For HIV-positive individuals on antiretroviral therapy (ART), the WorldHealth Organization (WHO) recommends routine viral load (VL) monitoring. Wereport on the cascade of care in individuals with unsuppressed VL afterintroduction of routine VL monitoring in a district in Lesotho.In Butha-Buthe district 12 clinics  send samples for VLtesting to the district laboratory. We included data from patients aged ≥15years from Dec 1, 2015 to November 1, 2018. As per WHO guidelines VL<1000 copies/mL are considered suppressed, those ≥1000copies/mLunsuppressed. Patients with unsuppressed VL receive adherence counseling andfollow-up VL within 8–12 weeks. Two consecutively unsuppressed VLs shouldtrigger switch to second-line ART. For analysis of the VL monitoring cascadewe defined care to be “according to guidelines” if patients withunsuppressed VL received a follow-up VL within <180 days and follow-up VLwas either re-suppressed, or again unsuppressed and the individual wasswitched to second-line within 90 days.For 9,949 individuals 24,948 VL tests were available. The majority werefemale (73%), median age 41 years (interquartile range 33–52), and 58% seenat rural clinics. Overall, 25% (260/1028) of individuals were managedaccording to guidelines: 40% (410/1028) had a follow-up VL within 180 daysof their initial unsuppressed VL and 25% (260/1028) of those eitherre-suppressed or switched to second-line within 90 days. Female patientswere more likely to have a follow-up VL done, (p = 0.015). In rural clinicsrates of two consecutively unsuppressed VLs were higher than in the hospital, and rural clinics were less likely to switchthese patients to second-line .Our data show that in a real-life setting availability of routine VLmonitoring may not be exploited to its potential. A lack of timely follow-upafter a first unsuppressed VL and reluctance to switch patients withconfirmed virological failure, reduce the benefit of VL monitoring, i.e. inthe rural clinics. Future studies will have to assess models of care whichensure that VL results are met with an action and make use of scalableinnovative approaches. Since 2013, the World Health Organization (WHO) recommends viral load (VL) as thepreferred monitoring strategy in persons living with HIV, who are takingantiretroviral therapy (ART).In case of virological failure (≥1000 copies/mL), the WHO recommends enhancedadherence counselling and a follow-up VL after 3 months. A second VL ≥ 1000copies/mL despite good adherence is defined as confirmed virological failure andshould trigger the switch to a second-line regimen. TohaveIn Lesotho, a pilot study conducted prior to nation-wide scale-up of VL monitoringshowed that among adult patients taking first-line ART, who had a first-timeunsuppressed viral load, 90% attended enhanced adherence counseling and 84% hadfollow-up VL within 3–6 months. Out of those with confirmed virological failure,only 73% were switched to second-line while the remaining continued on a failingregimen. RoutineRoutine viral load monitoring was introduced in the district of Butha-Buthe,Lesotho, in December 2015. A prospective open cohort study was started toinclude all HIV-positive individuals on ART who have received a VL test. Thisstudy includes all adult patients (age≥15 years) in the cohort with at least onerecorded VL result between December 1, 2015 and March 1, 2018. Follow-up forthese participants continued until November 1, 2018, to allow 180 days follow-upfor individuals with unsuppressed VL.The district of Butha-Buthe is characterized by mostly rural areas with anestimated population of 130,000, mainly subsistence farmers, mine workers, andconstruction or domestic labourers who work in neighbouring South Africa. Themain town of Butha-Buthe has approximately 25,000 inhabitants with the remainingpopulation living in villages scattered over a mountainous area. According tothe recent household-based national survey from 2017 the adult HIV prevalence inthe district is 17.8% .Roll-out of routine VL monitoring in November 2015 started in Butha-Buthedistrict hospital’s ART clinic, the only urban site. The 11 rural clinics of thedistrict began sending patients’ blood samples to the hospital laboratory forroutine VL monitoring in June 2016. The schedule for routine VL monitoringfollows current National Guidelines of Lesotho with a VL done after the first 6months on ART and, if suppressed, yearly thereafter. In case of unsuppressed VL(≥1000 copies/mL), the guidelines recommend enhanced adherence counselling witha follow-up VL after 8–12 weeks. Sustained unsuppressed VL despite goodadherence should trigger switch to a second-line regimen. In the case ofresuppression or a VL log-drop of >0.5, the individual is maintained onfirst-line ART  2–3) per person.During the study-period 1028 (11%) had at least one VL≥1000 copies/ml. The viral load cascade improved if longer time intervals were allowed.Considering all follow-up VLs done among the 1,028 patients with unsuppressed VLduring the study period, 759 (74%) had a follow-up VL during study period). Of these, 416 hadvirological failure. Of the 416 with virological failure, 227 (55%) were eitheralready on second-line (n = 33) or switched during follow-up (n = 194). Notconsidering time intervals, 563 (55%) of the 1,028 patients with unsuppressed VLwere followed as per guidelines during the study-period. Women were more likely to get a follow-up VL in case of unsuppressed VL . In case a follow-up VL was done, prevalence of virologicfailure was similar in men and women .rd VL instead . If switched to second-line, median time from confirmedvirological failure to switch was longer in rural clinics . In patients where a third VL was requested instead of switch tosecond-line after confirmed virologic failure, the 3rd VL was again≥1000 copies/mL in 84% of patients.At follow-up VL the rural clinics had higher rates of virologic failure (2consecutive VL≥1000 copies/mL) compared to the district hospital . Providers in rural health facilities were less likely toswitch patients with virological failure to second-line  and more likely to request a 3Of the 142 (65%) with a VL test after switch to second-line, 8% had anunsuppressed VL and the remaining 92% achieved re-suppression after switch. Intotal 9,949 patients received 24,948 VLs to trigger 194 switches to asecond-line regimen (129 VLs per regimen switch).The majority of samples from the district hospital were registered in thelaboratory on the same day they were sampled compared to 8 days (IQR 1–17) inrural health facilities . Median In this prospective cohort study, we assessed the VL cascade after introduction ofroutine VL monitoring in 11 rural clinics and the district hospital in a district inNorthern Lesotho in December 2015. Among those patients with a first unsuppressedVL, only 25% of individuals were managed correctly according to WHO guidelines. Theremaining either did not receive a follow-up VL within 6 months (60%) or were notswitched to a second-line regimen in the case of confirmed virological failure(15%). Women were more likely to have a follow-up VL done after an initialunsuppressed VL, but not more likely to have virological failure or to switch tosecond-line than men. In rural clinics patients had higher rates of virologicfailure, providers were, however, more reluctant in switching patients tosecond-line and if switched, the time interval between confirmed virologic failureand switch was substantially longer than in the district hospital. On average, ittook 129 VLs to trigger one switch in ART regimen.Publications on the VL cascade after implementation of routine VL monitoring remainscarce. However, all published data indicate large gaps in the cascade. RecentlyEtoori and colleagues reported findings from a rural region in Swaziland where 62%of patients with unsuppressed VL received follow-up testing within 6 months and only43% among those with confirmed virological failure switched to second-lineregimen. PeterseThere is no doubt that VL monitoring is the method of choice to monitor virologicalsuccess of ART and, inTherefore, ART programs need to combine roll-out of VL monitoring with strategiesthat ensure that patients with virological failure are followed-up and thatconfirmed virological failure results in action, in order to achieve virologicalre-suppression,7,19,20.This study has several limitations. First, this open cohort only includes patientswho received at least one VL measurement. We do not have precise data on how manypatients did not receive any VL determination. The overall percentage of patientswith unsuppressed VL may thus be higher. Second, we do not have resistance testingresults from patients with virological failure. We thus cannot determine if theprovider’s decision to postpone switch to second-line in some patients due tosuspected on-going poor adherence was justified or not. In a previous study in thesame setting, in only 13% of patients with virological failure genotypic resistancetesting found no major drug resistance mutation . Third, In line with previous publications, our data from Lesotho show that in areal-life setting the potential of routine VL monitoring for patients taking ARTis not optimized. A lack of timely follow-up after a first unsuppressed VL aswell as low switching rates among patients with confirmed virological failure,reduce the potential benefit of routine VL monitoring in resource-limitedsettings. Future studies should look at models of care that ensure that VLresults are met with an action. Such models should not only rely on more stafftraining and supervision, but make use of innovative information technologyapproaches that–if successful–can be scaled up.


