Differentiated models of HIV care (DMOC) aim to improve health care efficiency. We describe outcomes of five DMOC in KwaZulu-Natal, South Africa: facility adherence clubs (facility AC) and community adherence clubs (community AC), community antiretroviral treatment (ART) groups (CAG), spaced fast lane appointments (SFLA), and community pick up points (PuP). This retrospective cohort study included 8241 eligible patients enrolled into DMOC between 1/1/2012 and 31/12/2018. We assessed retention in DMOC and on ART, and viral load suppression (<1000 copies/mL). Kaplan-Meier techniques were applied to describe crude retention. Mixed effects parametric survival models with Weibull distribution and clustering on health center and individual levels were used to assess predictors for ART and DMOC attrition, and VL rebound (≥1000 copies/mL). Overall DMOC retention was 85%, 80%, and 76% at 12, 24 and 36 months. ART retention at 12, 24 and 36 months was 96%, 93%, 90%. Overall incidence rate of VL rebound was 1.9 episodes per 100 person-years. VL rebound rate was 4.9 episodes per 100 person-years among those enrolled in 2012–2015, and 0.8 episodes per 100 person-years among those enrolled in 2016–2018 . Prevalence of confirmed virological failure was 0.6% (38/6113). Predictors of attrition from DMOC and from ART were male gender, younger age, shorter duration on ART before enrollment. Low level viremia (>200–399 copies/mL) was associated with higher hazards of VL rebound and attrition from ART. Concurrent implementation of several DMOC in a large ART program is feasible and can achieve sustained retention on ART and VL suppression. During the last decade, several countries in sub-Saharan Africa introduced differentiated models of HIV care (DMOC), to address the needs of patients and reduce unnecessary burdens on the health system . DMOC ofSustainability remains a concern as implementation of DMOC at scale requires financial and human resources in order to ensure continuous clinical monitoring and counseling ,15. PatiBending the Curves” HIV/TB project [Since 2011 Médecins Sans Frontières (MSF) and the Department of Health (DoH) of KwaZulu-Natal have been implementing the community based “ project . The proThe DMOC program was initiated in 2012 with the introduction of counselor–led facility adherence AC and CAG. Adherence clubs (AC) are groups of 20–30 patients who meet every 2–3 months with a lay counselor to receive pre-packed medications, adherence counseling and peer support, either at a health facility (facility AC) or at a patient’s house or public venue (community AC). CAG are peer support groups of 4–6 patients, in which patients self-organize and take turns where one patient picks up medicines for the whole group. In 2014, the National Department of Health (NdoH) of South Africa adopted the Central Chronic Medicines Dispensing and Distribution (CCMDD) program in its National Adherence Guidelines for TB, HIV and NCDs (AGLs)  to improImplementation of DMOC occurred gradually, with facility AC starting in 2012, CAG in 2013, community AC in 2014, SFLA in 2015, and finally PuP in 2016. Rapid scale up of SFLA and PuP started in 2016, as a part of overall CCMDD program roll out in the country Eligibility criteria for DMOC included: age ≥18 years, being on the same ART regimen for at least 12 months, having a viral load (VL) in past 6 months, and two last VL <400 copies/ml, without active tuberculosis (TB), pregnancy, or other conditions requiring regular clinical consultations . PatientThis retrospective cohort study compared outcomes of patients enrolled into each of the five DMOC models  in 10 health centers in the Eshowe and Mbongolwane areas. We included in the analysis patients who were initially enrolled into a DMOC between 1 January 2012 and 31 December 2018. Patients who started DMOC without meeting the eligibility criteria  were excTIER.net, the national electronic register system for HIV and TB programs [Patients were identified and followed using routinely collected data. The main data source was programs .TIER.net, followed by data verification and clean up. TIER.net collects demographic, clinical and outcome data for every patient registered for ART at a health facility. Additionally, TIER.net captures patients’ visit to receive ART, including date, prescribed ART regimen, date of next appointment, and provider of ART. The later field (provider of ART) records SoC or type of DMOC . MSF provided technical assistance to health centers in setting up data capture of DMOC visits into TIER.net (details are outlined in TIER.net does not contain the date of enrollment or the date of exit from DMOC (there are no dedicated fields). However, information on enrollment into or exit from DMOC was routinely recorded in patients’ files and facility based DMOC registers.The dataset for this study was prepared by extracting data from DMOC visits information was assessed for accuracy and completeness to assure key visits such as the first visit (enrolment) and last DMOC visit were captured. For this analysis, the enrollment date into a DMOC was defined as the first documented DMOC visit.TIER.net, d) patients who were listed in a facility-based register as a DMOC participant but not indicated in TIER.net as such.We identified patients whose DMOC information required verification: a) patients who were enrolled in DMOC but were not meeting eligibility criteria; b) patients whose DMOC visits were not updated; c) patients who were recorded in registers as actively in DMOC but whose DMOC visits were not entered in TIER.net data through matching of personal identification information such surname, name, date of birth, and ART file number. Additionally, data was crossed checked manually through review of patients’ files.DMOC visit information was verified using patient files, facility AC and CAG registers, SFLA log books (available at some facilities), and Centralized Chronic Medicine Dispensing and Distribution (CCMDD) registers (both paper-based and electronic since 2019). CCMDD registers document medication distribution at the pick-up points. We verified active CCMDD participants by linking CCMDD electronic data with Baseline characteristics at the time of DMOC initiation included age, last known CD4 count, VL, ART regimen, and time on ART at enrollment. Patients’ age was grouped as 18–29, 30–39, and ≥40 years old. We categorised CD4 count into <200 and ≥200 cells/μL and prior VL into <50, 50 to 199, and 200 to 399 copies/ml. VL ≥50 copies/mL and <400 copies/mL were referred as low-level viremia (LLV).First line ART included regimens consisting of two nucleoside reverse transcriptase inhibitors (NRTI) and a non-nucleoside reverse transcriptase inhibitor (NNRTI) as recommended by national guidelines ,25. In oWe define two implementation periods, 2012–2015 and 2016–2018, to account for major changes in the DMOC program, coinciding with the rapid scale up of SFLA and PuP initiated in 2016.We assessed three outcomes: retention in DMOC, retention on ART and VL suppression.Retention in a DMOC was defined as the time from DMOC enrollment to the composite endpoint of death, loss to follow up (LTFU), or exit from DMOC to return to SoC clinic. In case of return, to SoC, date of return was the date of last DMOC visit. LTFU was defined as > = 90 days since last missed appointment to receive ART medicines; date of LTFU was the date of the last visit with a provider. If a patient changed between DMOC models, the follow up was censored on the date of transfer to the other model. For retention on ART, the outcome was the time from DMOC enrollment to the endpoint of death or LTFU, irrespective of whether the event occurred whilst in DMOC or upon return to SoC. For all analyses, censoring occurred in case of transfer out to other health facilities (non-study), or database closure on 31/12/2019.VL suppression was defined as VL <1000 copies/ml. VL rebound was defined as a VL ≥1000 copies/ml after enrollment into a DMOC (baseline at enrollment was VL <400 copies/ml). Virological failure (VF) was defined as two consecutive VL measurements ≥1000 copies/ml (taken two to twelve months apart). Date of second elevated VL was considered as a date of VF. For VL rebound, patients were followed from the date of DMOC enrollment until the date of VL rebound or censored on the date of last DMOC visit. Patients who had at least one VL test after DMOC enrollment were included into the VL rebound analysis.Patient characteristics were summarized as median and interquartile ranges for continuous variables, and as frequencies and proportions for categorical variables. Characteristics were compared using Chi-square or Fisher’s exact tests for categorical variables, and Kruskal Wallis tests for continuous variables.Kaplan-Meier techniques were applied to describe retention in DMOC and on ART. Log rank test was applied to assess differences in survival distributions among care models. For Kaplan Meier estimates, the follow up was restricted to the initial DMOC .We applied mixed-effects parametric survival models to estimate hazard ratios (HR) for factors associated with attrition from DMOC, attrition from ART, and VL rebound. To account for changes in DMOC types during the follow up, DMOC was modelled as a time varying exposure variable. We fitted models with Weibull, log-normal and loglogistic distributions, and evaluated models using Akaike Information Criterion (AIC) . The modPredictors tested in the models included: year of enrollment into a DMOC model, type of DMOC and personal characteristics at time of DMOC enrollment: age, gender, time on ART, last known CD4 count and VL, and ART regimen.p-value ≤0.05 was considered statistically significant.Data were cleaned, coded and analyzed using STATA version 16 . In all analyses, Ethical approval was received from the University of Cape Town Human Research Ethics Committee (HREC REF 036/2012), the Provincial Health Research Unit of the KwaZulu Natal Department of Health (HRKM104/12), and the Médecins Sans Frontières Ethics Review Board (Reference: ID 1204). As this was a study of routinely collected monitoring data, informed consent from the participants was not obtained. The named ethics committees waived the need for consent.Between 2012 and 2018, 9481 patients were enrolled in DMOC . Betweenp = 0.001). Overall, 2048 (24.8%) were men, with a higher proportion of men in community AC (34.6%), followed by SFLA (29.2%) and PuP . The last known CD4 count prior DMOC enrollment was a median 520 cells/μL (IQR 376–690); the lowest median CD4 count was among community AC patients (median 450 cells/μL), and highest among PuP . Time on ART prior to enrollment was 3.8 years (IQR 2.2–6.2); the time was lower among facility AC (median 3.2 years) and higher among SFLA participants . 415 (5%) were on second line ART at time of DMOC enrollment; the higher proportions of patients on second line were among community AC participants , followed by CAG (8%) and SFLA .Among 8241 included DMOC patients , 2721  returned to SoC, 472 (5.8%) were LTFU, 64 (0.8%) died . 