Dolutegravir (DTG) has shown effectiveness in combination with rilpivirine in with experience of antiretroviral therapy (ART) and with 3TC in naïve patients . The main objectives of this real-life study were to analyze the effectiveness and safety of 3TC plus DTG in virologically suppressed HIV-1 patients and to conduct a pharmacoeconomic analysis.We conducted an observational, retrospective and multicenter study of HIV+ patients pretreated for at least 6 months with ART that was then simplified to 3TC + DTG for any reason. We gathered data on viral loads (VLs) during exposure to the DT, calculating the rate with VL < 50 copies/mL at week 48, and on associated adverse effects.The 177 HIV+ patients were collected, 77.4% male, with average age of 48.5 years and mean count of 252.2cell/μL CD4+ nadir lymphocytes; 96.6% had VL < 50 copies/mL and 674 cells/μL CD4+ lymphocytes. Median time since HIV diagnosis was 15 years, and median ART duration was 13 years, and 34.5% of patients were on mono- or dual-therapy before the switch. At week 48, 82.4% of patients had VL < 50 cop/μL using an intention-to-treat (ITT) analysis, 89.6% according to mITT, and 96.7% according to Per-Protocol analysis. 3.3% patients had virological failure (VF). These effectiveness data and costs were compared with those for 2 reference triple therapies (DTG/ABC/3TC and EVG/cobi/FTC/TAF) in a cost minimization analysis, showing cost savings with administration of DTG+3TC (2741 €/year vs DTG/ABC/3TC and 4164 €/year vs EVG/cobi/FTC/TAF) and in a cost-effectiveness analysis, finding the DT to be the most cost-effective approach The combination of 3TC with DTG appears to be a safe and effective option for the simplification of ART in pretreated and virologically stable HIV-positive patients, being cost-effective and offering the same effectiveness as the triple therapy it replaces. Given the need to maintain ART for life to prevent disease progression and reduce the risk of morbidity and mortality, researchers have studied simplification options with new ARVs to minimize the toxicity and support the sustained administration and effectiveness of the treatment.The life expectancy of HIV positive patients is currently very similar to that of the general population.–7 as well as with raltegravir and dolutegravir (DTG), proving effective in >95% of patients, although sample sizes have been small. Recently, 2 clinical trials of DT with DTG plus rilpivirine (SWORD 1 and 2) demonstrated a similar effectiveness to that of triple therapy with no increase in the risk of resistance and an improvement in bone and renal parameters. The combination of DTG with 3TC also yielded excellent results in naïve patients in the PADDLE and GEMINI trials.Simplification strategies include dual therapies (DTs) with lamivudine (3TC), which have demonstrated their effectiveness in clinical trials in combination with bPI The objective of this study was to analyze the effectiveness and safety of 3TC (300 mg/QD) plus DTG (50 mg/QD) at week 48 in a large sample of real-life in virologically suppressed HIV-1 patients and to conduct a pharmacoeconomic study of this combination. Secondary objectives were to establish:(1)the frequency of adverse events;(2)the impact of the DT on lymphocyte subpopulations and biochemical parameters; and(3)the influence of the 184 V mutation on the effectiveness of the DT.22.1We conducted a multicenter, observational, and retrospective study of HIV patients pretreated for at least 6 months with virological suppression and no history of virological failure (VF) or presence of genotypic mutations that might compromise the effectiveness of either drug under study. DT was prescribed by attending physicians after obtaining the informed consent of the patients. The study included patients under outpatient treatment from seven Departments of Infectious Diseases in the regional health service who had initiated treatment with DTG (50 mg/QD) plus 3TC (300/QD) for any reason before 30 June 2017. The study was approved by the ethics committee of the hospital and registered with the Spanish Medicines Agency. The data were treated in compliance with Spanish legislation on personal data protection .2.2This was an observational retrospective study on prescriptions of approved drugs for the routine treatment of these patients and involved no direct pharmacological intervention2.3Presence of HIV infection, age ≥18 years, receipt of suppressor ART, and plasma VL < 50 copies/mL and ≤1 blip for at least 6 months before study enrolment.2.4The presence of active AIDS during the study period; co-infection with hepatitis B virus (HBV) treated with tenofovir (infection with HBV under effective treatment with 3TC and entecavir was not an exclusion criterion), pregnancy, previous presence of HIV genotyped with 3TC or DTG resistance mutations, and a history of adverse reactions to either drug.2.5Patients were followed for 48 weeks. At the baseline visit (V0), data were gathered on age, sex, active co-infections, toxic habits , risky practices, height, weight, bone, and/or renal toxicity from previous ART , date of HIV diagnosis, VL and CD4 and CD8 lymphocyte counts at diagnosis, CD4 nadir, previous ART lines, reason for change to DT , and analytical data in the 3 months before the change to DT. Data were also gathered at V0 and at the end of the follow-up on: VL, CD4 and CD8 lymphocyte counts and percentages, CD4/CD8 ratio, total cholesterol, HDL, LDL, and triglycerides; and GOT, GPT, GGT, bilirubin, alkaline phosphatase, and glomerular filtration (CKD-EPI).Clinical and analytical data and any adverse effects were recorded in follow-up visits at 6 ± 2 weeks (V1), 24 ± 8 weeks (V2) and 48 ± 8 weeks (V3) after the change. modified intention-to treat (mITT)  and per-protocol (PP) analyses. The following patients were excluded from mITT analysis: those with a life expectancy of <1 year, those asking to return to the previous ART in STR solely because they preferred a single pill, and those for whom the DT was started but then changed because they were prescribed with a drug incompatible with DTG plus 3TC.The effectiveness of this DT (DTG + 3TC) was determined by calculating the proportion of participants achieving viral suppression (defined as plasma HIV RNA < 50 cop/mL) at week 48 according to intention-to treat (ITT),A blip was defined by VL > 50 HIV-RNA copies/μL at 1 determination and VL < 50 HIV-RNA copies at the nextVF was defined by VL > 50 HIV-RNA copies/μL at 2 consecutive determinations.2.6A sample size of at least 151 patients was estimated to achieve an accuracy of 5% in the estimation of a proportion by means of a normal 95% CI, assuming that the proportion was 91% (effectiveness reported in the previous study) and assuming possible losses of 20%.2.7t test for independent variables or, for variables found to be non-normally distributed, the Mann–Whitney U test. Absolute and relative frequencies were calculated for qualitative variables followed by application of Pearson chi-square test or, when conditions were not met, Fisher chi-square test. The Kolmogorov–Smirnov test was applied to check the normality of variable distributions. SPSS 20.0 was used for statistical analyses.Means and standard deviations were calculated for quantitative variables, followed by the application of Student 2.8 and for EVG/cobi/FTC/TAF from the STUDY 109 trial, which are both clinical trials in patients with a history of ART, since it would not be methodologically correct to carry out this analysis using data from trials conducted under different conditions.In the pharmacoeconomic analysis, the DTG + 3TC regimen was compared with DTG/ABC/3TC and EVG/cobi/FTC/TAF as widely used reference treatments. Effectiveness data based on an intention-to-treat (ITT) analysis were obtained for DTG + 3TC from the present study, for DTG/ABC/3TC from the STRIIVING trial,We calculated the annual costs of each strategy according to the list of retail laboratory prices consulted in September 2018, without adding 4% VAT or subtracting the 7.5% discount agreed with the government to reduce the public deficit. It is usual in this type of research to study the gross price of the drug without considering value-added tax or administration discounts in order to facilitate comparisons of the price per unit of effectiveness among different countries. No account was taken of the costs of managing possible adverse effects, changing strategies or conducting resistance studies.We conducted a cost-minimization analysis to estimate the saving that would result from the adoption of DT with DTG+3TC instead of the triple therapies. We also carried out a cost-effectiveness ratio analysis, dividing the cost of each treatment by its effectiveness for virological suppression. The incremental cost-effectiveness ratio was determined by dividing the cost differences by the effectiveness increase.33.1The study included 177 HIV+ patients, 77.4% males, mean age of 48.5 years, mean CD4+ lymphocyte nadir of 252.2 cells/μL, diagnosis of HIV for a median of 15 years (IQR: 7–22), median of 13 years under ART (IQR: 4–18) and median of 5 previous treatment lines (IQR: 2–8); 96.6% had baseline VL of < 50 copies/mL and mean CD4 lymphocyte count of 697.7cells/μL; 38.9% had previously received INI. Results for the remaining study variables are exhibited in Table The main reasons for changing to DT with DTG and 3TC were toxicity of the previous regimen 41.8%), simplification/optimization (38.4%) and avoidance of drug interactions (19.7%)  analysis, 89.6% using mITT analysis and 83.6% using ITT analysis. Among the 151 patients in the final study sample, 5 (3.3%) had VF .Two of the 5 patients with VF underwent a genotypic resistance test, showing no amplification in one and detecting K103R and S147G mutations in the other (previously exposed to ABC/3TC + RAL); neither mutation reduces susceptibility or produces resistance to INI. The three remaining patients did not undergo a resistance study Table .P = .129).Among the 178 patients, 90 (50.5%) had undergone a baseline genotypic resistance test. Among the four patients (4.4%) with 184 V mutation, VF was recorded in 1 (25%) but not in the other 3 (3.3P = .023) increase in the CD4/CD8 ratio, significant reductions of 8 mg/dL in total cholesterol (P = .002), 25 mg/dL in HDL (P = .002), and 48 mg/dL in triglycerides (P = .0001), and a significant increase of 14 mg/dL in LDL (P = .003) and in the total cholesterol/HDL ratio (P = .0018) (Table The change to DT resulted in a significant P = .02 increase3.4The adverse effects leading to the discontinuation of DTG + 3TC treatment in 6 patients were: grade 2 diarrhea in week 2 (n = 1); insomnia and anxiety in week 4 (n = 2); asthenia in week 11 (n = 1); insomnia in week 13 (n = 1); and hypercholesterolemia in week 18 (n = 1).3.5The annual cost of treatment was estimated to be 7759 € for DTG + 3TC, compared with 10,500 € for DTG/ABC/3TC and 11,923 € for EVG/cobi/FTC/TAF. Change to this DT would therefore generate an annual saving of 2741 € (26%) vs DTG/ABC/3TC and 4164 € (35%) vs EVG/cobi/FTC/TAF. Virological effectiveness rates were 90, 83, and 97% for DTG + 3TC, DTG/ABC/3TC and EVG/cobi/FTC/TAF, respectively  and even with previous experience of INIs. Among the patients who completed the follow-up at week 48, DT achieved an undetectability rate close to 100%. Similar results have been reported for DT with DTG plus 3TC. Thus, the LAMIDOL study found that 97.1% of 110 patients with previous ART had undetectable VL at week 48 of treatment, There were 5 cases of VF in our study population (3.3%), and resistance analysis in one of these patients showed no resistance mutations to either ARV. Four of the five patients achieved virological suppression after the association of a third ARV, whereas VF persisted in the remaining patient despite triple therapy, attributed to poor adherence to the treatment. Likewise, another retrospective study found that the presence of the 184 V resistance mutation alone was not a predictor of VF, although they observed that peak HIV-RNA > 5,000,000 copies/mL independently predicted VF after adjusting for the presence of the M184 V resistance mutation and duration of virological suppression. In addition, a recent clinical trial of 91 pretreated patients randomized into 3 branches , and DTG in monotherapy) reported that 1 mutation-free VF developed in the DT branch. However, no case of VF was observed in a trial of 203 pretreated HIV-positive patients who received DTG+3TC, with a follow-up of 295 patient/years. Finally, the ASPIRE trial found DTG + 3TC and triple therapy to be equally effective in pretreated patients at weeks 24 and 48.In the present investigation, the presence of the 184 V mutation did not compromise the virological effectiveness of the DT, as also reported by the DOLULAM study.