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BackgroundAlthough patient attrition is recognized as a threat to the long-term success of antiretroviral therapy programs worldwide, there is no universal definition for classifying patients as lost to follow-up (LTFU). We analyzed data from health facilities across Africa, Asia, and Latin America to empirically determine a standard LTFU definition.Methods and findingsAt a set "status classification" date, patients were categorized as either "active" or "LTFU" according to different intervals from time of last clinic encounter. For each threshold, we looked forward 365 d to assess the performance and accuracy of this initial classification. The best-performing definition for LTFU had the lowest proportion of patients misclassified as active or LTFU. Observational data from 111 health facilities-representing 180,718 patients from 19 countries-were included in this study. In the primary analysis, for which data from all facilities were pooled, an interval of 180 d (95% confidence interval [CI]: 173-181 d) since last patient encounter resulted in the fewest misclassifications (7.7%, 95% CI: 7.6%-7.8%). A secondary analysis that gave equal weight to cohorts and to regions generated a similar result (175 d); however, an alternate approach that used inverse weighting for cohorts based on variance and equal weighting for regions produced a slightly lower summary measure (150 d). When examined at the facility level, the best-performing definition varied from 58 to 383 d (mean=150 d), but when a standard definition of 180 d was applied to each facility, only slight increases in misclassification (mean=1.2%, 95% CI: 1.0%-1.5%) were observed. Using this definition, the proportion of patients classified as LTFU by facility ranged from 3.1% to 45.1% (mean=19.9%, 95% CI: 19.1%-21.7%).ConclusionsBased on this evaluation, we recommend the adoption of ≥180 d since the last clinic visit as a standard LTFU definition. Such standardization is an important step to understanding the reasons that underlie patient attrition and establishing more reliable and comparable program evaluation worldwide. Please see later in the article for the Editors' Summary.

Background: The objective was to examine the short‐term risk and predictors of anaemia following initiation of combination antiretroviral therapy (cART) in HIV‐infected patients from the Western Africa, Eastern Africa, Southern Africa, Central Africa, Asian‐Pacific, and Caribbean and Central and South America regions of the International Epidemiologic Databases to Evaluate AIDS (IeDEA) collaboration. Methods: Anaemia was defined as haemoglobin of < 10 g/dL. Patients were included if they started cART with three or more drugs, had prior haemoglobin of > = 10 g/dL, and had one or more follow‐up haemoglobin tests. Factors associated with anaemia up to 12 months were examined using Cox proportional hazards models and stratified by IeDEA region. Results: Between 1998 and 2008, 19,947 patients initiated cART with baseline and follow‐up haemoglobin tests (7358, 7289, 2853, 471, 1550 and 426 in the Western Africa, Eastern Africa, Southern Africa, Central Africa, Asian‐Pacific, and Caribbean and Central and South America regions, respectively). At initiation, anaemia was found in 45% of Western Africa patients, 29% of Eastern Africa patients, 21% of Southern Africa patients, 36% of Central Africa patients, 15% of patients in Asian‐Pacific and 14% of patients in Caribbean and Central and South America. Among patients with haemoglobin of > = 10 g/dL at baseline (13,445), the risks of anaemia were 18.2, 6.6, 9.7, 22.9, 11.8 and 19.5 per 100 person‐years in the Western Africa, Eastern Africa, Southern Africa, Central Africa, Asian, and Caribbean and Central and South America regions, respectively. Factors associated with anaemia were female sex, low baseline haemoglobin level, low baseline CD4 count, more advanced disease stage, and initial cART containing zidovudine. Conclusions: In data from 34 cohorts of HIV‐infected patients from sub‐Saharan Africa, Central and South America, and Asia, the risk of anaemia within 12 months of initiating cART was moderate. Routine haemoglobin monitoring was recommended in patients at risk of developing anaemia following cART initiation., Background According to World Health Organization (WHO) estimations [1], access to combination antiretroviral treatment (cART) has improved dramatically in low‐ and middle‐income countries with limited resources. At the end of [...]