1546/82p = 0.003). Retention among PuP  and SFLA participants  did not differ (p = 0.4) but was lower as compared to facility AC (p = 0.003).Overall DMOC retention was 85%, 80%, and 76% at 12, 24 and 36 months . DMOC rep = 0.01).Overall annual all-cause DMOC attrition rate was 10.6 per 100 person-years during the study period. Attrition rate was 15.9 per 100 person-years in the first year, 6.7 and 4.9 per 100 person-years during the second and third year of follow up, respectively. Annual rate of attrition was 7.5 per 100 person-years among DMOC patients enrolled in 2012–2015, and 11.9 per 100 person-years among those enrolled in 2016–2018 . Patients who were more experienced on ART prior to joining a DMOC were less likely to leave the model . Relative to facility AC, patients in PuP . and CAG  were more likely to leave DMOC. Year of DMOC enrollment was associated with increased hazards of attrition .In the multivariate survival model , factorsp = 0.53). Retention among PuP , community AC  and CAG participants  did not differ (p = 0.4) but was lower as compared to SFLA (p = .006).ART retention at 12, 24 ad 36 months was 96%, 93%, 90% among DMOC patients overall . ART retFactors associated with all-cause attrition from ART (death or LTFU) were : age (186113/8241 (74.2%) DMOC patients had at least one VL in the follow-up period. Elevated VL ≥1000 copies/mL was documented among 4.4% (272/6113) DMOC patients. 244/272 with VL rebound had confirmatory VL test, and VF was confirmed among 15.6% (38/244). Overall prevalence of VF was during the study period was 0.6% (38/6113).Overall incidence rate of VL rebound was 1.9 episodes per 100 person-years; rate was 2.9 per 100 person-years in the first year of follow up, and 1.7 and 0.8 per 100 person-years the second and third year of follow up, respectively. VL rebound rate was 4.9 episodes per 100 person-years among those enrolled in 2012–2015, and 0.8 episodes per 100 person-years among those enrolled in 2016–2018 .Factors associated with VL rebound  were youOur results demonstrate the effectiveness of an HIV service delivery program offering five different DMOC implemented at scale in a large public sector cohort in KwaZulu-Natal, South Africa. In our study, 36-months outcomes among DMOC patients showed sustained retention on ART and VL suppression.High retention on ART and VL suppression among clinically stable patients in our study, irrespective of care model, agree with existing empirical evidence ,18,28–31The cumulative attrition from DMOC was 27%, largely due to return to SoC . The higp = 0.02) and from ART . Although we did not explore reasons for return to SoC clinic in this study, the national guidelines [The findings also highlight challenges with rapid scale up of PuP and SFLA in our study area. Higher attrition from DMOC was observed among those enrolled during 2016–2018 as compared to the earlier period. Compared to facility AC, PuP model was associated with a higher risk of all cause attrition from DMOC , shorter duration on ART prior the enrollment. Young adults were also at increased risk of viral load rebound. These baseline characteristics were found to be significant risk factors for sub-optimal outcomes in other studies ,7,37,38,Our study is among few in the Southern Africa region to provide insights on the importance of LLV and monitoring of patients who are on second line ART in the context of expanding DMOC programs. Low level viremia (>50–399 copies/mL) was associated with increased hazards of VL rebound and attrition from ART, as compared to virological suppression <50 copies/mL. This is in line with findings from a number of settings ,43 incluAdoption of CCMDD into AGL has significantly expanded access to ART and treatment of other chronic conditions in South Africa . In our Roll out of the five DMOC types may have offered many patients some flexibility in choosing a model that better meets their needs. Other studies in South Africa shown that patients were offered an opportunity to choose a preferred DMOC model ,53. DespAt the same time, our study identifies health system limits in adoption of DMOC. Implementation of DMOC types varied across ART centers, with apparent preferences for individual (PuP) and facility-based models  over community-based models . We did not conduct evaluation of how adoption of different models took place in participating clinics. Emerging evidence from other settings suggest that adoption of DMOC models at facility levels was often constrained due to complexities of managing group models , requirement of additional human resources, competing priorities for community workers, gaps in pharmacy chain, and cost and cost-effectiveness considerations ,56.Our study highlights the challenges with differentiating clinically stable patients, and importance of monitoring clinical status over time. Indeed, an estimated 13% of patients enrolled in DMOC in our area were not eligible at the time of enrollment . Clinical stability is a transient concept, depends on defining criteria  , and canTIER.net, and did not account for silent transfers, which may be misclassified as LTFU, leading to underestimates of retention in DMOC and on ART [The strengths of this study are the large sample size and long duration of follow up. Although the findings of this study are encouraging, we conclude with caution due to limitations inherent to the observational study design. In this study, we used the routine data collection system d on ART ,59. NeveIn conclusion, this study adds to the evidence that DMOCs shown sustained retention in care and viral suppression, while decreasing demands on patients and clinical staff at ART clinics. The study also shows that a wide offer of DMOCs can be effectively operated in a public sector setting in South Africa. Further evaluations are necessary to assess cost-effectives of DMOC models in comparison with the standard of care at clinics.S1 File(DOCX)Click here for additional data file.


Introduction: Single-tablet regimens (STRs) can increase treatment success and even improve the quality of life of human immunodeficiency virus (HIV) patients. In this study, we aim to analyze the real-life efficacy and tolerability data of people living with HIV (PLWH) initiated on or switched to bictegravir/emtricitabine/tenofovir alafenamide fumarate (BIC/FTC/TAF) as first-line treatment.Materials and methods: This retrospective analysis was performed in HIV-1-positive patients who were initiated BIC/FTC/TAF in the HIV clinic between June 2020 and June 2022. Patients who received BIC/FTC/TAF for at least 12 months were included in this study. Virological suppression, laboratory parameters, side effects, and immunological response were analyzed at one, three, six, nine, and 12 months.Results: A total of 116 patients, 66 (56.9%) treatment-experienced and 50 (43.1%) naive, were evaluated within the scope of the study. In the naive patient group, baseline HIV-RNA, CD4+ and CD8+ T cell counts, CD4/CD8 ratio, and estimated glomerular filtration rate (eGFR) values were significantly different in different follow-up months. The number of patients with HIV-1 RNA levels below 50 copies/mL was 55.9% in the first month, 73.7% in the third month, 90.2% in the sixth month, and 100% in the ninth and 12th months.Conclusion: In our real-life observational study, BIC/FTC/TAF treatment achieved rapid viral suppression, maintained viral suppression in virally suppressed patients, and was effective for immunological recovery in both treatment-experienced and naive HIV patients. No serious side effects were observed. Our study has proved the potential of BIC/FTC/TAF as an important option in the treatment of HIV patients. According to the Joint United Nations Programme on HIV/AIDS (UNAIDS), 39 million people in the world were living with human immunodeficiency virus (HIV) infection in 2022, and 630 thousand people died of acquired immunodeficiency syndrome (AIDS)-related illnesses. UNAIDS data show that today, 29.8 million of the 39 million people living with HIV (PLWH) globally are receiving life-saving treatment . Today, Combination antiretroviral therapy (cART) for human immunodeficiency virus (HIV) infection provides viral suppression and immunological restoration. Since the number of pills was high in cART regimens, which were first introduced in 1996, side effects and non-adherence to treatment were also high in people living with HIV (PLWH) . ReducinThe co-formulation of efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) was the first daily STR . There aA total of 29,284 adults were reported as being infected with HIV-1, and the proportion of ART patients was 79% by the end of 2020 in Turkey . VirologIn this study, we aim to describe the characteristics of PLWH that were initiated on BIC/FTC/TAF as a first-line treatment or switched to BIC/FTC/TAF from other treatment options at our center in Turkey and analyze real-life efficacy and tolerability data among these patients.PatientsThis retrospective analysis was performed in HIV-1-positive patients who were initiated BIC/FTC/TAF (either as first-line therapy or as a switch from a previous regimen (TAF/FTC/EVG/c or TDF+FTC+DTG) at the HIV clinic in Antalya, Turkey, between June 2020 and June 2022. Patients older than 18 years of age, diagnosed with HIV, and receiving BIC/FTC/TAF for at least 12 months were included in this study. A total of 116 patients were included in the study; 50 patients were naive, and 66 patients had previous treatment experience.Patient records were analyzed retrospectively. For the demographic data of the patients, age, gender, coinfection (hepatitis B and syphilis), comorbidities , baseline HIV-1 RNA, CD4+ T cell count, CD4/CD8 ratio, and regimens used in ART before switching were reported. Other laboratory parameters included baseline estimated glomerular filtration rate (eGFR), serum creatinine, hemoglobin, thrombocyte, glycosylated hemoglobin (HbA1C), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglyceride, and TC/HDL. These parameters were recorded at follow-up visits at one, three, six, nine, and 12 months. Data on previous ART, reasons for switching to BIC/FTC/TAF, discontinuation, and treatment modifications while on BIC/FTC/TAF were collected. Side effects occurring at the start of treatment or during a change of treatment and during the follow-up months were recorded. We also analyzed the virological suppression (HIV-1 RNA ≤ 50 copies/mL) and immunological response (CD4+ T cell count and CD4/CD8 ratio) at one, three, six, nine, and 12 months.Ethical approvalEthics committee approval was obtained at Health Sciences University Antalya Research and Training Hospital in Turkey in accordance with the 2008 Declaration of Helsinki (registration number: 14.10.2021 16/17).Statistical analysisPatient data collected within the scope of the study were analyzed using the IBM Statistical Package for the Social Sciences (SPSS) for Windows version 23.0 . Frequency and percentage are given for categorical data, and median and minimum and maximum descriptive values are reported for continuous data. The Wilcoxon test was used to determine the differences between the baseline measurements of each treatment group and the control measurements. The results were considered statistically significant when the p-value was less than 0.05.A total of 116 patients, 66 (56.9%) treatment-experienced and 50 (43.1%) naive, were evaluated within the scope of the study. The average age of treatment-experienced or naive patients was 34 in both groups. Of the 116 patients, 102 (87.9%) were male. The demographic and clinical findings of the patients are given in Table The distribution of side effects observed in the patients included in the evaluation is given in Table Table The CD4+ T cell count tended to increase