Although postoperative radioiodine (RAI) therapy has been used in patients with differentiated thyroid carcinoma (DTC) for many years, there is still lack of data defining the timing of RAI administration. A retrospective analysis was carried out to answer the question whether the time of postoperative RAI treatment demonstrated any impact on long-term outcomes, particularly in low-risk DTC.1b-T4N0-N1M0, who underwent total thyroidectomy and postoperative RAI therapy. According to the time interval between DTC diagnosis and RAI administration, patients were allocated to one of three groups: up to 9 months (N = 150), between 9 and 24 months (N = 323), and > 24 months (N = 228). Median follow-up was 12.1 years (1.5–15.2).The analyzed group involved 701 DTC patients staged pTBased on an initial DTC advancement and postoperative stimulated thyroglobulin concentration patients were stratified as a low-, intermediate-, and high-risk group. Low-risk patients, who received RAI therapy up to 9 months, demonstrated significantly lower risk of relapse comparing to those, in whom RAI was administered between 9 and 24 months and after 24 months since DTC diagnosis: 0%, 5.5%, and 7.1%, respectively. Regarding intermediate- and high-risk groups, the differences in the timing of postoperative RAI treatment were not significant.If postoperative RAI treatment is considered in low-risk DTC, any delay in RAI administration above 9 months since diagnosis may be related to poorer long-term outcomes. Differentiated thyroid carcinoma (DTC) is the most common endocrine malignancy, characterized by a very good prognosis with 5-year overall survival rate of 98.5% . A relat1b-T4N0-N1M0, admitted for the first time due to thyroid carcinoma between 1994 and 1997, subjected to a retrospective analysis. All patients underwent total thyroidectomy within 1 year and postoperative RAI treatment within 2 years following DTC diagnosis. The group included 579 women (82.6%) and 122 (17.4%) men at a median age at DTC diagnosis of 44.8 years (range 6.9–77 years). Papillary thyroid cancer was diagnosed in 494 (70.5%) patients, whereas in the remaining 207 (29.5%) cases—follicular thyroid cancer. Two hundred and ninety-five patients (42.1%) demonstrated multifocal tumor growth, 90 (12.8%) patients thyroid capsule infiltration, and 99 (14.1%) vascular invasion. The median tumor diameter was 20 mm (range 1–150 mm). Based on the TNM classification (revised in 1997), T1 feature was present in 81 (11.5%) patients, T2 in 240 (34.2%) cases, whereas T3 and T4 in 43 (9.6%) and 48 (9.3%) patients, respectively. In the remaining 248 (35.4%) cases, Tx was stated. One hundred and fifty-four (22.0%) patients had lymph node metastases (N1). Median follow-up was 12.1 years (range 1.5–15.2) , TSH-stimulated serum thyroglobulin (Tg) measurement, and whole body scan (WBS) with a diagnostic RAI activity of 2 mCi (74 MBq). Such diagnostics, aimed to assess the postoperative staging, was carried out after 4-week thyroxine (LT4) withdrawal. In selected cases, additional studies, such as bone scan, FNAB, CT etc., were done, if indicated.Postoperative RAI therapy was proceeded by 4–6-week LT4 withdrawal to achieve a required TSH level ≥ 25 IU/l. The median-administered RAI activity was 60 mCi (2220 MBq), range 27.8–150 mCi (1029–5550 MBq). WBS, together with a spot view of neck and chest, was done 72 h after RAI administration.Further DTC monitoring was based on the evaluation of serum TSH, Tg with Tg recovery, or Tg antibodies during thyroxine administration and neck US every 6 months following postoperative RAI therapy. The first evaluation of treatment outcomes was done 6–12 months after postoperative RAI treatment and involved neck US, TSH-stimulated Tg measurement, diagnostic WBS, chest X-ray, and other imaging procedures, if indicated. Complete remission was confirmed if no RAI uptake on diagnostic WBS was observed, stimulated serum Tg level was ≤ 10 ng/ml at the absence of Tg antibodies, and neck US and other imaging studies were normal. Persistent disease was diagnosed in patients with structural DTC . In patients who did not fulfill criteria for complete remission or structural DTC, doubtful remission  was stated.N = 150), between 9 and 24 months (N = 323), and > 24 months (N = 228).To evaluate the dependence between the time of postoperative RAI treatment and recurrence rate, patients were allocated to one of three groups, according to the time interval between DTC diagnosis and RAI administration: up to 9 months  and freedom-to-progression time (FFP). DFS was defined as a time from the confirmation of complete DTC remission after surgery to disease relapse, death, or last follow-up. In patients, in whom complete remission was not obtained, DFS was coded as zero, while FFP was a time from the first diagnostics after surgery or postoperative RAI treatment to disease relapse or progression.p value was reported. Quantitative variables were calculated for the association with time-to-event by Cox regression. P values below p < 0.05 were considered as statistically significant. Multivariate Cox regression was used, with stepwise backward feature elimination. The statistical was carried out by the use of IBM SPSS Statistics ver. 22  and JMP ver. 10.0 .Time-to-event data were analyzed using Kaplan-Meier method and compared by log-rank, Breslow, and Tarone-Ware tests; the highest p = 0.000). Tg level between 10 and 30 ng/ml increased the risk of recurrence nearly 3 times (p = 0.017), whereas lower stimulated Tg levels, below 1 ng/ml and 1–10 ng/ml, did not show any negative impact on the risk of recurrence. Lymph node metastases at DTC diagnosis (N1) were related to a nearly 4-fold higher recurrence risk than in patients without lymph node involvement . Other independent negative risk factors involved a larger tumor size > 4 cm (T3), extrathyroidal extension (T4) age above 60 years at DTC diagnosis, and low percentage of RAI uptake (T24) in thyroid bed before postoperative RAI treatment [The first part of the study, published in 2016 [Before postoperative RAI treatment, the patients were stratified according to the factors selected in a multivariate Cox regression as low, intermediate, or high risk. Low-risk group involved 374 patients staged T1-T3N0Nx with stimulated Tg level < 10 ng/ml. Intermediate-risk group comprised of 205 patients staged either T1-T3 with stimulated Tg level 10–30 ng/ml or T1-T3N1 and T4N0N1 with stimulated Tg < 10 ng/ml. High-risk group included 122 patients with either stimulated Tg above 30 ng/ml or staged T4 or N1 with Tg level ranged between 10 and 30 ng/ml . The risk of recurrence was 0% (no events) in patients who received RAI therapy up to 9 months from DTC diagnosis, whereas in groups with delayed RAI administration, between 9 and 24 months and after 24 months: 5.5% and 7.1%, respectively  is an important limitation of our study. Most patients from the study group underwent primary thyroid surgery between 1994 and 1997, some of them even earlier. The majority of them had two-stage total thyroidectomy. Moreover, in such cases, the primary surgery was carried out usually outside our center. Simultaneously, histopathological report that time was less accurate than current assessment. Therefore, if any doubts existed, Tx feature was diagnosed. Nevertheless, we would like to add that the differences in recurrence rate in Tx group regarding the time of RAI administration are similar to a low-risk class (data not shown).Another important issue is related to the risk stratification, used in our study. It is based on the results of a multivariate analysis, given in our previous paper . It invoMoreover, the papers discussed above used different time point to evaluate the role of postoperative RAI therapy. In our analysis, the use of shorter cut-off points at 3 or 6 months after DTC diagnosis was not possible due to too low number of patients in subgroups to reach a statistical significance. Relatively high number of patients were treated latter than 2 years after DTC diagnosis, what was related usually to low DTC advancement or sometimes patient preference. The first evaluation of treatment outcomes was carried out 6–12 months after postoperative RAI therapy. However, the patients were followed up much longer. The analysis summarizes the whole follow-up period, not only up to 6–12 months after postoperative RAI therapy.Our study was not aimed to be a voice in the ongoing discussion, whether postoperative RAI therapy is necessary in low-risk DTC or not. This is the role of currently ongoing prospective randomized clinical trials. But it is worthy to emphasize that, if postoperative RAI treatment is considered in low-risk DTC patients, any delay in RAI administration above 9 months from cancer diagnosis may be related to poorer long-term outcomes.


Antiretroviral therapy (ART) has been rapidly scaled up in Ethiopia since 2005, but factors influencing the outcome are poorly studied. We therefore analysed baseline predictors of first-line ART outcome after 6 and 12 months.874 HIV-infected patients, who started first-line ART, were enrolled in a countrywide prospective cohort. Two outcomes were defined: i) treatment failure: detectable viremia or lost-to-follow-up (LTFU) ; ii) LTFU only. Using stepwise logistic regression, four multivariable models identified baseline predictors for odds of treatment failure and LTFU.The treatment failure rates were 23.3% and 33.9% at 6 and 12 months, respectively. Opportunistic infections (OI), tuberculosis (TB), CD4 cells <50/μl, and viral load >5 log10 copies/ml increased the odds of treatment failure both at 6 and 12 months. The odds of LTFU at month 6 increased with baseline functional disabilities, WHO stage III/IV, and CD4 cells <50/μl. TB also increased the odds at month 12. Importantly, ART outcome differed across hospitals. Compared to the national hospital in Addis Ababa, patients from most regional sites had higher odds of treatment failure and/or LTFU at month 6 and/or 12, with the exception of one clinic (Jimma), which had lower odds of failure at month 6.In this first countrywide Ethiopian HIV cohort, a high ART failure rate was identified, to the largest extent due to LTFU, including death. The geographical region where the patients were treated was a strong baseline predictor of ART failure. The difference in ART outcome across hospitals calls the need for provision of more national support at regional level. The incidence and prevalence of the human immunodeficiency virus type 1 (HIV-1) infection in Ethiopia has decreased over the years . HoweverSince 2005, antiretroviral therapy (ART) has been made widely accessible in Ethiopia and there were 420 000 people living with HIV (PLHIV) on ART with 59% coverage by 2016 [In LIC, viral load (VL) has seldom been used for monitoring of ART, due to economic and logistic reasons. Hence, despite the WHO recommendation from 2013 to use VL , most suDespite a large number of patients receiving ART in Ethiopia, there are few reports on ART outcome, from only a few regions of the country. In order to fill this knowledge gap, this study aimed to identify baseline predictors of first-line ART outcome among PLHIV. Thus, unlike previous studies, this study has a wide geographical coverage, providing a more complete picture on the ART outcome at the national level.The study was conducted on PLHIV, who were enrolled in the Advanced Clinical Monitoring of Antiretroviral Treatment in Ethiopia (ACM) cohort ,9. BetweThe hospitals were distributed all over Ethiopia: Tikur Anbessa Specialized Hospital (TASH), a tertiary level national hospital in the capital Addis Ababa- Central region; Gondar- Northwest; Jimma- West; Mekelle- North; Harrar- East; Hawassa- South; and a mobile army unit at the Armed Forces General Hospital.