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 [...]

Data collected on HIV-infected patients from the Asia-Pacific region were centrally aggregated for analyses, with the first baseline and retrospective data transferred in September 2003. By the end of May 2004, 1887 patients had been recruited to the TREAT Asia HIV Observational Database.

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.

Abstract Background It is critical to understand the pattern of antiretroviral treatment (ART) prescription in different regions of the world as ART procurement needs to be anticipated. We aimed at exploring rates and predictors of ART combination changes in clinical practice in Treat Asia HIV Observational Database (TAHOD). Methods Rates of ART changes were examined in patients who started first line triple or more ART combination in TAHOD, and had at least one follow-up visit. Rates of ART changes were summarised per follow-up year, and factors associated with changes assessed using random-effect Poisson regression. The Kaplan-Meier method was used to determine durations of patients in their first, second and third regimen. Results A total of 1846 patients initiated an ART combination with at least three drugs. Median follow up time for the first treatment was 3.2 years. The overall rate of ART change was 29 per 100-person-year. In univariate analyses, rate of treatment change was significantly associated with exposure category, the country income category, the drug class combination, calendar year and the number of combinations. In multivariate analysis, compared to d4T/3TC/NVP, starting ART with another NNRTI-containing regimen, with PI only or with a triple NRTI regimen was associated with a higher risk of combination change (relative risk (RR) 1.6 (95% CI 1.64 – 1.96), p < 0.001, RR 3.39 (2.76 – 4.16) p < 0.001, RR 6.37 (4.51 – 9.00), p < 0.001). Being on a second or a third combination regimen was also associated with a decreased rate of ART change, compared with first ART combination (RR 0.82 (0.68 – 0.99), p = 0.035, RR 0.77 (0.61 – 0.97), p = 0.024). Sites with fewer than 12 drugs used had an increased rate of treatment changes (1.31 (1.13 – 1.51), p < 0.001). Injecting drug users, and other/unknown exposure was found to increase rate of treatment change (1.24 (1.00 – 1.54), p = 0.055). Percentages of patients who stopped treatment due to adverse events were 31, 27 and 32 in 1st, 2nd and 3rd treatment combinations, respectively. Conclusion Our study suggests that drug availability impacts on ART prescription patterns. Our data, reflecting real clinic use in Asia, suggest that around half of all patients require second combination ART by 3 years after treatment initiation.

Background: The objective was to examine the short-term risk and predictors of anaemia following initiation of combination antiretroviral therapy (cART) in HIV-infected patients from the Western Africa, Eastern Africa, Southern Africa, Central Africa, Asian-Pacific, and Caribbean and Central and South America regions of the International Epidemiologic Databases to Evaluate AIDS (IeDEA) collaboration. Methods: Anaemia was defined as haemoglobin of < 10 g/dL. Patients were included if they started cART with three or more drugs, had prior haemoglobin of > = 10 g/dL, and had one or more follow-up haemoglobin tests. Factors associated with anaemia up to 12 months were examined using Cox proportional hazards models and stratified by IeDEA region. Results: Between 1998 and 2008, 19,947 patients initiated cART with baseline and follow-up haemoglobin tests (7358, 7289, 2853, 471, 1550 and 426 in the Western Africa, Eastern Africa, Southern Africa, Central Africa, Asian- Pacific, and Caribbean and Central and South America regions, respectively). At initiation, anaemia was found in 45% of Western Africa patients, 29% of Eastern Africa patients, 21% of Southern Africa patients, 36% of Central Africa patients, 15% of patients in Asian-Pacific and 14% of patients in Caribbean and Central and South America. Among patients with haemoglobin of > = 10 g/dL at baseline (13,445), the risks of anaemia were 18.2, 6.6, 9.7, 22.9, 11.8 and 19.5 per 100 person-years in the Western Africa, Eastern Africa, Southern Africa, Central Africa, Asian, and Caribbean and Central and South America regions, respectively. Factors associated with anaemia were female sex, low baseline haemoglobin level, low baseline CD4 count, more advanced disease stage, and initial cART containing zidovudine. Conclusions: In data from 34 cohorts of HIV-infected patients from sub-Saharan Africa, Central and South America, and Asia, the risk of anaemia within 12 months of initiating cART was moderate. Routine haemoglobin monitoring was recommended in patients at risk of developing anaemia following cART initiation. [ABSTRACT FROM AUTHOR]

