Optimal adherence to antiretroviral therapy is critical to prevent HIV drug resistance (HIVDR) epidemic. The objective of the study was to investigate the best performing adherence assessment method for predicting virological failure in resource-limited settings (RLS).This study was a single-centre prospective cohort, enrolling 220 HIV-infected adult patients attending an HIV/AIDS Care and Treatment Centre in Dar es Salaam, Tanzania, in 2010. Pharmacy refill, self-report , pill count, and appointment keeping adherence measurements were taken.Univariate logistic regression (LR) was done to explore a cut-off that gives a better trade-off between sensitivity and specificity, and a higher area under the curve (AUC) based on receiver operating characteristic curve in predicting virological failure. Additionally, the adherence models were evaluated by fitting multivariate LR with stepwise functions, decision trees, and random forests models, assessing 10-fold multiple cross validation (MCV). Patient factors associated with virological failure were determined using LR.Viral load measurements at baseline and one year after recruitment were available for 162 patients, of whom 55 (34%) had detectable viral load and 17 (10.5%) had immunological failure at one year after recruitment. The optimal cut-off points significantly predictive of virological failure were 95%, 80%, 95% and 90% for VAS, appointment keeping, pharmacy refill, and pill count adherence respectively. The AUC for these methods ranged from 0.52 to 0.61, with pharmacy refill giving the best performance at AUC 0.61.Multivariate logistic regression with boost stepwise MCV had higher AUC (0.64) compared to all univariate adherence models, except pharmacy refill adherence univariate model, which was comparable to the multivariate model (AUC = 0.64). Decision trees and random forests models were inferior to boost stepwise model.Pharmacy refill adherence (<95%) emerged as the best method for predicting virological failure. Other significant predictors in multivariate LR were having a baseline CD4 T lymphocytes count < 200 cells/μl, being unable to recall the diagnosis date, and a higher weight.Pharmacy refill has the potential to predict virological failure and to identify patients to be considered for viral load monitoring and HIVDR testing in RLS.The online version of this article (doi:10.1186/1471-2458-14-1035) contains supplementary material, which is available to authorized users. Widespread antiretroviral scale-up programs are taking place in resource-limited settings (RLS) . Where rStrategies to measure adherence to ART include the Medication Event Monitoring System (MEMS), pharmacy refill records, pill count, appointment keeping, adherence diaries, and interviewer-administered or self-report questionnaires –13. CurrSelf-report utilizing structured questionnaires is popular in RLS, due to its ease of use in busy settings, affordability, and low staff requirements. Self-report has consistently been correlated with viral load response to therapy and has been proposed as a robust and appropriate indicator of adherence , 17. HowIn sub-Saharan Africa, adherence to ART has been touted to be equal to or even higher than levels in resource-rich settings (RRS) . HoweverPill count and appointment keeping adherence are among the early warning indicators (EWIs) recommended by the World Health Organization (WHO) as surrogate markers for emergence of HIVDR . Manual Another objective method that has higher potential is pharmacy refill adherence, which is commonly obtained in clinical care. It has been validated as a measure of ART adherence related to viral load . AlthougApparently, there is no single consensus tool to capture adherence to ART and no accepted gold standard to assess adherence especially in RLS , 25, 26.Validating adherence measurement against viral load is of utmost importance. An accurate and sensitive measure of adherence should give clinicians objective data to use during discussions on individuals’ non-adherence risk factors without causing shame or stigma to a patient . The feaThis was a single-centre prospective cohort study enrolling HIV-infected adult patients attending an HIV/AIDS Care and Treatment Centre (CTC) that provides ART at Amana District Hospital in Dar es Salaam, Tanzania, in 2010. Patients on ART are normally scheduled to return for antiretroviral (ARV) pick-ups at least once per month. During the visit, they also consult with the clinician after receiving adherence counselling from the nurses. CD4 T lymphocytes count measurements are taken at least once every six months. Two hundred and fifty-four patients were invited into the study during the months of May to July, 2010. Selection criteria were either starting ART or being on ART. Patients were conveniently sampled, as the study researcher continuously recruited patients who were referred by nurse counsellors, the first contacts at the clinic. Each day, 10-15 unselected patients were recruited into the study. Exclusion criteria were being younger than 18 years of age, pregnant, having opportunistic infections, or malignancy. Of the 254 patients recruited into the study, 34 (13.4%) were excluded from analysis for various reasons  Research Ethics Committee. Only patients who were willing to participate in the study and who signed an informed consent were recruited into this study. Patient codes were used to de-link the patient data in databases. Patients did not receive any payments to motivate them to participate in the study.Virological and immunological outcomes were assessed at the one-year follow-up. These outcomes were dichotomized according to the following definitions: Virological failure was defined as having a viral load above the detection limit of 400 copies/mL; and immunological failure was defined according to the WHO guidelines as having (i) a CD4 T lymphocytes count of 100 cells/μl at six months post ART, (ii) a CD4 T lymphocytes count of equal to or less than CD4 pre-ART at six months on ART, or (iii) 50% reduction from the on-ART peak CD4 T lymphocytes count , 29.Adherence was measured using pharmacy refill, self-report, pill count, and appointment keeping methods, as described for each method. Adherences measurements were taken at four time points during a one-year follow-up, including at recruitment (zero), one, two, and 12 months after recruitment. Overall adherence for each method was the mean of the measurements taken at the four time points and this mean was considered in subsequent analyses.Each refill period was identified as the interval between the last visit date and the scheduled refill date. Refill adherence was 100% if all pills during the scheduled refill period had been picked up on time. Refill percent values above 100 for patients who refilled earlier than scheduled were rounded to 100 percent. Refill adherence was not calculated on a monthly basis to reduce an error of a few additional pills left over at the end of each refill period. The calculation was based on cumulative sum of the days that a patient was late for ARV pick-up appointments in each month over the year, divided by the total number of days over all periods between pick-up periods in the year of study, resulting in the percentage of time the patient was without medication over the whole year.The researcher for this study administered a self-report questionnaire to patients to assess missed dosages over the previous one month. During a one-year follow-up, self-report was used to determine adherence at recruitment (zero), one, two, and 12 months after recruitment. For patients who started ART at recruitment, the measurement at month zero was not available. Patient self-reported adherence was investigated using a validated study tool . This vaAt each visit, pills remaining in bottles were counted and the proportion of these pills to the dispensed pills during the previous visit was calculated based on the dose and the number of days dispensed. The pill count adherence percent was obtained by dividing the number of pills consumed by the total number of pills at the beginning of the given interval and multiplied by 100.At this CTC, appointments were issued based on the period that the dispensed ARV stock would last, which usually this amounts to one month. Appointment keeping was deduced from the medical records and database. A patient visiting on the scheduled appointment was scored as 100% appointment adherent, whereas if an appointment was skipped entirely, it was scored as 0% adherence. For a delayed appointment, the proportions of days late  were subtracted from 100.Univariate analysis was done to explore a cut-off that gives a better trade-off between sensitivity and specificity, and a higher area under the curve (AUC), based on receiver operating characteristic (ROC) curve in predicting virological failure. For each method, we used a threshold cut-off beginning with 100% and decreasing to 50% in steps of 5. At the selected cut-off for pharmacy refill, VAS, pill count, and appointment keeping . The trade-off for sensitivity and specificity was analysed upon changing the adherence cut-off to predict virological failure at 12 months, which was dichotomized using two different viral load cut-off points: > 400 copies/mL or > 1,000 copies/mL. The 400 copies/ml virological cut-off was the detection limit of this study’s viral load measurement, while 1,000 represented a virologic cut-off widely used to perform genotyping. A model was also tested combining adherence and immunological outcome to predict virological failure. The performance criteria for all adherence measures were calculated with two-by-two tables and ROC analysis. Univariate logistic regression (LR) was used to determine patient baseline factors associated with virological outcome. Also, evaluation of the adherence models was done by fitting multivariate LR with stepwise functions (Akaike information criterion [AIC] and boost), decision trees, and random forests assessing extra-sample error via multiple 10-fold cross validation (MCV), repeated 50 times with random seeds. All models were analysed in terms of different performance (goodness-of-fit functions), specifically AUC, accuracy, true positive rate (sensitivity), and true negative rate (specificity). Performance distributions were compared pair-wise with a t-test adjusted for sample overlap (due to the MCV procedure) and multiple comparisons.Kaplan Meier survival analysis was used to determine the difference between the time taken to increase the CD4 T lymphocytes count by 50 cells/μl or by 100 cells/μl between adherent and non-adherent patients. Furthermore, Cox regression analysis was done to adjust for confounding factors such as age, gender, and CD4 T lymphocytes count at baseline. Descriptive analyses, including median interquartile range (IQR) for numerical variables, frequencies, and proportions