® HIV-1 Nucleic Acid Sequence-Based-Amplification (NASBA) assay (BioMérieux Diagnostics) with a lower detection limit of 150 HIV-1 RNA copies/ml.Clinical assessment and routine laboratory tests were performed at the study sites, using national ART clinic forms and hospitalization/intervening care forms. Data were entered into a site database and later uploaded to a central database at the Ethiopian Health and Nutrition Research Institute (EHNRI) after quality control checks. For this study, the following data were extracted at baseline, month 6 and 12 of ART from the central database: WHO clinical stage, onset or relapse of opportunistic infections (OI), weight, body mass index (BMI), ART regimen, months on ART, CD4 and CD8 cell counts/percentages, and plasma HIV-1 RNA load (VL). Tuberculosis (TB) was considered if an active TB was diagnosed or if the patient was receiving anti-TB therapy at ART initiation. CD4 and CD8 cells were determined at the local laboratories using BD FACSCalibur machines . VL was analysed centrally at EHNRI by NucliSENS easyQTwo ART outcome measures were defined at month 6 and 12: i) treatment failure defined as either failure to attain viral suppression (virologic failure) or LTFU ; ii) LTFU only. Both on-treatment and intention-to-treat (ITT) analysis were employed to assess ART outcome. Treatment failure at month 6 and 12 was defined using two threshold VL: 150 copies/ml (limit of detection of the assay) and 1000 copies/ml (WHO definition) .Binary logistic regression models were used to identify significant baseline predictors of treatment failure and LTFU at month 6 and 12. The following variables were considered as potential baseline predictors: study site, gender, age, educational status, employment status, marital status, spouse HIV serostatus, functional status, WHO clinical stage, TB, OI, treatment regimen (NRTI or NNRTI), BMI, weight, CD4 cells, CD4/CD8 ratio, and VL.Baseline factors that predicted the ART outcome in the bivariate analyses at 20% significance level were included in the final multivariable analysis for treatment failure and LTFU. At the beginning, six multivariable models were developed: four to assess treatment failures after month 6 and 12 , and two for LTFU at month 6 and 12. There were no substantial differences between the models developed to assess the treatment outcomes using the two VL threshold values (data not shown) and hence we used the 1000 copies/ml threshold and remained with two models predicting the treatment outcomes (at month 6 and 12). Finally, a total of four predictive models were presented to assess predictors of treatment failure outcomes and LTFU at month 6 and 12.p = 0.1 significance level were used to select variables included in the best final models. Odds ratios (OR) with the 95% confidence intervals were presented. P-value <0.05 was considered significant in the final multivariable models. Data analysis was performed using STATA software 14 .Both stepwise forward and backward methods in multivariable logistic regression at The study was approved by the National Research Ethics Review Committee in Ethiopia, and Institutional Review Board (IRB) of EHNRI. Written informed consent was obtained from all participants.2 of whom 41.5% were underweight (<18.5 kg/m2).A description of the baseline socio-demographic, clinical, and biomedical characteristics is given in One-fourth of the participants  with clinical data (n = 824) were TB co-infected: 64% pulmonary TB (PTB); 30% extra-pulmonary TB (EPTB); and 6% unknown type. TB patients had lower CD4 counts , and higher VL  than TB negative patients. Among 869 patients with clinical data, one or more other OI and/or AIDS-defining conditions were found in 38.4% .10 copies/ml).The mean ± SD CD4 count (n = 870) was 144 ± cells/μl  had lower CD4 count than females (n = 524) . Plasma HIV-1 RNA was detected in 99% (n = 844/855) subjects  started ART based on CD4 count; 230 (27.5%) on clinical presentations plus CD4 count; and 17 (2%) on clinical presentation only. All participants were prescribed two NRTI (tenofovir (TDF): 53.4%; zidovudine (ZDV): 41.4%; stavudine (d4T): 5.0%; abacavir (ABC): 0.2%; all with 3TC) and one NNRTI (efavirenz (EFV): 56.5%; nevirapine (NVP): 43.5%).At month 6, 131/874 (15.0%) patients were dead (n = 62) or LTFU due to other reasons (n = 69). A further 67 (8%) participants were still retained, but were excluded from the analysis due to lack of VL . Of the At month 12, 184/874 (21.1%) were dead (n = 75) or LTFU due to other reasons (n = 109). A further 231 subjects were still retained, but were excluded from the analysis due to lack of VL . There wAt bivariate analyses study site, gender, marital status, baseline functional status, WHO stage, TB, OI, CD4 count, and VL were significantly associated with treatment failure at month 6 and 12 .At month 6, in the multivariable model gender, TB, OI, CD4 count, VL and study sites predicted the odds of treatment failure . Males hAt month 12, functional status, TB, CD4 count and study site, predicted treatment failure . The oddThe study site differences were large. Patients from the regional hospitals Harrar, Hawassa, and Mekelle had nearly quadruple, triple and double odds of treatment failure  as compared to those from the national tertiary level hospital TASH . The treBivariate analyses revealed that study site, gender, functional status, WHO stage, TB, CD4 cells, and VL were significantly associated with odds of LTFU, including deaths, at month 6 and 12. Also, OI was significantly associated at month 12. We excluded BMI and CD4:CD8 ratios because of high number of missing values.At month 6, the multivariable model revealed functional status, WHO stage, CD4 cells and study sites as predictors of LTFU . AmbulatPatients from Harrar, Hawassa and Gondar had higher odds  as compared to those from TASH. Compared to TASH (10%), patients from Harrar (27%), Hawassa (20%), and Gondar (19%) had higher LTFU rates of both at month 6 and 12 .At month 12, gender, functional status, WHO stage, TB, CD4 cell count and study site, predicted the odds of LTFU . Males hParticipants from Harrar, Hawassa, and Gondar had double odds  compared to those from TASH. The LTFU rates were thus significantly higher in the regional hospitals  compared to TASH (17%) .This is the first countrywide prospective longitudinal study on ART outcome in Ethiopia. Using the WHO definition and OT analysis, the virological failure rate was 8.4% at month 6 and 7.4% at month 12. In the ITT analysis, the treatment failure rates, including both virological failure and LTFU due to death or other reasons, were much higher, 23.3% and 33.9%. The baseline factors associated with increased odds of treatment failure and LTFU were in line with those reported from other sSA countries. However, the countrywide design of our study allowed us to also identify the study site as a strong predictor for treatment failure and LTFU.The LTFU rate (including deaths) at month 6 (15%) and 12 (21%) were consistent with previous studies from other sSA countries, confirming that early death and LTFU are key features also in Ethiopia [In the OT analysis, using >1000 copies/ml cut-off, the virologic failure at month 6 and 12 (8.4% and 7.4%) were comparable to most other sSA studies –16 as weOverall the ITT analysis showed a high rate of treatment failure; 23.3% and 33.9% at 6 and 12 months, respectively. One possible reason for the observed high rate of treatment failure is the late presentation of patients as the majority of our study participants had low CD4 cell counts at ART initiation. Our study thus showed that despite better availability of ART in low and middle income countries, yet a substantial number of people are diagnosed/present late and start ART at later stages of the disease as described elsewhere ,20. In aIn Ethiopia, even though it has been reported that a large number of HIV-infected patients discontinue their treatment, so far only little research including a limited number of patients has been published . In our The advanced immunodeficiency at baseline in a high proportion of our patients calls for national strategies to overcome the problem, e.g. through the test and treat approach. In a study from Kenya and Uganda such approach was implemented which resulted in that at the population level the viral suppression target of UNAIDS was reached within two years . In contThe importance of the health care structure is illustrated by the intriguing and important finding in our study that the study sites were strong predictors of ART outcome. It is known that there are substantial regional variations in Ethiopia with regard to knowledge towards HIV and its prevention, as well as in prevalence of HIV and other sexually transmitted infections (STIs) ,27. Our In conclusion, in this first nationwide HIV cohort study in Ethiopia a high rate of treatment failure was identified. Early death dominated during the first 6 months and LTFU during the first year, rather than virological treatment failure among those retained in care. In addition to well established baseline predictors, such as advanced immunodeficiency, TB and OIs, we identified the care-giving hospital as a major predictive factor of ART failure. Provision of further national support at the regional levels in Ethiopia is therefore essential, both for an earlier initiation of ART  as well


Limited data are available on clinical outcomes of people living with HIV (PLWH) in China, especially after the implementation of the 2016 national treatment guideline. The objective of the current study is to examine the treatment patterns, clinical outcomes and their associated factors among PLWH in Guangxi, China before and after this new guideline.Data from three community-based projects conducted at different time points over a period of six years (2012–2017) in Guangxi were analyzed in our study. The interviewer-administered questionnaire was used for data collection. Measures of clinical outcomes were retrieved from the patients’ medical records. Descriptive analysis was employed to display treatment patterns and the time trends of clinical outcomes. Chi-square test or ANOVA was used to compare the differences in background characteristics and treatment history between different levels of clinical outcomes.3, and 82.5% were virally suppressed. An increasing trend in both ART coverage (from 72.1% to 91.2%) and CD4 count (from 318 cells/mm3 to 357 cells/mm3) was observed over time in the three samples, while rates of viral suppression did not show a similar trend. A number of socio-demographic characteristics  and treatment-related variables  were associated with improved clinical outcomes.Among the pooled sample of 4224 participants, 77.3% were receiving antiretroviral therapy (ART), the median CD4 count was 328 cells/mmWe observed a high rate of viral suppression and increasing trends in ART coverage and CD4 count over six years in Guangxi, China. However, suboptimal clinical outcomes continue to be a problem, particularly among some subgroups of PLWH. Future clinical management strategies should be tailored for PLWH with different sociodemographic characteristics and treatment trajectories. Antiretroviral therapy (ART) has been used worldwide and achieved great success in HIV treatment and prevention since its advent in the 1990s. The preventive benefits of the early use of ART in asymptomatic HIV infection have been proved with clinical evidence in the last decade . FurtherBased on the clinical evidence, World Health Organization (WHO) updated its guideline and recommended ART to all PLWH regardless of their CD4 counts . The Joi3 to ≤500 cells/mm3 [The HIV epidemic in China is still alarming. It is estimated that the accumulative number of PLWH has reached 1.25 million in 2018, and the reported number of PLWH is 850,000 . Followiells/mm3 . In 2016ells/mm3 .3 [Both CD4 count and HIV viral load are critical treatment indicators