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Administration of a single broadly neutralizing human immunodeficiency virus (HIV)-specific antibody to HIV-infected persons leads to the development of antibody-resistant virus in the absence of antiretroviral therapy (ART). It is possible that monotherapy with UB-421, an antibody that blocks the virus-binding site on human CD4+ T cells, could induce sustained virologic suppression without induction of resistance in HIV-infected persons after analytic treatment interruption.We conducted a nonrandomized, open-label, phase 2 clinical study evaluating the safety, pharmacokinetics, and antiviral activity of UB-421 monotherapy in HIV-infected persons undergoing analytic treatment interruption. All the participants had undetectable plasma viremia (20 copies of HIV RNA per milliliter) at the screening visit. After discontinuation of ART, participants received eight intravenous infusions of UB-421, at a dose of either 10 mg per kilogram of body weight every week (Cohort 1) or 25 mg per kilogram every 2 weeks (Cohort 2). The primary outcome was the time to viral rebound (≥400 copies per milliliter).A total of 29 participants were enrolled, 14 in Cohort 1 and 15 in Cohort 2. Administration of UB-421 maintained virologic suppression (20 copies per milliliter) in all the participants (94.5% of measurements at study visits 2 through 9) during analytic treatment interruption, with intermittent viral blips (range, 21 to 142 copies per milliliter) observed in 8 participants (28%). No study participants had plasma viral rebound to more than 400 copies per milliliter. CD4+ T-cell counts remained stable throughout the duration of the study. Rash, mostly of grade 1, was a common and transient adverse event; one participant discontinued the study drug owing to a rash. A decrease in the population of CD4+ regulatory T cells was observed during UB-421 monotherapy.UB-421 maintained virologic suppression (during the 8 to 16 weeks of study) in participants in the absence of ART. One participant discontinued therapy owing to a rash. (Funded by United Biomedical and others; ClinicalTrials.gov number, NCT02369146.).

Missed clinic visits can lead to poorer treatment outcomes in HIV-infected patients. Suboptimal antiretroviral therapy (ART) adherence has been linked to subsequent missed visits. Knowing the determinants of missed visits in Asian patients will allow for appropriate counselling and intervention strategies to ensure continuous engagement in care. A missed visit was defined as having no assessments within six months. Repeated measures logistic regression was used to analyse factors associated with missed visits. A total of 7100 patients were included from 12 countries in Asia with 2676 (37.7%) having at least one missed visit. Patients with early suboptimal self-reported adherence95% were more likely to have a missed visit compared to those with adherence ≥95% (OR = 2.55, 95% CI(1.81-3.61)). Other factors associated with having a missed visit were homosexual (OR = 1.45, 95%CI(1.27-1.66)) and other modes of HIV exposure (OR = 1.48, 95%CI(1.27-1.74)) compared to heterosexual exposure; using PI-based (OR = 1.33, 95%CI(1.15-1.53) and other ART combinations (OR = 1.79, 95%CI(1.39-2.32)) compared to NRTI+NNRTI combinations; and being hepatitis C co-infected (OR = 1.27, 95%CI(1.06-1.52)). Patients aged30 years (31-40 years OR = 0.81, 95%CI(0.73-0.89); 41-50 years OR = 0.73, 95%CI(0.64-0.83); and50 years OR = 0.77, 95%CI(0.64-0.93)); female sex (OR = 0.81, 95%CI(0.72-0.90)); and being from upper middle (OR = 0.78, 95%CI(0.70-0.80)) or high-income countries (OR = 0.42, 95%CI(0.35-0.51)), were less likely to have missed visits. Almost 40% of our patients had a missed clinic visit. Early ART adherence was an indicator of subsequent clinic visits. Intensive counselling and adherence support should be provided at ART initiation in order to optimise long-term clinic attendance and maximise treatment outcomes.

Introduction:Cardiovascular diseases (CVD) are becoming more prevalent in HIV-infected populations as they age largely due to improved treatment outcomes. Assessment of CVD risk and CVD risk factors in HIV-positive populations has focused on high income settings, while there are limited studies evaluating CVD in HIV-positive populations in the Asian region.Materials and Methods:We provided an overview of the prevalence and incidence of CVD and its risk factors in adult HIV-positive populations, and of the strategies currently in place for CVD management in the Asian region.Results:Studies from the Asian region showed that CVD and CVD risk factors, such as dyslipidaemia, elevated blood glucose, obesity and smoking, are highly prevalent in HIV-positive populations. A number of studies suggested that HIV infection and antiretroviral therapy may contribute to increased CVD risk. National HIV treatment guidelines provide some directions regarding CVD risk prevention and management in the HIV-infected population, however, they are limited in number and scope.Conclusion:Development and consolidation of guidelines for integrated CVD and HIV care are essential to control the burden of CVD in HIV-positive populations. To inform guidelines, policies and practice in the Asian region, research should focus on exploring appropriate CVD risk screening strategies and estimating current and future CVD mortality and morbidity rates.

In Human Immunodeficiency Virus–1 treatment-naive adults, a fixed combination of doravirine/lamivudine/tenofovir disoproxil fumarate demonstrated non-inferior antiretroviral efficacy to efavirenz/emtricitabine/tenofovir disoproxil fumarate at week 48, with similar immunologic effects, low viral drug resistance rates, and significantly fewer neuropsychiatric adverse events., Background Doravirine (DOR), a novel non-nucleoside reverse-transcriptase inhibitor (NNRTI), is active against wild-type Human Immunodeficiency Virus (HIV)-1 and the most common NNRTI-resistant variants, and has a favorable and unique in vitro resistance profile. Methods DRIVE-AHEAD is a phase 3, double-blind, non-inferiority trial. Antiretroviral treatment–naive adults with ≥1000 HIV-1 RNA copies/mL were randomized (1:1) to once-daily, fixed-dose DOR at 100 mg, lamivudine at 300 mg, and tenofovir disoproxil fumarate (TDF) at 300 mg (DOR/3TC/TDF) or to efavirenz at 600 mg, emtricitabine at 200 mg, and TDF at 300 mg (EFV/FTC/TDF) for 96 weeks. The primary efficacy endpoint was the proportion of participants with

