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Background Despite advancements in HIV treatment modalities, HIV-related stigma among healthcare providers (HCPs) persists, impacting people living with HIV. Methodology A cross-sectional research design with a non-probability consecutive sampling technique was used to assess HIV-related stigma, and its association with individual characteristic, fear, and knowledge of HIV among 100 HCPs at a university hospital in Nepal. Results The average age was 29.83 years, with work experience of 84.24 months. The fear score was 14.11, and the HIV knowledge score was 36.74. The stigma reflected a moderate stance. Age ( r s = −0.22, P < .05) and work experience ( r s = −0.29, P < .01) negatively correlated with stigma, while fear positively correlated ( r s = 0.45, P < .01), and no correlation was observed with HIV knowledge. Conclusion HCPs’ age, work experience, fear, and marital status are linked to HIV-related stigma. Interventions should tailor stigma reduction strategies considering these factors.

Objectives To determine the incidence of opportunistic infections (OIs) and the predictive factors for the development of OIs after antiretroviral therapy (ART) initiation among treatment-naïve patients with HIV infection. Results Of 401 HIV-infected patients, 38 (9.5%) HIV-infected patients developed OIs after initiating ART, with an incidence rate of 25.6/1000 person-years. The median time (IQR) from ART initiation to OI occurrence was 26.5 (14-73) days. In multivariate Cox proportional hazard regression, body mass index ≤18.5 kg/m 2 (adjusted hazard ratio [aHR] 2.28, 95% confidence interval [CI] 1.18-4.42, P = .015), symptoms at presentation (aHR 13.59, 95% CI 3.24-56.9, P 55 U/L (aHR 2.09, 95% CI 1.06-4.15, P = .035), and initiation of a dolutegravir-based regimen (aHR 4.39, 95% CI 1.54-12.48, P = .006) were significantly associated with OIs after ART initiation. Conclusion OIs after ART initiation are common. Malnutrition, symptomatic presentation, abnormal liver enzymes, and DTG-based regimens are predictors of OI occurrence after ART initiation. Physicians must monitor and appropriately treat OIs after ART initiation.

Objectives: To determine the optimal initial insulin dosage for controlling hyperglycemia in COVID-19 patients receiving steroids, an area with limited data. Methods: We retrospectively analyzed 156 COVID-19 patients with steroid-induced hyperglycemia treated with insulin. Patients were categorized by their total daily dose of subcutaneous insulin therapy when starting dexamethasone ⩾6 mg/day or equivalent dose of glucocorticoid: Group A (⩽0.29 units/kg), Group B (0.3–0.49 units/kg), Group C (0.5–0.69 units/kg), and Group B (⩾0.7 units/kg). Treatment failure was defined as mean blood glucose level > 280 mg/dL for two consecutive days after initiating insulin or any blood glucose ⩾ 400 mg/dL. Results: The mean age was 64 ± 14 years, with 50% male, and a mean body mass index of 26.9 ± 6.9 kg/m 2 . Most had preexisting type 2 diabetes (62%). Mean admission blood glucose and HbA1c were 233 ± 112 mg/dL and 7.8 ± 2.3%, respectively. Group A had the lowest HbA1c (6.7 ± 1.2%), while group D had the highest (9.8 ± 2.5%). Median daily dexamethasone dosage or equivalent was 36 (IQR 16.72) mg, with no significant differences in among groups. Group A had the lowest treatment failure rate. There were no significant differences in treatment failure rate between Groups B, C, and D. Additionally, there were no statistically significant differences in mean BG across the groups: Group A 232 ± 42 mg/dL, Group B 247 ± 57 mg/dL, Group C 247 ± 61 mg/dL, and Group D 227 ± 67 mg/dL ( p = 0.2). Group D had a significantly higher rate of level 1 hypoglycemia ( p = 0.008), while no differences in clinically significant hypoglycemia (level 2 or 3) were observed between groups. Conclusions: Among patients requiring TDD ⩾ 0.3 units/kg/day, there was no significant difference in treatment failure rate between Groups B, C, and D. Group D had the highest rate of level 1 hypoglycemia. This initial insulin dosage for hospitalized COVID-19 patients on high-dose steroid therapy should be personalized.

IntroductionToxoplasma gondii can cause symptomatic toxoplasmosis in immunodeficient hosts, including in people living with human immunodeficiency virus (PLWH), mainly because of the reactivation of latent infection. We assessed the prevalence of toxoplasmosis and its associated risk factors in PLWH in the Asia-Pacific region using data from the TREAT Asia Human Immunodeficiency Virus (HIV) Observational Database (TAHOD) of the International Epidemiology Databases to Evaluate AIDS (IeDEA) Asia-Pacific.MethodsThis study included both retrospective and prospective cases of toxoplasmosis reported between 1997 and 2020. A matched case-control method was employed, where PLWH diagnosed with toxoplasmosis (cases) were each matched to two PLWH without a toxoplasmosis diagnosis (controls) from the same site. Sites without toxoplasmosis were excluded. Risk factors for toxoplasmosis were analyzed using conditional logistic regression.ResultsA total of 269/9576 (2.8%) PLWH were diagnosed with toxoplasmosis in 19 TAHOD sites. Of these, 227 (84%) were reported retrospectively and 42 (16%) were prospective diagnoses after cohort enrollment. At the time of toxoplasmosis diagnosis, the median age was 33 years (interquartile range 28-38), and 80% participants were male, 75% were not on antiretroviral therapy (ART). Excluding 63 out of 269 people without CD4 values, 192 (93.2%) had CD4 ≤200 cells/μL and 162 (78.6%) had CD4 ≤100 cells/μL. By employing 538 matched controls, we found that factors associated with toxoplasmosis included abstaining from ART (odds ratio [OR] 3.62, 95% CI 1.81-7.24), in comparison to receiving nucleoside reverse transcriptase inhibitors plus non-nucleoside reverse transcriptase inhibitors, HIV exposure through injection drug use (OR 2.27, 95% CI 1.15-4.47) as opposed to engaging in heterosexual intercourse and testing positive for hepatitis B virus surface antigen (OR 3.19, 95% CI 1.41-7.21). Toxoplasmosis was less likely with increasing CD4 counts (51-100 cells/μL: OR 0.41, 95% CI 0.18-0.96; 101-200 cells/μL: OR 0.14, 95% CI 0.06-0.34; >200 cells/μL: OR 0.02, 95% CI 0.01-0.06), when compared to CD4 ≤50 cells/μL. Moreover, the use of prophylactic cotrimoxazole was not associated with toxoplasmosis.ConclusionsSymptomatic toxoplasmosis is rare but still occurs in PLWH in the Asia-Pacific region, especially in the context of delayed diagnosis, causing advanced HIV disease. Immune reconstitution through early diagnosis and ART administration remains a priority in Asian PLWH.