for categorical variables, and tested for association using Fisher and Chi-square tests for categorical variables, and Wilcoxon signed rank test for continuous values. The level of significance for all analyses was p < 0.05. All statistical analyses were performed using the R statistical package version 2.15.1  and WekaA total of 162 (73.6%) out of the 220 patients followed for a one-year period had a virological outcome, an immunological outcome, and adherence data at the one-year time point and were included in this study  months. This information was only available for patients with follow-up. With regard to duration of therapy at recruitment, there was no significance difference between included and excluded patients (p = 0.36).With regard to adherence measurements, performance for various cut-off points to predict a viral load above 400 or above 1,000 copies/ml is shown in Table At recruitment, 13% of patients who were on treatment for more than four months had detectable viral load. This rate increased to 34% of all patients after the one-year follow-up. Two of 15 patients who started ART at recruitment still had a detectable viral load after one year. The odds of virological failure for various predictors are shown in Table In univariate LR analysis, odds of virological failure were determined. The study suggests that, being able to recall the diagnosis date, being on an efavirenz-containing regimen, having a pharmacy refill adherence of > 95% and having an undetectable viral load at baseline were significantly associated with lower likelihood of virological failure. On the contrary, having a baseline CD4 T lymphocytes count less than 200 cells/μl, being on a triomune, nevirapine, or stavudine regimen, having a higher body weight or body mass index (BMI), longer therapy duration, and having drug holidays were predictors of poor virological outcome  in the study, despite high self-reporting adherence of > 95% in up to 87% of patients. Factors significantly associated with virological failure at the one-year of follow-up were having pharmacy refill adherence of < 95%, having baseline CD4 T lymphocytes count < 200 cells/μl, being on triomune-, stavudine-, or nevirapine-containing regimen, not being able to recall HIV diagnosis date, a unit increase in body weight even after correcting for age, and a baseline viral load. The association between the uses of triomune may be related to the negative correlation of both stavudine and nevirapine individually, rather than the fixed-dose therapy itself. These two drug components are both independently associated with virological failure after one year of therapy.Of the adherence measurements, only pharmacy refill adherence was positively correlated with the virological response in a dose response relationship per each increasing adherence rate stratified category. The dose response relationship between pharmacy refill adherence and virological outcome has also been observed in previous studies , 23, 33.Even though in this study the optimal cut-off for pharmacy refill was 95%, the dose response relationship shown in the comparison of virological outcome and grouped pharmacy refill adherence suggests that ARV regimens suppress viral load even at moderate adherence of > 70%. This may be related to current regimens that are more potent, and, thus, may sufficiently sustain complete viral suppression and avoid HIVDR, especially among patients initiating ART , 38.Pharmacy refill adherence measurement has a potential to be used in RLS , 39. In There are some limitations to the application of pharmacy refill adherence. First is the assumption that the drugs refilled are always consumed. There is no way to tell if the patient sold, shared, or dumped the medications after a refill. For that matter, this method is a mere proxy for adherence. A second drawback is inability to detect or predict all patients with viral rebound, given the relatively-low sensitivity for predicting virological failure around 60%). Moreover, with this method, it is not possible to discriminate patterns of adherence, such as treatment interruption, which may be more risky for non-nucleoside reverse transcriptase inhibitor resistance than a run of occasionally missed doses 0%. Moreo. An addiIn this study, self-report measures did not predict virological outcome. Self-reported adherence has not been consistently validated in RLS . In someFurthermore, in a Cox regression model, after accounting for age, gender, and immunological status, the groups of patients having pharmacy refill > 95% were more likely to recover immunologically in a relatively-shorter period than the non-adherent group. The cross validation after fitting the adherence in logistic regression indicate that adherence estimates combined with other variables performs better in predicting the virological outcome than adherence alone. These results indicated that a model combining only adherence and immunological response performs equally well, even better than using adherence alone. This model is important in routine clinical practice because immunological outcome is easily available, whereas other variables may not be so easily and routinely available to use for predicting therapy response.The study findings are limited by a small sample size obtained by convenient sampling of individuals who were initiating or continuing ART within the three months period of recruitment at the study site..Of the adherence methods investigated in this study, pharmacy refill method had the best performance in predicting virological failure. The performance improved when pharmacy refill adherence was combined with immunological response. The study found, this combination to have a reasonable sensitivity (around 70%) and specificity (around 60%) to predict virological failure. This combination could be useful to flag patients at risk for virological failure. It appeared to be more reliable than immunological and clinical response alone and was cost-saving. Thus, it had the potential for a wider application in ART follow-up in RLS. When combined with even more variables, such as treatment and demographic characteristics in the full logistic regression model, the prediction still improved, however this may become less straightforward and may, thus, lose applicability in RLS where doctors have very little time to devote to individual patientsSocio-demographic characteristics of participants included versus excluded. Socio-demographic characteristics of participants. (DOCX 20 KB)Additional file 1:Values of sensitivity, specificity, ROC curve area under the curve (AUC) by adherence assessment method at different cut-off points predicting virological failure  and immunological failure, using adherence measurement. Values of sensitivity, specificity and AUC by predicting virological failure or immunological failure using adherence measurements. (DOCX 24 KB)Additional file 2:Values of sensitivity, specificity, ROC curve AUC by adherence assessment method at different cut-off points predicting virological failure  at individual time points of adherence follow-up measurement. Description of data: Four time points 1 - 4 and the overall adherence outcome is shown per adherence measurement method. Key: SHCS-AQ = Swiss HIV Cohort Study Adherence Questionnaire; VAS = Visual Analog Scale; AUC = Area Under the Curve; ROC = Receiver Operating Characteristic; Sen = Sensitivity; Spe = Specificity; CI = confidence interval; PPV = positive predictive value; NPV = negative predictive value; DR = detection rate; DP = detection prevalence. AUC noted as “NA” indicated a situation when one of the two groups (adherent or non-adherent) was too small to calculate sensitivity and specificity. (XLSX 21 KB)Additional file 3:Socio-demographic characteristics of patients by detectable versus undetectable viral load at one year of follow-up. Comparison of social-demographic characteristics grouped by detectable versus undetectable viral load. (DOCX 19 KB)Additional file 4:ROC curve using sensitivity and specificity for predicting virological failure at different pharmacy refill adherence threshold cut-off points between 50 and 100. Note an increase in the area under the curve with increasing cut-off until optimum at 95%. ROC curve for predicting virological failure at different pharmacy refill adherence cut-off points. (EPS 5 KB)Additional file 5:Performance of and adherence univariate models versus full variable-null model using over 10-fold cross validation, repeated 50 times to predict virological failure (>400 copies/ml). Good-ness of fit of predicting virological failure using univariate versus full variable model. (DOCX 19 KB)Additional file 6:


We aimed at evaluating the efficacy and durability of a lopinavir/ritonavir-based dual regimen (LPV/r-DR) in virologically controlled HIV-infected individuals in current clinical practice.Patients who have initiated for the first time a LPV/r-DR with HIV-RNA<50 copies/mL were included in this observational study. The main endpoints were: time to virological rebound [VR=time of first of two consecutive viral loads (VL)>50 copies/mL] and time to experience either a single VL>200 copies/mL or discontinuation/intensification . Individuals’ follow-up accrued from the date of starting the LPV/r-DR to event or last available VL. Kaplan-Meier curves and Cox regression analysis were used. Covariates included in the multivariable analysis were gender, age, route of transmission, hepatitis co-infection, calendar year of starting the DR, nadir CD4+ count, VL at initiation of first cART, previous failures to protease inhibitors (PIs), time with undetectable VL before starting the DR and the type of DR . Results are presented as median  or frequency (%) as appropriate.108 individuals followed for 18  months were included; baseline (BL) characteristics are detailed in LPV/r was associated with a NRTI in 51, with a NNRTI in 10, with raltegravir in 29, and with maraviroc in 18 individuals. By 36 months from switching to the LPV/r-DR, the proportion of individuals with VR and TF was 10% (95% CI 3–17%) and 36% (95% CI 22–50%), respectively. We did not find any factor independently associated with the risk of VR. Older age (ARH=0.49 (95% CI 0.30–0.78) per 10 years older; p=0.003) was found to be protective from TF. Mean (SE) CD4+ cells/µL increase from BL to month 36 resulted significant: 195 (40.1) cells/µL (p=0.0028). We did not observe significant changes in AST, ALT, eGFR (MDRD formula), triglycerides and both total and HDL-cholesterol.A LPV/r-DR can be considered a valuable option in patients with HIV-RNA<50 copies/mL and ongoing toxicity from the third drug of the regimen, although up to 17% of patients showed viral rebound by 3 years. Older patients are at lower risk of failure with this strategy, but larger sample size is needed to identify who might benefit from this strategy instead of others.