Summary Background Effective two-drug regimens could decrease long-term drug exposure and toxicity with HIV-1 antiretroviral therapy (ART). We therefore aimed to evaluate the efficacy and safety of a two-drug regimen compared with a three-drug regimen for the treatment of HIV-1 infection in ART-naive adults. Methods We conducted two identically designed, multicentre, double-blind, randomised, non-inferiority, phase 3 trials: GEMINI-1 and GEMINI-2. Both studies were done at 192 centres in 21 countries. We included participants (≥18 years) with HIV-1 infection and a screening HIV-1 RNA of 500 000 copies per mL or less, and who were naive to ART. We randomly assigned participants (1:1) to receive a once-daily two-drug regimen of dolutegravir (50 mg) plus lamivudine (300 mg) or a once-daily three-drug regimen of dolutegravir (50 mg) plus tenofovir disoproxil fumarate (300 mg) and emtricitabine (200 mg). Both drug regimens were administered orally. We masked participants and investigators to treatment assignment: dolutegravir was administered as single-entity tablets (similar to its commercial formulation, except with a different film colour), and lamivudine tablets and tenofovir disoproxil fumarate and emtricitabine tablets were over-encapsulated to visually match each other. Primary endpoint was the proportion of participants with HIV-1 RNA of less than 50 copies per mL at week 48 in the intention-to-treat-exposed population, using the Snapshot algorithm and a non-inferiority margin of −10%. Safety analyses were done on the safety population. GEMINI-1 and GEMINI-2 are registered with ClinicalTrials.gov, numbers NCT02831673 and NCT02831764, respectively. Findings Between July 18, 2016, and March 31, 2017, 1441 participants across both studies were randomly assigned to receive either the two-drug regimen (n=719) or three-drug regimen (n=722). At week 48 in the GEMINI-1 intention-to-treat-exposed population, 320 (90%) of 356 participants receiving the two-drug regimen and 332 (93%) of 358 receiving the three-drug regimen achieved plasma HIV-1 RNA of less than 50 copies per mL (adjusted treatment difference −2·6%, 95% CI −6·7 to 1·5); in GEMINI-2, 335 (93%) of 360 in the two-drug regimen and 337 (94%) of 359 in the three-drug regimen achieved HIV-1 RNA of less than 50 copies per mL (adjusted treatment difference −0·7%, 95% CI −4·3 to 2·9), showing non-inferiority at a −10% margin in both studies (pooled analysis: 655 [91%] of 716 in the two-drug regimen vs 669 [93%] of 717 in the three-drug regimen; adjusted treatment difference −1·7%, 95% CI −4·4 to 1·1). Numerically, more drug-related adverse events occurred with the three-drug regimen than with the two-drug regimen (169 [24%] of 717 vs 126 [18%] of 716); few participants discontinued because of adverse events (16 [2%] in the three-drug regimen and 15 [2%] in the two-drug regimen). Two deaths were reported in the two-drug regimen group of GEMINI-2, but neither was considered to be related to the study medication. Interpretation The non-inferior efficacy and similar tolerability profile of dolutegravir plus lamivudine to a guideline-recommended three-drug regimen at 48 weeks in ART-naive adults supports its use as initial therapy for patients with HIV-1 infection. Funding ViiV Healthcare.

Treatment interruptions (TIs) of combination antiretroviral therapy (cART) are known to lead to unfavourable treatment outcomes but do still occur in resource-limited settings. We investigated the effects of TI associated with adverse events (AEs) and non-AE-related reasons, including their durations, on treatment failure after cART resumption in HIV-infected individuals in Asia.Patients initiating cART between 2006 and 2013 were included. TI was defined as stopping cART for1 day. Treatment failure was defined as confirmed virological, immunological or clinical failure. Time to treatment failure during cART was analysed using Cox regression, not including periods off treatment. Covariables with P0.10 in univariable analyses were included in multivariable analyses, where P0.05 was considered statistically significant.Of 4549 patients from 13 countries in Asia, 3176 (69.8%) were male and the median age was 34 years. A total of 111 (2.4%) had TIs due to AEs and 135 (3.0%) had TIs for other reasons. Median interruption times were 22 days for AE and 148 days for non-AE TIs. In multivariable analyses, interruptions30 days were associated with failure (31-180 days HR = 2.66, 95%CI (1.70-4.16); 181-365 days HR = 6.22, 95%CI (3.26-11.86); and365 days HR = 9.10, 95% CI (4.27-19.38), all P0.001, compared to 0-14 days). Reasons for previous TI were not statistically significant (P = 0.158).Duration of interruptions of more than 30 days was the key factor associated with large increases in subsequent risk of treatment failure. If TI is unavoidable, its duration should be minimised to reduce the risk of failure after treatment resumption.

Many HIV-infected individuals do not enter health care until late in the infection course. Despite encouraging earlier testing, this situation has continued for several years. We investigated the prevalence of late presenters and factors associated with late presentation among HIV-infected patients in an Asian regional cohort. This cohort study included HIV-infected patients with their first positive HIV test during 2003–2012 and CD4 count and clinical status data within 3 months of that test. Factors associated with late presentation into care (CD4 count

Background The World Health Organization recommends HBV–HIV-coinfected individuals start antiretroviral therapy containing tenofovir. Here we describe first-line tenofovir use and treatment outcomes in coinfected patients in Asia. Methods HBV surface antigen positive patients enrolled in the TREAT Asia HIV Observational Database who started first-line antiretroviral therapy were included. Logistic regression adjusted for period of treatment initiation was used to determine factors associated with tenofovir use. Generalized estimating equations were used to evaluate factors associated with alanine transaminase levels and CD4+ T-cell count on treatment. Results There were 548 eligible patients, of whom 149 (27.2%) started tenofovir. Patients treated in high/high-middle income countries (odds ratio 4.4 versus low/low-middle, 95% CI 2.6, 7.4; P+ T-cell response. Conclusions HBV–HIV-coinfected patients in Asia are most likely to receive tenofovir if they are treated in a high/high-middle income country, have elevated alanine transaminase levels and are hepatitis C antibody negative. Compared to other antiretroviral therapies, tenofovir-based regimens more effectively reduce liver inflammation in HBV–HIV-coinfection but do not result in superior CD4+ T-cell recovery.