in the follow-up months compared to the baseline measurement, and the measurement value at each follow-up was statistically significant compared to the baseline measurement (p<0.05). While the CD8+ T cell count decreased in the follow-up months compared to the baseline measurement, these changes were statistically significant because the measurements in the third and ninth months showed a significant decrease compared to the baseline measurement (p<0.05). Since the CD4/CD8 ratio increased compared to the baseline measurement and the eGFR value decreased compared to the baseline measurement, the measurement in each follow-up month was statistically significant compared to the baseline measurement (p<0.05). During follow-up, no statistically significant change was detected in lipid values compared to baseline.Due to the success of ART in achieving virological suppression, PLWHs are now living longer and developing age-related comorbidities with specific therapeutic and monitoring needs. Success in HIV treatment is possible with drug regimens that could potentially increase patient compliance and have fewer side effects than current drugs. In this regard, BIC/FTC/TAF as a single-tablet regimen, which has been approved by the FDA for patients with low renal and/or bone toxicity, has become a preferred regimen recently in clinical studies due to its high virological suppression rates and low side effect profile ,14. In TDiscontinuation of BIC/FTC/TAF was seen in four PLWHs. Rash and headache were adverse effects that resulted in the switch of the treatment regime. Central nervous system-related adverse effects, most commonly headache, are observed with this type of integrase inhibitor . NonetheThe clinical trials of BIC/FTC/TAF were reported to yield high virological responses. A randomized clinical meta-analysis of antiretroviral-naive and experienced PLWHs showed that BIC/FTC/TAF was effective at week 48 . In anotReal-life studies of the efficacy of BIC/FTC/TAF have generally been conducted in treatment-experienced patients. In a study conducted in patients over 50 years of age with treatment experience, virological success was observed to continue . A studyIn a real-life study from February to October 2021 from Romania, a total of 122 treatment-naive patients who started BIC/FTC/TAF displayed rapid immunological and virological response, with an increase to a median CD4+ T cell count of 320 cells/mm³ and a decrease in HIV viral load to a median of 156 copies/mL over the course of follow-up (the duration follow-up was not uniform) . In anot3, with an increase to over 757 cells/mm3 at 12 months. After INSTI use, the one-year increase in CD+4 T cells should be modified by 200 cells/mm3 or more per year. It is known that the number of CD4+ T cells increases annually by 100-150 cells/mm3 on average [In our study, the median CD4+ T cell count in naive patients was 527 cells/mm average . In a me average .In the BIC/TAF/FTC switch study, the median CD4+ T cell count increased from 568 cells/L at baseline to 610 cells/L after 48 weeks of follow-up. A statistically significant increase in CD4+/CD8+ ratio was also detected, from 0.72 to 0.81 . An obseOther clinical studies reported different results on serum cholesterol and triglyceride of BIC/FTC/TAF. The study by Maggiolo et al. showed significant reductions in total cholesterol and triglycerides among those who switched to B/FTC/TAF at week 48, with no significant change in low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, or total cholesterol/HDL ratio .In a study that analyzed five clinical trials, LDL/TC levels were increased by 2.7%/0.3% in the BIC/FTC/TAF treatment and 5.9%/2% in the comparator regimen . A real-In our study, baseline eGFR was found to be lower in the treatment-experienced patients than in the naive patients. No statistically significant difference was found in eGFR change in the treatment-experienced patients during the 48-week follow-up period. In the treatment-naive patients, baseline eGFR was higher than in the treatment-experienced patients, and it was statistically significantly lower during treatment, except for the third month. In the Bictegravir Single Tablet Regimen (BICSTaR) study, similar to our study, a statistically significant decrease in eGFR was found in treatment-naive patients at 12 months compared to baseline eGFR . In the The limitations of our study are that the analysis was retrospective, confounding factors could not be controlled, and data were obtained from a single center in Turkey, which limits generalizability to other populations.In our real-life observational study, BIC/FTC/TAF treatment achieved rapid viral suppression, maintained viral suppression in virally suppressed patients, and was effective for immunological recovery in both treatment-experienced and naive HIV patients. No serious adverse effects were observed. Our study has proved the potential of BIC/FTC/TAF as an important option in the treatment of HIV patients.


We describe clinical outcomes in a cohort of AHD patients at two regional hospitals in Lesotho. From November 2018–June 2019, we prospectively enrolled eligible patients (≥15 years) not on antiretroviral therapy (ART) presenting with WHO-defined AHD into a differentiated model of care for AHD (including rapid ART initiation) and followed them for six months. All patients received Tuberculosis (TB) symptom screening with further diagnostic testing; serum cryptococcal antigen (CrAg) screening was done for CD4 <100 cells/mm3 or WHO clinical stage 3 or 4. Medical record data were abstracted using visit checklist forms. Categorical and continuous variables were summarized using frequencies, percentages, and means, respectively. Kaplan-Meier was used to estimate survival. Of 537 HIV-positive patients screened, 150 (27.9%) had AHD of which 109 were enrolled. Mean age was 38 years and 62 (56.9%) were men. At initial clinic visit, 8 (7.3%) were already on treatment and 33% (36/109) had presumptive TB per symptom screening. Among 39/109 (40.2%) patients screened for CrAg at initial visit, five (12.8%) were CrAg-positive. Among 109 enrolled, 77 (70.6%) initiated ART at their initial clinic visit, while 32 delayed ART initiation (median delay: 14 days). Of the 109 participants enrolled, 76 (69.7%) completed the 6-month follow-up, 17 (15.6%) were lost to follow-up, 5 (4.6%) transferred to other health facilities and 11 (10.1%) died. The 6-month survival was 87.4%; among 74 patients with a viral load result, 6-month viral suppression  was 85.1%. Our study found that even after the implementation of Test and Treat of ART in 2016 in Lesotho, over 25% of patients screened had AHD. Patients with AHD had a high prevalence of TB and CrAg positivity, underscoring the need to assess for AHD and rapidly initiate ART within a package of AHD care for optimal patient outcomes.For adults and adolescents, the World Health Organization defines advanced HIV disease (AHD) as a CD4 (cluster of differentiation 4) count of <200 cells/mm Achievi disease –9.<100 cells/mm3 , treatment for cryptococcal meningitis (CM) or preemptive fluconazole therapy for those with cryptococcal infection without CM, and intensive follow-up. Despite the strong evidence base for the key interventions included in the WHO recommended package of care for PLHIV with AHD, implementation and coverage of these interventions in many countries remains suboptimal to date [The WHO recommends differentiated HIV care, tailored to the unique needs of different patient populations, that includes a package of care for patients presenting with AHD focused on preventing death and reducing morbidity detailed below ,5–7. The to date .3 at enrollment in care over the years in Lesotho [With an estimated HIV prevalence of 21.1% among adults aged 15–49 years, Lesotho has had the second-highest HIV prevalence in the world for many years [ Lesotho . In alig Lesotho . While tThis study evaluated the clinical outcomes  in a cohort of patients with AHD accessing care in these programs after the above AHD package of care was implemented within routine differentiated care services.We prospectively enrolled a cohort of adult participants with AHD in this project evaluation that started ART from November 2018 to June 2019 and we abstracted data from their medical records; the follow-up period was for 6 months.3 within six months prior to or ordered at project enrollment or WHO clinical stage 3 or 4) and either ART naïve  or with interrupted ART (not on ART and returned to care 7 or more days after a missed appointment).The study was conducted at the ART clinics at the Motebang and Berea government hospitals that are managed by the Leribe and Berea District Health Management Teams (DHMT), respectively. These are the two largest district hospitals in their respective districts serving one-third of Lesotho’s population. Motebang hospital provided services to 5,807 HIV-positive patients and Berea served 4,620 HIV-positive patients. From November 2018 to June 2019, we screened all HIV-positive patients and enrolled adults aged ≥15 years who met the WHO criteria of AHD,  were classified as an “urgent lab result” that required laboratory personnel to take immediate action to notify the clinical team of the results. Once a patient was designated as having AHD, a bright removable sticker was placed on the top of the medical chart and inside the personal medical booklet (bukana), which triggered clinic staff to use the AHD job aids and to place the appropriate job aid checklist in the patient’s chart. Participants with AHD were then given priority for consultation when they presented to the ART clinic.Job aids were developed and introduced to facilitate the delivery of the AHD package of care including an AHD care checklist to be used in the medical charts of all patients identified with AHD. Participants with WHO stage 3 and 4 disease were classified as “critical clinical staging” and participants with CD4 cell counts <200 cells/mmExtensive training of clinical and laboratory personnel on AHD and the AHD care package was undertaken using the new procedures and job aids to ensure all staff understood the need for prompt identification and treatment of patients with AHD. The training included prompt identification and triage of patients presenting with “danger signs” , the importance of referring AHD patients to a higher level of care and ensuring that ART initiation was not delayed while awaiting CD4 cell count results.The advanced HIV disease package of care for Lesotho highlighted the key interventions that were critical for PLHIV with advanced disease and promoted the timely receipt of the key interventions by including a suggested time parameter in accordance with the standard of care as endorsed by the MOH. The package included the following interventions and time parameters:TB screening at all visits followed by prompt initiation of TB treatment for those co- infected with TB within three days of positive TB diagnosis and prompt initiation of Isoniazid Preventive Therapy (IPT) for those screening negative for TB signs and symptoms within three days of negative TB screen;Documented clinical examination to evaluate for signs of any OI at each clinical visit or evidence of IRIS;<100 cells/mm3 or clinical stage 3 or 4 and prompt initiation of pre-emptive fluconazole for asymptomatic patients with a positive screen and without evidence of disseminated disease (on exam or by lumbar puncture (LP) when available);Same-day serum CrAg screening test for all patients enrolling in care with CD4 count Pneumocystis jirovecii pneumonia (PCP), toxoplasmosis, and serious bacterial infections;Same-day initiation of co-trimoxazole (or dapsone) preventive therapy for the prevention of Rapid initiation of ART within a seven-day timeframe from enrollment in care with note of the few caveats when delaying ART initiation is the standard of care/recommended by WHO -TB co-infection, or HIV/CrAg-positive);Intensive follow-up with weekly phone calls for the first four weeks of follow-up and active tracking of missed appointments  with more frequent clinical visits (including a visit at week eight and eighteen) to rescreen for OIs and signs of IRIS);Village health workers and other cadres tasked with tracking ART clients in the community were trained on new intensified follow-up procedures for PLHIV with advanced disease. Clinic staff were also trained to make weekly calls to clients based on a standard script and telephone findings were documented.Facility personnel provided routine care, identified patients with AHD and completed a standardized AHD checklist. Study nurses abstracted relevant clinical and laboratory data from medical records  and data were entered into a Microsoft Access (version 2013) database programmed with logical data validation checks. For patients with danger signs requiring inpatient care, data abstraction was carried out at the time of discharge from the health facility.Quantitative data analysis was performed using STATA version 15.1 . Categorical variables were summarized using frequencies and percentages and continuous variables using means (+/- standard deviation). Descriptive analysis was performed to capture patient outcomes. Kaplan Meier was used to estimate the risk of survival over time. Complete case analysis was performed with no missing data imputed.The study was approved and overseen for human subject protection locally in Lesotho by the Lesotho Ministry of Health research and ethics committee (REC) and in the USA by ADVARRA (formerly known as Chesapeake) institutional review board. We requested and obtained waiver of consent for several reasons, all of which conform with United States (US) Federal regulations OHRP-45CFR46.116, DHHS- 45CFR46.117(c), the local IRB requirements and HIPAA-CFR 164.512(i)(2)(ii).This program evaluation and all the procedures involved with collecting and analyzing routine program data imposed minimal risk to participants because it did not involve direct interaction between the program evaluation staff and HIV care and treatment clients. Routine procedures associated with the implementation of HIV care and treatment guidelines and activities undertaken to strengthen the HIV program did not normally require written consent outside of a research setting. In addition, there was an adequate plan to protect patient identifiers from improper use and disclosure; there was a plan to destroy patient identifiers at the earliest opportunity; and there was written assurances that all health information were protected and were not reused or disclosed to any other person or entity except as required by law. A waiver of consent did adversely affect the rights and welfare of participants because no identifiable information was recorded on CRFs to be entered into the evaluation database or in the evaluation database itself.<100 cells/mm3 and 23/72 (31.9%) had CD4 count result range of 101–199 cells/mm3. At the initial clinic visit, 65/109 (59.6%) screened negative for TB based on symptoms, 36/109 (33%) patients had presumptive TB based on positive TB symptom screening, and 8/109 (7.3%) were already on TB treatment  had a recent CD4 cell count test result within six months prior to enrollment or ordered at screening and 70/150 (46.7%) had a CD4 count result of <200 cells/mm3 . All par<100 cells/mm3 and/or WHO stage 3 or 4 and were eligible for serum CrAg screening. Among eligible participants, 45 (46.4%) were screened for serum CrAg; 39/97 (40.2%) were screened for serum CrAg at initial visit, and 6/97 (6.2%) were screened during follow-up visits. Among the 45 participants who received CrAg screening 8 (17.8%) were screened based on WHO stage 3 or 4 classification alone and 37 (82.2%) were screened based on CD4 count <100 cells/mm3. Among the 39 patients screened at the initial visit, five (12.8%) participants had positive serum CrAg test and had cerebrospinal fluid (CSF) sent for CrAg testing; 4 were confirmed CSF CrAg-positive and diagnosed with CM and initiated on induction treatment with Amphotericin B and fluconazole. The 6 participants screened during follow-up visits were all serum CrAg negative. All but one participant was initiated on cotrimoxazole prophylaxis at their first clinical visit. Overall, 52/97 (53.6%) were not screened for CrAg due to CD4 reagents and CrAg test kit commodity issues.A total of 97 participants had CD4 count Among the 109 participants with AHD, 102/109 (93.6%) were ART-naive and 7 reported prior ART exposure, but had stopped taking ART. More than 70% of participants (77/109) initiated ART within 7 days, either before or at their first study visit. Excluding CM and TB cases, 77/81 (95.1%) initiated ART rapidly. A total of 93% initiated (83/89) on a Tenofovir-Lamivudine-Efavirenz (TLE) regimen. Of 32 participants not initiated on ART at their first visit, 24 participants were on active TB treatment, 4 were diagnosed with CM  and 3 reported other illnesses ; 26/32 (81.2%) were initiated on ART during the study follow-up with a median ART delay of 14 days.This first study on AHD implementation in Lesotho in the Test and Treat era found that more than a quarter of newly diagnosed HIV patients (27.9%) were presenting with AHD. The implementation of the AHD package did not delay the rapid initiation of ART among most eligible patients and 98.1% of eligible patient were initiated on ART. Overall implementation of several elements of the package of care was successful, close to 100% received cotrimoxazole and nearly 90% of eligible patients received IPT. CD4 screening proved to be the most challenging aspect of the AHD package implementation with a coverage of only 28%. As less than a third of screened patients with AHD received CD4 testing, over half of eligible participants did not receive CrAg screening. Of importance, all those who were diagnosed with cryptococcal meningitis were initiated on the recommended treatment and survived during the six months of study follow up except one that had multiple pathologies including TB. In addition, retention and viral suppression rates were at 85%. Our results highlight the feasibility of implementing a differentiated care model for PLHIV with AHD with favorable outcomes of retention and viral load suppression (VLS) for this population.3, reported a mortality of 12.2% at 24 weeks and 14.4% at 48 weeks among patients who received standard prophylaxis [Most participants enrolled in this study were initiated on ART in a timely fashion with reasons for ART initiation delay due to diseases such as TB, cryptococcal infection and a small number of patients who were still under investigation for other diseases. Therefore, there were very few missed opportunities for rapid ART initiation. As per the national guidelines at the time, almost all patients in our study were initiated on TLE at a rate similar to the general ART population, which ranges from 85–95% from program data and other concurrent studies from Lesotho . We obsephylaxis . In our phylaxis . Nine ouphylaxis . Similarphylaxis –24. Our phylaxis . Over 85The VLS among AHD patients in our study was 85.1%, at six month-follow up. The 2016–2017 Lesotho Population-based HIV Impact Assessment (LePHIA) conducted shortly before our study and the 2020 LePHIA reported VLS of adults on ART of 87.7% and 92%, respectively ,27.Considering the mixed characteristics of a general population  and vulnDespite implementation of the Test and Treat approach, more than a quarter of patients who presented in the study sites had AHD with more than fifty-six percent of whom were male. These are important findings because it was expected that scale-up of Test and Treat would significantly reduce the proportion of patients who present with AHD. Similar to these findings, several studies in South Africa found AHD prevalence of 32.9% in 2016, 21.8% in 2017 while in Ethiopia, Lifson et al found that 60% of patients presented with AHD between 2015 and 2017 –35. MostDue to a shortage of CD4 reagents at the beginning of the study, CD4 testing could not be performed systematically for all patients screened which led to a reliance on clinical staging for identifying AHD. Over one-third of participants in our study with CD4<200 had clinical stage 1 or 2 disease. Several other studies have shown that clinical staging does not accurately predict immunological deterioration ,9–11. InOur study had some limitations. The study occurred in two sites that were purposively selected. These sites enrolled adults from rural and/or urbans areas. Several patients had AHD but were not enrolled because they opted to register for ART services elsewhere. We did not enroll patients currently on ART with AHD. Although the study findings may not be generalizable to pediatric patients given the youngest age band included was adolescents 15–19 years old, they still contribute to understanding the magnitude of AHD and associated comorbidities in the Test and Treat era. Another limitation is the impact of the stock-out of commodities in the context of program implementation; it is likely that the stock-out of CD4 commodities led to an underestimation of the AHD prevalence and less CrAg screening. Newer, rapid diagnostics tests for AHD diagnosis  were not yet available in Lesotho at the time of our study. Despite the above challenges, the observed study outcomes in this program context suggest the feasibility and scalability of our results in routine HIV clinical settings since the study took place in the real program setting.Ultimately, the Lesotho Ministry of Health, along with stakeholders have since taken the results of this AHD evaluation to inform the development of the National AHD Guidelines . AHD serOur study found a high rate of AHD in Lesotho three years after the implementation of the Test and Treat policy. The implementation of a differentiated model of care for patients with AHD did not prevent rapid ART initiation among those with no contraindications and most of the components of the AHD package were feasible to implement. We found VLS of more than 80%, which was comparable and within reach of the general population on ART. Optimal retention strategies and use of newer, rapid diagnostic tests for AHD need further exploration. While the overall survival rate was high, the leading cause of death was TB.We recommend rapid adoption of the AHD guidelines and scale-up of the AHD package and implementation of a differentiated service model for patients with AHD in other districts. This must include optimized point of care diagnosis for TB and rapid initiation of TB-HIV co-infected patient on treatment. Commodities security and health system optimization efforts are vital components for AHD and necessary for the successful diagnosis and management patients at high risk for morbidity and mortality.S1 File(DOCX)Click here for additional data file.