Background: Immunization against SARS-CoV-2 is essential for vulnerable solid organ transplant (SOT) recipients who are at risk of infection. However, there are concerns about suboptimal immunogenicity, especially in humoral immunity (HMI), and limited exploration of cell-mediated immune (CMI) responses. The primary objective of this study was to assess the immunogenicity of ChAdOx1 nCoV-19 vaccination in SOT recipients. The secondary endpoint was to evaluate factors that affect immunogenicity and adverse events (AEs) following immunization in SOT recipients. Methods: All adult SOT recipients who received the two-dose ChAdOx1 nCoV-19 vaccine at a 12-week interval underwent measurements of HMI by evaluating anti-receptor-binding domain (RBD) IgG levels and CMI by investigating SARS-CoV-2-specific T cell and B cell responses before and after complete vaccination, around 2–4 weeks post-vaccination, and compared to controls. AEs were monitored in all participants. Results: The study included 63 SOT recipients: 44 kidney recipients, 16 liver recipients, and 3 heart transplant recipients, along with 11 immunocompetent controls. Among SOT recipients, 36% were female, and the median (IQR) age was 52 (42–61). The median (IQR) time since transplant was 55 (28–123) months. After the second dose, the median (IQR) anti-RBD antibody levels were significantly lower in SOT recipients compared to those in the control group (8.3 [0.4–46.0] vs. 272.2 [178.1–551.6] BAU/mL, p < 0.01). This resulted in a seroconversion rate (anti-RBD antibody > 7.1 BAU/mL) of 51% among SOT recipients and 100% among controls (p = 0.008). Receiving the vaccine beyond one year post-transplant significantly affected seroconversion (OR 9.04, 95% CI 1.04–78.56, p = 0.046), and low-dose mycophenolic acid marginally affected seroconversion (OR 2.67, 95% CI 0.89–7.96, p = 0.079). RBD-specific B cell responses were also significantly lower compared to those in the control group (0 [0–4] vs. 10 [6–22] SFUs/106 PBMCs, p = 0.001). Similarly, S1- and SNMO-specific T cell responses were significantly lower compared to those in the control group (48 [16–128] vs. 216 [132–356] SFUs/106 PBMCs, p = 0.004 and 20 [4–48] vs. 92 [72–320] SFUs/106 PBMCs, p = 0.004). AEs were generally mild and spontaneously resolved. Conclusions: SOT recipients who received the full two-dose ChAdOx1 nCoV-19 vaccine demonstrated significantly diminished HMI and CMI responses compared to immunocompetent individuals. Consideration should be given to administering additional vaccine doses or optimizing immunosuppressant regimens during vaccination (Thai Clinical Trial Registry: TCTR20210523002).

This study aimed to assess second-line antiretroviral therapy (ART) outcomes in a National HIV Treatment program. People living with HIV aged ≥18 years initiating first-line ART who switched to second-line protease inhibitor-based regimens from January 2008 to May 2019, with a minimum of 1-year follow-up were studied. The primary outcome was second-line treatment failure (two consecutive virological failure episodes (viral load ≥1000 copies/mL)). Of 318,506 PLH initiating ART, 29,015 (9.1%) switched to second-line regimens after a median (IQR) ART duration of 1.63 (0.60-3.59) years. Lost to follow-up (LTFU) occurred in 5316 (18.3%) of whom 1376 (5%) remained LTFU and alive; 4606 (15.9%) died. Cumulative second-line failure incidence was 9.8% at 6 years, more common in females, younger PLH those with lower switch CD4 cell counts. Multidisciplinary, innovative support systems are needed to improve second-line treatment outcomes, particularly those relating to modifiable risk factors.

Abstract Background Chronic inflammation has been described in people living with HIV (PLHIV) receiving antiretroviral therapy (ART) despite viral suppression. Inflammation associated non-communicable diseases, including atherosclerosis, are becoming recognized complication of HIV infection. We studied the effect of pitavastatin on atherosclerotic-associated inflammatory biomarkers in PLHIV receiving ART. Methods A randomized, double-blind, crossover study was conducted in HIV-infected persons with dyslipidemia and receiving atazanavir/ritonavir (ATV/r) to evaluate the effect of 2 mg/day pitavastatin treatment versus placebo. High-sensitivity CRP (hs-CRP), cytokines, and cellular markers in PLHIV receiving 12 weeks of pitavastatin or placebo were investigated. Results A total of 24 HIV-infected individuals with a median (interquartile range) age of 46 (41–54) years were recruited, and the median CD4 T cell count was 662 (559-827) cells/mm3. The median duration of ATV/r use was 36 (24–48) months. Significant change in levels of basic fibroblast growth factor (FGF) between pitavastatin treatment and placebo at week 12 from baseline was observed (27.1 vs. 20.5 pg/mL; p=0.023). However, there were no significant changes from baseline of hs-CRP and other plasma cytokine levels at week 12 of pitavastatin or placebo. Regarding cellular markers, percentages of HLA-DR+CD38-CD4+ T cells and PD1+CD4+ T cells significantly decreased from baseline in PLHIV receiving pitavastatin for 12 weeks, as compared to placebo (− 0.27 vs. 0.02%; p=0.049 and − 0.23 vs. 0.23%; p=0.022, respectively). Conclusions Pitavastatin treatment increases basic FGF levels, and lowers HLA-DR+CD38-CD4+ T cells, and PD1+CD4+ T cells. Further study on the effects of pitavastatin on preventing cardiovascular diseases in PLHIV should be pursued.

Background: Diabetes mellitus (DM) and poor glycemic control significantly increase the risk of tuberculosis (TB) and adverse outcomes after TB treatment. However, DM screening is not universally performed. Method: Patients diagnosed with TB were enrolled and tested for fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) within 3 months after TB diagnosis. Results: A total of 216 patients with TB were included. Median (IQR) age was 60 years (53-73), and 57% were male. The prevalence of DM was 42.6%. Patients with TB with DM were more likely to have other comorbidities (76% vs 52%, p

Abstract Vaccination with inactivated SARS-CoV-2 virus produces suboptimal immune responses among kidney transplant (KT), peritoneal dialyzed (PD), and hemodialyzed (HD) patients. Participants were vaccinated with two-dose inactivated SARS-CoV-2 vaccine (V2) and a third dose of ChAdOx1 nCoV-19 vaccine (V3) at 1–2 months after V2. We enrolled 106 participants: 31 KT, 28 PD, and 31 HD patients and 16 controls. Among KT, PD, and HD groups, median (IQR) of anti-receptor binding domain antibody levels were 1.0 (0.4–26.8), 1092.5 (606.9–1927.2), and 1740.9 (1106–3762.3) BAU/mL, and percent neutralization was 0.9 (0–9.9), 98.8 (95.9–99.5), and 99.4 (98.8–99.7), respectively, at two weeks after V3. Both parameters were significantly increased from V2 across all groups (p 90% in PD, HD, and control groups, which was higher than that in KT recipients (74%, p