High rates of patient attrition from care between HIV testing and antiretroviral therapy (ART) initiation have been documented in sub-Saharan Africa, contributing to persistently low CD4 cell counts at treatment initiation. One reason for this is that starting ART in many countries is a lengthy and burdensome process, imposing long waits and multiple clinic visits on patients. We estimated the effect on uptake of ART and viral suppression of an accelerated initiation algorithm that allowed treatment-eligible patients to be dispensed their first supply of antiretroviral medications on the day of their first HIV-related clinic visit.3). In the rapid arm, 119/187 patients (64%) initiated treatment and were virally suppressed at 10 mo, compared to 96/190 (51%) in the standard arm (relative risk [RR] 1.26 [1.05–1.50]). In the rapid arm 182/187 (97%) initiated ART ≤90 d, compared to 136/190 (72%) in the standard arm . Among 318 patients who did initiate ART within 90 d, the hazard of attrition within the first 10 mo did not differ between the treatment arms . The study was limited by the small number of sites and small sample size, and the generalizability of the results to other settings and to non-research conditions is uncertain.RapIT (Rapid Initiation of Treatment) was an unblinded randomized controlled trial of single-visit ART initiation in two public sector clinics in South Africa, a primary health clinic (PHC) and a hospital-based HIV clinic. Adult (≥18 y old), non-pregnant patients receiving a positive HIV test or first treatment-eligible CD4 count were randomized to standard or rapid initiation. Patients in the rapid-initiation arm of the study (“rapid arm”) received a point-of-care (POC) CD4 count if needed; those who were ART-eligible received a POC tuberculosis (TB) test if symptomatic, POC blood tests, physical exam, education, counseling, and antiretroviral (ARV) dispensing. Patients in the standard-initiation arm of the study (“standard arm”) followed standard clinic procedures . Follow up was by record review only. The primary outcome was viral suppression, defined as initiated, retained in care, and suppressed (≤400 copies/ml) within 10 mo of study enrollment. Secondary outcomes included initiation of ART ≤90 d of study enrollment, retention in care, time to ART initiation, patient-level predictors of primary outcomes, prevalence of TB symptoms, and the feasibility and acceptability of the intervention. A survival analysis was conducted comparing attrition from care after ART initiation between the groups among those who initiated within 90 d. Three hundred and seventy-seven patients were enrolled in the study between May 8, 2013 and August 29, 2014  programs for HIV/AIDS in sub-Saharan Africa is late presentation of patients for care and high rates of attrition from care between HIV testing and ART initiation.One reason for this is that starting ART in many countries is a lengthy and burdensome process, imposing long waits and multiple clinic visits on patients; in South Africa, the country with the world’s largest HIV treatment program, patients must typically make five or six clinic visits, starting with an HIV test, before they receive medications.There have not yet been any controlled evaluations of an integrated, rapid HIV treatment initiation algorithm that allows patients to initiate ART in a single clinic visit, so the RapIT trial was done to find out if “same-day initiation” of ART would increase the number of patients starting treatment and improve overall health outcomes, compared to current practices.We randomly assigned 377 adult patients at two public clinics in Johannesburg, South Africa, who had provided consent to participate in the study to one of two groups.Patients in the group assigned to receive rapid treatment initiation were offered the chance to start treatment on the same day as their first clinic visit, using rapid, point-of-care laboratory tests and an accelerated sequence of other steps, including a physical exam, education, and counseling.Patients in the group assigned to receive standard treatment initiation followed the standard schedule for treatment initiation used by the clinics, which usually required three to five additional clinic visits over a 2–4 wk period.After the study enrollment visit, patients were followed up by reviewing their regular clinic medical records, to determine how many did start treatment and how many were still in care and had good outcomes, as indicated by a suppressed viral load, 10 mo later.We found that 97% of patients in the rapid initiation group had started ART by 90 d after study enrollment—three-quarters of them on the same day—compared to 72% of patients in the standard initiation group.By 10 mo after study enrollment, 64% of patients in the rapid group had good outcomes compared to 51% in the standard group.Rapid initiation group patients spent roughly two and a half hours in the clinic to complete all the steps required before they got their medications.The RapIT (Rapid Initiation of Treatment) trial showed that it is possible to initiate nearly all eligible patients on HIV therapy, and to do so in a much shorter time interval than previously required.By showing that offering the opportunity to start treatment on the spot, without delay, overcomes many barriers patients would otherwise face, this study demonstrates that same-day ART initiation is an effective strategy for improving health outcomes.More patients in the rapid initiation group dropped out of care after starting treatment than in the standard initiation group; although the rapid initiation group still had better health outcomes overall, adherence support after starting treatment remains essential.The findings of this study are limited because the study took place in only two clinics in one part of South Africa and was carried out by study staff, not by regular clinic staff.Based on this study’s results, consideration could be given to accelerating the process of ART initiation in many different settings and for different types of patients. To explore whether a delay in initiation was associated with different post-initiation outcomes, we compared patients who did initiate on the same day to those who delayed for any reason. There were no differences in either the primary outcome of viral suppression or the secondary outcome of retention in care between these two groups of patients . BecauseRetention in care, defined as making a clinic visit between months 5 and 10 after study enrollment, was 81% (151/187) in the rapid arm and 64% (121/190) in the standard arm, for a risk difference of 17% (5%–23%) and a crude relative risk of 1.27 (1.12–1.44). To explore further the rate of loss to care, we estimated attrition from care within the first 10 mo after initiation among the subsample of 318 patients who did initiate ART within 90 d. In the standard arm, during 1,250 mo of total person-time, 22/136 (16%) dropped out of care after ART initiation, for an attrition rate of 1.8 per 100 person-months. In the rapid arm, during 1,626 mo of total person-time, 30/182 (16%) dropped out of care, for a rate of 1.8 per 100 person-months. The hazard of attrition within the first 10 mo after ART initiation among those who initiated within 90 d did not differ between the treatment arms . We note that this result is subject to selection bias and confounding, however, due to the exclusion of those who did not start treatment within 90 d.3 initiated ART, but this difference did not persist through retention or viral suppression at 10 mo. As might be expected, patients who enrolled in the study at the time of receiving their CD4 count results , rather than at the time of having an HIV test, were slightly more likely to achieve all three outcomes, though only for retention in care was this difference statistically significant. Finally, patients who reported being employed at the time of study enrollment, while no more likely to initiate ART, had significantly better retention in care and viral suppression than did those who reported being unemployed.In pooled analysis of both study arms, none of the variables presented in In stratified analysis  we obserIn the rapid arm, for which TB diagnostic data were available, 29/187 patients (16%) presented with TB symptoms and were tested for TB using Xpert MTB/RIF. Four patients  had a confirmed TB diagnosis. All four initiated ART within the 90-d outcome defined above, with a range of 11–54 d between study enrollment and ART initiation.The results of the sensitivity analysis incorporating the six patients who were excluded after randomization for reasons other than ART eligibility or prior CD4 count, and assigning each a negative outcome, did not differ substantively from the findings presented above, with a relative risk of viral suppression by 10 mo of 1.22 [1.02–1.46].Rapid initiation, using the procedures described above and as implemented by the study, appeared acceptable to patients at the time it was offered and feasible to implement at both study sites. We were not able to assess acceptability after patients received the intervention, as the study had no post-initiation interaction with those enrolled, and thus can surmise acceptability only on the basis of acceptance of the intervention. The study refusal rate was very low ; nearly four out of five  patients offered the intervention accepted initiation on the same day or the next day, and rapid arm patients consistently expressed appreciation for the opportunity to start immediately.All steps in the rapid initiation process were completed on the same day as study enrollment for 72% (135/187) of those in the rapid arm, demonstrating the feasibility of the intervention, at least within the context of the study. From provision of informed consent (study enrollment) to dispensing of the first supply of ARV medications, rapid initiation took a median of 2.4 (IQR 2.1–2.8) hours for those who initiated on the same day as study enrollment. This interval was shorter for patients who already had CD4 count results in hand at study enrollment (median 2.25 hours). It was longer (median 4.5 hours) for those who required a TB test and did initiate ART on the same day, but 15/20 patients requiring TB tests did not initiate on the same day. The only obstacle encountered in implementing rapid procedures was fairly frequent power outages, a common occurrence in South Africa, at Site 1, which did not have a generator for backup power supply. Most rapid instrument tests could not be performed during power outages. The rapid test instruments otherwise performed well throughout the study, and no major delays or problems arose in the acceleration of clinic procedures.In this randomized controlled trial, we evaluated the effectiveness of an accelerated ART initiation algorithm that combined compressed and accelerated clinic procedures with point-of-care laboratory testing technologies that allowed eligible patients to initiate ART in a single clinic visit. This intervention increased the proportion of patients eligible for ART at study enrollment who initiated ART within 90 d by 25%, to 97% of all eligible patients and 100% of patients who were not delayed for TB treatment. By 10 mo after study enrollment, the intervention increased viral suppression among all treatment-eligible patients by 13% and retention in care by 17%. It was feasible and appeared acceptable at both study sites.The trial demonstrated that it is possible to initiate nearly all eligible patients on ART, and to do so in a much shorter time interval than previously required. The net benefit for overall viral suppression was clinically meaningful and may underestimate the true benefits of the intervention. Both the study sites were relatively well-managed, public sector clinics, resulting in a higher rate of ART initiation in the standard arm 72%) than is found elsewhere in the country, for example in rural KwaZulu Natal Province where the rate was 59% % than is, is anotThe patients who likely benefited most from RapIT were those who would not otherwise have initiated treatment at all, or who would have waited until they were sick enough to compromise their prognosis on treatment. In the standard arm, most patients who did not start treatment did not return to the study clinics for even one more visit, underscoring the importance of taking full advantage of the first visit to get as many patients started on treatment as possible. For those who would have initiated treatment, just not as soon, there is some evidence that even relatively short delays may be harmful. A recent modeling exercise using South African data estimated that compared to immediate initiation, a delay in initiating ART of 70 d would lead to a 34% increase in 12-mo mortality . DelayinWe hypothesize that the delays and multiple visits patients must endure before starting ART directly deter treatment initiation. Patients who cannot afford transport fare for multiple visits, have childcare obligations at home, or risk job or wage loss if they miss too many days of work may be directly deterred from returning. Others may simply grow impatient or lose their courage or motivation, particularly if they are asymptomatic when diagnosed. These patients are likely to drift away and only return when their CD4 counts are lower and symptoms have started, or to die before treatment can be started. Our results suggest that offering the opportunity to start treatment on the spot, without delay, overcomes these barriers, without risking poorer outcomes later on.Among patients who did initiate ART, post-initiation loss to care was higher in the rapid arm than the standard arm. This difference disappeared in the survival analysis, which controlled for number of months on ART but does not reflect the benefits of randomization. We speculate that some patients who did not want or were not ready for treatment chose to accept immediate initiation simply because it was offered or they wanted to participate in the study. For these patients, attrition from care was simply shifted from before ART initiation to after. While the intervention was successful in increasing the overall proportion of treatment-eligible patients with successful outcomes , the rate of post-initiation attrition is a reminder that early retention in care and adherence support once patients start treatment remain high priorities for further research and intervention.Other studies have gauged the impact on treatment uptake of a single POC technology  or changNothing in the rapid initiation procedures used in this study differed fundamentally from existing clinic procedures. The intervention was delivered by study nurses and counselors with the same qualifications as existing clinic staff, though with study-specific training and supervision. The intervention imposed no major burdens on site management, though managerial acquiescence to the study and operational flexibility were needed to adjust the schedule and content of patient visits, staff responsibilities, and record keeping to allow for rapid initiation . The maiAlthough South Africa has better clinic infrastructure than do many other countries in the region, the RapIT intervention does not require anything that most urban and many rural clinics cannot provide. We speculate that the RapIT intervention would be feasible and potentially even more effective in other high HIV prevalence areas, where patients travel farther to reach clinics and results from centralized laboratories take even longer to return. As the new WHO guidelines are adopted, moreover, laboratory test results may not be required prior to ART initiation for patients who are asymptomatic, reducing the need for POC technology.The generalizability of our results is limited in several ways. The study was conducted in only two clinics in one province of one country. The trial intervention was delivered by study staff; it is uncertain if clinic staff delivering the same intervention will achieve the same outcomes . As is typical in individually randomized trials of service delivery interventions, the possibility exists that quality of care in the standard arm was improved by the presence of the study, as clinic staff providing care for the standard arm may have been motivated by the study to make treatment initiation more efficient. If this occurred, the effect reported here would understate the true improvement in ART initiation that could be expected under routine implementation. As with many studies in which retention in care is an endpoint, we do not know the true outcomes of study patients who were not retained nor whether rapid arm patients who were not retained and who agreed to start treatment solely due to the presence of the study, and would otherwise not have done so, are at increased risk of developing ARV resistance. Finally, as reported above, rapid initiation under the study algorithm took 2–3 hours to complete, making same-day initiation impractical for patients who arrive late in the day (and for clinics with large numbers of such patients).We also do not know how clinic and patient characteristics will affect the net cost and cost-effectiveness of the intervention. Most of the changes introduced in the RapIT intervention entailed only adjustments in schedules and staff time, and we speculate that these will not result in a major net change to service delivery costs. The POC instruments used in the trial require an up-front investment, but it may be possible to initiate ART in a single visit without any POC instruments if there is no CD4 count threshold for initiation, patients with TB symptoms are identified and managed separately, and ARV regimen adjustments are routinely made at the first refill visit, rather than before initiation. Costs saved by patients, who must make just one clinic visit rather than four or five, should also be taken into account.The RapIT intervention as designed and implemented showed clinically meaningful improvements in ART uptake and viral suppression, providing “proof of principle” for a single-visit treatment initiation algorithm. Follow-on studies are needed to evaluate effectiveness and cost-effectiveness in routine practice in a variety of settings, and variations on the algorithm could also be considered. The RapIT trial has demonstrated that accelerating ART initiation can be effective and feasible in this setting and appeared acceptable to patients to whom it was offered; the next challenge will be adapting it to the range of settings and conditions found in clinics throughout Africa.S1 Table(DOCX)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.S3 Table(DOCX)Click here for additional data file.S4 Table(DOCX)Click here for additional data file.S1 Text(PDF)Click here for additional data file.S2 Text(PDF)Click here for additional data file.