This study uses data mining techniques to find out the risk factors for the tuberculosis (TB) patients with drug-induced liver injury (DILI). The Taiwan National Health Insurance Database is used for collection of domestic TB cases during 2004-2011 to study these TB patients and their drug prescribing patterns in order to build a model to predict the risk of drug-drug interaction between hepatitis B and C, acquired immune deficiency syndrome (AIDS) and TB. The results out of the total 188,032 TB patients have shown that 77,574 have taken anti-TB drugs. Afterwards, DILI occurred in 0.7% of the cases. Besides, for those DILI patients associated with TB and hepatitis B or C, this study reveals that DILI is associated with the use of ethambutol and rifampin. It is suggested that TB patients associated with hepatitis C should pay attention to their uses of rifampicin, and TB patients (especially males) associated with hepatitis B should pay attention to the ethambutol's impact on DILI. Moreover, our results also showed that having both AIDS and TB shows no significant effect on DILI.

Hematological malignancies have continued to be highly prevalent among people living with HIV (PLHIV). This study assessed the occurrence of, risk factors for, and outcomes of hematological and nonhematological malignancies in PLHIV in Asia.Incidence of malignancy after cohort enrollment was evaluated. Factors associated with development of hematological and nonhematological malignancy were analyzed using competing risk regression and survival time using Kaplan-Meier.Of 7455 patients, 107 patients (1%) developed a malignancy: 34 (0.5%) hematological [0.08 per 100 person-years (/100PY)] and 73 (1%) nonhematological (0.17/100PY). Of the hematological malignancies, non-Hodgkin lymphoma was predominant (n = 26, 76%): immunoblastic (n = 6, 18%), Burkitt (n = 5, 15%), diffuse large B-cell (n = 5, 15%), and unspecified (n = 10, 30%). Others include central nervous system lymphoma (n = 7, 21%) and myelodysplastic syndrome (n = 1, 3%). Nonhematological malignancies were mostly Kaposi sarcoma (n = 12, 16%) and cervical cancer (n = 10, 14%). Risk factors for hematological malignancy included age50 vs. ≤30 years [subhazard ratio (SHR) = 6.48, 95% confidence interval (CI): 1.79 to 23.43] and being from a high-income vs. a lower-middle-income country (SHR = 3.97, 95% CI: 1.45 to 10.84). Risk was reduced with CD4 351-500 cells/µL (SHR = 0.20, 95% CI: 0.05 to 0.74) and CD4500 cells/µL (SHR = 0.14, 95% CI: 0.04 to 0.78), compared to CD4 ≤200 cells/µL. Similar risk factors were seen for nonhematological malignancy, with prior AIDS diagnosis showing a weak association. Patients diagnosed with a hematological malignancy had shorter survival time compared to patients diagnosed with a nonhematological malignancy.Nonhematological malignancies were common but non-Hodgkin lymphoma was more predominant in our cohort. PLHIV from high-income countries were more likely to be diagnosed, indicating a potential underdiagnosis of cancer in low-income settings.

Purpose Renal disease is common among people living with human immunodeficiency virus (HIV). However, there is limited information on the incidence and risk factors associated with renal dysfunction among this population in Asia. Methods We used data from the TREAT Asia HIV Observational Database. Patients were included if they started antiretroviral therapy during or after 2003, had a serum creatinine measurement at antiretroviral therapy initiation (baseline), and had at least 2 follow-up creatinine measurements taken ≥3 months apart. Patients with a baseline estimated glomerular filtration rate (eGFR) ≤60 mL/min/1.73 m2 were excluded. Chronic kidney disease was defined as 2 consecutive eGFR values ≤60 mL/min/1.73 m2 taken ≥3 months apart. Generalized estimating equations were used to identify factors associated with eGFR change. Competing risk regression adjusted for study site, age and sex, and cumulative incidence plots were used to evaluate factors associated with chronic kidney disease (CKD). Results Of 2547 patients eligible for this analysis, tenofovir was being used by 703 (27.6%) at baseline. Tenofovir use, high baseline eGFR, advanced HIV disease stage, and low nadir CD4 were associated with a decrease in eGFR during follow-up. Chronic kidney disease occurred at a rate of 3.4 per 1000 patient/years. Factors associated with CKD were tenofovir use, old age, low baseline eGFR, low nadir CD4, and protease inhibitor use. Conclusions There is an urgent need to enhance renal monitoring and management capacity among at-risk groups in Asia and improve access to less nephrotoxic antiretrovirals.

Introduction Cotrimoxazole (CTX) is recommended as prophylaxis against Pneumocystis jiroveci pneumonia, malaria and other serious bacterial infections in HIV‐infected patients. Despite its in vitro activity against Mycobacterium tuberculosis, the effects of CTX preventive therapy on tuberculosis (TB) remain unclear. Methods Adults living with HIV enrolled in a regional observational cohort in Asia who had initiated combination antiretroviral therapy (cART) were included in the analysis. Factors associated with new TB diagnoses after cohort entry and survival after cART initiation were analysed using Cox regression, stratified by site. Results A total of 7355 patients from 12 countries enrolled into the cohort between 2003 and 2016 were included in the study. There were 368 reported cases of TB after cohort entry with an incidence rate of 0.99 per 100 person‐years (/100 pys). Multivariate analyses adjusted for viral load (VL), CD4 count, body mass index (BMI) and cART duration showed that CTX reduced the hazard for new TB infection by 28% (HR 0.72, 95% CI l 0.56, 0.93). Mortality after cART initiation was 0.85/100 pys, with a median follow‐up time of 4.63 years. Predictors of survival included age, female sex, hepatitis C co‐infection, TB diagnosis, HIV VL, CD4 count and BMI. Conclusions CTX was associated with a reduction in the hazard for new TB infection but did not impact survival in our Asian cohort. The potential preventive effect of CTX against TB during periods of severe immunosuppression should be further explored.