+ cell count and decrease in CD8+ cell count. These data suggest that an increasing CD4:CD8 ratio alongside undetectable HIV VL could be markers of effective ARV treatment with DT and a good prognosis.The CD4/CD8 ratio was improved by this DT. It naturally decreases with age, is associated with increased mortality, and is a marker of both acute and chronic inflammation; after the initiation of ART, there is an increase in CD4There were changes in the lipid profile, with an increase in CT/HDL ratio regardless of previous treatment with tenofovir or abacavir. Therefore, this DT seems to have a more atherogenic profile in comparison with previous ART.There was a small increase in creatinine levels. DTG inhibits organic cation transporter 2 on the basolateral side of proximal tubule cells of the kidney and leads to increased serum creatinine levels but no true impairment of renal function.The tolerance was good, with only 3.4% discontinuing the DT regimen due to an adverse effect (insomnia in 1.7% of patients), always during the first 3 months of treatment. Very similar findings were recently described for raltegravir and DTG in a triple-therapy regimen, with 3.6% discontinuing DTG for toxic effects, which were neurological in 1.7% of the patients and associated with the female sex; they also reported a VF rate of 0.1%.,30 Although the results do not rule out DTG/ABC/3TC or EVG/cobi/FTC/TAF as cost-effective options, especially in patients who are not good candidates for DT, the combination of DTG and 3TC proved to be a more cost-effective approach, reducing the costs by patient/yrs.Our comparative cost-effectiveness study was based on the present data and the available scientific evidence in pretreated HIV infected patients. Our results are similar to those of other studies on DT with DTG plus 3TC in pretreated HIV infected patients.Limitations of our study include its retrospective, open-label and non-randomized design. The restrictive exclusion criteria also limited information on the effectiveness and safety of DT in the excluded population. In addition, genotypic resistance testing was performed in only 2 of the 5 patients who developed VF, preventing conclusions being drawn on the reason for the failure of this DT. One of the main strengths of this multicenter investigation is the large sample size of patients in a real-life clinical setting rather than a clinical trialIn conclusion, these results suggest that the combination of 3TC and DTG is a novel, effective, safe and cost-effective option for ART simplification in virologically stable pre-treated patients without 3TC or DTG resistance mutations, even in those with previous experience of INIs. It appears to be no less effective than the triple therapy it replaces.Conceptualization: Carmen Hidalgo Tenorio, Jesús Santos, Coral García, Juan Pasquau.Data curation: Alicia Gutiérrez, Jesús Santos, Mohamed Omar, Carmen Galvez, Sergio Sequera, Samantha Eisabeth De Jesus, Franciso Tellez, Elisa Fernandez, Coral García, Juan Pasquau.Formal analysis: Carmen Hidalgo Tenorio, Sergio Sequera, Samantha Eisabeth De Jesus, Juan Pasquau.Investigation: Carmen Hidalgo Tenorio, Samantha Eisabeth De Jesus, Coral García, Juan Pasquau.Methodology: Carmen Hidalgo Tenorio, Samantha Eisabeth De Jesus, Coral García, Juan Pasquau.Project administration: Carmen Hidalgo Tenorio, Samantha Eisabeth De Jesus, Coral García.Resources: Mohamed Omar, Carmen Galvez, Coral García.Software: Alicia Gutiérrez, Jesús Santos, Mohamed Omar, Carmen Galvez, Sergio Sequera, Samantha Eisabeth De Jesus, Franciso Tellez, Elisa Fernandez, Coral García.Supervision: Luis López Cortés, Carmen Galvez, Sergio Sequera, Elisa Fernandez, Juan Pasquau.Validation: Luis López Cortés, Carmen Galvez, Sergio Sequera, Franciso Tellez, Coral García, Juan Pasquau.Visualization: Jesús Santos, Carmen Galvez, Sergio Sequera, Juan Pasquau.Writing – original draft: Carmen Hidalgo Tenorio.Writing – review & editing: Sergio Sequera, Juan Pasquau.


Adolescent HIV patients face enormous difficulty in accessing HIV care services. Given their vulnerability to risk-taking behaviour, this group also have worse treatment outcomes compared to other age groups. Poor treatment outcomes will impact negatively on HIV/AIDS management and control particularly in sub-Saharan Africa (SSA) as more than eight out of ten of the world’s HIV-infected adolescents live in this region of the world. Limited evidence exists on the effectiveness of service delivery interventions to support adolescents’ retention on antiretroviral therapy (ART) and adherence to ART. This trial is designed to evaluate the impact of conditional economic incentive and motivational interviewing on adolescents’ retention in HIV care and adherence to ART in Anambra State, Southeast Nigeria.The study will be a cluster randomised controlled trial that will be conducted in selected HIV treatment hospitals in Anambra State, Nigeria. Based on sample size calculation, 12 HIV treatment hospitals from Anambra will be selected for the study. Six HIV treatment hospitals each will be randomised to either the intervention or the control arm. A structured adherence support scheme termed the ‘Incentive Scheme’ will be applied to the intervention arm while the control arm will receive routine HIV care . Additionally, patients in the intervention arm will receive motivational interviewing at baseline and following initiation of antiretroviral therapy (ART), they will receive a gift voucher of US$5.6 when HIV viral load (VL) is < 20 copies/mL at 12 weeks, a gift voucher of US$2.8 if the VL remains suppressed for the next 3 months, and the next 6 months, and finally a gift voucher of US$5.6 if the VL remains < 20 copies/mL at 1 year. All gift vouchers will be conditional not only on VL results but attending the motivational interviews. The primary outcome for the trial will be the difference between groups in the proportion with HIV VL suppression (≤ 20 copies/mL) by 12 months and then 24 months after withdrawal of incentive.The findings of this proposed trial will provide evidence on the feasibility of applying conditional economic incentives combined with motivational interviewing to improve retention and adherence to antiretroviral therapy of adolescents living with HIV in Nigeria and possibly in other sub-Saharan African countries.PACTR201806003040425. Registered on 2 February 2018.Registered in the Pan African Clinical Trials Registry, ID: The online version of this article (10.1186/s13063-018-3095-4) contains supplementary material, which is available to authorized users. Adolescent HIV patients face enormous difficulty in accessing HIV care services and they have worse treatment outcomes compared to other age groups . Few stuPoor adherence in adolescents may be connected to the unique psychological, social and health needs that are particular to the adolescent stage. Adolescence is sometimes accompanied by a desire for self-discovery, an emerging sense of autonomy, separation from caregivers and the assertion of independence, the quest for recognition and acceptance, all of which could lead to risk-taking behaviour , 7. EvolThere is limited evidence on the effectiveness of service delivery interventions to support adolescents’ linkage from HIV diagnosis to ART initiation, retention on ART and adherence to ART. A systematic review by Kim et al. identified a small number of studies that assessed the effectiveness of interventions to support adolescents’ linkage from HIV diagnosis to ART initiation, retention on ART and adherence to ART . The sysThere is a theoretical foundation potentially underlying conditional economic incentives (CEI) for HIV treatment adherence. Micro- and behavioural-economic framework suggest that non-adherence is attributed to the perception of reduced utility due to out-of-pocket costs, side effects, perceived risks, delayed benefits, or other idiosyncratic reason . CEI, thIn Nigeria, the conditional economic incentive has been applied in the Subsidy Reinvestment and Empowerment Programme (SURE-P) Maternal and Child Health (MCH) programme with the aim to increase demand and access to maternal and neonatal health services. In the programme, conditional cash transfer was used to encourage pregnant women from poor households to seek maternal and child health in public hospitals. Conditional cash transfer in a MCH context showed the capacity of having a significant effect on service uptake although the authors concluded that there is a need to track beneficiaries throughout the continuum of care .If appropriately implemented, CEI could help improve patients’ adherence to HIV treatment in the short-term, while the incentives are in place. However, this does not necessarily create a lasting effect after the incentives are removed . Social Motivational interviewing is a counselling method informed by self-determination theory and represents a general and practical approach for changing behaviours by enhancing and facilitating a patient’s own internally motivated change process . MI recoBased on the systematic review by Kim et al. only one study has assessed the impact of financial incentive coupled with MI on treatment adherence of young adults . The stuThe main aim of the present study is to use the rigour of a randomised controlled trial (RCT) to evaluate the impact of financial incentive and MI on adolescents’ linkage, retention and adherence to antiretroviral therapy and HIV care in Anambra State, Nigeria. A cost-effectiveness analysis alongside the cluster randomised trial will be conducted as a secondary aim to assess the cost per additional patient achieving viral suppression through the proposed intervention. In-depth interview (IDI) with all the healthcare providers in the intervention arm will be conducted at the end of the study to assess their perspective on the programme’s feasibility. The main outcome will be measured at the level of an individual adolescent. Cluster randomisation is being chosen for practical reasons and to prevent treatment group contamination.The study will be a cluster randomised controlled trial. Clusters are HIV treatment hospitals in Anambra state. Hospitals (the clusters) will be matched by type of hospital (e.g. secondary or tertiary) and the paired