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.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 <400 copies/ml after 12 months) were also determined. Survival was assessed by the Kaplan-Meier method and log rank test.A total of 7,455 subjects were recruited by December 2012. Of patients tested, 591/5656 (10.4%) were HBsAg positive, 794/5215 (15.2%) were HCVAb positive, and 88/4966 (1.8%) were positive for both markers. In multivariate analysis, HCV co-infection, age, route of HIV infection, baseline CD4 count, baseline HIV RNA, and HIV-1 subtype were associated with immunological recovery. Age, route of HIV infection, baseline CD4 count, baseline HIV RNA, ART regimen, prior ART and HIV-1 subtype, but not HBV or HCV co-infection, affected HIV RNA suppression. Risk factors affecting mortality included HCV co-infection, age, CDC stage, baseline CD4 count, baseline HIV RNA and prior mono/dual ART. Shortest survival was seen in subjects who were both HBV- and HCV-positive.In this Asian cohort of HIV-infected patients, HCV co-infection, but not HBV co-infection, was associated with lower CD4 cell recovery after ART and increased mortality. There are similarities in the transmission routes of and risk factors for HIV, and the hepatitis B virus (HBV) and hepatitis C virus (HCV) infection,2, but eYet, compliance with hepatitis screening in HIV patients prior to initiation of ART is usually poor in resource-limited settings ,15, and As of December 2012, TAHOD included 7,455 HIV patients from 21 adult HIV treatment centers in 12 countries with 24,798 person-years of follow-up. Those who ever tested HBsAg positive or anti-HCV antibody positive within the duration of the study were regarded as having a history of HBV or HCV co-infection, respectively.The following data were collected in TAHOD: (i) patient demographics and baseline characteristics: date of clinic visit, age, sex, ethnicity, HIV exposure category, date of first positive HIV test, HIV subtype, and date and result of HBV, HCV and syphilis serology; (ii) stage of disease: CD4 and CD8 count, HIV viral load, prior and new AIDS defining illnesses, date and cause of death; (iii) treatment history: prior and current antiretroviral treatments, reason for treatment changes  and prophylactic treatments for opportunistic infections.All participating clinical sites, the data management and analysis center , and the coordinating center  obtained institutional review board approval for the study . Written consent was obtained when required by the local review boards.Factors associated with HBV and/or HCV co-infection were determined by univariate and multivariate logistic regression models. Immunological and virological response to ART was assessed using change in CD4 counts at 6 months after initiating ART. Factors associated with CD4 change after six months of ART and with viral load <400 after 12 months of ART were also determined. Patients were included in the later analysis if they had both baseline CD4 counts and CD4 counts at 180 days (90–270 days) after treatment initiation available. Baseline CD4 count was obtained before initiation of ART, with the value closest to ART start within a six month window used.Factors associated with overall survival were determined by univariate and multiple Cox proportional hazard models. All patients who were followed up were included in the survival analysis. Follow-up was censored at the last clinic visit for patients who survived. Survival of the HIV patients was estimated by the Kaplan Meier method and comparison of survival between subgroups was performed by the log rank test. Causes of death in TAHOD were collected through a standardized process that was previously validated by the D:A:D group. Specifically, the treating physician completed a set of forms documenting causes of death and associated clinical factors and lab test results, and the clinicians’ reports were reviewed by external investigators. Conflicting determinations of immediate and underlying causes of death were then adjudicated by a review committee.p value of less than 0.05 was considered statistically significant.Statistical analysis was done with SAS version 9.2 . A two tailed Among 7,455 subjects enrolled in TAHOD as of December 2012. Most of the study subjects were male (70.0%) and aged between 40–50 years (65%). The main ethnic groups were Thai (28%) and Chinese (23%). HIV infection occurred mainly by heterosexual contact (66%), homosexual contact (19%), and injecting drug use (IDU) (8%), and only 1% occurred by blood contact.A total of 5,656 (75.9%) underwent HBsAg testing, 5,215 (70%) underwent HCV antibody testing, and 4,966 (66.6%) underwent both HBsAg and HCV antibody testing. HBsAg was positive in 591/5656 (10.4%) subjects, and HCV antibody was positive in 794/5215 (15.2%) subjects.  AnalysisFemales had also a lower risk of HCV infection than males . When compared to heterosexual risk of HIV infection, homosexual contact was associated with a lower risk of HCV co-infection , whereas IDU , history of receiving blood products  and other routes of HIV infection  were associated with a higher risk of HCV co-infection. When compared with subjects with baseline CD4 counts <50 cells/μL, those with counts in the 50–200 cells/μL range  and in the 351–500 cells/μL range  were at decreased risk of HCV co-infection.CD4 counts were available at baseline and 6 months of ART in 4,795 subjects.  Six-montIn multivariate analysis, factors found to be associated with viral load <400 after 12 months of ART included age 31–50 , age >50 , mode of infection other than heterosexual or homosexual contact , baseline CD4 count 201–350 , baseline HIV viral load 80,001–200,000 , ART antiretroviral regimen containing nucleoside reverse transcriptase inhibitor and protease inhibitor , prior ART , and HIV-1 subtype C  . There wA total of 5656 patients were on ART, of whom 5130 (90.7%) were on an ART regimen containing lamivudine. Of the patients on ART, 591 (10.4%) were HBV co-infected. In these co-infected patients, ART containing lamivudine (518/591 = 87.6%) was most commonly prescribed, followed by ART containing emtricitabine (42/591 = 7.1%). Comparison of HBV co-infected patients with ART containing lamivudine with those with ART not containing lamivudine showed no statistically significant differences in CD4 change and VL suppression <400 at 12 months (data not shown). Outcomes in co-infected patients receiving the combination of lamivudine and tenofovir and those receiving emtricitabine and tenofovir were also similar (data not shown).Factors affecting survival were evaluated in all 7,455 study subjects, contributing 24,978 person-years of prospective follow-up . SubjectSurvival was shortest in subjects who were both HBV- and HCV-positive, and survival was worse in HCV-positive than in HBV-positive subjects .This study determined the effects of HBV or HCV co-infection on short- and long-term outcomes following ART in patients enrolled in TAHOD. Results showed that risk factors affecting CD4 change 6 months after ART included HCV co-infection, older age, injecting drug use, lower baseline CD4 count, higher HIV viral load, and HIV-1 subtypes 01AE and C. Risk factors affecting viral load suppression to <400 12 months after ART included age, mode of transmission, baseline CD4 count, baseline viral load, ART regimen, prior ART, and HIV-1 subtype C. HBV and HCV co-infection was not associated with virological response. Significant risk factors affecting mortality included HCV co-infection, older age, late CDC stage, lower baseline CD4 count, higher baseline HIV viral load, and prior mono or dual ART.The major limitation of this study was that we did not have sufficient data on HCV RNA to confirm the presence of chronic HCV infection. Antibody testing indicates that the patient had a history of HCV infection, which could be current or resolved. However, HCV RNA testing has rarely been available in routine HIV clinical care settings in the low- and middle-income country settings where the large majority of our patients receive care. The small number of patients who did have HCV RNA results were likely from high-income settings and/or were high-risk or had other indicators of liver disease, which makes it difficult to interpret their results in comparison to the overall cohort. Information on treatment of viral hepatitis that patients may have received beyond antiretrovirals active against HBV also was not available. In addition, as the 21 HIV treatment centers participating in TAHOD are mainly large urban referral hospitals, results from this study cannot be generalized to patients from different settings, notably rural areas, who may have a more limited access to medical care and disease monitoring.Another limitation of this study was that the timing of the hepatitis screening in relationship to outcome or ART initiation were at different times. The HBV and HCV test results reflected ever being tested. There could still be some misclassification , but we believe this misclassification would have underestimated effects.In this study, hepatitis B and C were detected in 10.5% and 15.2% of subjects undergoing screening, respectively. In contrast, a large African cohort of HIV-infected patients showed higher hepatitis B (17.8%) than hepatitis C (11.3%) co-infection prevalence. The HIV-A previous report from TAHOD with data from 1372 subjects who had undergone hepatitis screening up to December 2005 showed that hepatitis co-infection had no effect on survival.  