BACKGROUND Current treatment guidelines for HIV infection recommend routine CD4 lymphocyte (CD4) count monitoring in patients with viral suppression. This may have a limited impact on influencing care as clinically meaningful CD4 decline rarely occurs during viral suppression. METHODS In a regional HIV observational cohort in the Asia-Pacific region, patients with viral suppression (2 consecutive viral loads

Introduction Evidence about the optimal timing for total hip replacement (THR) in HIV-positive patients is scant. Hypothesis Preoperative criteria: cluster of differentiation 4 (CD4) counts > 200 cells/mm3 and an undetectable HIV virus load before THR, improve infection rates, aseptic loosenings, and functional outcomes. Materials and methods We recruited 16 HIV-positive patients who had undergone 25 THRs between 2003 and 2015. None had hemophilia, and none were intravenous drug users (IVDUs). Results Their mean age was 41.2 years (range: 24–60); minimum follow-up was 12 months (mean: 64.6); mean duration of prophylactic antibiotics was 2.9 days (range: 1–5); and mean hospital length of stay was 6.0 days (range: 4–11). No patients were treated with subsequent oral antibiotics. The mean preoperative CD4 count was 464.1 ± 237.0 (range: 235–904) cells/mm3. There were no early superficial surgical site infections, late periprosthetic joint infections, or aseptic loosenings. Post-surgery Harris Hip score was significantly (p Discussion A preoperative CD4 count > 200 cell/mm3 and an undetectable HIV virus load might indicate optimal timing for elective THRs in HIV-positive patients without hemophilia and not IVDUs. Level of evidence IV, retrospective or historical series.

Elevated CD8 counts with combination antiretroviral therapy (cART) initiation may be an early warning indicator for future treatment failure. Thus, we investigated whether elevated CD8 counts were associated with virological failure (VF) in the first 4 years of cART in Asian HIV-infected patients in a multicenter regional cohort. We included patients from the TREAT Asia HIV Observational Database (TAHOD). Patients were included in the analysis if they started cART between 1996 and 2013 with at least one CD8 measurement within 6 months prior to cART initiation and at least one CD8 and viral load (VL) measurement beyond 6 months after starting cART. We defined VF as VL ≥400 copies/mL after 6 months on cART. Elevated CD8 was defined as CD8 ≥1200 cells/μL. Time to VF was modeled using Cox regression analysis, stratified by site. In total, 2475 patients from 19 sites were included in this analysis, of whom 665 (27%) experienced VF in the first 4 years of cART. The overall rate of VF was 12.95 per 100 person-years. In the multivariate model, the most recent elevated CD8 was significantly associated with a greater hazard of VF (HR = 1.35, 95% CI 1.14–1.61; P = 0.001). However, the sensitivity analysis showed that time-lagged CD8 measured at least 6 months prior to our virological endpoint was not statistically significant (P = 0.420). This study indicates that the relationship between the most recent CD8 count and VF was possibly due to the CD8 cells reacting to the increase in VL rather than causing the VL increase itself. However, CD8 levels may be a useful indicator for VF in HIV-infected patients after starting cART.

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/Purpose In the past few years, many new subtypes in hepatitis C virus (HCV) genotype 6 have been identified. The aim of this study was to modify the multiplex real-time polymerase chain reaction (RT-PCR) protocol and use it to determine the HCV subtypes of a group of Taiwanese injection drug users (IDUs). Methods We used 76 serum specimens collected in northern Taiwan in 2008. Multiplex RT-PCR was used for HCV subtyping among those serum samples having anti-HCV antibodies. Twenty cases were randomly selected for comparison with subtyping results from Inno-LiPa II tests and phylogenetic tree analysis using NS5B sequences. Results Multiplex RT-PCR assays showed that 60.5% (46/76) of IDUs had single HCV infection. Three out of 76 (3.9%) had double HCV infection (1b/6a, 2a/2b and 2b/6a). Besides this, 27.6% (21/76) had no HCV signal. One IDU had subtype 6n and two had subtype 6w infection. Inno-LiPa II tests misclassified all 6n and 6w cases as 1b subtype. Conclusion Our modified multiplex RT-PCR protocol can be used to support molecular epidemiological studies and laboratory diagnoses of different HCV subtypes including genotype 6.

BackgroundProlonged exposure to combination antiretroviral therapy (CART) may result in hyperlipidemia and other metabolic complications. This study aimed to evaluate the clinical, virologic, and immunologic outcomes in HIV-infected patients with hyperlipidemia whose CART was switched to atazanavir-containing antiretroviral regimens.MethodsIn this 48-week prospective, observational study that was conducted at designated hospitals for HIV care in Taiwan, HIV-infected patients aged 18 years or older who had developed hyperlipidemia after receiving CART that did not contain atazanavir were enrolled. Antiretroviral regimens were switched to regimens containing two nucleoside reverse-transcriptase inhibitors plus atazanavir 400mg once daily or atazanavir 300mg boosted with ritonavir 100mg once daily. The lipid profiles, including total triglycerides, total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, CD4+ lymphocyte counts, and plasma HIV RNA load were determined every 3 months.ResultsSixty-six patients with hyperlipidemia were enrolled. At the end of the study, triglyceride levels declined by 49.0% (p=0.0002) and total cholesterol levels by 18.1% from baseline (p