units will be randomly assigned to the intervention or the control arm. The trial has two periods – intervention period and post-intervention period. Each of these periods will run for a 1-year duration. Further details of the trial are shown in Tables Twelve hospitals in Anambra State that offer HIV services will be randomly selected from all the hospitals in the state that provide HIV services. The hospitals included are registered by the National Agency for the Control of AIDS (NACA) to offer HIV services. The hospitals (the clusters) will be matched by type of hospital (e.g. secondary or tertiary) and the paired units will be randomly assigned to intervention or control.Eligibility criteria for participants will include the following: all patients with HIV who had transitioned from pediatric stage to a young person/adult; 10–19 years irrespective of CD4+ cell count; initiated into HIV care and antiretroviral therapy for minimum of 6 months; currently off ART despite multiple attempts to restart; poor medication adherence (< 95% adherence rate assessed through pill count or self-report); willing to restart therapy and sign a written informed consent  combined with attendance for motivational interviewing (MI) with an adherence counsellor trained in MI techniques. Table  14]. Tr. Tr14]. In addition to the usual care, participants in the intervention hospitals will receive MI at baseline and following initiation of ART, they will receive a gift voucher of US$5.6 when VL < 20 copies/mL at 12 weeks, a gift voucher of US$2.8 if the VL remains suppressed for the next 3 months, and the next 6 months, and finally a gift voucher of US$5.6 if the VL remains < 50 copies/mL at 1 year. All incentives will be conditional not only on patients meeting their VL target but attending for MI. Those with VL higher than the thresholds will not receive the incentive. The potential maximum cumulative financial incentive is US$16.8 if viral suppression is sustained for 12 months. The patient will have the liberty to withdraw from the scheme at any time point. Routine hospital data will be collected and outcomes will be assessed by changes in HIV VL and CD4+ count from baseline, at 12 months from enrolment and at 24 months to establish whether any benefit is seen from the intervention could be sustained when financial incentives cease. Each patient in the study will be assigned to a study nurse working in the HIV treatment hospital and they will be tracked with their mobile phone numbers.The primary outcome for the trial will be the difference between groups in the proportion with HIV VL suppression (≤ 20 copies/mL) by 12 months and 24 months. The secondary outcome measure will include the average change in CD4+ count, adherence to ART (measured using pill count) and adherence to an appointment with the hospital for individual participants. Viral load analysis will be done using the COBAS TaqMan 96 and the Amplilink software.g for 25 min prior to the plasma being separated into two aliquots in 2-mL cryovials and stored at − 88 °C in an ultralow freezer until the time of testing.Ten millilitres of whole blood will be collected from each patient into a Vacutainer EDTA-plasma specimen from patients who were confirmed to be HIV-1 seropositive and receiving ART. These EDTA-plasma samples will be submitted to the virology laboratory of Nnamdi Azikiwe University Teaching Hospital for routine HIV-1 VL testing by the CAP/CTM v2.0 . EDTA-blood tubes will be centrifuged at 1450 The VLs of these samples will be measured using the Roche COBAS AmpliPrep/COBAS TaqMan (CAP/CTM) commercial kits according to the manufacturer’s instructions. The plasma HIV-1 ribonucleic acid (RNA) levels will be determined as copies/mL.7 copies/mL. Each run will consist of tested samples and one high-positive control, one low-positive control, and one negative control from the kits. Results will be validated only when the three controls  have passed per run. The CD4+ count analysis will be performed using the CD4+ easy count kit and the Partec CyFlow  in accordance with the manufacturer’s instructions.Viral RNA will be extracted automatically and transferred to the COBAS TaqMan system for amplification and detection. The CAP/CTM v2.0 will be implemented along with the COBAS AmpliPrep automated nucleic acid extractor and TaqMan 96 analyser. The quantification range of the CAP/CTM v2.0 is from 20 copies/mL to 10The sample size was calculated using a web-based sample size calculator of the UCSF Clinical and Translational Science Institute . The samWe will stratify each cluster unit  according to the type of clinic (secondary or tertiary). We will randomly allocate each HIV treatment hospital in each stratum into the intervention arm or the control arm. The randomisation schedule will be done using Research Randomiser, a web-based computer random-number generator . The rant test. A two-sided p value of 0.05 will be used to indicate statistical significance.Statistical analysis will be conducted using IBM SPSS for Windows, Version 20 . As shown in Table Health resource implication and cost-effectiveness of the Incentive Scheme intervention will be assessed. Health resource use will be estimated from the health provider’s perspective, i.e. all cost incurred for providing the Incentive Scheme by a health service provider. Resource use items will include items such as staff time, consumables, cost of financial incentive and equipment. All patient and family resources will be excluded. An activity-based costing method will be used to measure resource use. Data-capture questionnaires will be developed and sent to all the study personnel in the different study sites to record all their activities or resource use. Resource use items will then be multiplied by unit costs to determine a cost item. The entire cost item will be summed up and divided by the number of participants to determine the cost of the incentive scheme intervention per patient. A cost-effectiveness analysis alongside the cluster randomised trial will be conducted to assess the cost per additional patient achieving viral suppression through the proposed intervention. Incremental cost-effectiveness ratio (ICER) of Incentive Scheme over usual care will be calculated to determine the cost-effectiveness of the former.A in-depth interview (IDI) with all the health providers in the intervention arm will be conducted at the end of the study to assess their perspective on the programme’s feasibility. The IDI instrument to be used will be developed using the Pathfinder International Tool Series guideline on conducting IDI . During Eligible adolescents will be recruited by the study personnel in the trial site . Each study participant will be assigned to a study nurse working in the HIV treatment hospital and they will be tracked with their mobile phone numbers.The major risk envisaged in this trial will be exposure of the data of study participants. In order to mitigate this risk, patients’ data will be treated with confidentiality. All personal data collection and processing will be carried out according to European Union (EU) and national legislation. Personal data collected are those necessary to establish the primary and secondary study outcomes. Unique identifiers and a password-protected database will be used to protect the personal information of the study participant. We will keep a written document with detailed information of the origin of all used human samples. All the study partners in the different study sites will receive training on procedures for handling pseudonymised data during study briefing/training. Training will be based on the principle of handling personal data elucidated in the ‘Article 29 Data Protection Working Party’. To ensure the protection of personal data, the principal investigator (PI)  will receive only key-coded data.Clinical failure: this is the presence of new or recurrent clinical event indicating severe immunodeficiency  following 6 months of effective treatment3 or 50% decline from on-therapy CD4+ cell count peak levelImmunological failure: this represents a CD4+ cell count fall to or below pre-treatment baseline value or persistent CD4+ levels below 100 cells/mmVirologic failure: this is the persistently detectable VL exceeding 1000 copies/mL  after at least 6 months of using antiretroviral drugsThere is a chance of anticipatable incidental findings due to the increased number of laboratory testing  and closer monitoring. These anticipatable incidental findings include early detection of the following:Any such anticipatable incidental findings will be disclosed to the participants and their parents/legal guardians (for those less than 18 years). Management of these anticipatable incidental findings will be in accordance to the National Guidelines for HIV Prevention, Treatment and Care. This entails the following: providing adherence support and treating opportunistic infections in any suspected case of treatment failure; reassessing VL and.CD4+ improvement after 3 months; and changing to second-line therapy in case of no improvement (i.e. VL > 1000 copies/mL).Any study-related adverse events (AEs) will be documented and reported to the Steering Committee/Data and Safety Monitoring Board. In the case of a serious adverse event (SAE), it will be reported to the Nnamdi Azikiwe University Ethics Committee within 14 days of the PI becoming aware of the event. SAE is defined as an untoward occurrence that (1) results in death; (2) is life-threatening; (3) requires hospitalisation or prolongation of existing hospitalisation; (4) results in persistent or significant disability or incapacity; (5) consists of a congenital abnormality or birth defect; and (6) is otherwise considered medically significant by the investigator.Conditions in which expedited reporting will not apply include hospitalisation for (1) treatment which was pre-planned, or for a pre-existing condition not associated with any deterioration in condition and (2) treatment on an emergency, outpatient basis for an event not fulfilling any of the definitions of serious as given above and not resulting in hospital admission. Patients will be asked if any adverse events have occurred when they attend for any trial-related visits.The Steering Committee will also serve as the Data and Safety Monitoring Board (DSMB). This committee is composed of two of the authors and three external, independent experts in HIV care, pharmacology and pharmacy . The SteA standard operating procedure defining the responsibilities, processes and deadlines for the monitoring of the ARA trial as well as a monitoring manual will be prepared. This is to ensure uniform monitoring of all the sites in the trial.https://pactr.samrc.ac.za/: PACTR201806003040425).This trial is registered in the WHO International Clinical Trials Registry through the WHO International Registry Network .This is protocol version 1.0 as at 23 August 2018. Recruitment is planned to begin on 1 December 2018 and completed on 28 February 2019.Additional file 1:Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) Checklist. (DOCX 20 kb)Additional file 2:Informed consent form (DOC 53 kb)