However,That the survival analysis identified HCV but not IDU as a risk factor of increased mortality is probably due to strong correlation between the 2 variables . In our CD4 counts at baseline or 6 months after ART were missing in 2660 (35.7%) of the patients. Comparison of these patients with those with both baseline and 6-month CD4 counts showed that a lower percentage of these patients who had less CD4 monitoring had previously received antiretroviral monotherapy  and had been infected with HIV via heterosexual contact . This potential bias is a limitation of our study. These patients were excluded from the CD4 assessments, but they were included in the overall HBV and HCV analysis.Previous studies showed an association between lower baseline CD4 cell count and HBV co-infection ,22,28 buEthics approval was granted for the TAHOD study design, methods and consent procedures by the University of New South Wales Human Research Ethics Committee. Site specific study governance was granted by site-relevant institutional review boards: Ministry of Health National Ethics Committee for Health Research (Cambodia), Ethical Committee of Beijing Ditan Hospital Affiliated to Capital Medical University (China), Research Ethics Committee Kowloon Central / Kowloon East, Hospital Authority IRB (China), Institutional Review Board Of YRG CARE (India), Institutional Ethics Committee Rao Nursing Home (India), Kerti Praja Foundation IRB (Indonesia), Committee of Medical Research Ethics, Faculty of Medicine University of Indonesia (Indonesia), National Center for Global Health and Medicine Human Research Ethics Committee (Japan), Medical Research & Ethics Committee, Ministry of Health , Medical Ethics Committee, University Malaya Medical Centre , Research Institute for Tropical Medicine, Department of Health (Philippines), National Healthcare Group IRB, Domain Specific Review Board (Singapore), Severance Hospital Yonsei University College of Medicine Institutional Review Board (South Korea), Institutional Review Board of Taipei Veterans General Hospital (Taiwan), The Internal Ethical Committee for Research in Human Subject, Chiangrai Prachanukroh Hospital (Thailand), Institutional Review Board Faculty of Medicine, Chulalongkorn University (Thailand), Committee on Human Rights Related to Research Involving Human Subjects Faculty of Medicine Ramathibodi Hospital, Mahidol University (Thailand), Research Ethics of the Faculty of Medicine, Chiang Mai University (Thailand), Siriraj Institutional Review Board, Mahidol University (Thailand), Ministry of Health, Hanoi School of Public Health IRB (Vietnam), and National Hospital of Tropical Diseases IRB (Vietnam).Written informed consent was not sought in TAHOD unless required by a site’s local institutional review board. The need for written consent was waived by the following ethics committees: Ministry of Health National Ethics Committee for Health Research (Cambodia), Ethical Committee of Beijing Ditan Hospital Affiliated to Capital Medical University (China), Research Ethics Committee Kowloon Central / Kowloon East, Hospital Authority IRB (China), Institutional Review Board Of YRG CARE (India), Institutional Ethics Committee Rao Nursing Home (India), Kerti Praja Foundation IRB (Indonesia), Committee of Medical Research Ethics, Faculty of Medicine University of Indonesia (Indonesia), Medical Research & Ethics Committee, Ministry of Health , Medical Ethics Committee, University Malaya Medical Centre , The Internal Ethical Committee for Research in Human Subject, Chiangrai Prachanukroh Hospital (Thailand), Ministry of Health, Hanoi School of Public Health IRB (Vietnam), and National Hospital of Tropical Diseases IRB (Vietnam).In this Asian regional HIV cohort, HBV or HCV co-infection by serological testing was common. Patients with HCV co-infection had significantly lower CD4 counts, worse CD4 cell recovery after 6 months of ART, and poorer survival than HIV mono-infected patients. These findings confirm the importance of screening for HBV and HCV co-infection and increasing access to confirmatory hepatitis testing, and support recommendations for use of antiretrovirals active against HBV in ART regimens for co-infected patients.


In order to reflect the currently predominant profile of HIV-positive patients across sub-Saharan Africa, we only included patients established on antiretroviral therapy (ART) with two nucleoside/nucleotide reverse transcriptase inhibitors plus efavirenz (n=89) or nevirapine (n=11), and excluded those not receiving ART (n=6) or receiving protease inhibitors (n=10).3 (361–711); 78% showed plasma HIV-1 RNA suppression (<40 copies/mL). Median AST, GGT and platelet counts were 32 U/L (25–39), 60 U/L (44–81) and 165×109/L (118–225), respectively. TE measurements were median 4.6 kPa (3.8–6.2). Of 100 patients, 18% and 7% were classified as having advanced fibrosis and cirrhosis, respectively. Factors significantly associated with TE measurements were GGT , AST , CD4 count , APRI , GPR  (Spearman's r) and male gender   were median 44 years old (IQR 38–48), had received ART for median 7.2 years (5.0–9.0) and had a CD4 count of median 572 cells/mmWhitney) ; there wGPR and APRI had good negative predictive values for excluding cirrhosis (96%) and, to a lesser extent, advanced fibrosis  . Overall3The non-invasive and routinely available biomarkers GPR and APRI cannot be recommended for the diagnosis of advanced fibrosis and cirrhosis in HIV/HBV coinfected population established on ART in West Africa due to insufficient positive predictive value.


The emergence of transmitted drug resistance (TDR) compromises the effect of antiretroviral therapy (ART), resulting in treatment failure of human immunodeficiency virus (HIV) disease. Although more than a decade has passed since ART was introduced into Indonesia, information on TDR is limited. Here, a genotypic study of TDR among ART-naïve individuals was conducted in Surabaya, Indonesia.HIV-1 seropositive participants were recruited from the communities of commercial sex workers and intravenous drug users as well as from the university teaching hospital in Surabaya. Protease (PR) and reverse transcriptase (RT) genes were sequenced in order to conduct HIV-1 subtyping and phylogenetic analysis and to detect TDR. TDR was defined as the presence of at least one surveillance drug resistance mutation on the WHO list or major drug resistance mutations in the International AIDS Society-USA panel.Fifty two and 47 of the PR and RT genes, respectively, were successfully sequenced in the 58 samples. HIV-1 subtyping revealed that 86.3% (50/58) of the sequenced samples were classified as CRF01_AE, 8.6% as subtype B, 3.4% as B/CRF01_AE, and 1.7% as A/G/CRF01_AE. TDR of PR inhibitors was not detected in this study. In contrast, TDR of RT inhibitors was detected in 4.3% (2/47) of samples. In addition, minor drug resistance mutations were detected in 98.1% (51/52) and 12.8% (6/47) of PR and RT genes, respectively.This study clarified the predominance of the CRF01_AE strain in Surabaya, Indonesia. The prevalence of TDR was below 5%, indicating that the currently available first-line regimen is still effective in Surabaya. However, the prevalence might be underestimated since we detected only major population of HIV-1 in individuals. Therefore, continuous surveillance is required in order to detect the emergence of TDR in the early phase.The online version of this article (doi:10.1186/s12981-015-0046-y) contains supplementary material, which is available to authorized users. Antiretroviral therapy (ART) achieved the reduction of viral transmission, morbidity and mortality associated with human immunodeficiency virus (HIV) disease. However, the emergence of transmitted drug resistance (TDR) as a consequence of ART expansion represents a serious public health problem because TDR affects the treatment efficacy and clinical outcome ,2. AlthoHIV-1 is subdivided into four groups, M (major), O (outlying), N , and P. Group M accounts for the majority of HIV-1 infections. The viruses in group M are further classified into subtypes, circulating recombinant forms (CRFs) and unique recombinant forms (URFs), which are prevalent in specific geographic regions. While subtype B of HIV-1 is the predominant subtype in the Americas, Europe, and Australia, there is a growing epidemic of non-B subtypes and CRFs in Africa and Asia . CRF01_A3 (WHO criteria), would reach 510,000 in 2013 [In Indonesia, the estimated number of people living with HIV has been increasing and reached 610,000 in 2012, even though that of other Southeast Asian countries is stable or in decline [ in 2013 , the cov in 2013 . The numThe first-line regimen of ART recommended in Indonesia is a combination of two nucleoside reverse-transcriptase inhibitors (NRTIs) and a non-nucleoside reverse-transcriptase inhibitor (NNRTI) . LamivudAlthough ART is successful in Indonesia, the emergence of drug resistance has been reported among treatment-failure patients . After aPeripheral blood samples were collected from the participants from the communities of commercial sex workers (CSWs) and intravenous drug users (IDUs) as well as from the university teaching hospital in Surabaya. All participants were confirmed to be ART naïve at interview and/or from medical records. RNA and DNA were extracted from plasma and peripheral blood mononuclear cells (PBMC), respectively, isolated from peripheral blood samples. If a viral gene fragment failed to be amplified from the cDNA even after multiple attempts, it was amplified instead from DNA. In order to examine the genomic fragment of the major viral population in a sample, PCR products amplified at the end-point dilution of DNA templates were subjected to sequencing analysis.As a result, 52 and 47 of the protease (PR) and reverse transcriptase (RT) genes, respectively, were successfully sequenced in the 58 samples. Of these, 13 and 22 of the PR and RT genes, respectively, were derived from DNA. The demographic data of the 58 individuals are shown in Table http://www.hiv.lanl.gov/content/sequence/HIV/CRFs/CRFs.html).HIV-1 subtyping was carried out for PR and RT gene sequences separately using recombinant identification program (RIP). Most PR and RT gene sequences were classified as CRF01_AE or subtype B. However, two RT gene sequences derived from SM11 and IDU11 were classified as B/CRF01_AE, and PR and RT gene sequences derived from PJ121 were G/CRF01_AE and A/G/CRF01_AE, respectively -USA panel or surveillance drug resistance mutation in world health organization (WHO) surveillance list ,11. AccoTwo of 47 samples 4.3%) possessed TDR in RT gene sequences. The RT gene fragment from SM18 contained a K101E mutation, which is a major drug resistance mutation to NNRTI; ETR and RPV [% possessHere we report the circulating HIV-1 subtype and the prevalence of TDR among 58 HIV-1-infected drug-naïve individuals in Surabaya, Indonesia. Of 58 sequenced samples, 50 (86.3%) were classified as CRF01_AE, 5 (8.6%) as subtype B, 2 3.4%) as B/CRF01_AE, and 1 (1.7%) as A/G/CRF01_AE. These results are consistent with a previous report on the predominance of CRF01_AE in Southeast Asian countries % as B/CR. The virGenotypic analysis of drug resistance revealed no evidence of the circulation of TDR against PIs in Surabaya. This was not surprising because access to PIs is limited in Surabaya, even though PI is recommended as the second-line regimen. Interestingly, each CRF01_AE strain possessed 3 to 8 minor drug resistance mutations based on the IAS-USA panel . AlthougIn contrast, the prevalence of TDR against RT inhibitors was 4.3% (2/47). This was consistent with a previous report that TDR in Asian countries was <5%, but is gradually increasing . HoweverFour minor mutations  conferring resistance to ETR and/or RPV were detected among 6 samples. However, they are considered natural polymorphisms because these mutations are excluded from the WHO list , and ETR+ T-cell counts above 500 cells/mm3) [In the WHO TDR surveillance guideline, the prevalence of TDR is categorized into three groups: <5% (low level), 5–15% (medium level) and >15% (high level) ,15. The lls/mm3) . Therefolls/mm3) ,16. Therlls/mm3) ,18. ConsThe prevalence of TDR among ART-naïve patients in Surabaya was <5%, which is categorized as low by WHO. However, additional or continuous surveillance must be conducted because this study had several limitations, and the prevalence might be underestimated and biased. The low TDR observed in this study calls for continuous monitoring of TDR in order to detect the emergence of TDR in the early