HR) 0.20/100 cells/microL; 95% confidence interval (CI) 0.17-0.23] and changes in CD4 count (HR 0.22/100 cells/microL; 95% CI 0.17-0.28). Factors in multivariate models (in which viral load was considered for inclusion) were CD4 count at baseline (HR 0.21/100 cells/microL; 95% CI 0.18-0.24), changes in CD4 count (HR 0.25/100 cells/microL; 95% CI 0.19-0.32) and detectable viral load (HR 1.94; 95% CI 1.20-3.13). Predictive factors (independent of viral load) were triple ART or highly active antiretroviral therapy (HAART) (HR 0.28; 95% CI 0.22-0.36) and detectable viral load at baseline (HR 2.96; 95% CI 2.24-3.91). Conclusions CD4 count at baseline and changes in CD4 count were important in predicting CD4 counts < or =200 cells/microL. Triple ART and detectable viral load at baseline were important in predicting detectable viral load.