HIV prevalence in Mozambique is estimated to be 13.2%. Routine viral load for HIV monitoring was first implemented in the rural area of Tete in 2014. Programmatic data showed an unexpected high proportion of high viral load results, with up to 40% of patients having a viral load above 1000 copies/ml.This qualitative study aimed to explore perceptions about virological failure and viral load monitoring from the perspective of HIV positive patients on first-line antiretroviral therapy (ART) and health-care workers.The study was conducted in seven rural communities in Changara-Marara district, Tete province, Mozambique. A total of 91 participants took part in in-depth interviews (IDIs) and focus group discussions (FGDs), including health-care workers (n = 18), patients on ART in individual care or Community Adherence Groups (CAGs) who experienced virological failure and virological re-suppression (n = 39) and CAG focal points (n = 34). Purposive sampling was used to select participants. Interviews and FGDs were conducted in Nhuengue and Portuguese. IDIs and FGDs were translated and transcribed before being coded and thematically analysed.Emergent themes showed that patients and health-care workers attributed great importance to viral load monitoring. A supressed viral load was viewed by participants as a predictor of good health and good adherence. However, some patients were confused and appeared distressed when confronted with virological failure. Viral load results were often little understood, especially when virological failure was detected despite good adherence. Inadequate explanations of causes of virological failure, delayed follow-up viral load results, repeated blood tests and lack of access to second-line ART resulted in reduced confidence in the effectiveness of ART, challenged the patient-provider relationship and disempowered patients and providers.In this rural context undetectable viral load is recognized as a predictor of good health by people living with HIV and health-care workers. However, a lack of knowledge and health system barriers caused different responses in patients and health-care workers. Adapted counselling strategies, accelerated viral load follow-up and second-line ART initiation in patients with virological failure need to be prioritized. HIV still represents a major public health challenge. Unprecedented efforts, including decentralization of HIV services to primary health care level, have increased access to Antiretroviral Therapy (ART) . Of the The HIV prevalence amongst adults in Mozambique (15–49 years old) is 13.2%  call us to come to the health centre and collect our blood and then they show us [our results]” .few patients referred to viral load testing as a tool to monitor the ‘quantity’ of the virus in their blood:A “I want to know the quantity … When I will know it, then it’s a reason for me to ask you to help me to show me how I can reduce my load.” waking up’:Patients had different perceptions of what virological failure meant. Many of them understood it as a failure related to irregular pill intake, witchcraft or unprotected sexual relationships. Being notified about virological failure can provoke intense sadness and thoughts of despair and death. In one example, the patient talked about how the virus is ‘“If you delay one hour [to take your pill], that hour it [the virus] is awake … It eats you at that very moment.” Patients feel confused when they are diagnosed with virological failure if they report being adherent to their daily treatment.“Sometimes I’m worried, I take the pills but the viral load is increasing, this worries me.” the pills are good or not” . Some reportedly want to stop treatment, as the drugs do not seem to be having an effect:Some patients with virological failure were reported to question whether the drugs are still effective, by asking if ‘“And also it may create a problem, the patient may want to stop his treatment. Some patients even say “if it’s like this, then I prefer to stop.” Most patients reported being shocked or saddened when they were told by health care providers that their results showed virological failure.“I take my pills every day, but then it goes up, goes down; I don’t know what’s going on. It hurts my heart, because even though I do what they [health care providers] tell me, my heart hurts.” “Sometimes I feel worried, I am taking my pills but the viral load is increasing, this worries me, what is happening? I am taking my medicine correctly, and my viral load is increasing.” now it’s going up, thus my life will end soon … I’m saying farewell to you.” Virological failure was also associated with death by some patients. This nurse described how one of her patients believed that virological failure meant that her life was ending: “Another interviewee described how she dreamed of death after she was notified of virological failure:“When I sleep, I end up dreaming of an urn, a coffin next to me. When I wake up I do not see anything, I’m always asking myself why this is happening to me.” Others patients such as the one cited below, believed that virological failure was a result of witchcraft that may affect her pill intake, leading to treatment failure:“They [people in the community] do that work of witchcraft, sorcery… They start putting on you other things and then all gets worse… How they do that exactly, I do not know, but now I do have that thing in my mind that this person can do me harm, and I get scared. Thus it [viral load] gets worse and at the end people start thinking that they are not taking the medicine correctly, and everything becomes complicated.” outside” of their relationship.Explanations of virological failure provided by patients include non-adherence, which in turn is often explained by a lack of regular or timeous pill intake, alcohol use, or being on treatment for an extended period of time. Some associate virological failure with betrayal and a lack of condom use when having sexual relationships ““Virological failure can be related to my boyfriend, because when we don’t have sex, everything goes well, but when we have sex, the viral load goes up immediately.” Patients and health-care workers report that they have heard about people who are not adhering well to treatment and who throw their pills away or store them at home. They report that supplies of ART can be found in the houses of those who become sick and die.“Some even throw away [their pills] in the latrine; sometimes they throw them away in the neighbourhood … Little children play with those medicines. Sometimes they give them to other people and say "I'm not sick, go, you take them.” “There are patients who always come. They do not fail to pick up their medicines, but when they get the drugs, once at home, they do not take them. They keep saving them, they keep saving them. When he dies, we take him [his body] to the funeral, and then we see so many bottles of the medicines [in his house].” Some patients discussed how their viral load remained high despite their efforts to improve adherence, and health-care workers explained that they do not understand why some patients present with virological failure. They described being puzzled that despite apparent good adherence after counselling, some patients still had high viral load results.In such cases, health-care workers suspect the patient was infected with a virus that was already resistant, and they proposed a second-line treatment regimen. When health-care workers introduce second-line ART and the patient has a re-supressed viral load, they conclude the patient was adherent throughout.“There is a family, a mother with her children, they are all on treatment, but they all had a high viral load. They had several counselling sessions. We visited them, to change their behaviour, but she is taking her pills, she is taking them well. She had shifted her line of treatment, the younger son too…and the other daughter too. They are saying that they are taking their pills. Then sometimes we think that these people already at the beginning, they got a resistant virus. Now, [that they are] already on second line, they had an undetectable viral load.” they have their machines over there in Maputo [the capital], they know what to do”. Nevertheless, viral load is perceived as a marker of their own adherence to pill-intake.Patients are informed about the procedures for viral load testing by health-care workers, but viral load is often perceived as something unfamiliar that they do not always have ownership over. In addition, patients do not always fully understand the flow of viral load testing, with one patient referring to the reference laboratory system with the words “They say that we are providing a blood sample that they can send to the white [people] to look for something, for them to do the analysis, to be able to see if it’s going up or not, the viral load.” ““They know where they are sending it, when they have the result they call us, they say yes, you are adherent or not.” Patients did not always fully understand the procedures for viral load testing and did not always feel a sense of ownership over the process:“It is important to do a [test], because as they have machines, they are able to tell if it’s going well like this … But by myself, I don’t know anything.” Patients and health-care workers alike complained about the delay between blood samples being taken and viral load results being ready. Health-care workers discussed how they need the results to decide whether a patient needs to start second line treatment, but also described how the results sometimes arrived when the patient’s condition had worsened, or even when the patient had died.“We could have been in the month of March, and today we are in August and still it did not appear … We then propose second line [treatment]. When the result arrives we have already lost the patient …died …because the viral load result was delayed a lot.” Some health-care workers would like to do a viral load test earlier, when the patient has been on ART for three months, to ensure a follow-up viral load, if needed, and detect failure earlier.“If we did it [viral load testing] a bit earlier, if we could do it at 3 months treatment, just for us to understand how we are doing in terms of patient adherence. After six months we could wait for the second viral load, to see which barriers this patient has, and if they were overcome.” The delay in obtaining viral load results can reduce patient trust in their clinicians. Clinicians, such as the medical officer cited below, described how he apologised for the delays, and the need to negotiate another blood sample.