phase.This study was conducted with approval from the ethics committee of the Airlangga University (permission number: 25-995/UN3.14/PPd/2013) and the medical ethics committee at Kobe University Graduate School of Medicine (permission number: 784), and written informed consent was obtained from study participants.Participants were recruited from the communities of CSWs and IDUs as well as from the university teaching hospital in Surabaya. The CSW study subjects were the same as in a previous report . All parViral RNA was reverse transcribed to cDNA using the SuperScript III First-Stand Synthesis kit . Generated cDNA was subjected to amplification of the viral gene for both the PR and RT encoding regions in a separate reaction by nested PCR using Ex Taq . Primer information is shown in Additional file Sequencing analysis of the amplified fragment was performed using the BigDye Terminator v3.1 Cycle Sequencing kit with an ABI PRISM 3500 × l genetic analyzer . Data were assembled and aligned using Genetyx ver. 10 software . Nearly the full length of the PR gene  and part of the RT gene  were sequenced and subjected to subsequent analysis.www.hiv.lanl.gov/). In addition, neighbor-joining (NJ) trees with a Kimura two-parameter model were constructed using MEGA5.2 software [http://jphmm.gobics.de/) [Obtained sequence data were subjected to HIV-1 subtyping using the RIP, available at the website of the HIV sequence database (software -22. Bootsoftware . If one ics.de/) . The nucHIV-1 TDRs were detected manually according to the IAS-USA panel and WHO surveillance list ,11. In thttp://aoki2.si.gunma-u.ac.jp/exact/fisher/getpar.html. P values ≤0.05 were considered to be significant.Statistical analysis was performed using Fisher’s exact test for categorical variables. The P value was calculated using the program available at the web site,


HIV testing and retention in care treatment are key strategies towards an AIDS free generation. Immediate treament of HIV patients with the lowest CD4 T cell counts is critical given their high rates of pre-antiretroviral therapy mortality. We evaluated the impact of adding an additional nurse-counsellor on HIV outcomes among patients enrolled in care in 7 urban public clinics in Kampala, Uganda.One additional research nurse per clinic was specifically tasked with identifying and tracking HIV-infected persons with CD4<100 cells/μL who were lost, and expediting ART initiation among patients enrolled after July 2012. Data were also retrospectively collected on all patients with CD4<100 cells/μL that registered at these clinics in the latter six months of 2011. We compared time from CD4 blood draw to ART initiation, frequency of CD4 testing and 6 month retention-in-care by time period. Analyses of categorical and continuous variables were conducted using Χ2 and Mann-Whitney tests.A total of 258 patients in the 2011 cohort and 593 in the 2012 cohort completed 6 months from clinic registration. Median age of patients in both cohorts was 32 years and 55% were female. Median CD4 cells/μL  count in the 2011 cohort was 34  and 43  in 2012 (p < 0.002). Median days from CD4 blood draw to ART initiation reduced from 42  in the 2011 to 33  in 2012, p < 0.001. Six-month retention in care was 62.0% (160/258) in 2011 cohort compared to 75.9% (450/593) in 2012 (p < 0.001). Among the patients retained in care, 24.4% (39/160) received a CD4 count test at 6 months versus 53.3% (240/450) in the 2012 cohort.The addition of one nurse per clinic to identify and follow severely immune-compromised new clinic patients with CD4<100 led to improved patient care and better outcomes. Funder: The study is an Implementation Science project funded by CDC.


This analysis was designed to characterize the treatment patterns, efficacy, and safety of nab-paclitaxel for MBC treatment using health claims data from US health plans associated with Optum.nab-paclitaxel for MBC treatment from January 1, 2005, to September 30, 2012, and who met eligibility criteria were selected from the Optum Research Database for this analysis. Patients were required to have complete medical coverage and pharmacy benefits, ≥ 6 months of continuous enrollment, and a diagnosis of MBC prior to nab-paclitaxel initiation. The pattern of use for nab-paclitaxel  and claims-captured toxicities were characterized by line of therapy. Overall survival (OS) and time to next therapy or death (TNTD) were described by line of therapy, regimen, and schedule.Women aged ≥ 18 years who initiated nab-paclitaxel patients, 172 (25.9 %) received it as first-line therapy, 211 (31.8 %) as second-line therapy, and 281 (42.3 %) as third-line or later therapy. Overall, the majority of patients received monotherapy (61 %) and followed a weekly (71 %) rather than an every 3 weeks treatment schedule. nab-Paclitaxel was often (31.7 %) combined with targeted therapy (57.5 % with bevacizumab and 23.9 % with trastuzumab or lapatinib). The median duration of therapy was 128 days (4.2 months). For the overall population, median OS was 17.4 months . Median TNTD was 6.1 months . For patients aged ≤ 50 years or with ≥ 3 metastatic sites, median OS was 15.6 months. No new safety signal was identified.Of the 664 nab-paclitaxel as second-line or later therapy, monotherapy, and weekly treatment. The efficacy and safety outcomes of nab-paclitaxel observed in this real-world setting appear consistent with those from clinical trial data.In this US healthcare system, the majority of patients received  Resnab-Paclitaxel has also been studied in combination with other cytotoxic or targeted agents for the treatment of MBC  and to estimate the OS and time to next therapy or death (TNTD) among patients who received International Classification of Disease, Ninth Revision Clinical Modification (ICD-9-CM) codes. Procedures map to ICD-9-CM, Current Procedural Terminology, and Healthcare Common Procedure Coding System codes. Pharmacy claims data include drug name, dosage form, drug strength, fill date, days of supply, financial information, and de-identified patient and prescriber codes, allowing for longitudinal tracking of medication refill patterns and changes in medications.In this retrospective cohort study, health insurance claims data were extracted from the Optum Research Database, which contains eligibility, pharmacy claims, medical claims, and other information, such as mortality data, from health plans associated with Optum. The health claims are linked to enrollment information with data covering the period from 1993 to present. The information in the claims database includes over 12 million individuals from geographically diverse locations across the United States who have both medical and pharmacy benefit coverage. Medical claims or encounter data were collected from all available healthcare sites  for virtually all types of provided services, including specialty, preventive, and office-based treatments. Diagnoses on the claims are recorded using nab-paclitaxel treatment. Patients were eligible for the study if they had complete medical coverage and pharmacy benefits; had ≥ 6 months of continuous enrollment in a US health plan from January 1, 2005 to September 30, 2012; and had a diagnosis of MBC prior to the initiation of nab-paclitaxel. Patients were selected for the claims analysis based on the criteria listed in Fig. The study population consisted of women aged ≥ 18 years with a diagnosis of MBC who received nab-paclitaxel were defined as those with a first dispensing of nab-paclitaxel within the study period , with no dispensing of nab-paclitaxel during the 6 months prior to the first dispensing (baseline period). Patients who received neoadjuvant (≤4 months prior to surgery) or adjuvant (≤90 days after surgery) therapy with nab-paclitaxel were excluded. The index date was defined as the date of nab-paclitaxel initiation. Patients who met the cohort entry eligibility criteria were further categorized into 3 subgroups by line of therapy  with nab-paclitaxel.New users of A patient must have received ≥ 1 cycle (defined as 30 days) of treatment prior to being defined as switching to a greater line of therapy. Any switching or addition of agents within 30 days of the start of each line of therapy was considered to be the same line of therapy.nab-paclitaxel was defined as initial dispensing of nab-paclitaxel as the first chemotherapy received after a diagnosis of metastatic disease. All agents received within 30 days following nab-paclitaxel were considered part of first-line therapy.First-line therapy with nab-paclitaxel was defined as dispensing of nab-paclitaxel as part of second-line therapy, defined as additional treatment different from the first-line therapy and initiated ≥ 30 days after the first chemotherapy or after a large gap  in therapy.Second-line therapy with nab-paclitaxel was defined as a first dispensing of nab-paclitaxel as part of third-line therapy, defined as any additional treatment different from any initiated first- or second-line therapy and after 60 days of the first chemotherapy or after a large gap  in therapy. Similar methods were used to identify later lines of therapy.Third-line or later therapy with nab-paclitaxel initiation. All-cause death was identified using Social Security Administration data linked to claims data. TNTD was used as a surrogate of progression-free survival (PFS). Major toxicities were identified following each line of therapy and determined by tabulating the 25 most frequent ICD-9-CM diagnoses codes. The toxicities of interest included select adverse events consistent with the known safety profile of nab-paclitaxel: neutropenia, anemia, thrombocytopenia, infections, peripheral neuropathy, asthenia, nausea, vomiting, diarrhea, fluid retention, myalgia/arthralgia, and alopecia.The study outcomes included all-cause death, TNTD, and major toxicities following nab-paclitaxel treatment patterns, and nab-paclitaxel toxicities of interest in patients with MBC by line of therapy. The background characteristics, including demographics and breast cancer risk factors, were ascertained during the 6-month baseline period. Treatment patterns of nab-paclitaxel were described in terms of treatment regimen (monotherapy or combination therapy), treatment schedule (weekly or q3w), duration of line of therapy, number of administrations, intervals between dispensings, and dose. The occurrence of toxicity claims of interest following nab-paclitaxel treatment was also summarized.A descriptive analysis was conducted to identify the background characteristics, nab-paclitaxel initiation in each line of therapy until the first occurrence of a study endpoint , disenrollment from the health plan , or the end of the study period . OS was defined as the interval between the first dispensing of nab-paclitaxel and death. TNTD was defined as the interval between the first dispensing of nab-paclitaxel and switching of line of therapy or death. Kaplan-Meier plots were used to depict the cumulative probability of OS and TNTD by line of therapy. The median OS and median