Prospective studies examining long‐term therapeutic outcomes of the Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF) regimen in human immunodeficiency virus (HIV) infection remain limited. This study assessed the actual efficacy and safety of BIC/FTC/TAF in HIV‐infected individuals in southwest China.n = 32) and ART‐experienced (n = 177) HIV‐infected patients administered BIC/FTC/TAF treatment between March 2022 and August 2022. The data were collected until February 28, 2023. Virological reactions and adverse events to the treatment were recorded, and patient subjective feelings in the form of Electronic Patient Reporting Outcome (ePRO) were collected. The primary endpoint was the rate of patients with HIV viral load <50 copies/mL at Week 24.This was a single‐center, prospective study enrolling ART‐naïve (p = .002) and 55.0 cells/μL (p = .022), respectively. By Week 24, no patients had discontinued the BIC/FTC/TAF treatment due to adverse events. Based on ePRO data, ART‐naïve and ART‐experienced patients at Week 24 had stable disease symptom burden, quality of life, and depression level after treatment with BIC/FTC/TAF.At Week 24, 87.5% and 95.5% of ART‐naïve and ART‐experienced HIV patients had a viral load <50 copies/mL, respectively. CD4 cell counts in ART‐naïve and ART‐experienced patients increased significantly by 163.5 cells/μL (BIC/FTC/TAF reduces the viral load in ART‐naïve patients with high viral load as well as ART‐experienced patients with residual viremia. The patient's subjective experience was maintained stable after treatment with BIC/FTC/TAF. This study also revealed a very low incidence for BIC/FTC/TAF drug‐related side effects. This study suggests BIC+FTC+TAF is a safe option for achieving and maintaining virological suppression, both in treatment‐naïve patients with high viral load and treatment‐experienced patients with baseline residual viremia. Since there were almost no drug‐related adverse events with this regimen, and patients' subjective experiences of their own disease symptom burdens, quality of life, and depression levels based on ePRO after treatment with this regimen remained stable, it can be deduced that patient compliance can be ensured. In this study, significant decreases in ALT, AST, and GLU levels were firstly detected in treatment‐naïve and treatment‐experienced patients at Week 24. In the future, the sample size and follow‐up time should be increased to confirm these findings." Patient compliance to ART determines treatment efficacy. To this end, there is an increasing international trend to apply compound single tablets with fixed doses to reduce the tablet burden on the patients, thereby ensuring patient compliance and improving the effectiveness of ART.Patient Reporting Outcome (PRO) is not interpreted by medical professionals, as a report directly from patients concerning their own health status and treatment effectiveness.22.1n = 32) and ART‐experienced (n = 177) HIV‐infected patients administered BIC (50 mg)/FTC (200 mg)/TAF (25 mg) from March 2022 to August 2022. The patients were followed up until February 28, 2023.This single‐center prospective cohort study recruited ART‐naïve . All participating patients provided signed informed consent.2.3Inclusion criteria were: (1) HIV infection; (2) ≥18 years of age; (3) treatment with BIC/FTC/TAF between March 2022 and August 2022, with available baseline and 24‐week CD4 counts and viral load data.2.4Exclusion criteria were: (1) pregnancy; (2) loss to follow‐up or death; (3) nonavailability of data such as viral load, CD4 count, and blood biochemistry indexes at baseline and 24 ± 4 weeks; or (4) inability to complete the HIV‐SI, the EQ‐5D‐5L, and the PHQ‐9 at the visit point.2.5Routine outpatient follow‐up was scheduled for Weeks 4, 12, and 24. The doctors scheduled the visits based on each patient's personal situation. The routine care is as follows: once ART was started, viral load, CD4 count, blood routine indexes, urine routine parameters, blood biochemistry indexes, electrocardiogram, chest X‐ray, ultrasound, and other related parameters were obtained for each patient at the baseline visit, and the symptom management, health status, and sunshine index scale was completed by the patient. At Weeks 4 and 12, the patient underwent routine blood and urine tests and blood biochemical tests, and completed the symptom management and sunshine index scale. At Week 24, viral load, CD4 count, blood and urine routine parameters, and blood biochemistry indexes were determined, and the patient completed the HIV‐SI, the EQ‐5D‐5L, and the PHQ‐9. Patient‐provided data were extracted from case report forms, the hospital information system, and electronic scale systems. Body weight, immune response, and blood biochemistry indexes were evaluated at baseline and Week 24, respectively. The clinical efficacy of BIC/FTC/TAF was evaluated based on virological inhibition and CD4 count increase at Week 24. All patient PRO scales were filled out through the digital information platform “Fortunately, You,” which is based on WeChat, the most widely utilized social media platform in China. Each patient entered the scale and filled it by scanning the hospital's exclusive Quick Response Code. The PRO data were exported from the platform's background.The effect of BIC/FTC/TAF treatment on the patient's subjective feelings was examined based on changes in the HIV‐SI, the EQ‐5D‐5L, and the PHQ‐9 scores. Safety was assessed throughout the study, recording adverse events, drug‐related adverse events, severe adverse events, BIC/FTC/TAF treatment discontinuation, and laboratory indicators. The primary endpoint was the proportion of patients with HIV viral load <50 copies/mL at Week 24. Secondary endpoints included changes in body weight, CD4 count, blood biochemistry indexes, and adverse events at Week 24, and changes in HIV‐SI, EQ‐5D‐5L, and PHQ‐9 scores. Blood lipid abnormality was defined as high total cholesterol (TC) ≥ 5.2 mmol/L, triglycerides (TG) ≥ 1.7 mmol/L, low high‐density lipoprotein cholesterol (HDL‐C) < 1.0 mmol/L), or low density lipoprotein cholesterol (LDL‐C) ≥ 3.4 mmol/L.The HIV‐SI is a validated PRO tool used to assess the burdens of 20 common symptoms associated with HIV treatment or disease.The EQ‐5D‐5L, developed by the European Organization for Quality of Life (Euro QoL Group), has two parts, including the health description system (EQ‐5D descriptive system) and the visual simulation scale (EQ‐VAS). The first part comprises five dimensions, including mobility, self‐care, daily activities, pain or discomfort, and anxiety or depression. Each dimension contains five options and scores: (1) no difficulty; (2) somewhat difficult; (3) moderately difficult; (4) severely difficult; (5) extremely difficult. The visual simulation scale scores between 0  and 100 . The respondents rate the individual's health on a given day. The Chinese version of the EQ‐5D‐5L scale has been evaluated for reliability and validity by domestic scholars.The PHQ‐9 is an internationally accepted self‐rating depression scale used for screening depression symptoms. It is simple and convenient, and has been shown to have good reliability and validity.2.6t test was performed to compare normally distributed independent variables between baseline and Week 24, while the Mann–Whitney U test was used for nonnormally continuous variables. Statistical significance was set at p < .05. SPSS version 23.0 (IBM) was used for data analysis.Qualitative variables were reported as frequency distributions, while quantitative data were expressed as median and interquartile range (IQR) or mean and standard deviation (SD). The Kolmogorov–Smirnov test was used to assess the normality of numerical variables. The Student's 33.1n = 209) included 32 ART‐naïve and 177 ART‐experienced patients. The patient baseline characteristics are shown in Table The patient selection process is summarized in Figure The ART‐naïve group mainly included men (93.6%), with a median age of 31.0 years , and 27 patients (84.4%) were younger than 45 years. In terms of infection route, 22 cases (68.8%) were MSM. In this patient group, 10 patients (31.3%) had a baseline HIV viral load >500,000 copies/mL, and 16 cases (50.0%) had a baseline CD4 count <200 cells/μL. The incidence of dyslipidemia was 71.9%. The main reason for choosing BIC/FTC/TAF was medication convenience (68.8%). Twelve patients (37.5%) had depression according to the PHQ‐9 score at baseline.Most ART‐experienced patients were also male (93.2%), with a median age of 36.0 years , and 78.5% of patients were younger than 45 years. In terms of infection route, 115 cases (65.0%) were MSM. At baseline, 83 patients (89.2%) had virological inhibition , and median CD4 count was 430.0 cells/μL . The main reasons for using BIC/FTC/TAF in this patient group included ease of administration (35.6%) and previous side effects of ART (22.0%). Before switching to BIC/FTC/TAF, 121 (68.4%) patients received tenofovir dipivoxil treatment (TDF), and 19 (10.7%) had detectable viral load levels (≥50 copies/mL). According to PHQ‐9 scores, 73 patients (41.2%) had depression.3.2At Week 24, the virological inhibition rate in the initial treatment group was 84.4% (27/32). The virological inhibition rates at Week 24 for baseline CD4 count <200 and ≥200 cells/μL were 81.3% and 93.8%, respectively  had a viral load <50 copies/mL at Week 24. Baseline CD4 counts <200 and ≥200 cells/μL at Week 24 were 93.8% and 95.7% for ART‐experienced cases, respectively , while the CD4+/CD8+ ratio significantly increased by 0.135 (p = .001). ALT, AST, CRCL, and blood glucose were significantly decreased , and CREA was significantly increased (p = .001). From baseline to Week 24, no significant changes were noted in body weight, BMI, CD8 count, TG, CH, HDL, and LDL , ALT, AST, CRCL, and GLU significantly decreased . LDL and CREA significantly increased . There were no significant changes in body weight, BMI, CD4+/CD8+ ratio, TG, CH, and HDL . Among the 177 ART‐experienced patients, no significant changes were found in HIV‐SI, EQ‐5D‐5L, and Visual Analog Scale (EQ‐VAS) scores . The proportion of patients with