BackgroundChronic hepatitis C virus (HCV) infection contributes to substantial morbidity and mortality among adults living with HIV. Cascades of HCV care support monitoring of program performance, but data from Asia are limited. We assessed regional HCV coinfection and cascade outcomes among adults living with HIV in care from 2010-2020.MethodsPatients ≥18 years old with confirmed HIV infection on antiretroviral therapy (ART) at 11 clinical sites in Cambodia, China, India, Indonesia, South Korea, Thailand and Vietnam were included. HCV- and HIV-related treatment and laboratory data were collected from those with a positive HCV antibody (anti-HCV) test after January 2010. An HCV cascade was evaluated, including proportions positive for anti-HCV, tested for HCV RNA or HCV core antigen (HCVcAg), initiated on HCV treatment, and achieved sustained virologic response (SVR). Factors associated with screening uptake, treatment initiation, and treatment response were analyzed using Fine and Gray's competing risk regression model.ResultsOf 24,421 patients, 9169 (38%) had an anti-HCV test, and 971 (11%) had a positive result. The proportion with positive anti-HCV was 12.1% in 2010-2014, 3.9% in 2015-2017, and 3.8% in 2018-2020. From 2010 to 2014, 34% with positive anti-HCV had subsequent HCV RNA or HCVcAg testing, 66% initiated HCV treatment, and 83% achieved SVR. From 2015 to 2017, 69% with positive anti-HCV had subsequent HCV RNA or HCVcAg testing, 59% initiated HCV treatment, and 88% achieved SVR. From 2018 to 2020, 80% had subsequent HCV RNA or HCVcAg testing, 61% initiated HCV treatment, and 96% achieved SVR. Having chronic HCV in later calendar years and in high-income countries were associated with increased screening, treatment initiation or achieving SVR. Older age, injecting drug use HIV exposure, lower CD4 and higher HIV RNA were associated with reduced HCV screening or treatment initiation.ConclusionsOur analysis identified persistent gaps in the HCV cascade of care, highlighting the need for focused efforts to strengthen chronic HCV screening, treatment initiation, and monitoring among adult PLHIV in the Asia region.

Tenofovir disoproxil fumarate (TDF) associates with renal tubular dysfunction (RTD) in some people living with HIV (PLWH). We studied clinical and genetic factors associated with RTD in Thai PLWH receiving TDF. RTD was diagnosed in 13 of 65 (20%) patients. The median (interquartile range) age and CD4 cell counts were 43.8 (40.4-50.9) years and 554 (437-716) cells/mm 3 , respectively. The median duration of TDF use was 46.9 (31.5-54.1) months. Univariate logistic regression demonstrated body mass index (BMI), concomitant use of protease inhibitor (PI), hyperlipidemia, and homozygous C/C SNP rs1059751 of ABCC4 gene as predisposing factors of RTD. In multivariate model, concomitant use of PI [adjusted odds ratio (aOR) 11.39; 95% confidence interval (CI), 1.59- 81.56; P = 0.015], hyperlipidemia (aOR 8.59; 95% CI, 1.46-50.40; P = 0.017), and BMI (aOR 0.76; 95% CI, 0.59-0.98; P = 0.037) remained associated with RTD in patients receiving TDF. PLWH receiving TDF with the presence of these factors should be closely monitored for RTD.

Abstract Background Infectious Diseases Society of America (IDSA) guidelines suggest 7–14 days’ duration of antibiotic treatment for uncomplicated Gram-negative bacteria (GNB) catheter-related bloodstream infection (CRBSI). The objectives of this study were to review microbial epidemiology, to determine rate and risk factors for relapse, and to compare clinical outcomes in patients receiving long- versus short-duration antibiotic therapy. Methods A retrospective phase 1 study was conducted between January 2010 and October 2016 to review microbial epidemiology and to determine the incidence of and risk factors for relapse in patients with GNB CRBSI, according to the IDSA guidelines diagnostic criteria. In phase 2 of the study, patients without risk factors for relapse between November 2016 and October 2017 were prospectively recruited to receive antibiotic therapy for 7 days after catheter removal. Matched patients from the retrospective phase 1 study who had received antibiotic therapy for ≥14 days were selected as a phase 2 control group to compare outcomes. Results In phase 1, three most common pathogens identified among 174 cases were Pseudomonas aeruginosa (22.0%), Klebsiella pneumoniae (16.7%), and Stenotrophomonas maltophilia (13.4%). Eighty-nine episodes of infection occurred while patients were receiving antibiotic therapy. Of 140 cases, the relapse rate was 6.4%. Catheter retention was the only risk factor strongly associated with relapse (odds ratio = 145.32; 95% confidence interval 12.66–1667.37, P

Studies investigating same-day antiretroviral therapy (ART) initiation demonstrate different clinical outcomes depending on settings. We retrospectively reviewed adults with newly positive human immunodeficiency virus (HIV) antibody testing. The proportion of individuals who were retained in care at 12 months was compared between early (≤2 weeks) and late (>2 weeks) ART initiation groups. Of all, the median (IQR) time from HIV diagnosis to ART initiation was 18 (9-30) days. This duration was 7 (7-13) days in the early ART initiation group (n = 116) and 28 (21-46) days in the late ART initiation group (n = 154). In the multivariate logistic regression, having pneumocystis pneumonia [odds ratio (OR) 9.30, 95% CI 2.56-33.75], tuberculosis (OR 2.21, 95% CI 1.03-4.73), and weight loss (OR 12.98, 95% CI 1.00-167.68) were associated with late ART initiation. The early ART initiation group had a slightly higher proportion of individuals retained in care at 12 months than those in the late ART initiation group (88.8% vs 80.5%, P = .066) and had a higher significant proportion of HIV viral load suppression (81.0% vs 70.1%, P = .041). No significant differences were observed in the proportion of individuals who died at 12 months (2.6% vs 3.2%, P = 1.000) between the two groups. Early ART initiation trends to retain individuals in care and higher HIV viral load suppression was determined. Nevertheless, ART initiation timing might not be a solely important factor in improving HIV care and minimizing mortality among HIV-infected individuals in a university hospital setting.