for determining the clinical stages of HIV infection, for evaluating the efficacy of treatment, and for changing the medication when necessary , 15. How3 –19. The 3 –21. Howe3 , certain3 , 21, or 3 . The parAs one of the regions with the fastest growing HIV epidemic in China, Guangxi has reported a total of 124,282 HIV/AIDS cases by the end of 2017, indicating a 78.7% increase since June 2011  and placing Guangxi second among 31 Chinese provinces in terms of HIV seropositive cases , 23. TheThe primary objective of our study, therefore, is to examine the treatment patterns and clinical outcomes before and after the implementation of the latest national treatment guideline using data from three samples in Guangxi. In addition, we compared the differences in background characteristics and treatment history between different levels of immunologic and virologic outcomes.Data used in the current study were derived from three different community-based projects conducted in Guangxi, China. All the participants in the three projects were recruited from community-based treatment settings, following similar inclusion and exclusion criteria , 28.The first study was a cross-sectional study which aimed to understand the health status  of PLWH in Guangxi . The datThe second study was a theory-based HIV disclosure intervention trial and primarily aimed to assist parents living with HIV/AIDS to plan or make a developmentally appropriate disclosure of their HIV status to their seronegative children (aged 6–15 years). The baseline data of the intervention project were collected from July 2013 to March 2014. In this project, eight cities and eight rural counties with the largest cumulative number of reported HIV/AIDS cases in 2012 were selected as study sites. We further identified all the HIV clinics with at least 200 HIV/AIDS cases in these urban districts and rural townships, and randomly selected 40 of them to participate in the intervention trial. We then randomly invited about 20 eligible HIV-infected parents from each clinic to participate in the trial. The main inclusion criteria for parents include: 1) at least 18 years of age; 2) a confirmed diagnosis of HIV or AIDS; 3) living with at least one child 6 to 15 years of age; and 4) having not disclosed their HIV status to their children. A total of 791 participants completed the baseline survey, with the refusal rate being around 5%.The third study, where the data were collected after the implementation of the latest national ART guideline , was an exploratory longitudinal study and aimed to investigate the mechanism of the effects of HIV disclosure on clinical outcomes. In this project, we selected two cities (urban centers) and eight rural counties with the largest number of reported HIV/AIDS cases by 2014 as our study sites. With a similar approach in the first and second studies, we identified HIV clinics in the urban districts and rural townships which has at least 200 HIV/AIDS cases. We randomly selected 40 these clinics  to participate in our study. The local research team randomly selected about 10 PLWH who were diagnosed since January 2014 (“recently diagnosed”) from each clinic. The main inclusion criteria of this project were similar to the first two projects, with the exception that only those “recently diagnosed” PLWH were included. A total of 446 participants completed the baseline survey.The survey procedures of the three projects were similar and had been described elsewhere . BrieflyParticipants were asked about their socio-demographics, which include gender, age, education level , employment status , marital status , monthly household income in Chinese Yuan (CNY) , and HIV transmission mode .3, 350–500 cells/mm3 and >500 cells/mm3), using the cutoffs in different versions of the national treatment guidelines [The most recent CD4 count and the most recent plasma viral load were retrieved from patients’ medical records. For the purpose of data analysis in the current study, CD4 count was categorized into three groups  and virologic outcomes (HIV RNA<50 copies/ml vs ≥50copies/ml). SAS 9.4 was used for all the statistical analyses.Descriptive analysis was employed to describe the socio-demographic characteristics, treatment history, the immunologic (CD4 counts) and virologic outcomes  in three different samples. Chi-square test or ANOVA was used to compare the differences in background characteristics and treatment history between different levels of immunologic ; around one sixth (16.6%) of the participants had at least one kind of co-morbidity . The three samples were similar in terms of background characteristics , except As shown in 3. The CD4 count increased from 318 cells/mm3 in 2012–2013 (sample 1) to 347 cells/mm3 in 2013–2014 (sample 2) and 357 cells/mm3 in 2016–2017 (sample 3). In the pooled sample, over half of them (54.2%) were having CD4 counts ≤350 cells/mm3, one fourth of them (24.5%) having CD4 counts between 350–500 cells/mm3, while around 20% of them having CD4 counts >500 cells/mm3. The proportion of PLWH with CD4 counts ≤350 cells/mm3 decreased from 56.0% in 2012–2013 to 50.5% in 2013–2014 and 49.3% in 2016–2017, while those with CD4 counts >500 cells/mm3 increased from 19.6% in 2012–2013 to 23.6% in 2013–2014 and 27.9% in 2016–2017.  with a median value of 328 cells/mm16–2017. Data on viral load were available from 52.7% of the pooled sample . Among those participants, 82.5% had viral suppression. Similar rates were observed in the three individual samples, although the rates in sample 2 (85.8%) and sample 3 (82.7%) were both slightly higher than that in sample 1 (81.6%). In terms of immunological outcome, PLWH who were female (p < .0001) and younger (p<0.01) were more likely to have a higher CD4 count than their counterparts in all three samples. In sample 1, those PLWH who had no job or only part-time job had a lower CD4 count (p<0.05), while this relationship was not significant in the other two samples. In addition, PLWH who were diagnosed for a longer time (p<0.001), being on ART (p<0.001), being virally suppressed (p = 0.01), and lower prevalence of comorbidity (p = 0.003) were having higher CD4 counts in sample 1, while the latter two factors were not significant in the other two samples. The participants who had been on ART for a longer time were more likely to have a higher CD4 count (p<0.05) in all three samples. With respect to virologic outcome, the study 3 participants who were of Han ethnicity had a higher rate of viral suppression (p = 0.01); the study 1 participants who did not have a full-time employment  (p = 0.007) or had no stable partner  (p = 0.04) reported a lower level of viral suppression. A longer duration of HIV diagnosis was associated with viral suppression in both samples 1 and 3 (p<0.001). Being on ART (p<0.05) and receiving ART for a longer time (p<0.001) were positively associated with viral suppression in all three samples. In addition, fewer treatment interruptions (p = 0.0006) and more knowledge on ART (p = 0.0003) were positively associated with viral suppression in the first sample. 3) also suggested a room for improvement in immune recovery, because the decline of CD4 count can lead to an increase of both opportunistic infections and mortality [In our study, the ART coverage and rate of viral suppression (HIV RNA <50 copies/ml) were both relatively high across different time points among PLWH who received care in Guangxi. The rates are comparable with previous studies conducted in China , 26 and ortality . ExpandiThe increasing trend in ART coverage and CD4 count over time might be attributed to the implementation of the updated treatment guidelines. It is worth noting that, different from existing studies, our samples were collected from community-based clinics in mostly rural settings. Compared with those studies using the data from major health care facilities, such as urban hospitals, our study showed similar clinical outcomes. This finding suggests that the HIV care can be delivered effectively in community settings, which was also supported by the research conducted in other settings , 36.Our study demonstrated that female and younger PLWH had higher CD4 counts than their counterparts. This is consistent with the previous studies –40. It s3 till May 2014 and ≤500 cells/mm3 till June 2016). Therefore, free ART was historically prioritized to those with lower CD4 counts, which resulted in a higher ART coverage among patients with CD4 counts ≤350 cells/mm3.The higher proportion of co-morbidity with other infections  was associated with lower CD4 counts. Previous studies showed that the co-infection of acute bacterial STI  resulted in increased HIV viremia and a decrease in CD4 counts , 42. WitOur findings demonstrated that ethnic minority, unemployment, and absence of stable partners were associated with suboptimal viral suppression among different samples. Guangxi is among one of the provinces that have multiple ethnic groups. Owning to sparse population distribution and province-wide low socio-economic status, the PLWH in Guangxi generally received lower levels of education and less likely to have stable jobs. Furthermore, the participants who were not married or didn’t have a boyfriend or girlfriend might have less social support for HIV treatment compared with PLWH with stable partners. All these characteristics could affect the ART adherence  and therOur data also suggested that many challenges exist to achieve viral suppression during the course of treatment. For example, participants who had less knowledge of HIV treatment and more treatment interruptions were less likely to be virally suppressed in sample 1. ART interruptions undermine the effectiveness of ART by prompting viral load rebound , 45, theOur study has several limitations. First, the three samples might not be totally comparable. While all three studies were conducted in similar community-based treatment settings , the samples could be different because of some specific inclusion criteria in each study. Second, there might be some overlap in samples between sample 1 and sample 2 due to the similar settings and timing of the studies. However, such possibility was considered small because of the specific inclusion criteria . Third, our samples consisted of PLWH who were largely engaged in HIV care or treatment. Therefore, the clinical outcomes reported in this study may not be representative of other PLWH who were not retained in care or experienced interrupted care. Fourth, all the participants were recruited in Guangxi, thus caution should be taken when generalizing our results to other regions, especially, given the fact that Guangxi has been the only region in China that has witnessed a decrease in the number of newly diagnosed HIV cases in the past six years . Fifth, In summary, the increasing trends in ART coverage and CD4 count across the six years reflected the positive impacts of the HIV treatment program, especially the new treatment guidelines. However, suboptimal clinical outcomes continue to be a problem, particularly among some subgroups of PLWH. Future studies should examine whether clinical management strategies should be tailored for PLWH with different sociodemographic characteristics and treatment trajectories. Expanding the HIV testing and improving early linkage to care could be helpful to get more PLWH on treatment before their immunological functioning become deteriorated, which would also result in better treatment outcomes. Helping the patients to gain more knowledge of ART, emphasizing the importance of optimal treatment adherence and reducing treatment interruptions probably could benefit the viral suppression for the patients. Future longitudinal studies may be needed to improve our understanding of potential factors that affect the clinical outcomes among PLWH in Guangxi, China and other resource-poor settings.


