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Background: Pneumocystis jiroveci pneumonia (PCP) prophylaxis is recommended for patients with CD4 counts of less than 200 cells/mm[sup.3]. This study examines the proportion of patients in the TREAT Asia HIV Observational Database (TAHOD) receiving PCP prophylaxis, and its effect on PCP and mortality. Methods: TAHOD patients with prospective follow up had data extracted for prophylaxis using co‐trimoxazole, dapsone or pentamidine. The proportion of patients on prophylaxis was calculated for each calendar year since 2003 among patients with CD4 counts of less than 200 cells/mm[sup.3]. The effect of prophylaxis on PCP and survival were assessed using random‐effect Poisson regression models. Results: There were a total of 4050 patients on prospective follow up, and 90% of them were receiving combination antiretroviral therapy. Of those with CD4 counts of less than 200 cells/mm[sup.3], 58% to 72% in any given year received PCP prophylaxis, predominantly co‐trimoxazole. During follow up, 62 patients developed PCP (0.5 per 100 person‐years) and 169 died from all causes (1.36/100 person‐years). After stratifying by site and adjusting for age, CD4 count, CDC stage and antiretroviral treatment, those without prophylaxis had no higher risk of PCP, but had a significantly higher risk of death (incident rate ratio 10.8, p < 0.001). PCP prophylaxis had greatest absolute benefit in patients with CD4 counts of less than 50 cells/mm[sup.3], lowering mortality rates from 33.5 to 6.3 per 100 person‐years. Conclusions: Approximately two‐thirds of TAHOD patients with CD4 counts of less than 200 cells/mm[sup.3] received PCP prophylaxis. Patients without prophylaxis had significantly higher mortality, even in the era of combination ART. Although PCP may be under‐diagnosed, these data suggest that prophylaxis is associated with important survival benefits., Background Pneumocystis jiroveci pneumonia (PCP) remains a major cause of morbidity and mortality among HIV‐infected persons presenting with advanced infection [1]. Although PCP rates have dropped in the combination antiretroviral [...]

Abstract Background Accurate interpretation of HIV drug resistance (HIVDR) testing is challenging, yet important for patient care. We compared genotyping interpretation, based on the Stanford University HIV Drug Resistance Database (Stanford HIVdb), and virtual phenotyping, based on the Janssen Diagnostics BVBA’s vircoTYPE™ HIV-1, and investigated their level of agreement in antiretroviral (ARV) naive patients in Asia, where non-B subtypes predominate. Methods Sequences from 1301 ARV-naive patients enrolled in the TREAT Asia Studies to Evaluate Resistance – Monitoring Study (TASER-M) were analysed by both interpreting systems. Interpretations from both Stanford HIVdb and vircoTYPE™ HIV-1 were initially grouped into 2 levels: susceptible and non-susceptible. Discrepancy was defined as a discordant result between the susceptible and non-susceptible interpretations from the two systems for the same ARV. Further analysis was performed when interpretations from both systems were categorised into 3 levels: susceptible, intermediate and resistant; whereby discrepancies could be categorised as major discrepancies and minor discrepancies. Major discrepancy was defined as having a susceptible result from one system and resistant from the other. Minor discrepancy corresponded to having an intermediate interpretation in one system, with a susceptible or resistant result in the other. The level of agreement was analysed using the prevalence adjusted bias adjusted kappa (PABAK). Results Overall, the agreement was high, with each ARV being in “almost perfect agreement”, using Landis and Koch’s categorisation. Highest discordance was observed for efavirenz (75/1301, 5.8%), all arising from susceptible Stanford HIVdb versus non-susceptible vircoTYPE™ HIV-1 predictions. Protease Inhibitors had highest level of concordance with PABAKs all above 0.99, followed by Nucleoside Reverse Transcriptase Inhibitors with PABAKs above 0.97 and non-NRTIs with the lowest PABAK of 0.88. The 68/75 patients with discordant efavirenz results harboured the V179D/E mutations compared to 7/1226 with no efavirenz discrepancy (p-value Conclusions The two systems agreed well with lowest concordance observed for efavirenz. When interpreting HIVDR, especially in non-B subtypes, clinical correlation is crucial, in particular when efavirenz resistance is interpreted based on V179D/E.