The use of holding regimens for people living with HIV (PLWH) without effective antiretroviral options can have effects on outcomes and future treatment options. We aimed to investigate the use of holding regimens for PLWH in Asian countries. Data from adults enrolled in routine HIV care in IeDEA Asia-Pacific cohorts were included. Individuals were considered to be on holding regimen if they had been on combination antiretroviral therapy for at least 6 months, had two confirmed viral loads (VL) ≥1000 copies/mL, and had remained on the same medications for at least 6 months. Survival time was analyzed using Fine and Gray's competing risk regression. Factors associated with CD4 changes and VL 50 years compared to age 31-40 years (sub-hazard ratio [SHR] 3.29, 95% CI 1.45-7.43, p = 0.004), and VL ≥1000 copies/ml compared to VL

BackgroundImmunization stress-related responses presenting as stroke-like symptoms could develop following COVID-19 vaccination. Therefore, this study aimed to describe the clinical characteristics of immunization stress-related responses causing stroke-like events following COVID-19 vaccination in Thailand.MethodsWe conducted a retrospective study of the secondary data of reported adverse events after COVID-19 immunization that presented with neurologic manifestations. Between March 1 and July 31, 2021, we collected and analyzed the medical records of 221 patients diagnosed with stroke-like symptoms following immunization. Two majority types of vaccines were used at the beginning of the vaccination campaign, including CoronaVac (Sinovac) or ChAdOx1 (AstraZeneca). Demographic and medical data included sex, age, vaccine type, sequence dose, time to event, laboratory data, and recovery status as defined by the modified Rankin score. The affected side was evaluated for associations with the injection site.ResultsOverall, 221 patients were diagnosed with immunization stress-related responses (stroke-like symptoms) following CoronaVac (Sinovac) or ChAdOx1 (AstraZeneca) vaccinations. Most patients (83.7%) were women. The median (interquartile range) age of onset was 34 (28-42) years in patients receiving CoronaVac and 46 (33.5-60) years in those receiving ChAdOx1. The median interval between vaccination and symptom onset for each vaccine type was 60 (16-960) min and 30 (8.8-750) min, respectively. Sensory symptoms were the most common symptomology. Most patients (68.9%) developed symptoms on the left side of the body; 99.5% of the patients receiving CoronaVac and 100% of those receiving ChAdOx1 had a good outcome (modified Rankin scores ≤2, indicating slight or no disability).ConclusionsImmunization stress-related responses presenting as stroke-like symptoms can develop after COVID-19 vaccination. Symptoms more likely to occur on the injection side are transient (i.e., without permanent pathological deficits). Public education and preparedness are important for administering successful COVID-19 vaccination programs.

Abstract Background Rapid influenza diagnostic test (RIDT) is a diagnostic tool that detects the influenza virus nucleoprotein antigen. The RIDT is widely used in clinical practice because it is simple and cost‐effective, and provides results within 10‐15 minutes. Objective We aimed at evaluating the sensitivity and specificity of the Sofia® RIDT compared with the Luminex® multiplex polymerase chain reaction (PCR). The other goal was to determine the predicting factors for diagnosing influenza among individuals with influenza‐like illness (ILI). Method Patients with ILI who had the results of both tests were retrospectively reviewed. We determined the performances of the RIDT. Results A total of 473 patients were included with a median age of 58 (interquartile range 41‐74) years. Of these, 47.1% were male, and 16.2% were diagnosed with influenza by the RIDT or RT‐PCR's positive test. For influenza A, the RIDT showed a sensitivity of 76.3% (95% confidence interval [CI] 59.8‐88.6) and a specificity of 97.9% (95% CI 96.1‐99.0), whereas for influenza B, it showed a sensitivity of 47.1% (95% CI 23.0‐72.2) and a specificity of 97.1% (95% CI 95.2‐98.5). Patients with influenza were more likely to present with fever (81.8% vs 63.1%), cough (81.8% vs 66.1%), and rhinorrhea (41.6% vs 26.5%) compared to those without influenza (P

Background: The efficacy and safety of a single tablet regimen (STR) of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) was analyzed in Phase 3 clinical trials in antiretroviral therapy (ART)-naive and ART-experienced Asian participants infected with human immunodeficiency virus (HIV)-1 through 96 or 144 weeks. Objective: In Asian population requiring treatment, it is imperative to have data specific to this group, particularly as there is a general concern that Asians with lower body weight have increased risk of tenofovir disoproxil fumarate (TDF)-related renal dysfunction. Methods: Studies -104 and 111 were randomized, double-blind, placebo-controlled, 144-week studies conducted in ART-naive participants, comparing E/C/F/TAF versus E/C/F/TDF. Study 109 was a randomized, open-label, 96-week study conducted in virologically suppressed, ART-experienced participants, who switched to E/C/F/TAF from ritonavir/cobicistat-boosted atazanavir ATV+(RTV or COBI) + F/TDF regimens, from non-nucleoside reverse transcriptase inhibitors (NNRTI) + F/TDF regimens, or from E/C/F/TDF. Study 112 was a single arm, open-label, 144-week study conducted in HIV suppressed, ART-experienced participants with mild-moderate renal impairment, who switched to E/C/F/TAF. Results: Asian participants in these studies had sustained efficacy safety and tolerability. In Study 104/111, Asian participants achieved 93% virologic suppression on TAF vs 88% on TDF at week 144. At baseline, there were numerically more Asians with median CD4 counts < 200 cells/uL and VL > 100,000 c/mL. In Study 109, 95% of Asians on TAF vs 86% on TDF maintained virologic suppression at week 96. Lastly, in Study 112, 91% maintained virologic suppression at week 144. There were no discontinuations due to renal AE, no cases of PRT or Fanconi syndrome in any of the studies.

Background: There are limited data describing the care outcome of youth living with HIV in Asia. We assessed attrition and treatment outcomes among youths with behaviourly acquired HIV (BIY) and adolescents with perinatally acquired HIV (PIY) who initiated antiretroviral treatment (ART) through the National AIDS Program (NAP) in Thailand. Methods: People living with HIV aged 10–24 years who initiated antiretroviral therapy (ART) from 2008 to 2013 through the Thai NAP and who were followed up until 2014 were included in the analysis. We assessed youths initiating ART: BIY aged 15–19 years (BIY1) and BIY aged 20–24 (BIY2) compared against PIY aged 10–14 years. Attrition rates (mortality and loss to follow-up [LTFU]) were calculated and potential associations were assessed using Cox regression. Logistic regression was used to assess associations with treatment failure. Results: Of 11,954 individuals, 9909 (83%) were BIY with a median follow-up of 2.1 years and 17% were PIY with 4.2 years of follow-up. The median baseline CD4 cell count in BIY was higher (190 vs 154 cells/mm3) compared to PIY. Mortality rates were not significantly different among PIY (2.5 per 100 person years [PY], BIY1 3.1/100 PY and BIY2 2.9/100 PY, P=0.46). Compared to PIY with a crude LTFU rate of 2.9/100 PY, LTFU was higher in BIY1 (13.9/100 PY) and BIY2 (9.5/100 PY), P