“Sometimes we have cases that we lose because viral load tests are delayed and we were waiting for it … We apologize to our patients [for the delay] until we’re tired and sometimes they treat us like liars: “you always say that the result will arrive soon…” Thus we are compromised …” “we are always here, giving blood, actually, are you selling our blood?” Patients reported frequently having multiple blood samples taken to obtain a single viral load result. In one FGD, a health-care worker described how a patient asked if their blood was being sold To the best of our knowledge, this is the first qualitative study on perceptions of virological failure and viral load monitoring in a rural African setting. Our findings revealed a range of perceptions about the meaning of virological failure, viral load monitoring practices and their effect on treatment adherence and the relationship between provider and patient.Patients gave great importance to having a viral load test and receiving the results. We found that an undetectable viral load was meaningful for patients re-suppressing their viral load. It is synonymous with good health, and enables them to continue with their daily lives and activities. Indeed, perceived treatment efficacy is since long recognized by previous research as an important motivating factor in chronic disease care , 23.On the other hand, many of the patients in the study perceived virological failure as a serious issue that put their general health at risk. Within the informal social networks of PLHIV in the study districts (such as the networks that form within CAGs), many patient stories are shared about non-adherence resulting in illness and then death. Patient stories find their origin in events that are witnessed in the community, and messages shared by counsellors and clinicians.A high viral load result is perceived as a shock, can provoke intense sadness and a feeling of loss, and may lead to feelings of depression or a loss of confidence in their ability to manage their own health. Previous studies have identified depression as a predictor of virological failure . HoweverAs may be expected, we observed that patients used a different kind of language from the health-care workers providing the services when talking about their viral load results and virological failure. Health-care workers used language characterized by biomedical terms, whereas patients seemed to think and talk using symbols, such as the virus ‘waking up’. Likely, messages shared during counselling sessions may be not completely understood by patients. Counselling has been recognized as an important enabler of HIV service utilization  however,Only a few of the patients in our study fully understood the viral load monitoring procedures and that viral load monitoring was a tool that could help them to take control of their HIV infection. Most described blood collection as a practice that must be done, without having a clear idea of how the results can help them to manage better their condition. Patients gave great importance to having a viral load test and receiving their test results. We found that an undetectable viral load had a very positive meaning for patients who had a re-suppressed viral load. We speculate that an undetectable viral load is perceived as a sign of good health, which enables them to continue with their treatment and continue with their daily lives and activities. In addition, patients are less likely to adhere to a drug they perceive as ineffective  22]. Th. Th22]. Moreover, most patients do not understand how the blood sample chain works, as samples are sent by plane to the capital city of Maputo, and results are then sent to individual clinics by email. On the one hand it is a distant intervention that they cannot control, whereas on the other hand the results can have a profound impact upon their life . Some paClinicians may also be concerned or confused when patients have a high viral load result despite apparent good adherence, especially if this was verified through home visits. However, as clinicians become more familiar with the concept of resistance, including acquired and transmitted resistance, they wish to shift patients with virological failure onto second line treatment. However, they are confronted with delays when they request a follow-up viral load, which can put health-care workers in a very difficult position. They are committed to ensuring that patients receive proper clinical care and the appropriate treatment regimen, but are also reliant on the limited resources of the national health system. Given that confidence is essential for an effective patient-provider relationship, ,30 it isThe present study has several limitations. Interviews were not conducted with patients who were considered lost to follow up, although they may have had a different perception of virological failure or viral load monitoring to our study population. Secondly, the themes identified by the present study are dependent to the extent the interviewees disclosed topics they found important or relevant to share. Thirdly, over half of the interviews were conducted in local Nhuengue by a non-Mozambican researcher with the assistance of a Mozambican translator, which may have caused some cultural and language barriers and affected the level of disclosure of the interviewee. Finally, since IDIs and FGDs were conducted in a very rural context, findings may not be generalizable to urban contexts. Despite these limitations, the present study has some important strengths. First, at the end of every interview emerging codes were identified and saturation was discussed. Secondly, formal interim analysis and final analysis was conducted independently by two investigators, who discussed areas of agreement and divergence. Given that qualitative research is not designed to test a hypothesis or determine the frequency of events, the themes that emerged in this study may inform future research. Moreover, additional qualitative studies are needed to explore experiences with adherence strategies in patients with virological failure.Even though our findings are not generalizable to other rural contexts, this qualitative study on the perceptions of virological failure and viral load monitoring in rural Mozambique showed that most patients and health-care workers placed great importance to viral load testing. Structural delays of the actual system in obtaining viral load results also made virological failure difficult for clinicians to manage and in turn made patients and clinicians felt frustrated and disempowered.Counselling strategies should be adapted to the local context, and should include clear messages for different scenarios, including virological failure in patients reporting good adherence. Viral load monitoring should be coupled with a clear plan to start those identified as failing on second-line ART.


The World Health Organization has set an ambitious goal of eliminating viral hepatitis as a major public health threat by 2030. However, in sub-Saharan Africa, antiviral treatment of chronic hepatitis B (CHB) is virtually unavailable. Herein, we present the 1-year results of a pilot CHB treatment program in Ethiopia.At a public hospital in Addis Ababa, CHB patients were treated with tenofovir disoproxil fumarate based on simplified eligibility criteria. Baseline assessment included liver function tests, viral markers, and transient elastography (Fibroscan). Changes in laboratory markers were analyzed using Wilcoxon signed-rank tests. Adherence to therapy was measured by pharmacy refill data.p < 0.001), 172 of 202 (85.1%) patients with available pharmacy refill data had taken ≥ 95% of their tablets, and 161 of 189 (85.2%) patients with viral load results had suppressed viremia. Virologic failure (≥ 69 IU/mL) at 12 months was associated with high baseline HBV viral load  and suboptimal adherence .Out of 1303 patients, 328 (25.2%) fulfilled the treatment criteria and 254 (19.5%) had started tenofovir disoproxil fumarate therapy prior to September 1, 2016. Of the patients who started therapy, 30 (11.8%) died within the first year of follow-up (28 of whom had decompensated cirrhosis), 9 (3.5%) self-stopped treatment, 7 (2.8%) were lost to follow-up, and 4 (1.6%) were transferred out. In patients who completed 12 months of treatment, the median Fibroscan value declined from 12.8 to 10.4 kPa . Registered 16 January 2015. Chronic infection with hepatitis B virus (HBV) is a leading cause of cirrhosis, hepatic decompensation, and hepatocellular carcinoma (HCC). Approximately 257 million people worldwide are living with chronic hepatitis B (CHB), and an estimated 887,000 deaths per year are attributable to HBV infection . DespiteStudies from high-income countries have shown that antiviral treatment of CHB reduces the risk of disease progression . Long-teIn sub-Saharan Africa, treatment for viral hepatitis is rarely available in the public sector. Patients with CHB are left untreated and physicians are left to merely follow the natural course of the disease and provide palliative care. Paradoxically, the recommended first-line drug for CHB, tenofovir disoproxil fumarate (TDF), is registered in most African countries for the treatment of HIV, but not for hepatitis. Therefore, patients mono-infected with HBV cannot access life-saving treatment, whereas those with HIV/HBV co-infection receive free treatment through donor agencies.In 2016, the World Health Organization (WHO) published the Global Health Sector Strategy of Viral Hepatitis  and set Herein, we present results from one of the first and largest public treatment programs for hepatitis B in sub-Saharan Africa. Many of the barriers to treatment in Ethiopia, such as lack of diagnostic facilities, absence of public funding, and restrictions on antiviral drugs, are shared by most low-income countries; therefore, we believe that our findings can be relevant in the global scaling-up of antiviral treatment of CHB.Ethiopia is a low-income country in East Africa with an estimated prevalence of hepatitis B at 7.4% . A pilotAs this was the first public healthcare facility offering CHB treatment in the country, patients were referred from various hospitals, health centers, blood banks, and antenatal clinics for evaluation and treatment. Patients aged 18 years or above with CHB, defined as a persistently positive HBsAg test for more than 6 months, were enrolled in the program. Since previous HBsAg testing was usually performed in other hospitals or private clinics, and often years back, we accepted the patients’ recollection of a previous positive result without demanding a written laboratory report. Patients who were HIV positive at presentation were not included, but rather transferred to the nearest HIV care and treatment center. Likewise, individuals with a known terminal disease such as HCC were referred for further management elsewhere.Point-of-care rapid diagnostic tests: HBsAg, HIV (further tests were not performed in patients found to be HBsAg negative or HIV positive)Routine chemistry: complete blood count, bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinineSerology: HBsAg, hepatitis C virus (HCV) antibody, hepatitis D virus (HDV) antibodyHBV DNA viral loadAt enrollment, all patients were interviewed by a trained nurse in their own language. A full diagnostic work-up was performed, including laboratory tests and transient elastography. The following laboratory tests were performed at the first visit:Patients with signs or symptoms of decompensated liver disease, such as ascites or jaundice, were scheduled to see a physician within 1–2 weeks. These patients would usually receive symptom-directed therapy such as diuretics for ascites/edema; however, within our simplified setup, we did not systematically perform endoscopic treatment of esophageal varices or other more advanced procedures.Patients without signs or symptoms of advanced liver disease were appointed to a physician after 3 months when the viral load result would usually be available. The decision to start therapy was made by a physician using the predefined criteria given below; otherwise, the follow-up was nurse led.Those who started antiviral therapy were followed-up after 2 and 4 weeks, and thereafter 3-monthly. The main focus at each visit was adherence counseling (including pill count) and monitoring for side effects. Untreated individuals were followed-up at 3-month intervals.3-monthly: complete blood count, ALT, AST, 6-monthly: HBsAg, HBV viral loadThe following laboratory tests were performed during follow-up (tests in parenthesis were only performed in patients on treatment):Blood tests were performed using commercially available kits and assays. HBsAg was detected on-site using a WHO-approved rapid diagnostic test . HIV testing was done