Background Information regarding human immunodeficiency virus (HIV) infections and acquired immunodeficiency syndrome (AIDS) in the elderly of Taiwan is limited. This study looked into the aforementioned issues. Methods Data from the National HIV/AIDS Registry, relating to individuals diagnosed in 2007, were analyzed. Results Among 1,975 HIV-infected individuals diagnosed in 2007, the elderly group (age ≧50 years) consisted of 153 subjects and the younger (control) group (age 15–39 years) consisted of 1,458 individuals. Some markers, such as primarily males/local Taiwanese, being unemployed, one third of subjects infected by means of intravenous drug use, and primarily diagnosed in hospitals, were similar between the two groups. The elderly group had more married, divorced, and separated individuals, and widows/widowers than the younger group. The causes of death differed insignificantly between the two groups. The younger group had more variety than the elderly group in distribution of occupations. Fewer prison-diagnosed HIV, high ratio of individuals developing AIDS, heterosexuals, high mortality, and unsupported marital status were significant markers of elderly HIV-infected subjects. Conclusion In Taiwan, elderly HIV infections have reflected the aforementioned characteristics. Some specific issues concerning elderly HIV infections, such as heterosexual predominance, high mortality and fewer men who have sex with men, are similar with reports from other countries. These characteristics can guide possible directions of social and health care interventions.

Background Doravirine (DOR) is a novel non-nucleoside reverse-transcriptase inhibitor (NNRTI). In the phase 3 DRIVE-AHEAD trial in HIV-1-infected treatment-naïve adults, DOR demonstrated noninferior efficacy to efavirenz (EFV) and favorable profiles for neuropsychiatric tolerability and lipids at 48 weeks. We present data through week 96. Methods DRIVE- AHEAD (Clinical Trials Registration: NCT02403674) is a phase 3, multicenter, double-blind, noninferiority trial that compared DOR with EFV. Eligible participants were HIV-1-infected treatment-naïve adults with pre-treatment HIV-1 RNA ≥1,000 copies/mL. Participants were randomized (1:1) to a fixed-dose regimen of DOR 100 mg, lamivudine 300 mg and tenofovir disoproxil fumarate 300 mg (DOR/3TC/TDF) QD or EFV 600 mg, emtricitabine 200 mg and TDF 300 mg (EFV/FTC/TDF) QD for up to 96 weeks. Randomization was stratified by screening HIV-1 RNA (≤/>100,000 copies/mL) and hepatitis B/C co-infection (yes/no). The efficacy endpoint of interest at week 96 was HIV-1 RNA Results Of 734 participants randomized, 728 received study drug and were included in analyses (mean age 33 years, 85% male, 48% white, 19% black, 34% Hispanic). At week 96, HIV-1 RNA Conclusion Week 96 results support non-inferiority of DOR/3TC/TFD to EFV/FTC/TDF established at Week 48 with no additional DOR resistance between week 48 and 96. DOR/3TC/TDF was safe and well-tolerated with fewer neuropsychiatric and rash events and favorable lipid profile compared with EFV/FTC/TDF. Disclosures C. Orkin, AbbVie, Abbott, Boehringer Ingelheim, BMS, Gilead, GSK, Janssen, ViiV: Grant Investigator and Research Contractor, Research grant and Research support. K. Squires, Merck & Co., Inc.: Ad Board, Ad Board. Gilead Sciences: Grant, Ad Board. VIIV: Ad Board, Ad Board. Bristol Myers Squibb: Ad Board, Ad Board. Janssen: Ad Board, Ad Board. J. M. Molina, Gilead: Scientific Advisor, Consulting fee. Merck: Scientific Advisor, Consulting fee. ViiV: Scientific Advisor, Consulting fee. Teva: Scientific Advisor, Consulting fee. P. Sax, Gilead: Consultant and Grant Investigator, Consulting fee, Grant recipient and Research grant. ViiV Healthcare: Consultant and Grant Investigator, Consulting fee, Grant recipient and Research grant. Merck: Consultant and Grant Investigator, Consulting fee, Grant recipient and Research grant. Janssen: Consultant, Consulting fee. BMS: Grant Investigator, Grant recipient and Research grant. W. Wong, Merck & Co., Inc.: Research Contractor, Research grant. G. Lin, Merck Sharp & Dohme, a subsidiary of Merck & Co., Inc.: Employee and Shareholder, May hold stock/stock options in the company and Salary. S. Kumar, Merck & Co., Inc.: Employee and Shareholder, Salary. G. Hanna, Merck & Co., Inc.: Employee and Shareholder, Salary. C. Hwang, Merck & Co., Inc.: Employee and Shareholder, Salary. E. Martin, Merck & Co., Inc.: Employee and Shareholder, Salary. H. Teppler, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA: Employee, May hold stock/stock options in the company and Salary.

Introduction Evidence about the optimal timing for total hip replacement (THR) in HIV-positive patients is scant. Hypothesis Preoperative criteria: cluster of differentiation 4 (CD4) counts > 200 cells/mm3 and an undetectable HIV virus load before THR, improve infection rates, aseptic loosenings, and functional outcomes. Materials and methods We recruited 16 HIV-positive patients who had undergone 25 THRs between 2003 and 2015. None had hemophilia, and none were intravenous drug users (IVDUs). Results Their mean age was 41.2 years (range: 24–60); minimum follow-up was 12 months (mean: 64.6); mean duration of prophylactic antibiotics was 2.9 days (range: 1–5); and mean hospital length of stay was 6.0 days (range: 4–11). No patients were treated with subsequent oral antibiotics. The mean preoperative CD4 count was 464.1 ± 237.0 (range: 235–904) cells/mm3. There were no early superficial surgical site infections, late periprosthetic joint infections, or aseptic loosenings. Post-surgery Harris Hip score was significantly (p Discussion A preoperative CD4 count > 200 cell/mm3 and an undetectable HIV virus load might indicate optimal timing for elective THRs in HIV-positive patients without hemophilia and not IVDUs. Level of evidence IV, retrospective or historical series.