The significance of interethnic variation in CD4 counts between Asian and Caucasian populations is not known. Patients on combination antiretroviral therapy from Treat Asia and Australian HIV Observational Databases (TAHOD, predominantly Asian, n = 3356; and AHOD, predominantly Caucasian, n = 2312, respectively) were followed for 23 144 person-years for AIDS/death and all-cause mortality endpoints. We calculated incidence-rates and used adjusted Cox regression to test for the interaction between cohort (TAHOD/AHOD) and time-updated CD4 count category (lagged by 3 months) for each of the endpoints. There were 382 AIDS/death events in TAHOD (rate: 4.06, 95%CI: 3.68-4.50) and 305 in AHOD (rate: 2.39, 95%CI: 2.13-2.67), per 100 person-years. At any given CD4 count category, the incidence-rates of endpoints were found to be similar between TAHOD and AHOD (in the adjusted models, P > .05 for the interaction term between cohort type and latest CD4 counts). At any given CD4 count, risk of AIDS or death was not found to vary by ethnicity, suggesting that the CD4 count thresholds for predicting outcomes defined in Caucasian populations may be equally valid in Asian populations. [ABSTRACT FROM PUBLISHER]

Background: It is critical to understand the pattern of antiretroviral treatment (ART) prescription in different regions of the world as ART procurement needs to be anticipated. We aimed at exploring rates and predictors of ART combination changes in clinical practice in Treat Asia HIV Observational Database (TAHOD). Methods: Rates of ART changes were examined in patients who started first line triple or more ART combination in TAHOD, and had at least one follow-up visit. Rates of ART changes were summarised per follow-up year, and factors associated with changes assessed using random-effect Poisson regression. The Kaplan-Meier method was used to determine durations of patients in their first, second and third regimen. Results: A total of 1846 patients initiated an ART combination with at least three drugs. Median follow up time for the first treatment was 3.2 years. The overall rate of ART change was 29 per 100-person-year. In univariate analyses, rate of treatment change was significantly associated with exposure category, the country income category, the drug class combination, calendar year and the number of combinations. In multivariate analysis, compared to d4T/3TC/NVP, starting ART with another NNRTI-containing regimen, with PI only or with a triple NRTI regimen was associated with a higher risk of combination change (relative risk (RR) 1.6 (95% CI 1.64 - 1.96), p < 0.001, RR 3.39 (2.76 - 4.16) p < 0.001, RR 6.37 (4.51 - 9.00), p < 0.001). Being on a second or a third combination regimen was also associated with a decreased rate of ART change, compared with first ART combination (RR 0.82 (0.68 - 0.99), p = 0.035, RR 0.77 (0.61 - 0.97), p = 0.024). Sites with fewer than 12 drugs used had an increased rate of treatment changes (1.31 (1.13 - 1.51), p < 0.001). Injecting drug users, and other/unknown exposure was found to increase rate of treatment change (1.24 (1.00 - 1.54), p = 0.055). Percentages of patients who stopped treatment due to adverse events were 31, 27 and 32 in 1st, 2nd and 3rd treatment combinations, respectively. Conclusion: Our study suggests that drug availability impacts on ART prescription patterns. Our data, reflecting real clinic use in Asia, suggest that around half of all patients require second combination ART by 3 years after treatment initiation. [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.