in accordance with the National algorithm, i.e., using a WHO-approved rapid test kit  for screening, and another rapid test kit  for confirmation. Other routine laboratory investigations for hematology , biochemistry , and serology  were performed locally.Aspartate aminotransferase to platelet ratio index (APRI) and FIB-4 were derived from standard blood test results using the following formulas:HBV viral load testing was unavailable in Ethiopia at the time the program was set up; thus, baseline viral load testing was performed after shipment of samples to the Norwegian Public Health Institute . The Abbott RealTime HBV assay  was used, following the manufacturer’s instructions. From 2016, HBV viral load testing was established at a private laboratory in Addis Ababa using the Abbott RealTime HBV assay and therefore all follow-up samples for HBV viral load monitoring were tested locally.HDV antibodies were detected using an enzyme-linked immunosorbent assay (ELISA) method  from EDTA plasma samples. A second anti-HDV ELISA assay  was used to confirm indeterminate or weak positive results obtained with the Diasorin assay, as suggested by the manufacturer when plasma is used instead of serum. These analyses were performed at the Centre national de référence des hépatites B, C et Delta, Hôpitaux universitaires de Paris-Seine-Saint-Denis, France.Liver fibrosis was assessed using transient elastography . Patients were instructed to fast for at least 2 h prior to the examination, and the procedure was performed by an experienced operator as per the manufacturer’s instructions. The median of 10 readings was employed, and the result was discarded if the interquartile range (IQR) divided by the median exceeded 30%.Based on a previous meta-analysis and a study from West Africa , 12, we Since this program opened prior to the launch of the WHO Hepatitis B Guidelines in 2015 , treatmeDecompensated cirrhosisCompensated cirrhosis (confirmed with ultrasound and/or Fibroscan)Significant fibrosis (Fibroscan > 7.9 kPa) and viral load > 2000 IU/mLModerate/severe liver inflammation (ALT > 80 U/L) and viral load > 2000 IU/mLHCC among first-degree relatives and viral load > 2000 IU/mLThus, patients who fulfilled the following criteria were considered eligible for treatment:Patients who met the treatment criteria were given adherence counseling and educated about the disease and the need for life-long follow-up. Preventive measures were recommended, including HBV vaccination to the patients’ partner and children. Based on its potency, safety profile, and high barrier to resistance, TDF  300 mg once daily was used in this program. Treatment for HCV and HDV co-infections were not available through this program.In patients who started antiviral treatment, TDF was initially dispensed for 1 month’s duration, and thereafter at 3-monthly intervals. At each visit to the clinic, the patients were told to bring their old pill boxes so that the remaining pills could be counted. Adherence was calculated by dividing the total amount of tablets dispensed by the total number of days since initiating therapy, expressed as percentage. This method (‘pharmacy refill’ or ‘pill count’) has previously been proven accurate in HIV programs in resource-limited settings .2 tests for categorical and Mann–Whitney U-tests for continuous variables. Changes over time in levels of ALT, viral load, and transient elastography were compared using Wilcoxon signed-rank tests. Intra-individual changes in Fibroscan measurements of more than 20% were considered significant [Baseline characteristics were summarized using descriptive statistics. Groups were compared using χnificant .p value below 0.2 in univariable analyses were included in multivariable logistic regression models, using a forward stepwise method. HBV viral load < 69 IU/mL was considered as viral suppression to allow comparison with previous CHB studies [Logistic regression models were used to study associations between baseline variables and clinically relevant outcomes . Variables with a  studies , and > 1p < 0.05. Results were reported in accordance with the Strengthening the Reporting of Observational studies in Epidemiology (STROBE) statement guidelines [SPSS version 23.0 software  was used to analyze the data. The level of significance was set at idelines .The study was approved by the National Research Ethics Review Committee (Ref. No.: 3.10/829/07) in Ethiopia and by the Regional Committees for Medical and Health Research Ethics (Ref. No.: 2014/1146) in Norway. The study was conducted in accordance with the Declaration of Helsinki. Written informed consent was obtained from all study subjects. p < 0.001) and a lower APRI score  compared to those who started treatment; other distinguishing features could not be identified.Between February 9 and December 14, 2015, a total of 1303 adults with CHB were enrolled in the program. Of these, 328 (25.2%) fulfilled the treatment criteria and 254 (19.5%) started treatment prior to September 1, 2016  were from the capital city, Addis Ababa. The median ALT at baseline was 36 U/L (IQR 24–50), the median viral load was 26,700 IU/mL , and the median Fibroscan value was 15.5 kPa (IQR 9.0–28.9).Among those who started treatment, 197 (77.6%) were men and the median age was 35 years (IQR 27–42). The majority , moderate/severe liver inflammation , HCC in a first-degree relative , or other criteria . The latter groups mainly comprised patients who had initiated treatment through the private sector or ‘black market’, and who could not be assessed using the standard criteria, since most of had suppressed viral load at enrollment.Most patients in this cohort started treatment based on a diagnosis of cirrhosis. A total of 105 (41.3%) patients had clinical ascites or a history of ascites and were classified as decompensated cirrhosis, whereas 81 (31.9%) patients without ascites had a Fibroscan value above 9.9 kPa and were classified as compensated cirrhosis. The remaining started treatment based on significant liver fibrosis  started immediately , mainly due to decompensated cirrhosis, whereas 116 (45.7%) started treatment between 1 and 6 months of enrollment. Only 27 (10.6%) started later than 6 months after enrollment.p = 0.531), age , nor co-infections  predicted subsequent death.Overall, 30 (11.8 %) patients died within the first 12 months after starting antiviral treatment, 28 of whom had decompensated cirrhosis at baseline. Among the decompensated patients, neither sex  1.54, 95% confidence interval (CI) 0.40–5.91, Another 20 (7.9%) patients failed to complete 12 months of TDF therapy; 7 (2.8%) were lost to follow-up, 9 (3.5%) refused to continue treatment for various reasons, and 4 (1.6 %) were transferred out. In the latter group, 3 were diagnosed with HCC and transferred to palliative care, and 1 was diagnosed with HIV on her 3-month follow-up visit and transferred to HIV care. Baseline characteristics of the 3 patients who developed HCC are summarized in Table p = 0.062), and the median Fibroscan value was 12.8 kPa (IQR 8.8–23.6) at baseline and 10.4 kPa (IQR 6.8–17.4) at 12 months (p < 0.001). A total of 140 patients had paired Fibroscan results at baseline and 12 months for comparison; the median intra-individual improvement in liver stiffness at 12 months was 3.4 kPa (IQR 0.4–7.0)  at baseline and 32 U/L (IQR 24–39) at 12 months  experienced HBsAg loss, i.e., they had two consecutively negative HBsAg results; 4 of these developed anti-HBs antibodies. In retrospect, however, 2 cases might have been acute hepatitis B since HBsAg positivity 6 months prior to inclusion could not be documented.Out of 189 patients who had a viral load test performed at 12 months, 161 (85.2%) had suppressed viremia  and only 6 3.2%) had major virologic failure . Genotypic resistance testing was performed in these 6 samples; 3 had wild type virus and 3 failed amplification due to low viral loads. The proportion of patients with suppressed viremia at 6 and 12 months is given in Fig. .2% had mTDF therapy was generally well tolerated and only one individual with underlying comorbidities  discontinued due to progressive worsening of renal function. This patient was under treatment with several drugs, including diuretics and an angiotensin-converting enzyme inhibitor, and the role of TDF in the development of renal failure remains unclear.p = 0.326), age , nor decompensated liver disease  were significantly associated with suboptimal adherence .Pharmacy refill data was available for 202 out of 204 patients who completed 12 months of antiviral treatment. Out of these, 172 (85.1%) individuals had excellent adherence, i.e., they took more than 95% of their tablets; 24 (11.9%) had medium adherence, i.e., they took between 80 and 95% of their tablets; and 6 had poor adherence, i.e., they took less than 80% of their tablets. Neither sex  improved significantly during the initial 12 months of therapy. Reversal of liver fibrosis during antiviral therapy has previously been described by Marcellin et al. , who repThe program loss in the present study was relatively low; overall, 6.3% were lost to follow-up or self-stopped treatment. Although the follow-up time in our study was shorter, this drop-out rate was lower than results from a recent multicenter study in Germany involving 33 sites across the country , where 7Adherence to therapy was high in this cohort; 85.1% of patients took at least 95% of their medication; this is in line with studies from high-income countries. In a study from USA , non-adhIn the present program, treatment decisions were based on viral load testing and liver stiffness measurements. However, in most countries in sub-Saharan Africa, these tests are practically unavailable. Although the WHO recommends the initiation of treatment based on clinical and laboratory markers such as the APRI, experiences from our cohort shows that this marker fails to detect 90% of those in need of treatment . TransieWith regard to viral load measurements, we have previously shown that dried blood spots can be used to reliably quantify HBV DNA , which mOur study had certain limitations. First, although the treatment program was set up at a local public hospital, external financial support was provided to purchase a Fibroscan device and run viral load testing. Nevertheless, the clinic was run exclusively with local staff, most of whom had no previous experience with hepatitis B management, and we believe the setup can be duplicated in other countries in sub-Saharan Africa. Second, since this was the first treatment center for CHB in the country, patients with symptomatic  liver disease were overrepresented. The high early mortality in the program reflects this, and as treatment becomes more accessible mortality can be expected to decline.The current pilot study showed that treatment for CHB can be successful in terms of adherence to therapy and retention in care. Furthermore, there was significant improvement in liver stiffness during the initial 12 months of treatment, with the majority of patients achieving viral suppression. However, initial mortality was high, given that many patients presented with advanced cirrhosis. Therefore, earlier detection of HBV infection and timely initiation of treatment – prior to the development of irreversible complications – is needed to reach the WHO goal of eliminating viral hepatitis as a public health threat by 2030. This pilot program can provide valuable information for other African countries aiming to expand access to antiviral treatment of CHB.