A hospitel is a hotel that has been designated as an extension of the healthcare facilities during the COVID-19 pandemic in resource-limited settings. However, the clinical course and outcomes of patients with COVID-19 admitted to this unique type of facility have never been studied. We retrospectively reviewed the medical records of adult patients with COVID-19 who were admitted to a single hospitel in Bangkok, Thailand. Risk factors with respect to chest X-ray progression and clinical progression were analyzed using a logistic regression. A total of 514 patients were recruited, with a mean (standard deviation) age of 35.6 (13.4) years, and 58.6% were women. Patients were admitted after a median (interquartile range) of 3 (2–6) days of illness and were classified with mild (12.3%), moderate (86.6%), and severe (1.1%) conditions. Favipiravir and corticosteroids were prescribed in 26.3% and 14.9% of patients, respectively. Chest X-ray progression was found in 7.6% of patients, and hospital transfer occurred in 2.9%, with no deaths. Favipiravir use (odds ratio (OR) 3.3, 95% confidence interval (CI) 1.4–7.5, p = 0.005), nausea/vomiting after admission (OR 32.3, 95% CI 1.5–700.8, p = 0.03), and higher oxygen saturation on admission (OR 1.99; 95% CI 1.22–3.23, p = 0.005) were factors associated with chest X-ray progression. Additionally, an oxygen requirement on admission was an independent risk factor for hospital transfer (OR 904, 95% CI 113–7242, p < 0.001). In a setting where the hospitel has been proposed as an extension facility for patients with relatively non-severe COVID-19, most patients could achieve a favorable clinical outcome. However, patients who require oxygen supplementation should be closely monitored for disease progression and promptly transferred to a hospital if necessary.

The durability of a three-dose extended primary series of COVID-19 vaccine in dialysis patients remains unknown. Here, we assessed dynamic changes in SARS-CoV-2-specific humoral and cell-mediated immunity at baseline, 3 months, and 6 months after the extended primary series in 29 hemodialyzed (HD), 28 peritoneal dialyzed (PD) patients, and 14 healthy controls. Participants received two doses of inactivated SARS-CoV-2 vaccine followed by a dose of ChAdOx1 nCoV-19 vaccine. At 6 months, median anti-RBD IgG titers (IQR) significantly declined from baseline in the HD (1741 (1136–3083) BAU/mL vs. 373 (188–607) BAU/mL) and PD (1093 (617–1911) BAU/mL vs. 180 (126–320) BAU/mL) groups, as did the mean percent inhibition of neutralizing antibodies (HD: 96% vs. 81%; PD: 95% vs. 73%) (all p < 0.01). Age and post-vaccination serological response intensity were predictors of early humoral seroprotection loss. In contrast, cell-mediated immunity remained unchanged. In conclusion, humoral immunity declined substantially in dialysis patients, while cell-mediated immunity remained stable 6 months after the extended heterologous primary series of two inactivated SARS-CoV-2/ChAdOx1 nCoV-19 vaccine. A booster dose could be considered in dialysis patients 3 months after this unique regimen, particularly in the elderly or those with a modest initial humoral response.

BackgroundPeople living with HIV (PLHIV) have an elevated risk of atherosclerotic cardiovascular disease (ASCVD) compared to their uninfected peers. Expanding statin use may help alleviate this burden. We evaluated the cost-effectiveness of reducing the recommend statin initiation threshold for primary ASCVD prevention among PLHIV in Thailand.MethodsOur decision analytic microsimulation model randomly selected (with replacement) individuals from the TREAT Asia HIV Observational Database (data collected between 1/January/2013 and 1/September/2019). Direct medical costs and quality-adjusted life-years were assigned in annual cycles over a lifetime horizon and discounted at 3% per year. We assumed the Thai healthcare sector perspective. The study population included PLHIV aged 35-75 years, without ASCVD, and receiving antiretroviral therapy. Statin initiation thresholds evaluated were 10-year ASCVD risk ≥10% (control), ≥7.5% and ≥5%.ResultsA statin initiation threshold of ASCVD risk ≥7.5% resulted in accumulation of 0.015 additional quality-adjusted life-years compared with an ASCVD risk threshold ≥10%, at an extra cost of 3,539 Baht ($US113), giving an incremental cost-effectiveness ratio of 239,000 Baht ($US7,670)/quality-adjusted life-year gained. The incremental cost-effectiveness ratio comparing ASCVD risk ≥5% to ≥7.5% was 349,000 Baht ($US11,200)/quality-adjusted life-year gained. At a willingness-to-pay threshold of 160,000 Baht ($US5,135)/quality-adjusted life-year gained, a 30.8% reduction in the average cost of low/moderate statin therapy led to the ASCVD risk threshold ≥7.5% becoming cost-effective compared with current practice.ConclusionsReducing the recommended 10-year ASCVD risk threshold for statin initiation among PLHIV in Thailand would not currently be cost-effective. However, a lower threshold could become cost-effective with greater preference for cheaper statins.

Rationale: Clinical features of central nervous system tuberculosis (CNS-TB) are nonspecific. The decision for treatment of the disease in an endemic area is challenging. Objectives: We aimed to study predictive factors for a definite diagnosis and outcome of patients with CNS-TB. Methods: A case-control study was performed in adults with a provisional diagnosis of CNS-TB in Thailand to determine predictive factors for a definite diagnosis of CNS-TB. Predictive factors for a definite diagnosis of CNS-TB were analyzed by multivariable logistic regression analysis. Factors associated with two-year mortality after the diagnosis of definite CNS-TB were determined using a cox regression analysis. Measurements and main results: A total of 114 patients received a provisional diagnosis of CNS-TB during the study period. A median (interquartile range) age was 40.8 (31.7–55.4) years, and 75 patients (65.8%) were male. Of these, 66 cases (57.9%) had definite CNS-TB, and 43 cases (38.4%) had HIV coinfection. By logistic regression, age, confusion, and nausea/vomiting were associated with definite CNS-TB (odds ratio [OR] 0.96, 95% confidence interval [CI] 0.93–0.99; p = 0.015, OR 2.86, 95% CI 1.03–7.94; p = 0.044, and OR 0.30, 95% CI 0.11–0.82; p = 0.019, respectively). In patients with definite CNS-TB, age and HIV coinfection were associated with two-year mortality (hazard ratio [HR] 1.07, 95% CI 1.01–1.13; p = 0.022, and HR 11.81, 95% CI 2.09–66.78; p = 0.005, respectively). Conclusions: Younger age, confusion, and absence of nausea/vomiting are predictive factors of a definite diagnosis of CNS-TB. In patients with definite CNS-TB, older age and HIV coinfection are associated with higher mortality. The results of this study might be helpful for the management of suspected CNS-TB cases as well as predicting the prognosis of CNS-TB cases in an endemic area.

More than half of newly diagnosed HIV-infected patients enter to care with a low CD4 count. A retrospective cohort study was conducted among newly diagnosed HIV-infected adults who were hospitalized. Of 148 patients, median (interquartile range [IQR]) age was 39.3 (30.5-47.1) years and 114 (77%) patients were male. Baseline median (IQR) CD4 count was 79 (24-218) cells/mm 3 . The median (IQR) length of hospital stay was 8 (4-16) days. Half of the patients were hospitalized with AIDS-defining illness (ADI). Common opportunistic infections were Pneumocystis jirovecii pneumonia (20.3%) and tuberculosis (18.9%). CD4 count was statistically significantly associated with hospitalization with ADI (odds ratio: 0.85, per 10 cells/mm 3 increased; 95% confidence interval: 0.80-0.90). The mortality was 5.4%. In conclusion, half of newly diagnosed Thai HIV-infected patients were hospitalized with ADI. Early detection of HIV infection leading to early antiretroviral therapy initiation and prevention of serious complications is essential.