TNTD as well as their 95 % CIs were also estimated. These survival analyses were conducted overall, by line of therapy, by regimen, and by schedule. A subgroup analysis was also performed among patients aged ≤ 50 years or with ≥ 3 metastatic sites.A survival analysis using an intent-to-treat approach was performed to evaluate the OS and TNTD. Each patient was followed from nab-paclitaxel initiators identified during the study period. After the eligibility criteria were applied, a total of 664 patients remained in the final analysis  as second-line therapy, and 281 (42.3 %) as third-line or later therapy. Overall, there were 405 (61.0 %) users who had nab-paclitaxel administered as monotherapy and 259 (39.0 %) who had nab-paclitaxel administered as combination therapy. When nab-paclitaxel was given as a combination therapy, targeted agents were often used (57.5 % bevacizumab and 23.9 % trastuzumab or lapatinib). Bevacizumab combination was more often prescribed in first-line therapy with nab-paclitaxel vs trastuzumab or lapatinib (81.0 vs 4.8 %). Trastuzumab combination therapy was more often given in the third line or later (39.5 %) compared with first-line (4.8 %) or second-line (17.1 %) therapy. Of the 605 users whose treatment schedules could be determined, a majority (n = 428 [70.7 %]) received weekly treatment and 177 (29.3 %) received q3w treatment. The median durations that patients received nab-paclitaxel as first-line, second-line, and third-line or later therapy were 159 days (5.2 months), 119 days (3.9 months), and 122 days (4.0 months), respectively , the median OS was 15.6 months , and the median TNTD was 5.7 months . Patients who received nab-paclitaxel combination therapy had a median survival time of 18.7 months compared with 16.8 months for those who received nab-paclitaxel monotherapy  were most often prescribed. Patients treated with nab-paclitaxel in the first line appeared to have favorable survival relative to patients treated in later lines of therapy. However, the treatment effect of nab-paclitaxel as first-line therapy may have been overestimated because the criteria for first-line therapy required patients to be treated for at least 30 days. Therefore, patients who discontinued treatment early may not have been captured. Overall, the safety and efficacy profiles of nab-paclitaxel in this setting of US women with MBC were consistent with clinical trial experience  for ≥ first-line treatment of MBC (Table nab-paclitaxel .–19.nab-pstration . The efftive MBC .nab-paclitaxel toxicities  ranged from 15 % to 26 % and was lower than that noted in clinical trials (Table nab-paclitaxel [The common adverse events identified in the clinical trials were also explored in this claims-based study. The occurrence of select known clitaxel –12, indinab-paclitaxel recruited patients according to highly restrictive criteria, and the patients received a specific line of nab-paclitaxel therapy, treatment regimen, or treatment schedule during the study period. For example, the phase two trials often targeted first-line therapy with various doses and schedules, whereas the pivotal phase three trial mixed lines of therapy at a q3w dose/schedule (Table Although claims analyses are extremely valuable for the efficient and effective examination of healthcare outcomes, treatment patterns, and healthcare resource utilization, it is challenging to compare our study findings with those from clinical trials. Historical trials of le Table . In addiFurthermore, because claims are collected for the purpose of payment and not research, inherent limitations in our claims analysis included the potential for incorrect reporting of diagnosis codes, mixing patients with early-stage breast cancer with patients with MBC, missing information on hormone receptor status, misinterpreting disease-onset dates, misclassifying the line of therapy, and inaccurately estimating actual drug dosages and schedules. However, the application of a well-defined algorithm, including the combination of diagnoses, procedures, and medications, reduced the potential for false-positive cases and the misclassification of line of therapy.nab-Paclitaxel is administered more frequently as a single agent on a weekly schedule and as second-line or later therapy to patients with MBC in a US healthcare system. This analysis demonstrates the use of nab-paclitaxel weekly or q3w and its use for the treatment of patients aged ≤ 50 years or with ≥ 3 metastatic sites. The benefit observed in this US healthcare system is consistent with that from previously reported clinical trials. No new safety signals were identified. Furthermore, our analysis showed that, when used in combination, nab-paclitaxel was most often combined with bevacizumab in first-line therapy. However, because the accelerated approval of bevacizumab for MBC was withdrawn due to the lack of an OS advantage in the RIBBON-1 and AVADO trials [nab-paclitaxel combination partners are being evaluated in patients with MBC, including gemcitabine or carboplatin in patients with triple-negative MBC [nab-paclitaxel combination regimen may provide additional options for patients with MBC. Finally, outcomes of this real-world claims analysis are consistent with the data demonstrated in key clinical trials, affirming the effectiveness and manageable safety profile of nab-paclitaxel across all lines of therapy in patients with MBC.O trials , bevaciztive MBC . Identif


The HIV-Brazil Cohort Study was established to analyze the effectiveness of combination antiretroviral therapy (cART) and the impact of this treatment on morbidity, quality of life (QOL) and mortality. The study design, patients’ profiles and characteristics of cART initiation between 2003 and 2010 were described.+ T-cell count ≤200 cells/mm3. The medications most often used in the various treatment regimens were efavirenz (59.7%) and lopinavir/ritonavir (18.2%). The proportion of individuals achieving viral suppression within the first 12 months of cART use was 77.4% (95% CI 76.1–78.6). Nearly half (45.4%) of the patients presented HIV-related clinical manifestations after starting cART, and the AIDS mortality rate was 13.9 per 1,000 person-years.Since 2003, the HIV-Brazil Cohort has been following HIV-infected adults receiving cART at 26 public health care facilities, using routine clinical care data and self-reported QOL questionnaires. When not otherwise available, data are obtained from national information systems. The main outcomes of interest are diseases related or unrelated to HIV; suppression of viral replication; adverse events; virological, clinical and immunological failures; changes in the cART; and mortality. For the 5,061 patients who started cART between 2003 and 2010, the median follow-up time was 4.1 years (IQR 2.2–5.9 years) with an 83.4% retention rate. Patient profiles were characterized by a predominance of men , with a mean age of 36.9 years (SD 9.9 years); 55.2% had been infected with HIV via heterosexual contact. The majority of patients (53.4%) initiated cART with a CD4Results from cART use in the daily practice of health services remain relatively unknown in low- and middle-income countries, and studies with the characteristics of the HIV-Brazil Cohort contribute to minimizing these shortcomings, given its scope and patient profile, which is similar to that of the AIDS epidemic in the country. In 1996, Brazil adopted a policy of universal access to combination antiretroviral therapy (cART), which was free of charge to human immunodeficiency virus (HIV)-infected individuals. Since then, immunological and virological treatment monitoring, as well as genotype-resistance testing for treatment failure management, have been incorporated into that policy. As of 2012, approximately 217,000 patients in Brazil were being treated with first-, second- or third-line antiretroviral therapy, including newer antiretroviral options for salvage therapy management, leading to an overall reduction in the morbidity and mortality associated with HIV infection In recent years, there has been a reduction in the magnitude of the impact that opportunistic diseases have had on morbidity and mortality in cART patients in Brazil, although there has been an increase in the incidence of complications unrelated to infection by HIV, such as cardiovascular events, impaired renal function, liver disease and neoplasia The impact of the Brazilian policy has been the object of nationwide studies, mostly focused on mortality Furthermore, recently, important changes have occurred in the use of cART therapy due to the proven efficacy of these drugs to reduce the risk of acquiring and transmitting HIV infection, as well as increased evidence that early initiation of cART has significant health benefits These circumstances increase the relevance of studies assessing the various dimensions of access to diagnosis and treatment of HIV infections; the efficacy and effectiveness of such treatment; and the impact of this treatment on morbidity, mortality, and QOL. Therefore, the HIV-Brazil Cohort Study was established to gather further knowledge on the context of the Brazilian epidemic and to generate scientific evidence to make informed decisions regarding the planning and implementation of public policies, taking into consideration the regional disparities, as well as the specificities of the Brazilian population and of the national health care system There are 13 sites participating in the study, involving 26 public health facilities in 11 cities across four of the five regions of the country . The facThe number of patients under treatment at the participating sites ranged from 519  to 34,932 , with 7 of the 13 sites being responsible for treating more than half of the AIDS cases identified in their municipalities. Across the 13 sites, the mean ratio of outpatients to infectious disease specialists or general clinicians is 299∶1 . Among the patients on cART, the interval between clinical consultations has ranged from 3 to 6 months, and 6 of the 13 sites have adopted outreach strategies for patients who miss appointments .At most of the sites , the heaAs of November 2012, 6,109 HIV-infected adults (≥18 years of age) had been enrolled in the cohort. All the included individuals had initiated antiretroviral treatment on or after January 1, 2003 , and had had at least one clinical follow-up appointment after treatment initiation. The inclusion occurred in two phases. Between 2009 and 2011, patients who had been started on cART between January 2003 and December 2010 were enrolled, whereas in the second phase, patients who had been started on cART on or after 1 January 2011 were enrolled. The first phase was aimed at observing events of interest that had occurred before the patients had been included in the cohort (retrospective phase), and the second phase was aimed at observing such events as they occurred, over the course of follow-up performed as routine clinical outpatient services (prospective phase).