depression in the initial treatment group showed no change, while the proportion of cases with depression in ART‐experienced cases increased slightly, with no statistically significant difference.After 24 weeks of treatment with the BIC/FTC/TAF regimen, changes in HIV‐SI, EQ‐5D‐5L, and EQ‐VAS scores were determined  of the 32 ART‐naïve patients had a baseline viral load >500,000 copies/mL, and 7 had a VL < 50 copies/mL at Week 24, consistent with previous findings.After starting ART, CD4 count increased while CD8 count decreased.In patients with HIV and associated comorbidities, simplified medication regimens can reduce drug interactions and decrease the risk of renal dysfunction. In this study, 84.4% of patients with no previous ART and 78.5% of those with ART experience were younger than 45 years old. However, due to factors such as regional dietary habits, these patients still had high proportions of comorbidities, including cardiovascular diseases, cerebrovascular diseases, dyslipidemia, and impaired liver and kidney functions.The main reason for choosing BIC/FTC/TAF was the low likelihood of drug interactions,p = .001 and p < .001, respectively), while creatinine clearance significantly decreased  both in ART‐naïve and ART‐experienced patients at 24 weeks, but were within the normal ranges. This observation is consistent with previous findings.In this study, blood creatinine levels significantly increased (p = .001) was found after 24 weeks of BIC/FTC/TAF treatment in ART‐experienced patients, as well as a slight decrease in TG levels (p = .492) and a slight increase in HDL‐C (p = .097), which may not be clinically significant.Dyslipidemia characterized by elevated LDL‐C levels is an important risk factor for atherosclerosis and cardiovascular disease.In addition, no significant changes in body weight and BMI were observed at 24 weeks. This finding contradicted Emond et al.p = .027 and p = .001, respectively; p = .033 and p < .001, respectively; p = .008 and p < .001, respectively), which may be the first time these phenomena are detected. In the future, we will expand the sample size and extend the follow‐up time to confirm these findings.We observed significant decreases in ALT, AST, and GLU levels in both ART‐naïve and ART‐experienced patients at Week 24 , and PHQ‐9 scores in both ART‐naïve and ART‐experienced patients. This indicates that the subjective experiences of patients with their own disease symptom burdens, quality of life, and depression levels after treatment with the BIC/FTC/TAF regimen remained stable. In this study, there was also no discontinuation of the BIC/FTC/TAF regimen due to drug‐related adverse events occurring by Week 24, suggesting BIC/FTC/TAF is tolerable and safe, with no aggravation of adverse events based on the patient's subjective experience. This plays a very important role in improving patient compliance and ensuring adherence to long‐term treatment.The main limitations of this study included its single‐center nature, small sample, and noncontrol design. In addition, restrictive exclusion criteria also limited information about the efficacy and safety of BIC/FTC/TAF in the excluded populations. Furthermore, patients were generally young and middle‐aged male, which may lead to limited applicability of these research results in the elderly or female population. Moreover, the follow‐up period of this study was only 24 weeks. In future studies, the follow‐up period may be extended to 48 or 96 weeks to observe long‐term efficacy, safety, and subjective patient experience for the BIC/FTC/TAF regimen.5This study suggests BIC/FTC/TAF is a safe option for achieving and maintaining virological suppression, both in ART‐naïve patients with high viral load and ART‐experienced patients with baseline residual viremia. Since there were almost no drug‐related adverse events with this regimen, and patients' subjective experiences of their own disease symptom burdens, quality of life, and depression levels based on ePRO after treatment with this regimen remained stable, it can be deduced that patient compliance can be ensured. In this study, significant decreases in ALT, AST, and GLU levels were first detected in ART‐naïve and ART‐experienced patients at Week 24. In the future, the sample size and follow‐up time should be increased to confirm these findings.Linghong Kong: Formal analysis; investigation; methodology; visualization; writing—original draft. Xiaoxin Xie: Conceptualization. Yanhua Fu: Methodology. Lin Gan: Conceptualization; methodology; project administration. Xiaoyan Yang: Data curation; supervision; visualization. Shujing Ma: Investigation. Hai Long: Conceptualization; project administration; resources.The authors declare no conflict of interest.The study followed the Declaration of Helsinki and was approved by the Ethics Committee of Guiyang Public Health Treatment Center (REC: 202226). All participating patients provided signed informed consent.Supporting information.Click here for additional data file.


The drug–drug interaction between rifampicin and dolutegravir can be overcome by supplemental dolutegravir dosing, which is difficult to implement in high-burden settings. We aimed to test whether virological outcomes with standard-dose dolutegravir-based antiretroviral therapy (ART) are acceptable in people with HIV on rifampicin-based antituberculosis therapy.ClinicalTrials.gov, NCT03851588.RADIANT-TB was a phase 2b, randomised, double-blind, non-comparative, placebo-controlled trial at a single site in Khayelitsha, Cape Town, South Africa. Participants were older than 18 years of age, with plasma HIV-1 RNA greater than 1000 copies per mL, CD4 count greater than 100 cells per μL, ART-naive or first-line ART interrupted, and on rifampicin-based antituberculosis therapy for less than 3 months. By use of permuted block (block size of 6) randomisation, participants were assigned (1:1) to receive either tenofovir disoproxil fumarate, lamivudine, and dolutegravir plus supplemental 50 mg dolutegravir 12 h later or tenofovir disoproxil fumarate, lamivudine, and dolutegravir plus matched placebo 12 h later. Participants received standard antituberculosis therapy . The primary outcome was the proportion of participants with virological suppression (HIV-1 RNA <50 copies per mL) at week 24 analysed in the modified intention-to-treat population. This study is registered with 10 copies per mL (4·6–5·7). At week 24, 43  of 52 participants in the supplemental dolutegravir arm and 44  of 53 participants in the placebo arm had virological suppression. No treatment-emergent dolutegravir resistance mutations were detected up to week 48 in the 19 participants with study-defined virological failure. Grade 3 and 4 adverse events were similarly distributed between the study arms. The most frequent grade 3 and 4 adverse events were weight loss (4/108 [4%]), insomnia (3/108 [3%]), and pneumonia (3/108 [3%]).Between Nov 28, 2019, and July 23, 2021, 108 participants  were randomly assigned to supplemental dolutegravir (n=53) or placebo (n=55). Median baseline CD4 count was 188 cells per μL (IQR 145–316) and median HIV-1 RNA was 5·2 logOur findings suggest that twice-daily dolutegravir might be unnecessary in people with HIV-associated tuberculosis.Wellcome Trust. WHO's preferred first-line antiretroviral therapy (ART) regimen for adults and adolescents with HIV is the second-generation integrase strand transfer inhibitor dolutegravir, combined with tenofovir and lamivudine or emtricitabine.90) in a study of healthy volunteers.Implementing an additional dose of dolutegravir with antituberculosis therapy is challenging in high-burden settings, illustrated by the finding of a Botswanan study in which standard-dose dolutegravir was used in almost half of patients on dolutegravir-based ART during antituberculosis therapy, despite national guidelines recommending double-dose dolutegravir.Evidence before this studyWe searched PubMed for clinical studies on the dosing of dolutegravir with rifampicin-based antituberculosis therapy published between Jan 1, 2010, and Oct 10, 2022, using the search terms (“tuberculosis” AND “dolutegravir” AND “HIV”) with no language restrictions. Our search yielded one non-comparative randomised trial and one retrospective observational cohort study. INSPIRING was a non-comparative, active control, randomised, open-label study among people living with HIV who were naive to antiretroviral therapy (ART) with CD4 counts of at least 50 cells per μL. Participants were randomly assigned to receive either dolutegravir-based or efavirenz-based ART. Dolutegravir was dosed at 50 mg twice daily during and for 2 weeks after antituberculosis therapy. Week 48 virological suppression (HIV-1 RNA <50 copies per mL) in INSPIRING was reported in 75% (52/69) of participants in the supplemental dolutegravir group and 82% (36/44) of participants in the efavirenz group. These results support the hypothesis that twice-daily dolutegravir is effective for people with HIV who are on rifampicin-based antituberculosis therapy. Twice-daily dolutegravir was well tolerated. Although INSPIRING generated high-quality evidence, the study was not powered for between-arm comparisons. A retrospective observational cohort study in Botswana reported on the viral load suppression rates achieved with dolutegravir-based ART in people with HIV who were co-infected with tuberculosis under programmatic conditions. A high proportion of patients (322 [44%] of 739) received once-daily dolutegravir instead of the twice-daily dosing recommended in their national guidelines, which indicates the difficulty of implementing supplemental dolutegravir dosing in a high-burden setting. Virological suppression, which was determined while participants were on antituberculosis therapy, was reported in 204 (95%) of 214 individuals in the once-daily dosing group and in 241 (95%) of 254 individuals in the twice-daily dosing group. The risk of bias is high in retrospective cohort studies but the relatively large sample size and the almost identical viral suppression rates in the two dolutegravir dosing groups suggest that supplemental dolutegravir dosing