The Taiwanese government has provided free highly active antiretroviral therapy since April 1997. Previously, we have reported on the molecular epidemiology of HIV-1 in Taiwan from 1988 to 1998. In addition, an outbreak of circulating recombinant form (CRF) 07_BC among intravenous drug users was noted in 2004. Therefore, the purposes of this study were to elucidate the distribution of HIV-1 subtypes among different high-risk groups in Taiwan from 1999 to 2000 and to conduct surveillance on drug resistance among treatment naïve patients from 1997 to 2000. Blood samples from 239 HIV-1/AIDS patients and their subtypes were examined using DNA sequencing and phylogenetic analysis. The results showed that among 226 male patients, 213 (94.2%) had subtype B, 11 (4.9%) had CRF01_AE, 1 had unique recombinant strain related to both CRF07_BC and CRF08_BC (strain T12-99TW) and 1 had CRF08_BC (strain L9312-00TW). The patients infected with T12-99TW and L9312-00TW were intravenous drug users and had needle-sharing experiences in Yunnan Province, China. Of the 13 HIV-1-infected females, 7 (53.8%) had subtype B, 5 (38.5%) had CRF01_AE, and 1 (7.7%) had subtype C. Phylogenetic analysis demonstrated that the neither strain T12-99TW nor L9312-00TW clustered with CRF07_BC strains isolated from Taiwanese intravenous drug users in 2004. In addition, 126 treatment naïve patients were selected for genotypic DR analysis and the results showed that 4.3% (2/47) homosexual males had M184V mutations. This is the first report on the identification of CRF08_BC and a unique recombinant strain related to both CRF07_BC and CRF08_BC in Taiwan.

A 23-year-old Asian man presented to our clinic with pitting edema of the lower limbs for 3 days and a small ulcer on his glans penis. He previously had unprotected sexual intercourse with different male partners and had previously used ketamine and ecstasy (3,4-methylenedioxy-N-methamphetamine). The patient had noticed a diffuse skin rash on his trunk, limbs, palms, and soles since several months ago, and secondary syphilis (RPR: >144 RU, TPHA: 2310 TU) was diagnosed 2 weeks prior to admission. A dose of benzathine penicillin was given upon admission, and fever developed the same evening. One week later, human immunodeficiency virus (HIV) infection was confirmed with western Blot analysis (his CD4-positive lymphocyte count was 500/cumm, viral load was 1230 copies/ml). A urinalysis result was positive for protein (3+) by dipstick. Biochemical examinations revealed hypoalbuminemia and massive proteinuria (blood urea nitrogen level, 15 mg/dl; creatinine level, 0.81 mg/dl; albumin level, 1.2 g/dl; urine protein-to-creatinine ratio, 13.8 g/g; and HbA1c level, 5.8%). Laboratory tests were negative for anti-nuclear antibodies, hepatitis B surface antigen, and anti-hepatitis C virus. Both kidneys were found to be enlarged on sonography. The renal biopsy findings are depicted in Figure 1.

Introduction. Benzodiazepines (BZDs) and zolpidem, zopiclone, and zaleplon (Z-drugs) are commonly prescribed to HIV-infected patients. We hypothesized that frequent BZD and Z-drug use among these patients may be associated with psychiatric illnesses, particularly in long-term users.Methods. We included 1,081 patients with HIV between 1998 and 2011 from the Taiwan National Health Insurance Research Database and matched them according to age, sex, and comorbidity with uninfected controls to investigate the psychiatric diagnoses and prescriptions of BZDs and Z-drugs. Cumulative defined daily dose (cDDD) was assessed as the indicator of the duration of medication exposure. Patients exhibiting a cDDD exceeding 180 were defined as long-term users.Results. The patients with HIV had an increased risk of any use (odds ratio (OR): 8.70, 95% confidence interval (CI): 6.82–10.97) and long-term use (OR: 5.06, 95% CI: 3.63–7.04) of BZD and Z-drugs compared with those without HIV during the follow-up after demographic data and psychiatric comorbidities were adjusted.Conclusion. A large proportion of the HIV-infected patients received prescriptions of BZDs and Z-drugs. Mood disorders, insomnia, anxiety disorders, HIV infection, and substance use disorder were substantial predictors among the BZD and Z-drug users. These findings suggest that providing psychiatric services for HIV-infected patients is vital.

In Taiwan, sexual transmission is responsible for most HIV-1 infections with two dominant subtypes, subtype B and CRF01_AE, distributing among homosexual and heterosexual groups, respectively. Recently, intravenous drug use has become an emerging route of HIV-1 transmission and contributed to a significant increase of HIV-1 infection. To characterize the HIV isolates responsible for the outbreak among intravenous drug users (IDUs), phylogenetic analysis was performed to analyze the protease/RT sequences amplified from HIV-1-infected IDUs at National Taiwan University Hospital and Taipei City STD Control Center. CRF07_BC, which is circulating in northern China, was demonstrated to account for the majority of HIV-1 infection in IDUs in the past 2 years. Although these Taiwanese CRF07_BC sequences shared the same breakpoint positions as those described in the CRF07_BC reference sequences, they formed a unique cluster in the phylogenetic tree, suggesting they originated from a founder virus. This finding was further supported by the relative low genetic diversity and unique sequence features. Our results demonstrated the emergence of CRF07_BC and its association with the HIV-1 outbreak among IDUs between 2004 and 2005 in Taiwan. This finding not only helps us to have a better understanding of the HIV evolution in Asia, but also has important implications for vaccine design in the future.