Guidelines for antiretroviral therapy recommend enhanced adherence counselling be provided to individuals with an initial elevated viral load before making a decision whether to switch antiretroviral regimen. We undertook this systematic review to estimate the proportion of patients with an initial elevated viral load who resuppress following enhanced adherence counselling.Two databases and two conference abstract sites were searched from January 2012 to October 2019 for studies reporting the number of patients with an elevated viral load whose viral load was undetectable when subsequently assessed. Data were pooled using random effects meta‐analysis.Fifty‐eight studies reported outcomes of 45,720 viraemic patients, mostly from Africa (48 studies), and among patients on first‐line antiretroviral therapy (43 studies). Almost half  of patients with an initial elevated viral load resuppressed following an enhanced adherence intervention. Of those on first‐line ART with confirmed virological failure , only 53.4% (40.1% to 66.8%) were appropriately switched to a different regimen. Resuppression was higher among studies that provided details of adherence support. The proportion resuppressing was lower among children  and adolescents  compared to adults . No important differences were observed by date of study publication, gender, viral failure threshold, publication status, time between viral loads or treatment regimen. Information on resistance testing among people with an elevated viral load was inconsistently reported.The findings of this review suggest that in settings with limited resources, current guideline recommendations to provide enhanced adherence counselling can result in resuppression of a substantial number of these patients, avoiding unnecessary drug regimen changes. Appropriate action on viral load results is limited across a range of settings, highlighting the importance of viral load cascade analyses to identify gaps and focus quality improvement to ensure that action is taken on the results of viral load testing. Key challenges include ensuring that patients with an elevated viral load receive enhanced adherence counselling and a follow‐up viral load, and those whose viral load remains elevated are switched to a new antiretroviral regimen A review published in 2013 found that the majority of patients (71%) with an elevated viral load were subsequently found to have resuppressed following an adherence intervention. We undertook this systematic review to provide an updated estimate of the proportion of patients who resuppress following an initial elevated viral load.2This study has been designed and reported according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analysis (PRISMA) statement An initial search strategy was developed and refined iteratively by reviewing known missing studies to identify additional terms to include in the final search strategy. Two investigators , independently searched MEDLINE via PubMed and Embase, from 1 January 2012 , extracted data in accordance with a predefined protocol using a pre‐defined extraction form. The following information was extracted: study setting, age, sex, drug regimen, first or second‐line antiretroviral therapy (as defined by the studies) counselling and other support provided, viral load threshold, and number of patients with an elevated viral load who subsequently resuppressed and the number switched to second‐line ART. Indicators of study quality were also extracted according to predefined criteria, and used to assess the certainty of the evidence We calculated proportions and corresponding 95% confidence intervals (95% CIs) for patients resuppressed, and pooled data after transformation through random‐effects meta‐analysis 3Of the 1282 titles screened, 58 studies reporting outcomes of 45,720 viraemic patients met the inclusion criteria and were included in this review  and almost half (28 studies) were available only as conference abstracts. Enhanced adherence counselling was documented for 37 studies, but details of adherence support were provided by only 14 studies. Only 13 studies carried out drug resistance testing on a sample with an elevated viral load. The certainty of the evidence was rated as low. Assessment of methodological quality is summarized in Table Overall, almost half  of patients with an initially elevated viral load had resuppressed when viral load was subsequently measured; resuppression was higher among studies providing details of adherence support  compared to studies where this was not described   Twenty studies reported action taken for patients on first‐line ART in whom virological failure was confirmed (6352 patients); just over half of these patients  were appropriately switched to second‐line ART. Information on resistance testing among people with an elevated viral load was inconsistently reported: only 11 studies reported data on resistance testing, which was only done on a sample of patients; however, as method of selecting patients for resistance testing was unclear, these data were not summarized.Elements of enhanced adherence counselling varied across studies and countries. Patients with initial elevated viral loads were supported through frequent individual counselling sessions, depression and substance use screening, focus group discussions, and the provision of educational materials, cell phone and electronic reminder devices and pillboxes. However, only a minority of studies reported details of enhanced adherence counselling and approaches were too varied to be able to identify which specific approaches led to greater resuppression. Approaches provided and the corresponding proportion of patients who resuppressed are summarized in Table 4This systematic review found that around half of patients with an initial elevated viral load had a suppressed viral load at subsequent measurement. These findings confirm that, in the absence of genotyping, enhanced adherence counselling helps to avoid unnecessary switching of ART in patients whose elevated viral load is due to suboptimal adherence.The proportion of patients whose viral load was resuppressed was higher for those studies in which enhanced adherence counselling was documented. Resuppression following enhanced adherence counselling varied according to type and intensity of adherence support. One study, from eSwathini, found that in logistic regression the odds of resuppression increased when additional enhanced adherence counselling sessions was provided, compared to no intervention Timeliness of EAC varied between studies. In one study from Uganda, in which only 25% of patients resuppressed, over half of patients received their first session more than six months after an elevated viral load was first detected Without drug resistance testing, it is difficult to determine with certainty whether elevated viral loads are the result of poor adherence or drug resistance. Due to high costs and complexity, viral load is used as a proxy indicator of treatment failure; however, it is important to ensure quality enhanced adherence counselling after an initial elevated viral load to more confidently ensure that patients with a second elevated viral load are switched to an alternative regimen on the assumption of acquired drug resistance. In this review, studies that provided details of enhanced adherence counselling tended to have higher rates of resuppression, which possibly reflects greater support provided during enhanced counselling. A study from several countries in West Africa assessed the effectiveness of an intensive adherence counseling intervention in patients with second‐line ART failure. In this study, 67% of patients (130/193) achieved viral resuppression; post study genotype resistance testing on stored samples found that the decision made based on enhanced adherence counseling alone was appropriate in 75% (145) of patients (15). Further studies are needed to help define the components of effective enhanced adherence counselling.This review also found that only around half of patients on first‐line ART with virological failure confirmed by at least two viral load tests were switched to an alternative regimen. Several studies included in this review documented failure to take action at each step in the viral load cascade from initial viral load test, to adherence counselling and repeat testing, and regimen change in the case of persistent high viral load Strengths of this review include a broad search to identify both published studies and conference abstracts, allowing for inclusion of data from over 45,000 patients with an initial elevated viral load. This expands the dataset considerably compared to the previous systematic review; this prior review found a higher proportion of patients resuppressing compared to the current review , but this was based on just five studies contributing 406 patients to the analysis 5In conclusion, the findings of this review suggest that in settings with limited resources and restricted access to drug resistance testing, current guidance to provide enhanced adherence counselling and support to patients presenting with a first elevated viral load can result in resuppression of a substantial number of these patients, avoiding unnecessary drug regimen changes.The recommendation to first provided enhanced adherence support before deciding to switch treatment regimen is all the more relevant in settings adopting dolutegravir as part of first‐line antiretroviral therapy as the likelihood that high viral load is a consequence of suboptimal adherence rather than drug resistance is high, given the low levels of dolutegravir resistance.The authors declare that they have no conflicts of interest to disclose.NF and ZS designed the study, extracted and analysed the data. LV and CO contributed to the interpretation of the data. NF wrote the first draft of the manuscript which was reviewed, improved and approved by all authors prior to publication.This review was supported by funds from the Bill & Melinda Gates Foundation.Table S1. Characteristics of included studiesClick here for additional data file.Table S2. Risk of biasClick here for additional data file.Data S1. Systematic review protocolClick here for additional data file.


Persons with human immunodeficiency virus (HIV) who get and keep a suppressed viral load are unlikely to transmit HIV. Simple, practical interventions to help achieve HIV viral suppression that are easy and inexpensive to administer in clinical settings are needed. We evaluated whether a brief video containing HIV-related health messages targeted to all patients in the waiting room improved treatment initiation, medication adherence, and retention in care.In a quasi-experimental trial all patients  attending two HIV clinics from June 2016 to March 2017 were exposed to a theory-based, 29-minute video depicting persons overcoming barriers to starting treatment, taking medication as prescribed, and keeping medical appointments. New prescriptions at index visit, HIV viral load test results, and dates of return visits were collected through review of medical records for all patients during the 10 months that the video was shown. Those data were compared with the same variables collected for all patients  visiting the clinics during the prior 10 months (August 2015 to May 2016). Among patients exposed to the video, there was an overall 10.4 percentage point increase in patients prescribed treatment . Additionally, there was an overall 6.0 percentage point improvement in viral suppression , however mixed results between sites was observed. There was not a significant change in rates of return visits (77.5% to 78.8%). A study limitation is that, due to the lack of randomization, the findings may be subject to bias and secular trends.Showing a brief treatment-focused video in HIV clinic waiting rooms can be effective at improving treatment initiation and may help patients achieve viral suppression. This feasible, low resource-reliant video intervention may be appropriate for adoption by other clinics treating persons with HIV.http://www.ClinicalTrials.gov (NCT03508310). Early initiation of antiretroviral therapy (ART) for patients infected with the human immunodeficiency virus (HIV) and subsequent lifelong viral suppression have important clinical and prevention benefits. , 2 HIV tCompendium of Evidence-Based Interventions and Best Practices for HIV Prevention has identified 24 interventions with varying levels of efficacy for improving either medication adherence (N = 14) or retention in, linkage to, and re-engagement in HIV care (N = 11) among PWH. [CDC’s ong PWH.  