Rifamycins are a group of antibiotics mainly used in the treatment of tuberculosis (TB), however they interact with antiretroviral therapy (ART). Rifabutin allows more regimens options for concomitant imunodeficiency virus (HIV) treatment compared to rifampicin.  Compare the outcomes of TB-HIV co-infected patients who used rifampicin or rifabutin. We analysed data from a prospective cohort study at National Institute of Infectious Diseases Evandro Chagas, Rio de Janeiro (RJ), Brazil. Patients who were treated for TB and HIV with rifampicin or rifabutin, from February 2011 to September 2016 were included. There were 130 TB-HIV patients, of whom 102 were treated with rifampicin and 28 with rifabutin. All patients in the rifabutin-treated group and 55% of the rifampicin-treated group patients were ART-experienced. Patients treated with rifampicin had similar abandon and cure rates, interruptions in treatment due to adverse reactions, immune reconstitution inflammatory syndrome and a similar mortality rate as those treated with rifabutin. However, rifampicin-treated patients had higher CD4 counts and more frequently undetectable HIV viral load by the end of treatment  compared to rifabutin-treated patients, even when only ART-experienced patients were evaluated . Patients who used rifabutin had worst immune and virological control. This group had more ART-experienced patients. New and simpler regimens are needed for patients who do not respond to previous antiretroviral therapies. RMP-based regimens can be used concomitantly with efavirenz or nevirapine (non-nucleoside reverse transcriptase inhibitors ― NNRTI), raltegravir (integrase inhibitor) or lopinavir-ritonavir (protease inhibitor ― PI).,Rifamycins are the most important class of drugs used to treat TB, with RMP as the preferred first-line of therapy, followed by rifabutin (RFB).,,Due to the cost of RFB, in Brazil it is primarily used in situations where RMP is inappropriate. Since there are no fixed dose combination regimens with RFB available,The best concomitant treatment for both TB-HIV remains unknown, particularly for ART-experienced patients, since all of the alternatives available have disadvantages. The aim of this study was to analyse the outcomes of HIV patients on ART, treated with RMP for TB for the entire duration of anti-TB therapy, or with RFB during at least part of the treatment period.We analysed data from an ongoing prospective cohort study, described elsewhere,Mycobacterium tuberculosis culture was positive in any sample collected or when there was a positive smear or when suggestive imaging analysis (x-ray or computed tomography) showed positive results and clinical signs and symptoms were present and improved with TB treatment. Patients included without a positive culture were considered with a positive therapeutic response if they have improved signs, symptoms and imaging analysis results after the intensive therapy phase.A diagnosis of TB was made when During the baseline visit, TB therapy was prescribed after data collection, which included sex, age, marital status, monthly income, education, alcohol use (using CAGE questionnaire), drug use, history of smoking (current or past), sexual behaviour, weight loss, clinical presentation of TB, the date of first positive HIV serology, history of a previous episode of TB, current and previous ART used. In addition, results of laboratory tests such as microscopic examination of sputum, culture of sputum, blood and other clinical specimens for mycobacteria and fungal pathogens, blood cell counts, serum levels of creatinine, albumin and liver enzymes, CD4 cell count and HIV viral load were recorded. ART was also adjusted when necessary in previously experienced patients.Data recorded in follow-up visits included: clinical manifestations associated with TB or HIV infection, the occurrence of immune reconstitution syndrome (IRIS), adverse reactions related to ART or TB therapy, subsequent laboratorial tests results including CD4 cell count and HIV viral load and resistance to TB drugs. ART was initiated in naïve patients during follow-up visits after at least 15 days of TB treatment. Patients were followed-up until the end of TB treatment. After the end of TB treatment, patients continued to be examined in an HIV outpatient clinic at INI-Fiocruz, and if a TB relapse was suspected, they were referred to our TB outpatient clinic.,ART was offered according to contemporary Brazilian National Guidelines.Chi-square and Fisher’s exact test were used to compare the distribution of categorical variables among patients who received RMP for the entire duration of anti-TB therapy with those who received RFB during at least part of the treatment duration. The distribution of continuous variables was compared using Wilcoxon’s rank sum test or analysis of variance (ANOVA). Two-sided p ≤ 0.05 was considered statistically significant. Data was analysed with SPSS 17.0 programme.Among the 130 TB-HIV patients studied, 102 were treated with RMP and 28 with RFB. Among these 28 patients treated with RFB, 18 started on RMP and changed to RFB to accommodate their ART regimen or because of efavirenz resistance (11 after the intensive phase of TB treatment), two were started on RFB and changed to RMP after adjusting their lopinavir-ritonavir dosage, two were started without rifamycin and changed to a regimen with RFB, and six used RFB from the beginning until the end of the TB treatment period. Median duration of TB treatment was 191 days (IQR 158-254) and was significantly different between the RMP (189 days) and RFB treatment groups . However, when analysing only the days that patients in the RFB group received this medication, the median duration of RFB treatment was 172 days (IQR 125-259).Among the 130 patients included, 60 were ART-naïve and 70 were ART-experienced. The median start day of ART after TB treatment initiation in naïve patients was 28 days (IQR 14-33). ART-experienced patients were using ART for a median of five years (IQR 2-9). All of the 28 patients in the RFB group used a ritonavir-boosted PI regimen during TB treatment; however, three started with efavirenz and RMP and changed to a ritonavir-boosted PI regimen and RFB (two due to primary resistance to efavirenz and one due to an adverse reaction). Eighty-five patients used RMP with efavirenz, one with nevirapine, four with raltegravir and 12 with the double of standard dose of lopinavir-ritonavir.3, and was not significantly different between the groups  were cured. Six patients included without a positive culture abandoned treatment (15%) and one died. The other 32 (82%) patients without a positive culture improved clinical signs and symptoms during the intensive phase of TB therapy and were considered TB cases. All were considered cured at the end of the TB treatment. There were no significant differences in the number of cured patients (p = 0.29), deaths (p = 0.51) and default (p = 0.22) rates between patients with or without a positive culture.Twenty-one patients (23%) with a positive culture for Patients treated with RMP had a similar TB treatment default and cure rates, interruption of therapy due to adverse reactions and IRIS as those treated with RFB in our cohort Table). In terms of ART response, patients had higher median CD4 cell counts, lower median HIV viral load and more frequently undetectable HIV viral load by the end of treatment in the RMP group  had undetectable viral load. These 16 patients used NRTI + NNRTI (14 efavirenz and one nevirapine) or NRTI + raltegravir. Twenty-two patients (of 28) who used RFB had done HIV viral load in the end of TB treatment and only eight  had undetectable viral load, significantly less compared to the RMP group (p = 0.039). All these 22 patients used NRTI + PI.We found no difference in mortality between the groups. There were two TB related deaths, both from the RMP-treated group .,,In Brazil, RFB is used to treat patients on ART that do not qualify for RMP, mainly those using ritonavir-boosted PI regimens different from lopinavir-ritonavir regimens with doses adjusted to accommodate RMP use.,In our study, the median initial CD4 cell counts were not significantly different between the groups, which probably justify the similar incidence of IRIS among patients who used RMP and RFB. Rawson et al.We had a low and identical percentage of TB treatment interruptions due to adverse reactions in both groups, unlike Rawson et al, who showed treatment interruptions were slightly more common in patients who used RFB in the British cohort.Although patients who used RMP were more undernourished and presented more frequently with disseminated TB, they achieved better results of CD4 cell count and HIV viral load by the end of TB treatment compared to those who used RFB in our cohort. Most of patients who used RMP were ART-naïve, therefore had effective NNRTI regimen options. Patients who used RFB were ART-experienced and when the regimen already being used was not effective, there were few options to overcome HIV resistance, which made it difficult to treat. In the study of Rawson et al.,When we compared patients who used RFB to the ART-experienced patients in the RMP group, we also found better outcomes of CD4 cell count and HIV viral load in the RMP group. Most ART-experienced patients in the RMP group were first-time ART users or never used NNRTI, and had the possibility to use this class of antiretroviral drug during TB treatment. However, most patients in the RFB group had already used several ART regimens and achieving a satisfactory immunological and virological response proved difficult.TB was cured in a similar proportion of patients in both groups, possibly because treatment adherence and interruptions due to adverse reactions did not differ significantly.,Mortality was low and similar in both groups. This was also observed in other studies,This study has limitations. We compared a group of patients who used RMP including ART-naïve and ART-experienced patients, to a group of only ART-experienced patients who used RFB. In addition, the RFB group had fewer patients than the RMP group, what may have compromised the comparison of the groups. Since this was a cohort study, ART was prescribed to naïve patients, and modified in ART-experienced patients, based on the doctor decision and not on a date stipulated by a study protocol.In conclusion, we found similar outcomes in HIV patients who used RMP or RFB as part of their TB treatment regimen, except for a worst immune and virological response in the RFB group, confirming the need for more effective treatment regimens for ART-experienced HIV-TB patients. The development of better strategies to treat TB and HIV in ART-experienced patients is urgent, as drug-drug interactions and therapy adherence are still a major concern and a limitation to both treatments.