Relatively little is known regarding HIV disease natural history and response to antiretroviral treatments among Asian people infected with HIV. The Therapeutics Research, Education, and AIDS Training in Asia (TREAT Asia) HIV Observational Database (TAHOD) is a recently established collaborative observational cohort study that aims to assess HIV disease natural history in treated and untreated patients in the Asia-Pacific region.Observational data are collected on HIV-infected patients from 11 sites in the Asia-Pacific region. Data are centrally aggregated for analyses, with the first baseline and retrospective data transferred in September 2003. Retrospective data were analyzed to assess the response to highly active antiretroviral treatment (HAART) over a 6-month period in terms of changes in CD4 count and proportions of patients achieving an undetectable HIV viral load (400 copies/mL).By the end of May 2004, 1887 patients had been recruited to the TAHOD. Seventy-two percent of patients were male, with median age 36 years. Seventy-eight percent of patients reported HIV infection through heterosexual contact. Forty-three percent of patients had a previous AIDS diagnosis, of whom 55% had tuberculosis. The mean 6-month CD4 count increase was 115 cells/muL (SD=127) after starting triple-combination therapy. Smaller CD4 count increases were associated with a higher CD4 count before starting treatment, prior treatment with monotherapy or double therapy, and treatment with a HAART regimen containing a nucleoside reverse transcriptase inhibitor (NRTI) and/or protease inhibitor (PI) but without a nonnucleoside reverse transcriptase inhibitor (NNRTI). Five hundred and ninety-eight patients started HAART and had a viral load assessment at 6 months, with 69% attaining an undetectable viral load. Older patients, patients not exposed to HIV through heterosexual contact, and patients treated with HAART containing NRTIs and NNRTIs but without PIs were found to be more likely to achieve an undetectable level.Analyses of retrospective data in the TAHOD suggest that the overall response to HAART in Asian populations is similar to that seen in Western countries.

Neuropsychiatric complications of human immunodeficiency virus (HIV) infection or acquired immune deficiency syndrome (AIDS) may present clinically as acute or chronic organic brain syndrome, or mimic functional psychiatric diseases. Among such psychiatric diseases, mania tends to occur with increased frequency after the onset of AIDS. We report a case in which manic manifestations were noted before the diagnosis of AIDS. The patient had no past or family history of mood disorders, but had risk factors for HIV infection. He had a rapid downhill course from initial manic symptoms to depression, dementia and then death within 10 months. Such rapid cognitive deterioration into AIDS dementia after mania is consistent with previous reports. Cases like this will become more common with spread of the AIDS pandemic in Asian regions, including Taiwan. Clinicians should be mindful of HIV infection/AIDS as a differential diagnosis in patients with manic episodes and risk factors for HIV infection.

Objectives:To rapidly establish a temporary isolation ward to handle an unexpected sudden outbreak of severe acute respiratory syndrome (SARS) and to evaluate the implementation of exposure control measures by healthcare workers (HCWs) for SARS patients.Design:Rapid creation of 60 relatively negative pressure isolation rooms for 196 suspected SARS patients transferred from 19 hospitals and daily temperature recordings of 180 volunteer HCWs from 6 medical centers.Setting:A military hospital.Results:Of the 196 patients, 34 (17.3%) met the World Health Organization criteria for probable SARS with positive results of serologic testing for SARS-associated coronavirus (SARS-CoV), reverse transcriptase polymerase chain reaction (RT-PCR) from nasopharyngeal or throat swabs for SARS-CoV, or both. Seventy-four patients had suspected SARS based on unprotected exposure to SARS patients; three of them had positive results on RT-PCR but negative serologic results. The remaining 88 patients did not meet the criteria for a probable or suspected SARS diagnosis. Of the 34 patients with probable SARS, 13 were transferred to medical centers to receive mechanical ventilation due to rapid deterioration of chest x-ray results, and three patients died of SARS despite intensive therapy in medical centers. During the study period, one nurse developed probable SARS due to violation of infection control measures, but there was no evidence of cross-transmission to other HCWs.Conclusions:Despite the use of full personal protection equipment, the facility failed to totally prevent exposures of HCWs to SARS but minimized the risk of nosocomial transmission. Better training and improvements in infection control infrastructure may limit the impact of SARS.

Of the first 10 patients in the epidemic of severe acute respiratory syndrome (SARS) in Taiwan, 4 were closely associated with a SARS patient in an airplane. Loose stools or diarrhea, hemophagocytosis syndrome, and high serum levels of interleukin (IL)-6, IL-8, and tumor necrosis factor-a associated with lung lesions were found in all 10 patients.

Introduction Although substitutions of antiretroviral regimen are generally safe, most data on substitutions are based on results from clinical trials. The objective of this study was to evaluate the treatment outcomes of substituting antiretroviral regimen in virologically suppressed HIV‐infected patients in non‐clinical trial settings in Asian countries. Methods The study population consisted of HIV‐infected patients enrolled in the TREAT Asia HIV Observational Database (TAHOD). Individuals were included in this analysis if they started combination antiretroviral treatment (cART) after 2002, were being treated at a centre that documented a median rate of viral load monitoring ≥0.8 tests/patient/year among TAHOD enrolees, and experienced a minor or major treatment substitution while on virally suppressive cART. The primary endpoint to evaluate outcomes was clinical or virological failure (VF), followed by an ART class change. Clinical failure was defined as death or an AIDS diagnosis. VF was defined as confirmed viral load measurements ≥400 copies/mL followed by an ART class change within six months. Minor regimen substitutions were defined as within‐class changes and major regimen substitutions were defined as changes to a drug class. The patterns of substitutions and rate of clinical or VF after substitutions were analyzed. Results Of 3994 adults who started ART after 2002, 3119 (78.1%) had at least one period of virological suppression. Among these, 1170 (37.5%) underwent a minor regimen substitution, and 296 (9.5%) underwent a major regimen substitution during suppression. The rates of clinical or VF were 1.48/100 person years (95% CI 1.14 to 1.91) in the minor substitution group, 2.85/100 person years (95% CI 1.88 to 4.33) in the major substitution group and 2.53/100 person years (95% CI 2.20 to 2.92) among patients that did not undergo a treatment substitution. Conclusions The rate of clinical or VF was low in both major and minor substitution groups, showing that regimen substitution is generally effective in non‐clinical trial settings in Asian countries.