+ T-cell count were observed. The principal differences observed were that the proportion of females was greater in the non-probabilistic sample of the São Paulo Municipal Network than in the patients of the southeastern cohort (36.4% vs. 31.8%) and that the mean CD4+ T-cell count was higher in the non-probability sample of the Federal University of Minas Gerais than in the patients of the southeastern cohort (204.2 cells/mm3 vs. 174.2 cells/mm3).The cohort data were obtained as part of the routine clinical care provided at the health service centers included (routine-care based cohort) and were abstracted from the patients’ clinical records by trained abstractors onto standardized forms. These clinical records were reviewed at intervals not exceeding six months to investigate events recorded during the routine clinical follow-up visits performed within each period. To determine the consistency and completeness of the information, the forms were checked at the cohort coordination level. Approximately 5% of the forms were crosschecked against the information in the clinical records. From 2012 on, information has been collected using an online system developed on the Research Electronic Data Capture platform Information on QOL started being collected in 2011, using the World Health Organization self-report questionnaire  validated for use in Brazil The main outcomes of interest are the occurrence of diseases related or unrelated to HIV; suppression of viral replication ; antiretroviral treatment modifications ; treatment failure ; adverse events; and death. Clinical and epidemiological data were collected for the entire clinical follow-up period, including socio-demographic data; HIV transmission category; use of illicit drugs, alcohol and tobacco; individual or family history of metabolic disorders, hypertension or cardiovascular disease; AIDS-related and non-AIDS-related manifestations; initial and subsequent cART regimens used for prophylaxis and treatment; occurrence of adverse events related to the use of cART, prophylaxis for opportunistic diseases and vaccines; CD4, viral load and genotyping results, as well as safety laboratory tests for cART monitoring; and mortality.+ T-cell counts, viral load and mortality data–were systematically checked across the national information systems.To enhance the level of completeness, missing data–notably, demographic data, CD4+/CD8+ T Lymphocyte Count and Viral Load Network Laboratory Test Control System ; the National System for the Logistic Control of Medications (for information regarding the dispensing of cART); and the National Mortality Information System . The screening was conducted annually, through electronic matching, checking for perfect combinations of key fields . Patients not located through this procedure were then investigated using an alphabetically sorted list.Individuals were censored in case of loss of clinical follow-up, relocation for follow-up in another clinical setting or death. To check the status of patients in the cohort, those categorized as lost to clinical follow-up were traced in the national information systems managed by the Brazilian National Ministry of Health: the National CD4+ T-cell count, viral load determination or ART dispensation elsewhere after the date of the last entry in the clinical record. AIDS-related deaths were defined as those in which the official record listed AIDS as being the underlying cause of death.Loss of follow-up was defined as an absence of patient contact with the health care center for more than 12 months  and the non-identification of the patient in the national information systems, as described above, up to July 2011. Patients were classified as having been relocated for follow-up in another clinical setting when relocations were noted in the clinical record or when the patients were identified in the information systems as performing their CD4Proposals from external researchers to use our data are encouraged and welcomed, and requests will be analyzed by the Cohort Steering Committee that is composed of the Cohort Principal Investigators. The use of data pertaining to the individual sites is restricted to the sites themselves. In all circumstances, the confidentiality of each participant’s related data must be preserved.This protocol was approved by the Institutional Review Boards (IRB) of the participating sites , according to the Brazilian regulation for research with human subjects. In the first phase, the IRB waived the requirement for written informed consent and requested the confidentiality of the individual’s data, which was ensured at all stages of the project. In the second phase, all participants provided written consent for participation in the study.The socio-demographic, clinical and immunological profiles of the 5,061 patients enrolled during the first phase of the study (those started on cART between 2003 and 2010) are shown in As shown in The largest proportion of patient loss  was observed in the first year of cohort follow-up, with reductions over time. The loss to follow-up rate ranged from 19.8 per 1,000 PY in the first 12 months to 1.1 per 1,000 PY after the sixth year of observation, with an overall loss rate of 10.1 per 1,000 PY. The greatest risk of loss  was obse+ T-cell count of 177.5 cells/mm3 (SD 121.7 cells/mm3) and 169.0 cells/mm3 (IQR 75.0–250.0 cells/mm3), respectively. These values remained stable over the years evaluated . The majority of patients (53.4%) initiated cART with a nadir CD4+ T-cell count ≤200 cells/mm3, and the CD4+ T-cell count at cART initiation was ≤350 cells/mm3 in 84.8% of the sample.Information on the pre-cART immunological status is available for 89.6% of the patients, who presented with a mean and median nadir CD4The initial treatment regimens prescribed were in line with the current recommendations of the Brazilian National Ministry of Health The median number of regimens used per patient was 1 , and the mean duration of the first-line regimens was 30.4 months (95% CI 29.7–31.2). The number of individuals achieving viral suppression (VL <400 copies/ml [2003 to 2006] and <50 copies/ml [after 2007]) within the first 12 months after cART initiation was 77.4% (95% CI 76.1–78.6). During the 6.5 years of observation, 88.2% (95% CI 87.2–89.1) of the patients achieved viral suppression at some point after cART initiation. The lowest rates of viral suppression in the first year of cART were observed in individuals aged between 18 and 29 years (66.2%), in transmission category injection drug use (73.7%), with cocaine use before treatment (74.1%), in service areas with lower economic development  and showing no adverse ARV events (85.2%).Nearly half (45.4%) of the patients presented with HIV-related clinical manifestations after starting cART, and the most frequent were oral candidiasis and tuberculosis. The AIDS mortality rate for the period evaluated was 13.9 per 1,000 PY.The HIV-Brazil Cohort Study, with a long follow-up period and a significant number of observations, is an important asset to increase the availability of data on the countrywide outcomes of the National AIDS Program related to cART in public health care services. A special feature of our cohort is that HIV-infected individuals in Brazil have been exposed to a broad array of antiretroviral drugs–21 antiretroviral drugs of all classes (including 10 generic drugs) used in first-, second- and third-line treatment regimens The characteristics of the HIV-Brazil Cohort Study facilitates analyses of the short-, medium- and long-term impact of using antiretroviral drugs in the context of the routine care of patients at publically funded health care centers, providing complementary evidence to that obtained through clinical efficacy trials. The evidence obtained from the analyses performed in this cohort will enable field evaluations and further improvement of the national public health policies The socio-demographic profile of the HIV-Brazil Cohort Study is similar to that represented by the cases of AIDS in adults reported to the Brazilian National Ministry of Health between 2003 and 2010 . The two+ T-cell count, such as gender, age and transmission category, did not differ (p<0.05) from the other patients included in the cohort. Although the analysis of outcomes directly related to the CD4+ T-cell count showed few significant variations when excluding individuals without baseline information on CD4+ T-cell count, the mortality rate rose from 13.9 to 14.2 per 1,000 PY.The quality assessment of the data collected showed a satisfactory degree of completeness of the information for essential variables . A lack An important aspect to be highlighted is the relatively low rate of loss of follow-up, similar to what is observed in high-income countries and in the middle- and low-income countries reporting the lowest rates of loss of follow up The analysis presented in this article aims to outline the scope and potential use of the information derived from the HIV-Brazil Cohort Study. First-line non-nucleoside reverse-transcriptase-based regimens were the most prescribed first-line cART in Brazil and resulted in high levels of viral suppression in the first year of treatment, comparable to single-site observational studies + T-cell counts ≤200 cells/mm3) or AIDS-related diseases at cART initiation. This finding was higher than the results of previously reported studies that reviewed the clinical and immunological status at the time of arrival to the health services for initial clinical follow-up in Brazil The majority of patients presented with severe immunodeficiency (CD4It is also noteworthy that the mean CD4+ T-cell count at the beginning of cART did not show a trend of increase over time, indicating the urgent need for increased access to earlier HIV diagnosis and linkage to care countrywide, considering the fact that Brazil has a concentrated epidemic in social sectors with a high degree of stigma and a pattern of service use that is more restricted than in the general population Another important aspect is the fact that the worst results were observed in regions with the lowest economic development levels in the country, indicating that the reduced ability of these regions to obtain optimal results from the therapies available for AIDS may lead to an increase in the health inequalities existing in the country through increase HIV incidence and HIV-associated mortality.The study design, characteristics of patients included and the initiation of cART presented in this paper show the scope of investigation conducted by the HIV-Brazil Cohort Study, which is the main initiative to analyze the effects of cART use in public health services in the country. Thus, the results shown herein and those yet to be produced can contribute to advancing the knowledge generated from clinical trials, particularly considering the context of medium- and low-income countries, which in recent years have greatly expanded their programs to access cART. This is important in the formulation of better health policies for the needs of people living with HIV in resource-constrained situations.