To manage coronavirus disease 2019 (COVID-19), a national health authority has implemented a case definition of patients under investigation (PUIs) to guide clinicians' diagnoses. We aimed to determine characteristics among all PUIs and those with and without COVID-19. We retrospectively reviewed clinical characteristics and risk factors for laboratory-confirmed COVID-19 cases among PUIs at a tertiary care center in Bangkok, Thailand, between March 23 and April 7, 2020. Reverse transcription-polymerase chain reaction for SARS-CoV-2 RNA was performed. There were 405 evaluable PUIs; 157 (38.8%) were men, with a mean age ± SD of 36.2 ± 12.6 years. The majority (68.9%) reported no comorbidities. There were 53 (13.1%) confirmed COVID-19 cases. The most common symptoms among those were cough (73.6%), fever (58.5%), sore throat (39.6%), and muscle pain (37.4%). Among these patients, diagnoses were upper respiratory tract infection (69.8%), viral syndrome (15.1%), pneumonia (11.3%), and asymptomatic infection (3.8%). Multivariate analysis identified close contact with an index case (OR, 3.49; 95%CI, 1.49-8.15; P = 0.004), visiting high-risk places (OR, 1.92; 95%CI, 1.03-3.56; P = 0.039), productive cough (OR, 2.03; 95%CI, 1.05-3.92; P = 0.034), and no medical coverage (OR, 3.91; 95%CI, 1.35-11.32; P = 0.012) as independent risk factors for COVID-19 among the PUIs. The majority had favorable outcomes, though one (1.9%) died from severe pneumonia. COVID-19 was identified in 13% of PUIs defined per a national health authority's case definition. History of contact with a COVID-19 patient, visiting a high-risk place, having no medical coverage, and productive cough may identify individuals at risk of COVID-19 in Thailand.

ObjectivesWe extend the method of Significant Zero Crossings of Derivatives (SiZer) to address within-subject correlations of repeatedly collected longitudinal biomarker data and the computational aspects of the methodology when analyzing massive biomarker databases. SiZer is a powerful visualization tool for exploring structures in curves by mapping areas where the first derivative is increasing, decreasing or does not change (plateau) thus exploring changes and normalization of biomarkers in the presence of therapy.MethodsWe propose a penalized spline SiZer (PS-SiZer) which can be expressed as a linear mixed model of the longitudinal biomarker process to account for irregularly collected data and within-subject correlations. Through simulations we show how sensitive PS-SiZer is in detecting existing features in longitudinal data versus existing versions of SiZer. In a real-world data analysis PS-SiZer maps are used to map areas where the first derivative of weight change after antiretroviral therapy (ART) start is significantly increasing, decreasing or does not change, thus exploring the durability of weight increase after the start of therapy. We use weight data repeatedly collected from persons living with HIV initiating ART in five regions in the International Epidemiologic Databases to Evaluate AIDS (IeDEA) worldwide collaboration and compare the durability of weight gain between ART regimens containing and not containing the drug stavudine (d4T), which has been associated with shorter durability of weight gain.ResultsThrough simulations we show that the PS-SiZer is more accurate in detecting relevant features in longitudinal data than existing SiZer variants such as the local linear smoother (LL) SiZer and the SiZer with smoothing splines (SS-SiZer). In the illustration we include data from 185,010 persons living with HIV who started ART with a d4T (53.1%) versus non-d4T (46.9%) containing regimen. The largest difference in durability of weight gain identified by the SiZer maps was observed in Southern Africa where weight gain in patients treated with d4T-containing regimens lasted 59.9 weeks compared to 133.8 weeks for those with non-d4T-containing regimens. In the other regions, persons receiving d4T-containing regimens experienced weight gains lasting 38-62 weeks versus 55-93 weeks in those receiving non-d4T-based regimens.DiscussionPS-SiZer, a SiZer variant, can handle irregularly collected longitudinal data and within-subject correlations and is sensitive in detecting even subtle features in biomarker curves.

Abstract Background Abacavir and rilpivirine are alternative antiretroviral drugs for treatment-naïve HIV-infected patients. However, both drugs are only recommended for the patients who have pre-treatment HIV RNA 30 kg/m2 (OR 2.4 vs. 350 cells/mm3 (OR 3.9 vs. 2000 cells/mm3 (OR 1.7 vs. 25 yielded the sensitivity of 46.7%, specificity of 79.1%, positive predictive value of 67.7%, and negative predictive value of 61.2% for prediction of pre-treatment HIV RNA

Pituitary tuberculoma is extremely rare, even in endemic regions of tuberculosis and much less frequently as a presentation of pituitary apoplexy. We describe a 25-year-old female presented with sudden onset of headache and vision loss of left eye which mimicking symptoms of pituitary apoplexy. MRI of the pituitary gland showed a rim-enhancing lesion at the intrasellar region extending into the suprasellar area, but absence of posterior bright spot with enhancement of the pituitary stalk. Pituitary hormonal evaluation revealed panhypopituitarism and diabetes insipidus. An urgent transphenoidal surgery of the pituitary gland was undertaken for which the histopathology showed necrotizing granulomatous inflammation with infarcted adjacent pituitary tissue. Despite negative fungal and AFB staining, pituitary tuberculoma was presumptively diagnosed based on imaging, pathology and the high incidence of tuberculosis in the country. After the course of anti-tuberculosis therapy, the clinical findings were dramatically improved, supporting the diagnosis. Pituitary tuberculoma is extremely rare in particular with an apoplexy-like presentation but should be one of the differential diagnosis list of intrasellar lesions in the patient presenting with sudden onset of headache and visual loss. The presence of diabetes insipidus and thickened with enhancement of pituitary stalk on MRI were very helpful in diagnosing pituitary tuberculosis.