The global transition to use of dolutegravir (DTG) in WHO-preferred regimens for HIV treatment is limited by lack of knowledge on use in pregnancy. Here we assessed the relationship between drug concentrations , including in breastmilk, and impact on viral suppression when initiated in the third trimester (T3).th March 2017 and 16th January 2018, with follow-up until six months postpartum. The primary endpoint was pharmacokinetics of DTG in women and breastfed infants; secondary endpoints included maternal and infant safety and viral suppression. Intensive pharmacokinetic sampling of DTG was undertaken at day 14 and 2wPP following administration of a medium-fat breakfast, with additional paired sampling between maternal plasma and cord blood, breastmilk and infant plasma.In DolPHIN-1, HIV-infected treatment-naïve pregnant women , weight 67kg (45–119), all Black African) in Uganda and South Africa were randomised 1:1 to dolutegravir (DTG) or efavirenz (EFV)-containing ART until 2 weeks post-partum (2wPP), between 910 copies/mL both arms) and CD4 count (343 vs 466 cells/mm3) were observed between DTG (n = 29) and EFV (n = 31) arms. Although DTG Ctrough was below the target 324ng/mL  in 9/28 (32%) mothers in the third trimester, transfer across the placenta (121% of plasma concentrations) and into breastmilk (3% of plasma concentrations), coupled with slower elimination, led to significant infant plasma exposures . Both regimens were well-tolerated with no significant differences in frequency of adverse events . No congenital abnormalities were observed. DTG resulted in significantly faster viral suppression (P = 0.02) at the 2wPP visit, with median time to <50 copies/mL of 32 vs 72 days. Limitations related to the requirement to initiate EFV-ART prior to randomisation, and to continue DTG for only two weeks postpartum.No differences in median baseline maternal age, gestation (31 vs 30 weeks), weight, obstetric history, viral load  or dolutegravir-based therapy.For those on dolutegravir, intensive pharmacokinetic sampling was undertaken at steady-state and post-partum, accompanied by paired cord and maternal blood samples at delivery, and paired maternal plasma and breast milk, and infant plasma sampling.We observed high in-utero transfer, and modest breastmilk transfer of dolutegravir to the infant. This, coupled with the delayed elimination of dolutegravir in newborn infants, resulted in high dolutegravir exposure in infants in-utero and in the first two weeks of life.Standard dolutegravir dosing appears safe and is potentially beneficial in late pregnancy.The high infant exposures to dolutegravir in utero, and in the first week of life, may offer additional prophylaxis against HIV transmission.Dolutegravir resulted in superior virological suppression compared to efavirenz among women commencing antiretroviral therapy in late pregnancy. Approximately 1.5 million HIV-infected women become pregnant worldwide each year, the majority from low- or middle- income countries. In sub-Saharan Africa, a significant proportion of women are diagnosed late in pregnancy, with as much as 20% initiating anti-retroviral therapy (ART) in the third trimester in South Africa  (M = F) in which subjects with missing data at two weeks post-partum were assessed as experiencing failure, and 2) missing viral load equals excluded (M = X) in which subjects with missing data at two weeks post-partum were excluded from the analysis. As a sensitivity analysis, the Wilcoxon rank-sum test was used to compare log10HIV RNA at 2 weeks post-partum between arms for patients with an evaluable result at this timepoint (M = X). Kaplan-Meier survival curves were used to estimate time to viral suppression (defined as HIV RNA <50 copies/mL) by treatment group and were compared by the log-rank test. Analyses were performed using Stata v14.2  and p<0.05 was used to determine significance. Virological failure was defined as <1 log10 reduction by week 4 of treatment or evidence of blunting of virological response between weeks 2 and 4.Viral load over time was presented as log10 copies/mL both arms) and CD4 count (343 vs 466 cells/mm3) occurred between DTG-ART and EFV-ART arms  were 2435 (1462–3986) ng/mL, 642 (188–3088) ng/mL and 35322 (19196–67922) ng.h/mL respectively. Twenty three participants underwent intensive post-partum PK sampling following delivery; the six participants who underwent sampling before seven days postpartum were excluded from analysis. The remaining 17 participants were sampled at a median of 10 (range 7–18) days following delivery, with Cmax, C24 and AUC0-24 of 2899 (1397–4224) ng/mL, 777 (348–1210) ng/mL and 40127 (22795–59633) ng.h/mL, respectively. No significant differences were observed in the geometric mean ratios of Cmax, C24 and AUC0-24 in 14 mothers who underwent sampling in the third trimester of pregnancy and at post-partum visit  and was excluded from analysis. Of the remaining twenty-eight participants, in third trimester, Cum visit , Table 2Paired cord and maternal blood samples were available in 16 mother-infant pairs. In one individual, both samples were below the limit of quantitation (BLQ), and non-adherence was reported. Analysis of the remaining 15 samples revealed a median C:M ratio of 1.21 (range 0.51–2.11) .max of 84.6 (43.8–171) ng/mL and a BMtrough of 22.3 (3.0–64.3) ng/mL. A milk to plasma (M:P) ratio of 0.03 was observed throughout the dosing interval  ng/mL and an Infanttrough of 60.9 (16.3–479) ng/mL (max and 0.08 (0.00–0.17) at Infanttrough. After discontinuation of maternal DTG, detectable concentrations were noted in 100%, 80% and 80% breastfed infants at 48, 72 and 96 hours following final maternal dose, respectively (DTG was detectable in the plasma of breastfed infants with an Infant9) ng/mL , Table 2ectively .Both regimens were well-tolerated in mothers, with no significant differences in adverse events between arms see  Tables, Of 28 live births in the DTG-ART arm, median (range) gestational age at delivery was 39 35–43) weeks, compared with 38 (34–42) weeks for the 31 live births in the EFV-ART arm, with no significant differences for gestational age or birth weight . There was no difference in days since first ART between arms (67 IQR 55–94 for DTG-ART and 63 IQR 42–82 for EFV-ART). Three patients discontinued prior to the 2-week post-partum visit (2 DTG-ART and 1 EFV-ART). One participant in the DTG-ART arm discontinued for lack of efficacy after week 4. The patient had undetectable DTG concentrations in third trimester and admitted non-adherence. Another individual in the DTG-ART arm experienced resistance and had a viral load of 2217 copies/mL at the post-partum visit. She had multi-class resistance demonstrated on her baseline sample  and attained virological suppression after transition to a regimen containing DTG and ritonavir-boosted darunavir. The two patients that discontinued prior to the post-partum visit for other reasons (one in each arm) both had a viral load <200 copies/mL at the point of discontinuation (4 weeks).DolPHIN 1 demonstrated similar maternal DTG concentrations between the third trimester of pregnancy and postpartum, with both transplacental and transmammary exposure to the infant. Furthermore, superior virological responses were demonstrated with DTG-ART compared to EFV-ART when initiated in late pregnancy, and DTG appeared to be safe and well-tolerated in this population.24 geometric mean 642 ng/mL) and postpartum (C24 geometric mean 696 ng/mL) than those previously reported in non-pregnant participants [24 was at or below the clinically-derived EC90 (324ng/mL)[90 of 64 ng/mL [0-24, was 35,322 ng.h/mL. This is similar to findings from the US IMPAACT P1026s study in pregnant HIV-infected women [max  in 9/28 64 ng/mL , and thaed women . DTG is ed women ; this sued women , we failConsistent with other studies, DTG was found to cross the placenta with a C:M ratio of 1.21 . This isDolPHIN-1 provides confirmatory evidence that the superior virological responses observed with DTG-based combination therapy in non-pregnant adults is also seen in pregnancy. Given that differences are most marked during the first 12 weeks of therapy, DTG has a potential role in prevention of mother to child transmissions among women who are initiated on ART in the third trimester.In women initiating ART in the third trimester of pregnancy, DTG-ART appeared safe and well-tolerated, although our sample size is small. Preliminary data from Botswana reported an increased frequency of neural tube defects among mothers who conceived on DTG  leading Two important limitations of the study related to the requirement to initiate immediate EFV-ART at HIV diagnosis, and the need to limit exposure of newborn and breastfed infants to what was not a recommended first-line regimen during the study period. However, randomisation ensured balance between arms in initial EFV-ART exposure, and these limitations would only have reduced any real differences between arms. The ongoing DolPHIN-2 study (NCT03249181) will provide more detailed evaluation of the safety and effectiveness of DTG in women and their infants where DTG-ART is initiated in the third trimester with follow-up until 72 weeks postpartum.Furthermore, some women attended for postpartum visit earlier than the proposed two weeks, potentially minimising differences in DTG exposure as a result of late pregnancy. Notwithstanding, we demonstrate here that standard doses of DTG are sufficient for mothers in the third trimester of pregnancy.In summary, we found that DTG-ART resulted in a significantly shorter time to undetectable viral load, which is likely to be important in reducing MTCT when ART is initiated in late pregnancy. This is despite low steady-state exposures of DTG in the third trimester of pregnancy. We also observed significant transplacental transfer of DTG, which together with breast milk transfer, and likely delayed clearance of DTG resulted in significant DTG exposures in newborn infants.S1 Table(DOC)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.S3 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.