might be unnecessary for people with HIV on rifampicin-based antituberculosis therapy.Added value of this studyTo our knowledge, RADIANT-TB is the first randomised trial to assess the need for twice-daily dosing with dolutegravir when co-administered with rifampicin-based antituberculosis therapy. We found similar rates of virological suppression in both dolutegravir dosing arms. None of the participants who had study-defined virological failure developed treatment-emergent integrase strand transfer inhibitor resistance and no major safety issues were reported in either arm. Our findings suggest that twice-daily dolutegravir dosing with rifampicin-based antituberculosis therapy might be unnecessary, but we did not have the power to compare outcomes by study arm.Implications of all the available evidenceThe findings of our study together with those of the Botswanan retrospective cohort study suggest that once-daily dolutegravir is as effective as twice-daily dolutegravir for virological suppression in patients on rifampicin co-treatment for tuberculosis.We aimed to determine whether virological outcomes with standard-dose dolutegravir-based ART would be acceptable in people with HIV on rifampicin-based antituberculosis therapy.RADIANT-TB was a phase 2b, randomised, double-blind, non-comparative, placebo-controlled trial at a single clinical site in Khayelitsha, Cape Town, South Africa. National regulatory and ethical approval (Human Research Ethics Committee of the University of Cape Town) were obtained before commencing the study. The detailed study protocol plan has been published online.Patients were referred to the study from three primary care clinics in Khayelitsha. Inclusion criteria were age older than 18 years, seropositivity for HIV-1, plasma HIV-1 RNA greater than 1000 copies per mL, CD4 count greater than 200 cells per μL (subsequently changed to more than 100 cells per μL), ART naivety or first-line ART interruption (with ART duration <6 months or HIV-1 RNA <50 copies per mL <6 months before interruption), and being on rifampicin-based antituberculosis therapy for less than 3 months. Women of childbearing potential were placed on appropriate contraceptives for the duration of the study. Among the exclusion criteria were alanine aminotransferase more than three times the upper limit of normal, allergy or intolerance to one of the drugs in the regimen, and an active psychiatric condition or substance abuse judged likely to affect adherence. All participants gave written informed consent (in English or isiXhosa) before enrolment. Sex was self-reported, selecting either a male or female option.vs first-line ART interruption).By use of permuted block (block size of 6) randomisation, participants were assigned (1:1) to either receive oral tenofovir disoproxil fumarate 300 mg daily, oral lamivudine 300 mg daily, and oral dolutegravir 50 mg daily plus supplemental 50 mg dolutegravir 12 h later or tenofovir disoproxil fumarate, lamivudine, and dolutegravir plus matched placebo 12 h later. Randomisation was stratified by baseline ART status  provided by the local tuberculosis programme. The duration of maintenance therapy was extended if necessary  by local tuberculosis clinics. ART was initiated 8–12 weeks after initiation of antituberculosis therapy, except for a 5-month period during the early COVID-19 pandemic, when national treatment guidelines recommended ART initiation within 2 weeks of starting antituberculosis therapy, regardless of CD4 count. Participants were instructed to take the single oral tenofovir disoproxil fumarate 300 mg daily, oral lamivudine 300 mg daily, and oral dolutegravir 50 mg daily tablets with food in the morning and the 50 mg dolutegravir or matching placebo orally with food 12 h later. The supplemental dolutegravir or placebo was continued for 2 weeks after antituberculosis therapy was stopped. Dolutegravir 50 mg (Myltega) and matching placebo were donated by Mylan Pharmaceuticals . Participants were asked to return all unused study medication for collection and counting by study staff. Co-trimoxazole preventive therapy was supplied by the local tuberculosis programme .Tuberculosis diagnoses were made by local tuberculosis clinics and classified as microbiological or histological  or clinical or radiological (or both). Tuberculosis was classified as either pulmonary, extrapulmonary, or disseminated.Screening procedures were HIV-1 RNA testing, CD4 cell count (if no result <3 months old available), safety laboratory testing, and clinical assessment. Plasma HIV-1 RNA viral load was determined with the Abbott Alinity M HIV-1 test . If the screening CD4 count was between 50 cells per μL and 99 cells per μL the test was repeated when ART was planned to start to reassess eligibility. Woman of childbearing potential had a urinary pregnancy test.Participants were enrolled within 8 weeks of the screening visit. Follow-up visits occurred at weeks 4, 8, 12, 16, 20, 24, and 48. Safety laboratory tests and plasma HIV-1 RNA were done at weeks 4, 8, 12, 24, and 48. CD4 counts were repeated at weeks 24 and 48. Plasma for dolutegravir trough concentrations and dried blood spots for tenofovir diphosphate were taken at weeks 4, 8, 12, 24, and 48. Pharmacokinetic samples were analysed by the Clinical Pharmacology Laboratory, University of Cape Town  with accredited methods.12Participants with unsuppressed HIV-1 RNA (≥50 copies per mL) received adherence counselling and repeat HIV-1 RNA sampling every 4 weeks until suppression or study-defined virological failure (defined as HIV-1 RNA >1000 copies per mL at week 24 or if HIV-1 RNA was <50 copies per mL and then rebounded to >1000 copies per mL at any timepoint). Genotypic antiretroviral resistance testing was done on participants with study-defined virological failure . Resistance was defined as potential low-level, intermediate-level, or high-level resistance according to the Stanford HIV Drug Resistance Database. We also did genotypic antiretroviral resistance testing on stored baseline samples if integrase strand transfer inhibitor resistance was detected.The primary outcome was proportion of participants with virological suppression, defined as HIV-1 RNA less than 50 copies per mL at week 24, analysed in the modified intention-to-treat population and according to the US Food and Drug Association snapshot approach, which defines failure as any one of the following: HIV-1 RNA of 50 copies per mL or greater, missing HIV-1 RNA within the window period (±16 days), or if ART is discontinued. We did not regard switching of tenofovir or lamivudine for intolerance as a failure.90 at weeks 4, 24, and 48; ART adherence assessment determined by tenofovir diphosphate in dried blood spots at weeks 12, 24, and 48; occurrence of grade 3 and 4 and serious adverse events; change in modified mini screen (MMS)Secondary outcomes included proportion of participants with HIV-1 RNA of less than 50 copies per mL at weeks 12 and 48, analysed in the modified intention to treat and per-protocol populations; change in CD4 count from baseline to weeks 24 and 48; proportion of participants with dolutegravir trough concentrations above the PA-ICAdverse events were recorded at every visit and graded according to the Division of AIDS (DAIDS) adverse event grading tables.We assumed that 85% of participants would achieve virological suppression at week 24.2 test (or Fisher's exact test if the number in any cell was ≤5 or McNemar's test for paired observations) for categorical data and Wilcoxon rank sum test for continuous data.The primary outcome analysis was by modified intention to treat, which included all participants who received at least one dose of dolutegravir, and excluded those who switched from dolutegravir because of wishing to become pregnant, becoming pregnant, transfer out of the study for non-clinical reasons, and death from non-HIV-related and non-drug-related causes (as assessed by the study investigator). The per-protocol analysis included the same exclusions as modified intention to treat, but also excluded any participants lost to follow-up, missing an HIV-1 RNA measurement in the study visit window (±16 days around a visit date), and participants switched from dolutegravir for reasons other than failure of the regimen. The proportions of participants with virological suppression were determined with 95% CI. Between-group differences for secondary endpoints, where relevant, were analysed by use of χDried blood spot tenofovir diphosphate concentrations were used to measure adherence based on predefined concentration criteria for men and women.90 (0 × 064 μg/mL).The time windows for dolutegravir trough concentrations were 12 h (±2 h) for participants on supplemental dosing with placebo or dolutegravir , and 24 h . Participants still on supplemental dolutegravir or placebo at weeks 24 and 48 were excluded from analyses at these timepoints. Dolutegravir trough concentrations are expressed as geometric means with 90% CIs, and represented as proportion of participants above the PA-ICFor the safety analysis, we report the proportions of participants with grade 3 or 4 adverse events in either arm and all serious adverse events. ISI results were expressed as proportion of participants with any treatment-emergent insomnia  after baseline and MMS results as the proportion of participants with a change in score of at least one point from baseline.ClinicalTrials.gov, NCT03851588.Statistical analyses were done with Stata (version 16.1). The study is registered with The funder of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report.Between Nov 28, 2019, and July 23, 2021, we screened 140 patients for the study . 108 patBaseline characteristics were similarly distributed between arms . 