Whether ong PWH. VOICES/VOCES (V/V) and Safe in the City (SITC), were tested in sexually transmitted disease (STD) clinics and found to be cost-beneficial and effective in reducing STD incidence. [V/V and SITC [V/V [SITC [Taking Care of Me (TCOM), an intervention video with supporting posters for use in HIV clinic waiting rooms. This paper describes its impact on treatment initiation, medication adherence, and retention in care.Two widely disseminated video-based interventions, cidence. –14 It isand SITC  would haITC [V/V  and SITC/V [SITC  educatioWe used a commercial institutional review board (IRB) because CDC was not involved in data collection and none of the study sites had an affiliated IRB. On April 6, 2016 the IRB approved the study with a waiver of informed consent since patients and providers would not be actively recruited or surveyed, and only routinely collected data from each clinic’s EMR would be used . The intIRB information:www.wirb.comWestern Institutional Review Board | 1019 39th Avenue SE Suite 120 | Puyallup, WA 98374–2115 Office: (360) 252–2500 | Toll Free: (800) 562–4789 Study number: 1163249Protocol number: 20160574Online tracking: 11–434725http://www.ClinicalTrials.gov (NCT03508310)Trial registration: >55% black or African American (hereafter referred to as black) and/or Hispanic or Latino, and agree not to participate in another behavioral intervention study during our study. Also, the clinic’s population had to include >500 HIV-infected patients. Using these criteria, we selected one HIV clinic in Huntsville, AL, another in Atlanta, GA and an HIV case management center affiliated with an HIV clinic in Miami, FL. All patients visiting the clinics or center during the 20-month study period were included in the study.To be eligible for participation, HIV clinics had to be located in a community with high AIDS prevalence, use an electronic medical record (EMR) system, have a patient population that is TCOM video follows the V/V and SITC model of incorporating key prevention messages into dramatic soap-opera style content involving diverse characters. [TCOM’s conceptual framework incorporates Social Cognitive Theory, Information-Motivation-Behavioral Skills model, and Social Action Theory, which together address cognitive and behavioral factors related to study outcomes. [TCOM video includes three vignettes and a 2-part animation about main characters who model overcoming challenges to optimal HIV care. The video was played on continuous loop in recognition of typically short patient wait times. Waiting room posters used images from TCOM to direct patients’ attention to the video and reinforce prevention messages.The racters.  Multipleutcomes. , 11, 13 TCOM is a variant of videos with demonstrated efficacy in randomized control trials; therefore, we opted for a more resource- and time-efficient method to test our addition to this set of videos. We used a quasi-experimental design, in which the intervention condition  was implemented for 10 months  and the historical comparison condition  was the prior 10-month period . Funding for our study and difficulty in finding eligible HIV clinics precluded use of contemporaneous controls. No patients were recruited and enrolled in the study. Instead, routinely collected data were abstracted electronically from the clinic EMRs for all patients age 18 and older who attended the clinic during the historical comparison period (retrospective data collected June 2016) and during the intervention period (prospective data collected May 2017). Data were de-identified and included dates of index and subsequent outpatient ambulatory medical care (OAMC) visits, sex, gender identity, race, ethnicity, age at index visit, year of HIV diagnosis, date of first ART prescription at the clinic, risks for HIV infection, and HIV viral load laboratory test dates and results.The primary study outcome was ART medication adherence. Adherence was measured by whether viral load suppression (<200 RNA copies/mL) was achieved by 6 months (183 days) after the patient’s index visit; undetectable viral load (<50 RNA copies/mL) also was assessed. Primary outcome data were lab test results in patient EMRs. The secondary study outcomes included treatment initiation and retention in HIV medical care. Treatment initiation was measured by a patient’s receipt of an ART prescription on, before, or within 7 days after, their index visit, as documented by OAMC visits in patient EMRs. Retention in HIV care was measured by an adaptation of the Health Resources and Services Administration’s (HRSA) definition in the Annual Ryan White HIV/AIDS Program Services Report (RSR): “all clients who have had at least 2 or more OAMC visits for any reason at least 90 days apart in the past year divided by all active clients who had had at least one such visit in the past year and are greater than 12 years of age.”  HRSA’s dSimplified sample size calculations were performed for rejecting the null hypothesis of equality in the proportions of successes for the study’s primary outcome, assuming equal numbers of patients in each period. These calculations correspond to an analysis using Fisher’s exact test with a two-sided significance level of α = 0.05. We assumed if the true proportions of successes for the two periods were 70% and 77% , then sample sizes of 650 patients already prescribed ART per period would be required to have 80% power to reject the null hypothesis. Allowing for an annual attrition rate of 25%, sample sizes of 1157 patients per period would be required to have 80% power to reject the null hypothesis.We reviewed EMRs for all patients >17 years of age who had one or more OAMC visits during either the historical comparison or intervention period (100% chart recovery from two sites). Unfortunately, EMR data from the Miami site  were incomplete. Miami uses a different EMR system than Huntsville and Atlanta, and important variables were missing or could not be abstracted. Therefore, data from Miami were excluded from our analyses. We analyzed all patients regardless of their exposure to the intervention video.We computed summary proportions for selected categorical socio-demographic variables  by site for the comparison and intervention groups . We did p-values for Fisher’s exact test. For time-to-event outcomes, we computed Kaplan-Meier proportions at 183 days (6 months) in the comparison and intervention arms, the percentage point change with approximate 95% confidence intervals, and p-values based on the normal approximation.Planned primary analyses included outcomes of ART prescription within 7 days of index visit , follow-We performed planned subgroup analyses to assess whether intervention effects varied by clinic and by selected categorical socio-demographic variables . All analyses were performed using SAS statistical software  and were conducted by one author (CBB). All statistical tests were two-tailed. We did not adjust for the overlap between the comparison and intervention groups, which tends to give conservative significance tests assuming positive correlations between outcomes.There were a total of 4003 patients across both study conditions  , Table 1For HIV treatment initiation we found a significant (p < 0.01) overall increase of 10.4 percentage points between study periods and significant intervention effects at both sites.  SignificDifferences in retention in HIV care, although observed in the anticipated direction for both sites combined (1.4 percentage point increase), were not statistically significant and did not differ substantially by site . RetentiViral suppression was the primary measure of medication adherence. At Huntsville and Atlanta combined, viral suppression improved 6.0 percentage points (p < 0.01) between study periods.  However,Similar findings were observed with respect to the secondary measure of laboratory-confirmed undetectable viral load. At both sites combined, undetectable viral load improved 3.8 percentage points (p = 0.03) between study periods.  The siteTCOM video, we found a significant overall increase in the percentage of treatment initiators among patients who visited the sites while the video played and posters were displayed (intervention condition), compared to patients who visited without the video and posters (comparison condition). The overall positive change in treatment initiation also was observed in sub-group analyses of demographic  and behavioral characteristics . The nature of the study design allows us to draw conclusions about association but not causation. Given that TCOM featured multiple vignettes that modeled PWH of diverse racial/ethnic backgrounds and sexual orientations, it is not surprising that the video showed evidence of changing behavior among a heterogeneous patient population. However, the overall effects for retention in HIV care were statistically non-significant. Medication adherence, measured by viral suppression and undetectable viral load, was significantly greater during the intervention period than the comparison period in Atlanta and both sites combined. Other co-occurring factors may have contributed to observed results, although their potential effect is unclear. For example, the findings from the Strategic Timing of Antiretroviral Therapy (START) study, which showed the benefit of early ART initiation, were published in August 2015. [In our evaluation of the st 2015.  Finally,Unlike Atlanta, Huntsville’s adherence results were negative. The reason is unclear. We were unable to explore influences of socioeconomic status, educational attainment, or health insurance coverage because the study did not collect these EMR data. Stratifying by race/ethnicity, age, HIV risk, and time since HIV diagnosis did not explain the difference between sites. Sub-group analyses of adherence in Huntsville showed negative results across all groups, suggesting systemic  or environmental  factors at work. We contacted the Huntsville clinic to inquire about any such changes between study conditions. The Huntsville clinic confirmed there had been a 23.5% increase in the number of new patients during the intervention period but reported no environmental, political, policy, or other changes in the clinic or Huntsville that could have contributed to the observed intervention effects . It is hSITC [TCOM.The results presented in this paper extend the findings of Warner et al. (2008)  by showiSITC  would beTCOM represents the first stand-alone video-based intervention we are aware of that is effective at improving HIV-related health outcomes for PWH. The relative overall change in treatment initiation  for TCOM is comparable to the level of change in incident STDs  for SITC (10%). [V/V in the first 20 months of its availability [SITC in its first 15 months. [TCOM has the potential to be an important addition to the V/V and SITC set of videos. The time and resources required for rigorous evaluation are barriers to developing and evaluating new videos, and changes in societal norms and advances in HIV prevention and treatment may influence a video’s continued relevance. Given the relative scarcity of public health resources, the trade-offs between faster dissemination and lengthy evaluation should be considered. By forgoing intensive evaluation of videos that follow successful models, new prevention videos could be made available sooner. This could likely have a significant positive impact on the health of PWH, reduce future health care costs, and help achieve national HIV prevention, care, and treatment goals.Video as an intervention tool continues to be prominent in current public health approaches.  TCOM repC (10%).  Althoughlability , and ove months.  TCOM hasTCOM exposure. It is plausible that the observed intervention effects are due partly to the video’s embedded prevention messages and its appeal to a wide patient audience. However, the intervention may have had an indirect effect if clinicians watched the video and learned how to effectively dialogue with patients about the benefits of early treatment. For both measurement levels of medication adherence, males, blacks, and older patients appeared to have benefited from exposure to TCOM. The significant intervention effects for both adherence measures seen among Atlanta, but not Huntsville, patients are difficult to explain. In addition to a possible ceiling effect, it is probable that Huntsville’s simultaneous increases in patient population and treatment initiation temporarily increased clinic-wide viral load levels. Retention in care is a difficult outcome to measure in a standard way. HRSA’s definition needed to be adapted for this study design, and the study’s 10-month intervention period may not have been enough time to see the full effects of the intervention.Our study suggests that there were significant intervention effects among specific sub-groups for treatment initiation and medication adherence outcomes. For treatment initiation, most demographic and behavioral characteristic groups appeared to have benefited from The study had a number of limitations. First, it was not possible to randomly assign patients to one or the other study condition; therefore, the findings may be subjected to bias. Second, the quasi-experimental study design is subject to secular trends . Third, we did not measure exposure to the video, so we do not know whether or not patients paid attention to the video or saw it multiple times. Fourth, Huntsville played the Spanish-captioned video uninterrupted, while Atlanta played the English-captioned video with minor interruptions and some competition from another television. Finally, the sample size was affected by the exclusion of Miami’s data.TCOM into the waiting room environment of two HIV clinics, we were able to evaluate intervention effectiveness in increasing treatment initiation and medication adherence among a relatively large clinic population of PWH. Our evaluation used medical outcomes and routinely collected EMR data rather than behavioral outcomes and self-reported data. Consequently, our overall treatment initiation and medication adherence findings are likely generalizable to other HIV-infected patients at these and other clinics with similar patient characteristics. Similar to our previous work [Our study design also had several strengths, especially with regard to rapid intervention development and evaluation to promote improved HIV outcomes. Similar to our previous video-based intervention studies in STD clinics , 11, 13,TCOM video into standard clinical practice.We found that a brief video-based behavioral intervention in a clinic setting was effective at improving HIV-related outcomes among PWH. Due to its ease of delivery in a waiting room setting and low cost to sustain, it is important for HIV clinics and other healthcare settings serving PWH to consider integrating the S1 Appendix(DOCX)Click here for additional data file.S2 Appendix(PDF)Click here for additional data file.S3 Appendix(PDF)Click here for additional data file.S1 Dataset(ZIP)Click here for additional data file.