HIV. The literature contains few descriptions, though, of populations starting treatment since adoption of universal eligibility. Using baseline data from a clinical trial of same‐day ART initiation, we describe the populations presenting for HIV testing or care at study clinics in Kenya and South Africa in 2017‐18, during the era of same‐day initiation.Many African countries have had at least two years’ experience with universal treatment eligibility for SLATE) trials in Kenya (SLATE I) and South Africa (SLATE II) were multicenter, non‐blinded, individually randomized, pragmatic trials evaluating simple, standardized algorithms to determine eligibility for same‐day initiation of ART without relying on laboratory results, point of care tests or multiple clinic visits. In Kenya, enrolment occurred during July 2017 to April 2018. In South Africa, enrolment occurred during March to September 2018. We describe demographic, socioeconomic and clinical characteristics of patients randomized to the same‐day initiation arm for both studies.The Simplified Algorithm for Treatment Eligibility , believed they already had adequate knowledge to begin ART , and preferred to start ART immediately (same‐day) (98% in both countries). About 40% of all patients had at least one symptom related to tuberculosis  and/or cryptococcal meningitis (continuous headache). More than a third of patients  presented with advanced disease (CD4 <200 cells/mm3), a fifth presented with very advanced disease (CD4 < 100), and approximately 1 in 20 presented with very advanced disease and were asymptomatic.A total of 240 and 296 participants were enrolled in Kenya and South Africa. The majority were female (59% and 64% respectively), with a median age of 35 years. In both countries, most subjects were newly diagnosed with ART in Kenya and South Africa, in 2017‐2018 more than half of HIV‐positive patients presenting at public sector clinics were not yet aware of their status, and more than a third presented for care with advanced HIV disease. These proportions remain similar to those observed before the introduction of universal eligibility.Despite >2 years of universal eligibility for  Using baseline data from these companion clinical trials, we describe characteristics of patients presenting for HIV testing or care, but not yet on ART, from mid‐2017 to mid‐2018 in South Africa and Kenya. These data help to assess the early impact of universal treatment in promoting treatment uptake prior to disease progression.2The Simplified Algorithm for Treatment Eligibility (SLATE) trials in South Africa and Kenya are multicenter, non‐blinded, individually randomized (1:1), pragmatic trials evaluating simple, standardized algorithms to determine eligibility for same‐day initiation of ART without relying on laboratory results, point of care tests or multiple clinic visits The SLATE studies were carried out in typical public sector clinics in both countries. In Kenya, these were outpatient HIV clinics in county‐level hospitals in Kericho, Nandi and Kisumu counties. In South Africa, study sites were primary health clinics serving urban informal and formal communities in the Johannesburg and Ekurhuleni metropolitan areas. Patient inclusion and exclusion criteria for study eligibility are detailed in published protocols In Kenya (SLATE I), the study was powered to detect a 15% difference in the primary outcome of initiation of ART within 28 days and alive, in care and retained on ART 8 months after study enrolment. We aimed for a sample size of 240 per arm  in Kenya and 300 per arm  in South Africa SLATE I and II included a baseline questionnaire eliciting basic demographic and other information about prior HIV care. Patients in the intervention arms were assessed for eligibility for same‐day ART initiation by a study clinician using the SLATE I (Kenya) or SLATE II (South Africa) algorithm 33.1In Kenya, 240 patients were randomized to the intervention arm in SLATE I between July 13, 2017 and April 17, 2018. In South Africa, 296 patients were randomized to the intervention arm in SLATE II between March 14 and September 18, 2018.3.2Table 3.3The majority in both countries had not visited the study clinic for any kind of HIV care prior to the baseline study visit Table . Common 3.4In Table 3.5A brief medical history addressed topics relevant to ART initiation, including: (1) prior experience on ART; (2) TB treatment for less than two weeks; and (3) currently taking other medications that could complicate ART. Roughly one of the ten patients were reengaging in HIV care and treatment after initiating previously. Few patients had started recent TB therapy, and little pertinent information pertaining to ART initiation were identified in the medical histories.Results of the physical examination revealed that few patients had a fever on the day of assessment, based on thermometer measurement by study clinician . A small share of patients in South Africa (7%) and a larger share in Kenya (22%) were underweight. Elevated blood pressure was common.Following the physical exam, the clinician could recommend further assessment prior to ART initiation due to clinical signs/symptoms . This information from the readiness assessment with the clinician is consistent with responses to the baseline questionnaire.3.73) in Kenya and South Africa respectively. Very advanced disease (CD4 < 100 cells/mm3) was also common, with 21% in Kenya and 18% in South Africa presenting with very advanced disease.The distributions of baseline CD4 cell counts (based on the day of enrolment) were very similar in each country  but reported at least one symptom listed in Table Two‐thirds of all patients presented higher CD4 counts ≥200 cells/mmIn Kenya, 15 of the 221 patients in Table The two study populations described here, both presenting for HIV care and treatment, share six characteristics. First, more than half of patients presenting during mid‐2017 to mid‐2018 to facilities in both countries (62% in Kenya and 55% in South Africa) stated that they had not previously tested positive for HIV. This includes patients who had never tested as well as those testing negative previously. While these numbers may be somewhat inflated, with some patients preferring not to reveal a previous positive test, they remain worrisome. Efforts to expand testing—and to facilitate immediate treatment initiation for all those testing positive and to reinforce HIV prevention for those testing negative—remain critical for the success of universal treatment.Second, generally all patients stated that they preferred to initiate ART on that same day if recommended by the clinician. A stated short‐term preference does not, of course, ensure long‐term adherence, but this result from 98% of patients in both countries does suggest that once patients learn their infected status, they are eager to move forward with treatment.Third, about 1 in 10 patients were returning to the clinic for treatment after prior defaulting. In Kenya, these prior defaulters presented with substantially lower CD4 cell counts than did naïve patients, while in South Africa the CD cell count distribution was similar in both groups. As an increasing proportion of patients re‐enter treatment after dropping out sometime in the past Fourth, a large proportion of patients presenting at public sector clinics in the two study countries report symptoms that can be indicative of tuberculosis, cryptococcal meningitis, and/or other serious conditions , with symptoms of tuberculosis most common. Multiple symptoms were common in Kenya (27% with 3 or more symptoms), but less so in South Africa (8% with 3 or more symptoms).3Fifth, more than a third (36‐37%) of patients presenting from mid‐2017 to mid‐2018 had advanced HIV disease (CD4 ≤ 200) at presentation, and a fifth had very advanced disease (CD4 < 100). These proportions remain similar to those estimated before implementation of UTT 3) and were asymptomatic. A lack of a consistent correlation between CD4 cell count and reported symptoms is consistent with prior literature And finally, a small but important number of patients presented with advanced HIV disease  and about the need for additional care (despite the absence of relevant symptoms). While healthcare providers around the world already face these decisions on a daily basis, a goal of future research should be to provide better guidance to the nurses, clinical officers, and in some cases lay health workers, to maximize immediate ART initiation and identify and respond to patients who require additional care.WDFV sits on antiretroviral initiation guideline committees, both local and international, has accepted speaking honoraria from multiple manufacturers of antiretrovirals and is on several advisory boards. The remaining authors declare that they have no competing interests.SR conceived of and designed the work. ATB, MM, BAL, IT, MB and WDFV contributed to designing the work. ATB, MM, BAL and SR wrote the first draft of the manuscript. All authors reviewed and revised the manuscript, approved the manuscript's results and conclusions, and have read, and confirmed that they meet ICMJE criteria for authorship.


In response to suboptimal adherence and retention, South Africa’s National Department of Health developed and implemented National Adherence Guidelines for Chronic Diseases. We evaluated the effect of a package of adherence interventions beginning in January 2016 and report on the impact of Fast‐Track Treatment Initiation Counselling (FTIC) on ART initiation, adherence and retention.We conducted a cluster‐randomized mixed‐methods evaluation in 4 provinces at 12 intervention sites which implemented FTIC and 12 control facilities providing standard of care. Follow‐up was by passive surveillance using clinical records. We included data on subjects eligible for FTIC between 08 Jan 2016 and 07 December 2016. We adjusted for pre‐intervention differences using difference‐in‐differences (DiD) analyses controlling for site‐level clustering.We enrolled 362 intervention and 368 control arm patients. Thirty‐day ART initiation was 83% in the intervention and 82% in the control arm . After adjusting for baseline ART initiation differences and covariates using DiD we found a 6% increase in ART initiation associated with FTIC . We found a small decrease in viral suppression within 18 months  with no difference after adjustment  or when considering only those with a viral load recorded (84% intervention vs. 86% control). We found reduced crude 6‐month retention in intervention sites . However, differences attenuated by 12 months . Qualitative data showed FTIC counselling was perceived as beneficial by patients and providers.We saw a short‐term ART‐initiation benefit to FTIC (particularly in districts where initiation prior to intervention was lower), with no reductions but also no improvement in longer‐term retention and viral suppression. This may be due to lack of fidelity to implementation and delivery of those components that support retention and adherence. FTIC must continue to be implemented alongside other interventions to achieve the 90‐90‐90 cascade and fidelity to post‐initiation counselling sessions must be monitored to determine impact on longer‐term outcomes. Understanding the cost‐benefit and role of FTIC may then be warranted. To mitigate the impact such delays have on retention, several studies have demonstrated that rearranging initiation algorithms to allow faster or same‐day initiation 3) for rapid ART initiation, as per the 2015 ART treatment guidelines. In September 2016, universal test‐and‐treat was introduced enabling HIV‐positive patients to initiate treatment on the day eligibility was ascertained. However, the content of counselling sessions has not been formally adapted to fit with these changes, nor have patient records or systems been fully updated to record these, and as such the extent and content of counselling provided remains unknown and likely varies by facility and healthcare provider.South Africa has the largest HIV treatment programme worldwide We sought to determine if these interventions were effective at maintaining or increasing initiation rates, and determining whether adherence and retention post‐initiation is equivalent or better than under current guidelines. We worked with NDOH to conduct a cluster‐randomized mixed‐methods evaluation at early learning sites to inform future iterations of the adherence guidelines. Here we report the impact of FTIC on treatment initiation, viral suppression and retention.22.1We evaluated five of the adherence interventions . We excluded patients <18 years old, pregnant women, and patients with TB or cryptococcal meningitis. Intervention participants were a sample of those eligible and recorded as having received the intervention (either in their patient file or on an FTIC register) at an intervention site. Controls were patients at control sites who would have been eligible for the intervention had it been offered, using the criteria above . At control sites lists were used to identify