Abstract Background The aim of this study was to examine the relationship between trends in CD4 counts (slope) and HIV viral load (VL) after initiation of combination antiretroviral treatment (cART) in Asian patients in The TREAT Asia HIV Observational Database (TAHOD). Methods Treatment-naive HIV-infected patients who started cART with three or more and had three or more CD4 count and HIV VL tests were included. CD4 count slopes were expressed as changes of cells per microliter per year. Predictors of CD4 count slopes from 6 months after initiation were assessed by random-effects linear regression models. Results A total of 1676 patients (74% male) were included. The median time on cART was 4.2 years (IQR 2.5-5.8 years). In the final model, CD4 count slope was associated with age, concurrent HIV VL and CD4 count, disease stage, hepatitis B or C co-infection, and time since cART initiation. CD4 count continues to increase with HIV VL up to 20 000 copies/mL during 6-12 months after cART initiation. However, the HIV VL has to be controlled below 5 000, 4 000 and 500 copies/mL for the CD4 count slope to remain above 20 cells/microliter per year during 12-18, 18-24, and beyond 24 months after cART initiation. Conclusions After cART initiation, CD4 counts continued to increase even when the concurrent HIV VL was detectable. However, HIV VL needed to be controlled at a lower level to maintain a positive CD4 count slope when cART continues. The effect on long-term outcomes through the possible development of HIV drug resistance remains uncertain.

Abstract Background To assess the risk and the prognostic significance of tuberculosis (TB) diagnosis in patients from The TREAT Asia HIV Observational Database, a multi-centre prospective cohort of HIV-infected patients receiving HIV care in the Asia-Pacific region. Methods The risk of TB diagnosis after recruitment was assessed in patients with prospective follow-up. TB diagnosis was fitted as a time-dependent variable in assessing overall survival. Results At baseline, 22% of patients were diagnosed with TB. TB incidence was 1.98 per 100 person-years during follow up, with predictors including younger age, lower recent CD4 count, duration of antiretroviral treatment, and living in high TB burden countries. Among 3279 patients during 6968 person-years, 142 died (2.04 per 100 person-years). Compared to patients with CDC category A or B illness only, mortality was marginally higher in patients with single Non-TB AIDS defining illness (ADI), or TB only (adjusted HR 1.35, p = 0.173) and highest in patients with multiple non-TB AIDS or both TB and other ADI (adjusted HR 2.21, p < 0.001). Conclusion The risk of TB diagnosis was associated with increasing immunodeficiency and partly reduced by antiretroviral treatment. The prognosis of developing TB appeared to be similar to that following a diagnosis of other non-TB ADI.

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) Results: A total of 105 patients from 10 sites in Thailand, Hong Kong, Indonesia, Malaysia and Philippines were included. There were 97/105 (92%) patients harbouring ≥1 RAMs at first‐line failure, 39/105 with multi‐NRTI RAMs: six with Q151M; 24 with ≥2 TAMs; and 32 with M184V+≥1 TAM. Factors associated with multi‐NRTI RAMs were CD4 ≤200 cells/µL at genotyping (OR=4.43, 95% CI [1.59–12.37], p=0.004) and ART duration >2 years (OR=6.25, 95% CI [2.39–16.36], p Conclusions: Multi‐NRTI RAMs at first‐line failure were associated with low CD4 level and longer duration of ART. With many patients switching to highly susceptible regimens, good adherence was still crucial in achieving virological response. This emphasizes the importance of continued adherence counselling well into second‐line therapy., Introduction In resource‐limited settings, first‐line antiretroviral therapy (ART) for HIV‐positive patients consists of nucleoside and non‐nucleoside reverse transcriptase inhibitors (NRTIs and NNRTIs). Protease inhibitors (PIs) are usually the core component [...]

HIV drug resistance assessments and interpretations can be obtained from genotyping (GT), virtual phenotyping (VP) and laboratory-based phenotyping (PT). We compared resistance calls obtained from GT and VP with those from PT (GT-PT and VP-PT) among CRF01-AE and subtype B HIV-1 infected patients. GT predictions were obtained from the Stanford HIV database. VP and PT were obtained from Janssen Diagnostics BVBA's vircoTypeTM HIV-1 and Antivirogram1, respectively. With PT assumed as the "gold standard," the area under the curve (AUC) and the Bland-Altman plot were used to assess the level of agreement in resistance interpretations. A total of 80 CRF01-AE samples from Asia and 100 subtype B from Janssen Diagnostics BVBA's database were analysed. CRF01-AE showed discordances ranging from 3 to 27 samples for GT-PT and 1 to 20 samples for VP-PT. The GT-PT and VP-PT AUCs were 0.76-0.97 and 0.81-0.99, respectively. Subtype B showed 3-61 discordances for GT-PT and 2-75 discordances for VP-PT. The AUCs ranged from 0.55 to 0.95 for GT-PT and 0.55 to 0.97 for VP-PT. Didanosine had the highest proportion of discordances and/or AUC in all comparisons. The patient with the largest didanosine FC difference in each subtype harboured Q151M mutation. Overall, GT and VP predictions for CRF01-AE performed significantly better than subtype B for three NRTIs. Although discrepancies exist, GT and VP resistance interpretations in HIV-1 CRF01-AE strains were highly robust in comparison with the gold-standard PT. [ABSTRACT FROM AUTHOR]