BACKGROUND:Health care providers usually focus on index HIV-infected patients and seldom obtain information from their partners. We aimed to determine HIV-preventative measures among couples, the prevalence of HIV infection, and treatment outcomes of partners. METHODS:This cross-sectional study was conducted in two hospital settings, a university hospital in Bangkok and a general hospital in northeastern Thailand, from January 2011-October 2015. Factors associated with serodiscordant relationships were determined by logistic regression. RESULTS:A total of 393 couples were enrolled for analysis; 156 (39.7%) were serodiscordant. The median relationship duration of serodiscordant couples was shorter than that of seroconcordant couples (6.4 years vs 11.6 years, p < 0.001). Of 237 HIV-infected partners, 17.7% had AIDS-defining illness, the median nadir CD4 count (interquartile range) was 240 (96-427) cells/mm3, 83.5% received antiretroviral therapy (ART), 98.3% had adherence > 95%, 90.3% had undetectable HIV RNA, and 22.9% had a prior history of treatment failure. There was no significant difference in condom usage in the prior 30 days between serodiscordant and seroconcordant couples. Factors of index HIV-infected patients associated with serodiscordant relationships were younger age (odds ratio [OR] 1.04 per 5 years; 95% confidence interval [CI] 1.01-1.06), receiving care at the general hospital (OR 1.73; 95% CI 1.08-2.78), a shorter duration of relationship (OR 1.04 per year; 95% CI 1.01-1.07), a higher nadir CD4 count (OR 1.06 per 50 cells/mm3; 95% CI 1.1-1.13), and not receiving a protease inhibitor-based regimen (OR 2.04; 95% CI 1.06-3.96). CONCLUSIONS:A high number of serodiscordant couples was determined. Partners' information should be retrieved as a holistic approach. Interventions for minimizing HIV transmission within serodiscordant couples should be evaluated and implemented.

The clinical syndrome of disseminated nontuberculous mycobacterial (NTM) infection in patients who were previously healthy is now well recognized to be associated with an acquired autoantibody to Interferon gamma (Anti IFN- γ autoantibody). However, the risk factors of this syndrome remain unknown.We performed an unmatched case control study among patients with NTM diseases who were diagnosed and treated at Siriraj Hospital, Bangkok, Thailand. Anti-IFN autoantibody was detected by enzyme-linked immunosorbent assay (ELISA) method. Cases were patients with NTM diseases and detectable anti IFN- γ autoantibody. Controls were randomly selected from those with undetectable anti IFN- γ autoantibody. Data from both groups including demographic data, clinical presentation, laboratory results, other risk factors and HLA genotypes were collected. Univariate and multivariate analyses were performed to identify independent risk factors for this syndrome.70 cases (mean age 50 ± 11 years) and 70 controls (mean age 58 ± 18 years) were enrolled into the study. Mycobacterial abscessus was the most common NTM pathogen found in both groups (72.9% in cases and 41.4% in controls respectively). However, disseminated NTM disease was significantly more common in cases (92.9%) than in the controls (14.3%, p

Introduction Outbreaks of syphilis have been described among HIV‐infected men who have sex with men (MSM) in Western communities, whereas reports in Asian countries are limited. We aimed to characterize the incidence and temporal trends of syphilis among HIV‐infected MSM compared with HIV‐infected non‐MSM in Asian countries. Methods Patients enrolled in the TREAT Asia HIV Observational Database cohort and with a negative non‐treponemal test since enrolment were analyzed. Incidence of syphilis seroconversion, defined as a positive non‐treponemal test after previously testing negative, was evaluated among patients at sites performing non‐treponemal tests at least annually. Factors associated with syphilis seroconversion were investigated at sites doing non‐treponemal testing in all new patients and subsequently testing routinely or when patients were suspected of having syphilis. Results We included 1010 patients from five sites that performed non‐treponemal tests in all new patients; those included had negative non‐treponemal test results during enrolment and subsequent follow‐ups. Among them, 657 patients were from three sites conducting regular non‐treponemal testing. The incidence of syphilis seroconversion was 5.38/100 person‐years (PY). Incidence was higher in MSM than non‐MSM (7.64/100 PY vs. 2.44/100 PY, p

BACKGROUND: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. METHODS: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 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. RESULTS: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 50 vs. ≤30, hazard ratio [HR] 5.39, 95%CI 2.52-11.50, p

BACKGROUND:HIV drug resistance (HIVDR) is the major cause of treatment failure after scaling up of antiretroviral therapy (ART). HIVDR testing prior to ART initiation is not routinely performed in resource-limited settings. We aimed to assess the prevalence of primary HIVDR by short reverse transcriptase (RT) genotypic resistance assay and evaluate of the impact of the mutations on the treatment outcomes. METHODS:A prospective cohort study was conducted in treatment-naïve HIV-infected patients. Fourteen major mutations of codon 99-191 on the RT gene were selected (K103N, V106A/M, V108I, Q151M, Y181C/I, M184V/I, Y188C/L/H, and G190S/A) at a cost of testing of 35 USD. The association between the presence of primary HIVDR and undetectable HIV RNA (

BACKGROUND:We assessed the effects of hepatitis B (HBV) or hepatitis C (HCV) co-infection on outcomes of antiretroviral therapy (ART) in HIV-infected patients enrolled in the TREAT Asia HIV Observational Database (TAHOD), a multi-center cohort of HIV-infected patients in the Asia-Pacific region. METHODS:Patients testing HBs antigen (Ag) or HCV antibody (Ab) positive within enrollment into TAHOD were considered HBV or HCV co-infected. Factors associated with HBV and/or HCV co-infection were assessed by logistic regression models. Factors associated with post-ART HIV immunological response (CD4 change after six months) and virological response (HIV RNA

BACKGROUND:Dyslipidemia as a risk factor of cardiovascular disease is common especially in HIV-infected patients who are using protease inhibitors (PIs) including atazanavir. Pitavastatin has less drug-drug interactions and demonstrable efficacy in decreasing lipid levels in non HIV-infected individuals. MATERIALS AND METHODS:This study was a randomized, double-blind, crossover study comparing the safety and efficacy of pitavastatin vs placebo in HIV-infected patients with dyslipidemia and receiving atazanavir/ritonavir (ATV/r). Patients were randomized to receive either placebo or pitavastatin for 12 weeks. The follow-up visits were every 4 weeks until the end of the study. RESULTS:A total of 12 HIV-infected patients were enrolled to each study group. Of all, 14 (58%) patients were men and mean (standard deviation, SD) age was 48.1 (1.8) years. At 12 weeks of treatment with pitavastatin compared to placebo; mean [95% confidence interval (CI)] total cholesterol (TC) was 207 (187.3, 226.8) mg/dL vs 246.3 (226.5, 266) mg/dL (p