patient files to confirm eligibility. Patients were selected until the sample size was reached. Follow‐up data came from routinely collected clinic records including TIER.Net and patient files beginning at ART eligibility, with all patients followed for up to 18 months to assess primary outcomes. Unfortunately, recording of counselling sessions was poor on both the registers and patient files. Despite attempts to match registers to patient files it was difficult to determine which counselling sessions patients received.2.63) within nine months of ART eligibility . We excluded viral loads within two months of ART eligibility to prevent inclusion of baseline viral loads. Our secondary outcome was the proportion of patients initiating ART within one week of eligibility. As we had additional follow‐up data, however, we also present outcomes up to 18 months for viral suppression and at 12 months for retention. Suppression within 18 months was defined as any viral load <400 copies/mL3 within two to eighteen months of eligibility. If there were discordant results (one suppressed and one unsuppressed) the outcome was classified as suppressed. In order to understand whether this definition impacted the outcome measure, we compared the risk difference from this definition to the risk difference had we classified discordant viral load results based upon the suppression status of the last viral load measure in the data set. Twelve‐month retention was defined as being listed as retained in TIER.Net, defined as not transferred, become lost‐to‐follow‐up (failure to attend the clinic within 90 days of a scheduled ART visit), or died at 12 months. A patient could be retained without initiating ART. We considered those without a viral load as not suppressed and those who transferred as not retained.Our short‐term primary outcome was the proportion of patients initiating ART within 30 days of eligibility. Our long‐term primary outcomes were the proportion of patients virally suppressed  and 95% confidence intervals (CI)accounting for site‐level clustering using linear regression and generalized estimating equations with an unstructured correlation matrix. Models were adjusted for age , sex, baseline CD4 count  and WHO stage (I/II vs. III/IV).ij signifies a binary outcome indicator for the ith person in period j, period is an indicator variable  and FTIC is an indicator variable for treatment arm . β3 is the coefficient for the interaction between period and FTIC and represents the effect of FTIC adjusted for baseline outcome differences. Xij indicates a vector of covariates for adjustment and µij is the error term.As the sample size was moderate and our matching was coarse, baseline imbalances between arms could occur by chance. We therefore used a difference‐in‐differences (DiD) in addition to our original proposed analyses 2.8a priori according to the evaluation questions with additional themes added as they emerged. Full details around the methods and results from this qualitative component are reported elsewhere At one pair of sites in each province we collected data from patients and providers to understand the implementation process and acceptability of interventions. Data were collected through quantitative surveys (n = 113), focus group discussions (FGDs) with patients (n = 22) and in‐depth interviews with healthcare providers (n = 48). Eligible patients were identified with assistance from facility staff and approached at clinic visits. Provider participants were purposively selected from each cadre of providers implementing adherence interventions. The estimated sample size was 70 patients at each of eight survey sites; ten patients per FGD (one FGD per site) focused on newly diagnosed patients; and interviews with up to six providers per site. Data were analysed in NVivo11© . Coding themes were identified 2.9The trial was approved by the Human Research Ethics Committee of the University of the Witwatersrand Johannesburg and the Boston University Institutional Review Board. Both approved use of routine data collection with no patient contact for the impact evaluation and approved interviewing of both patients and providers after informed consent for the implementation evaluation. The study is registered at clincialtrials.gov (NCT02536768).33). Intervention and control arms were largely balanced on baseline characteristics.We included 730 patients eligible for FTIC between 8 January and 7 December 2016 . There were 202 patients excluded from the intervention arm because they were not eligible  and 77 excluded from the control arm (69% did not meet FTIC criteria). Participants were mostly under 40 years old (65%) and 61% were female  initiated ART Table .Although baseline characteristics were balanced, intervention sites had roughly 4% lower 30‐day ART initiation than control sites pre‐intervention (1 January 2015 to 31 December 2015)  Table . Using d3.2Intervention sites had increased 6‐month viral suppression  versus control sites Table . Viral s3.3At six months, retention was lower in the intervention compared to the control arm  Table . This wa3.4Overall 113 patients eligible for FTIC completed the cross‐sectional survey. Intervention arm patients (n = 55) reported a median of one fewer clinic visits prior to initiation (median 2 vs. 3) than control arm patients. More reported feeling involved in decisions affecting their care (51% vs. 41%). They were also more likely to receive counselling after ART initiation than control arm patients (27.3% vs. 13.8%). FGD patients receiving FTIC reported feeling supported by the additional counselling and indicated it helped with adherence. Providers noted that post‐initiation counselling was important to intervention success but also highlighted some confusion between FTIC and “treat all,” as these new guidelines were implemented at roughly the same time. Consequently providers were uncertain how the policies differed and unsure which patients should be prioritized for rapid initiation potentially explaining the drop in initiation seen during the post‐intervention period. To improve FTIC, patients and providers recommended initiating treatment at the first counselling session to further improve the initiation process.4Given the high risk of attrition from HIV care between ART eligibility and initiation We found that FTIC, when implemented as routine care without additional external resources, increased 30‐day initiation by approximately 6%. While the benefit was modest, it could be meaningful given initiation rates were high before the intervention – >80% in most control sites – making large differences unlikely. This is evidenced by the greater FTIC benefit in Gauteng (roughly 11 percentage‐points), where initiation without intervention was only about 70%. However, as this was not a pre‐specified comparison Short‐term initiation increases did not lead to improved viral suppression or retention. We saw no difference in suppression between arms and possibly reduced 12‐month attrition though our findings were imprecise. There has been concern that if patients initiate treatment quickly (or early) attrition post initiation may increase Our study adds to the evidence supporting rapid ART initiation Our evaluation suggested that FTIC benefits patients and providers by requiring fewer clinic visits before initiation. There was also a perceived increase in participation and decision‐making by patients who reported feeling better supported in their HIV care and being more satisfied with care. These benefits resonate with NDOH’s aims of efficiency gains in the ART programme, reducing unnecessary clinic visits and pre‐ART tracing, and delivery of more patient‐oriented care models. Even at intervention sites, feedback on the quality of care was not always positive and both patients and providers recommended improvements so that initiation could happen on the day of first counselling. Quality of follow‐up sessions was also seen as key to influencing long‐term adherence. Unfortunately, poor recording of counselling sessions meant we were unable to determine the quality of those sessions and survey outcomes suggest many patients may not have received sessions addressing issues of mobility and viral load. Fidelity to the intervention and recording delivery of sessions may be key to improving outcomes, otherwise FTIC differs little from pre‐ART counselling previously implemented. That said, the 6% ART initiation increase associated with FTIC comes on top of gains likely already made by accelerating treatment for the sickest patients. FTIC may increase clinic capacity to initiate the hundreds of thousands of new patients newly eligible for ART under “treat all,” many of whom will have relatively high CD4 counts and understanding the cost‐benefit of FTIC in light of this, is warranted.Our study has numerous strengths, including a cluster‐randomized evaluation of an NDOH programmatic rollout and a difference‐in‐differences approach to account for baseline differences. It also has some important limitations. First, we used routinely collected data by design, as any attempt to collect data directly from patients could influence ART initiation. While we tried to improve routine data collection at study sites, we had some missing data and likely some misclassification. Second, because this was not an individually randomized trial, we were subject to potential baseline differences between arms. While our covariate and difference‐in‐differences adjustment attempted to mitigate this, some residual confounding may remain. Third, we did not control implementation of the intervention, which was conducted entirely by the NDOH and study clinics. We could therefore not identify which controls were likely to have been given the intervention beyond applying the eligibility criteria, nor were we able to control fidelity to implementing the intervention, determine why some eligible patients did not receive the intervention or how many counselling sessions intervention patients received. If the intervention was targeted towards those deemed more (or less) likely to succeed, some bias may have occurred. In addition, we defined retention as remaining in care at the original facility, but many patients move to new sites and are still retained 5We found that Fast‐Track Treatment Initiation Counselling was a viable approach to improving ART uptake with no reductions in, but also no evidence of a benefit in suppression or retention. As roll out of the Adherence Guidelines continues it will be important to strengthen post‐initiation counselling, to monitor fidelity to implementation, and to pair FTIC in newly initiated patients with interventions designed to improve retention and adherence so that any short‐term gains turn into long‐term benefits to both patients and clinics.The authors declare that they have no competing interests.NF, SP, MP, MG, SR and MPF all contributed to developing the protocol. ANH, JM, DW and YP all contributed substantive changes to the protocol. MPF drafted the manuscript. All authors were involved in editing the final manuscript.This work was supported by World Bank Trust funds from several governments and Government of South Africa domestic health financing.Figure S1. Kaplan‐Meier curve showing days to ART initiation for all those patients eligible for Fast Track Treatment Initiation Counselling in the enrolled cohort.Table S1. ART initiation within 30 days for all those who would have been eligible for Fast Track Treatment Initiation Counselling cohort in the period prior to the rollout of the interventions (1 January 2015 through 31 December 2015) (pre‐period)Table S2. Regression coefficients for final model for difference‐in‐differences analysis of ART initiation within 30 days adjusted for site level clusteringTable S3. ART initiation within 30 days for those eligible for Fast Track Treatment Initiation Counselling cohort during the intervention periodTable S4. 6‐month viral suppression (defined as two to nine months) for those eligible for Fast Track Initiation Counselling in the enrolled cohortTable S5. 18‐month viral suppression (defined as two to eighteen months) for all those who would have been eligible for Fast Track Initiation Counselling cohort in the period prior to the rollout of the interventions (1 January 2015 through 31 December 2015) (pre‐period)Table S6. Regression coefficients for final model for difference‐in‐differences analysis of within 18‐month viral suppression (defined as two to eighteen months) adjusted for site level clusteringTable S7. Retention  at six months for those eligible for Fast Track Initiation Counselling in the enrolled cohortTable S8. Long‐term retention outcome  for all those who would have been eligible for Fast Track Initiation Counselling cohort in the period prior to the rollout of the interventions (1 January 2015 through 31 December 2015) (pre‐period)Table S9. Regression coefficients for final model for difference‐in‐differences analysis of retention  at 12 months adjusted for site level clusteringClick here for additional data file.