Seventy-two adult Chinese HIV-positive treatment-naïve patients were recruited in a study to evaluate prospectively the associations between CYP2B6 516 G/T polymorphisms and sleep quality following treatment with an efavirenz-based regimen. Overall, the patients gave an allelic frequency of 0.3 for CYP2B6 516 T, and a genotype frequency of 9.4% for TT. Compared to GG, GT gave a higher median value of plasma efavirenz level at four weeks (3.77 mg/L vs 2.59 mg/L, p < 0.001) and 12 months (3.57 mg/L vs 2.97 mg/L, p = 0.026). Using generalised estimating equations analysis to track the variance over time, there was poorer Pittsburgh Sleep Quality Index in GT compared to GG, while GT was associated with a higher efavirenz level of >4 mg/L. There was however no difference in the component sleep scores nor was there direct association between sleep quality and plasma efavirenz levels. The results suggested that CYP2B6 genotype was associated with different patterns of sleep problems, further investigation of which is warranted with the objective of optimizing therapy with efavirenz-based regimens. [ABSTRACT FROM AUTHOR]

Introduction: Adherence to antiretroviral therapy (ART) plays an important role in treatment outcomes. It is crucial to identify factors influencing adherence in order to optimize treatment responses. The aim of this study was to assess the rates of, and factors associated with, suboptimal adherence (SubAdh) in the first 24 months of ART in an Asian HIV cohort. Methods: As part of a prospective resistance monitoring study, the TREAT Asia Studies to Evaluate Resistance Monitoring Study (TASER-M) collected patients’ adherence based on the World Health Organization-validated Adherence Visual Analogue Scale. SubAdh was defined in two ways: (i) <100% and (ii) <95%. Follow-up time started from ART initiation and was censored at 24 months, loss to follow-up, death, treatment switch, or treatment cessation for >14 days. Time was divided into four intervals: 0–6, 6–12, 12–18 and 18–24 months. Factors associated with SubAdh were analysed using generalized estimating equations. Results: Out of 1316 patients, 32% ever reported <100% adherence and 17% ever reported <95%. Defining the outcome as SubAdh <100%, the rates of SubAdh for the four time intervals were 26%, 17%, 12% and 10%. Sites with an average of >2 assessments per patient per year had an odds ratio (OR)=0.7 (95% confidence interval (CI) (0.55 to 0.90), p=0.006), compared to sites with ≤2 assessments per patient per year. Compared to heterosexual exposure, SubAdh was higher in injecting drug users (IDUs) (OR=1.92, 95% CI (1.23 to 3.00), p=0.004) and lower in homosexual exposure (OR=0.52, 95% CI (0.38 to 0.71), p<0.001). Patients taking a nucleoside transcriptase inhibitor and protease inhibitor (NRTI+PI) combination were less likely to report adherence <100% (OR=0.36, 95% CI (0.20 to 0.67), p=0.001) compared to patients taking an NRTI and non-nucleoside transcriptase inhibitor (NRTI+NNRTI) combination. SubAdh decreased with increasing time on ART (all p<0.001). Similar associations were found with adherence <95% as the outcome. Conclusions: We found that SubAdh, defined as either <100% and <95%, was associated with mode of HIV exposure, ART regimen, time on ART and frequency of adherence measurement. The more frequently sites assessed patients, the lower the SubAdh, possibly reflecting site resourcing for patient counselling. Although social desirability bias could not be excluded, a greater emphasis on more frequent adherence counselling immediately following ART initiation and through the first six months may be valuable in promoting treatment and programme retention. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented on a study to examine impact of sex on viro-immunological responses to highly active antiretroviral therapy.

Background: The availability of HIV antiretroviral therapy (ART) has been associated with the development of transmitted drug resistance-associated mutations (TDRM). TDRM can compromise treatment effectiveness in patients initiating ART and the prevalence can vary in different clinical settings. In this study, we investigated the proportion of TDRM in treatment-naïve, recently infected HIV-positive individuals sampled from four urban locations across Asia between 2007-2010., Methods: Patients enrolled in the TREAT Asia Studies to Evaluate Resistance - Surveillance Study (TASER-S) were genotyped prior to ART initiation, with resulting resistance mutations analysed according to the WHO 2009 list., Results: Proportions of TDRM from recently infected individuals from TASER-S ranged from 0% to 8.7% - Hong Kong: 3/88 (3.4%, 95% CI (0.71%-9.64%)); Thailand: Bangkok: 13/277 (4.7%, 95% CI (2.5%-7.9%)), Chiang Mai: 0/17 (0%, 97.5% CI (0%-19.5%)); and the Philippines: 6/69 (8.7%, 95% CI (3.3%-18.0%)). There was no significant increase in TDRM over time across all four clinical settings., Conclusions: The observed proportion of TDRM in TASER-S patients from Hong Kong, Thailand and the Philippines was low to moderate during the study period. Regular monitoring of TDRM should be encouraged, especially with the scale-up of ART at higher CD4 levels.