Background Although substitutions of antiretroviral regimen are generally safe, most data on substitutions are based on results from clinical trials. The objective of this study was to evaluate the safety of substituting antiretroviral regimen in virologically suppressed HIV-infected patients in non-clinical trial settings in Asian countries. Methods HIV-infected patients enrolled in the TREAT Asia HIV Observational Database (TAHOD) were included in this analysis if they started combination antiretroviral therapy (cART) after 2002, were being treated at a center that documented a median rate of viral load (VL) monitoring ≥ 1 tests/patient/year, and experienced a minor or major treatment substitution while on virally suppressive cART (VL < 200 copies/mL). Minor regimen substitutions were defined as within-class changes and major regimen substitutions were defined as changes to a drug class. Virologic failure was defined as having had two viral load measurements > 400 copies/mL. The patterns of substitutions and rate of virologic failure after substitutions were analyzed. Results Of 3,994 adults who started ART after 2002, 3,119 (78.1%) had at least one period of virological suppression. Among these, 1,170 (37.5%) underwent a minor regimen substitution, and 296 (9.5%) underwent a major regimen substitution during suppression. The rates of virological failure were 1.48/100person years (95% CI 1.14–1.91) in the minor substitution group and 2.85/100person years (95% CI 1.88–4.33) in the major substitution group, and 2.53/100person years (95% CI 2.20–2.92) among patients that did not undergo a treatment substitution. Conclusion The rate of virological failure was relatively low in both major and minor substitution groups, showing that regimen substitution is generally safe in non-clinical trial settings in Asian countries. Disclosures All authors: No reported disclosures.

Background 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. Methods 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. Results 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

The circulating recombinant form (CRF) 07_BC is the most prevalent HIV-1 strain among injection drug users (IDUs) in Taiwan. It contains a 7 amino-acid deletion in its p6gag. We conducted a cohort study to compare viral loads and CD4 cell count changes between patients infected with subtype B and CRF07_BC and to elucidate its mechanism. Twenty-one patients infected with CRF07_BC and 59 patients with subtype B were selected from a cohort of 667 HIV-1/AIDS patients whom have been followed up for 3 years. Generalized estimated equation was used to analyze their clinical data and the results showed that patients infected with CRF07_BC had significantly lower viral loads (about 58,000 copies per ml less) than patients with subtype B infection (p = 0.002). The replicative capacity of nine CRF07_BC and four subtype B isolates were compared and the results showed that the former had significantly lower replicative capacity than the latter although all of them were CCR5- tropic and non-syncytium inducing viruses. An HIV-1-NL4-3 mutant virus which contains a 7 amino-acid deletion in p6gag (designated as 7d virus) was generated and its live cycle was investigated. The results showed that 7d virus had significantly lower replication capacity, poorer protease-mediated processing and viral proteins production. Electron microscopic examination of cells infected with wild-type or 7d virus demonstrated that the 7d virus had poorer and slower viral maturation processes: more viruses attached to the cell membrane and higher proportion of immature virions outside the cells. The interaction between p6gag and Alix protein was less efficient in cells infected with 7d virus. In conclusion, patients infected with CRF07_BC had significantly lower viral loads than patients infected with subtype B and it may due to the deletion of 7 amino acids which overlaps with Alix protein-binding domain of the p6gag.

Among 254 Neisseria gonorrhoeae isolates from a sexually transmitted infection (STI) clinic in northern Taiwan, 69 isolates were found to contain the mosaic penA (MA) gene and were associated with elevated cefixime and ceftriaxone MICs. Most of these MA gene-harboring isolates were also resistant to penicillin (71.4%) and ciprofloxacin (100%) and were from men who have sex with men (MSM) or from bisexual men (81.2%). Three major sequence types (ST835, ST2180, and ST2253) constituted 55.7% of these isolates. The major sequence types harboring the mosaic penA gene may represent major sexual networks responsible for the emergence/introduction and the spread of the multidrug-resistant clones in Taiwan.

Conjunctival swabs were used in combination with polymerase chain reactions (PCR) or virus culture to aid to confirm the diagnosis of cytomegalovirus (CMV) retinitis in AIDS patients. Based on ophthalmoscopic findings, 13 AIDS patients were diagnosed as having CMV retinitis and treated with systemic ganciclovir from January 1997 to December 1998. Nine of 13 AIDS patients with CMV retinitis were found to be positive for CMV DNA by using a conjunctival swab with PCR (CS-PCR). CMV was also isolated from the conjunctival swab culture in 2 AIDS patients with CMV retinitis. Following 1 month of systemic ganciclovir treatment, except for 1 patient who had disease progression and remained positive for CMV DNA by using CS-PCR, 12 patients were negative for CMV with a concordant lesion regression. Results of this study also indicate that this CS-PCR method is valuable for confirming the diagnosis of CMV retinitis and monitoring the ganciclovir effect on the treatment of CMV retinitis in AIDS patients.

Penicillium marneffei is a rare fungal pathogen which can cause human infections in people predominantly living in South-east Asia and the southern portion of China. We report three cases of systemic P. marneffei infection in patients infected with HIV who lived in or had travelled to endemic areas. The clinical manifestation includes high fever, chills, weight loss, general malaise, chronic cough, haemoptysis, multiple skin lesions, abnormal liver function, etc. Chest X-ray showed single or multiple cavitary lesions with smooth or irregular thin wall. P. marneffei is cultured from blood, sputum, skin biopsy, sono-guide aspiration and bronchoscopic biopsy. After antifungal therapy with intravenous amphotericin B or oral fluconazole, skin lesions resolved completely within 2 weeks and cavitary lesions in the lungs changed to chronic fibrotic and interstitial processes after several months to a few years later. Our two cases had been treated as either pulmonary tuberculosis or suspected malignancy. A definite diagnosis and early treatment are important because this fungal infection is a marker of AIDS in South-east Asia.