Regional and subtype-specific mutational patterns of HIV-1 transmitted drug resistance (TDR) are essential for informing first-line antiretroviral (ARV) therapy guidelines and designing diagnostic assays for use in regions where standard genotypic resistance testing is not affordable. We sought to understand the molecular epidemiology of TDR and to identify the HIV-1 drug-resistance mutations responsible for TDR in different regions and virus subtypes.We reviewed all GenBank submissions of HIV-1 reverse transcriptase sequences with or without protease and identified 287 studies published between March 1, 2000, and December 31, 2013, with more than 25 recently or chronically infected ARV-naïve individuals. These studies comprised 50,870 individuals from 111 countries. Each set of study sequences was analyzed for phylogenetic clustering and the presence of 93 surveillance drug-resistance mutations (SDRMs). The median overall TDR prevalence in sub-Saharan Africa (SSA), south/southeast Asia (SSEA), upper-income Asian countries, Latin America/Caribbean, Europe, and North America was 2.8%, 2.9%, 5.6%, 7.6%, 9.4%, and 11.5%, respectively. In SSA, there was a yearly 1.09-fold (95% CI: 1.05-1.14) increase in odds of TDR since national ARV scale-up attributable to an increase in non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance. The odds of NNRTI-associated TDR also increased in Latin America/Caribbean (odds ratio [OR] = 1.16; 95% CI: 1.06-1.25), North America (OR = 1.19; 95% CI: 1.12-1.26), Europe (OR = 1.07; 95% CI: 1.01-1.13), and upper-income Asian countries (OR = 1.33; 95% CI: 1.12-1.55). In SSEA, there was no significant change in the odds of TDR since national ARV scale-up (OR = 0.97; 95% CI: 0.92-1.02). An analysis limited to sequences with mixtures at less than 0.5% of their nucleotide positions—a proxy for recent infection—yielded trends comparable to those obtained using the complete dataset. Four NNRTI SDRMs—K101E, K103N, Y181C, and G190A—accounted for >80% of NNRTI-associated TDR in all regions and subtypes. Sixteen nucleoside reverse transcriptase inhibitor (NRTI) SDRMs accounted for >69% of NRTI-associated TDR in all regions and subtypes. In SSA and SSEA, 89% of NNRTI SDRMs were associated with high-level resistance to nevirapine or efavirenz, whereas only 27% of NRTI SDRMs were associated with high-level resistance to zidovudine, lamivudine, tenofovir, or abacavir. Of 763 viruses with TDR in SSA and SSEA, 725 (95%) were genetically dissimilar; 38 (5%) formed 19 sequence pairs. Inherent limitations of this study are that some cohorts may not represent the broader regional population and that studies were heterogeneous with respect to duration of infection prior to sampling.Most TDR strains in SSA and SSEA arose independently, suggesting that ARV regimens with a high genetic barrier to resistance combined with improved patient adherence may mitigate TDR increases by reducing the generation of new ARV-resistant strains. A small number of NNRTI-resistance mutations were responsible for most cases of high-level resistance, suggesting that inexpensive point-mutation assays to detect these mutations may be useful for pre-therapy screening in regions with high levels of TDR. In the context of a public health approach to ARV therapy, a reliable point-of-care genotypic resistance test could identify which patients should receive standard first-line therapy and which should receive a protease-inhibitor-containing regimen.

Introduction First‐line antiretroviral therapy (ART) failure often results from the development of resistance‐associated mutations (RAMs). Three patterns, including thymidine analogue mutations (TAMs), 69 Insertion (69Ins) and the Q151M complex, are associated with resistance to multiple‐nucleoside reverse transcriptase inhibitors (NRTIs) and may compromise treatment options for second‐line ART. Methods We investigated patterns and factors associated with multi‐NRTI RAMs at first‐line failure in patients from The TREAT Asia Studies to Evaluate Resistance – Monitoring study (TASER‐M), and evaluated their impact on virological responses at 12 months after switching to second‐line ART. RAMs were compared with the IAS‐USA 2013 mutations list. We defined multi‐NRTI RAMs as the presence of either Q151M; 69Ins; ≥2 TAMs; or M184V+≥1 TAM. Virological suppression was defined as viral load (VL) 2 years (OR=6.25, 95% CI [2.39–16.36], p

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

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.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.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

In resource-constrained settings, tuberculosis (TB) is a common opportunistic infection and cause of death in HIV-infected persons. TB may be present at the start of antiretroviral therapy (ART), but it is often under-diagnosed. We describe approaches to TB diagnosis and screening of TB in ART programs in low- and middle-income countries.We surveyed ART programs treating HIV-infected adults in sub-Saharan Africa, Asia and Latin America in 2012 using online questionnaires to collect program-level and patient-level data. Forty-seven sites from 26 countries participated. Patient-level data were collected on 987 adult TB patients from 40 sites (median age 34.7 years; 54% female). Sputum smear microscopy and chest radiograph were available in 47 (100%) sites, TB culture in 44 (94%), and Xpert MTB/RIF in 23 (49%). Xpert MTB/RIF was rarely available in Central Africa and South America. In sites with access to these diagnostics, microscopy was used in 745 (76%) patients diagnosed with TB, culture in 220 (24%), and chest X-ray in 688 (70%) patients. When free of charge culture was done in 27% of patients, compared to 21% when there was a fee (p = 0.033). Corresponding percentages for Xpert MTB/RIF were 26% and 15% of patients (p = 0.001). Screening practices for active disease before starting ART included symptom screening (46 sites, 98%), chest X-ray (38, 81%), sputum microscopy (37, 79%), culture (16, 34%), and Xpert MTB/RIF (5, 11%).Mycobacterial culture was infrequently used despite its availability at most sites, while Xpert MTB/RIF was not generally available. Use of available diagnostics was higher when offered free of charge.

BACKGROUND:The emergence and transmission of HIV-1 drug resistance (HIVDR) has raised concerns after rapid global antiretroviral therapy (ART) scale-up. There are limited data on the epidemiology of primary HIVDR in resource-limited settings in Asia. We aimed to determine the prevalence and compare the distribution of HIVDR in a cohort of ART-naïve Asian patients with recent and chronic HIV-1 infection. METHODS:Multicenter prospective study was conducted in ART-naïve patients between 2007 and 2010. Resistance-associated mutations (RAMs) were assessed using the World Health Organization 2009 list for surveillance of primary HIVDR. RESULTS:A total of 458 patients with recent and 1,340 patients with chronic HIV-1 infection were included in the analysis. The overall prevalence of primary HIVDR was 4.6%. Recently infected patients had a higher prevalence of primary HIVDR (6.1% vs. 4.0%, p = 0.065) and frequencies of RAMs to protease inhibitors (PIs; 3.9% vs. 1.0%, p

This study examined characteristics of HIV-infected patients in the TREAT Asia HIV Observational Database who were lost to follow-up (LTFU) from treatment and care. Time from last clinic visit to 31 March 2009 was analysed to determine the interval that best classified LTFU. Patients defined as LTFU were then categorised into permanently LTFU (never returned) and temporary LTFU (re-entered later), and these groups compared. A total of 3626 patients were included (71% male). No clinic visits for 180 days was the best-performing LTFU definition (sensitivity 90.6%, specificity 92.3%). During 7697 person-years of follow-up, 1648 episodes of LFTU were recorded (21.4 per 100-person-years). Patients LFTU were younger (P=0.002), had HIV viral load ≥500 copies/mL or missing (P=0.021), had shorter history of HIV infection (P=0.048), and received no, single- or double-antiretroviral therapy, or a triple-drug regimen containing a protease inhibitor (P