35% 38.Table 1BThe primary outcome, virological suppression at week 24 by modified intention to treat, was acceptable, with the lower bound of the 95% CI equal to our predefined margin of 70% in both arms . Six of The proportion of participants with virological suppression at week 48 decreased in both arms from week 24 . SecondaParticipants with study-defined virological failure were similarly distributed between groups . All parAdherence as assessed by tenofovir diphosphate concentrations in dried blood spots was similar between the study arms at weeks 12, 24, and 48, but decreased from week 24 to week 48 . Tenofov90 at week 4  and week 24 , but at weeks 24 and 48 all participants had dolutegravir trough concentrations above the dolutegravir PA-IC90  at week 24 were excluded from analysis of dolutegravir trough concentrations at weeks 4, 24, and 48 . The pri PA-IC90 .Median CD4 count increase from baseline was 111 cells per μL in the supplemental dolutegravir arm and 101 cells per μL in the placebo arm at week 24, and 149 cells per μL in the supplemental dolutegravir arm and 163 cells per μL in the placebo arm at week 48.vs no patients; p=0·12; Self-reported grade 3 or 4 insomnia events occurred more frequently in the supplemental dolutegravir arm than in the placebo arm . At week 24 participants were issued a 6-month supply of ART without follow-up visits between weeks 24 and 48 as per local guidelines, to reduce clinic burden during the COVID-19 epidemic, which could have accounted for reduced adherence.Our finding that standard-dose dolutegravir is as effective as double-dose dolutegravir in people living with HIV on rifampicin-based antituberculosis therapy is consistent with findings of two other studies. A small trial in Thailand, which randomly assigned people with HIV with tuberculosis to dolutegravir once daily or twice daily, reported virological suppression in 18 of 20 patients in both groups.A key question is whether a phase 3 trial is necessary to confirm our findings. The probable delay in policy change that running a phase 3 trial would entail is illustrated by the experience of researchers exploring different dosing strategies for the first-generation integrase strand transfer inhibitor raltegravir in people with HIV on rifampicin-based antituberculosis therapy. Plasma concentrations of raltegravir are substantially reduced by rifampicin and double dosing is recommended.None of our participants with study-defined virological failure developed treatment-emergent resistance mutations to dolutegravir. Our findings are in keeping with the INSPIRING study, in which no acquired resistance mutations occurred in the dolutegravir arm.In our study, solicited and self-reported insomnia events occurred earlier and more frequently in the supplemental dolutegravir arm than in the placebo arm, but these differences were not statistically significant. Dolutegravir treatment is associated with an increased risk of insomnia29Our study has limitations. First, the study was not powered to make efficacy comparisons between arms. Second, our findings might not be generalisable to people on dolutegravir-based second-line ART or to people with CD4 counts below 100 cells per μL. Third, we only enrolled participants who were ART-naive or had interrupted first-line ART without virological failure. Our findings might not be generalisable to people with dolutegravir in second-line ART. Fourth, we did not detect treatment-emergent dolutegravir resistance in the placebo arm, but larger sample sizes will be needed to determine the risk of resistance. Fifth, more participants in the placebo arm had dolutegravir trough concentrations below the lower limit of quantitation at weeks 4 and 24. However, as we did not observe the previous dose, we cannot be sure that the plasma sample was taken in the specified time window. Sixth, our study was done at a clinical research trial site; virological outcomes might be worse in real-world settings.In conclusion, we found similar rates of virological suppression in the supplemental dolutegravir and placebo arms when prescribed with rifampicin-based antituberculosis therapy, and there were no treatment-emergent integrase strand transfer inhibitor resistance mutations among participants with study-defined virological failure. Our findings suggest that twice-daily dolutegravir dosing might be unnecessary in people with HIV-associated tuberculosis. More evidence, from cohort studies or possibly a phase 3 trial, might be necessary to change policy on the need for a supplemental dolutegravir dose with rifampicin-based antituberculosis therapy.gary.maartens@uct.ac.za. The study protocol, statistical analysis plan, and informed consent have been published online.Study data will not be publicly available. Data can be made available by the corresponding author to any researcher interested. Deidentified participant data and a data dictionary can be made available and shared under a data transfer agreement. Requests for access to the RADIANT-TB study data should be sent to BS did statistical analysis for HIV-related and tuberculosis-related clinical trials for MetaVirology. GMe lectured for Gilead Sciences and participated in a data safety monitoring board or advisory board for Otsuka. All other authors declare no competing interests.


We assessed progress in HIV viral load (VL) scale up across seven sub-Saharan African (SSA) countries and discussed challenges and strategies for improving VL coverage among patients on anti-retroviral therapy (ART).A retrospective review of VL testing was conducted in Côte d’Ivoire, Kenya, Lesotho, Malawi, Namibia, Tanzania, and Uganda from January 2016 through June 2018. Data were collected and included the cumulative number of ART patients, number of patients with ≥ 1 VL test result (within the preceding 12 months), the percent of VL test results indicating viral suppression, and the mean turnaround time for VL testing.Between 2016 and 2018, the proportion of PLHIV on ART in all 7 countries increased (range 5.7%–50.2%). During the same time period, the cumulative number of patients with one or more VL test increased from 22,996 to 917,980. Overall, viral suppression rates exceeded 85% for all countries except for Côte d’Ivoire at 78% by June 2018. Reported turnaround times for VL testing results improved in 5 out of 7 countries by between 5.4 days and 27.5 days.These data demonstrate that remarkable progress has been made in the scale-up of HIV VL testing in the seven SSA countries. Remarkable progress was made between 2013 and 2018 to curb the HIV epidemic. In 2013, 12.9 million people living with HIV (PLHIV) had access to ART worldwide . UNAIDS The implementation of the 2013 WHO recommendations for the use of VL as the preferred monitoring test for patients on ART presented substantial challenges for countries in SSA with limited resources. At the beginning of VL scale-up, multiple SSA countries had limited molecular diagnostic capabilities, primarily due to high operational costs. Several factors played a role in the successful implementation and scale-up of VL testing in resource-limited settings at this time. First, effective global partnerships have been critical, involving key stakeholders such as the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR), UNAIDS, the World Health Organization (WHO), the Global Fund to Fight AIDS, Tuberculosis and Malaria (GFATM), the Clinton HIV Access Initiative (CHAI), United Nations Children’s Fund (UNICEF), and others. Contributions of these stakeholders include sustained advocacy, funding, and technical assistance, including development and dissemination of tools to facilitate VL scale-up , 6. SecoPEPFAR’s support of national programs together with stakeholders and other donors has been critical for millions of individuals to know their HIV status, initiate ART, and receive treatment monitoring to measure success towards achieving HIV epidemic control –23. MiniThe aim of this study was to assess progress in scale-up of VL testing in seven countries in SSA between 2016 and 2018, and to discuss barriers as well as solutions for improvements.This study assessed the progress of VL scale-up in seven SSA countries  between January 2016 and June 2018. These countries were selected based on their willingness and agreements with the MOH of each country to participate in this study and availability of reported data. Six of the seven countries have adopted WHO recommendations for VL monitoring at 6 and 12 post-ART initiation and every 12 months thereafter for stable patients. In Malawi, VL monitoring was conducted every 24 months for stable patients, until the policy changed in 2019 to WHO standard care [A questionnaire was designed and used for data collection from multiple sources including laboratory information systems, laboratory and clinic registers, and/or MOH national dashboards. Data from each of the 7 countries were collected between January 2016 and June 2018. MOH and CDC program officers jointly collected information on cumulative number of ART patients (adults and children), the number of ART patients with ≥ 1 VL test result, and the mean turnaround time (TAT). The mean TAT was defined as the time (in days) from sample collection to the time VL results were returned from the testing laboratory to the collecting facility. The number of results with viral suppression was calculated by dividing the number of viral load tests with <1000 copies/mL by total number of VL test results. Data on the number of PLHIV were obtained from the UNAIDS database  and usedThe percentage of VL tests with viral suppression and the mean TAT for return of VL results were calculated and compared across countries.The study protocol was reviewed in accordance with the U.S. Centers for Disease Control and Prevention (CDC) human research protection procedures and was determined to be non-research. Applicable federal law for ethical review include: 45 C.F.R. part 46.102(l)(2), 21 C.F.R. part 56; 42 U.S.C. §241(d); 5 U.S.C. §552a; 44 U.S.C. §3501 et seq. Ethical clearance on this non-research project was also received from the Ministry of Health from Cote d’ Ivoire, Kenya, Lesotho, Malawi, Namibia, Tanzania, and Uganda.All 7 countries had VL testing laboratory networks that supported the goal of increasing VL testing coverage of patients on ART. Côte d’Ivoire, Kenya, Lesotho, Malawi, Namibia, Tanzania and Uganda had 14, 8, 5, 10, 8, 16 and 1 laboratories, respectively, that supported specific clinical sites, with the goal of establishing quality laboratory services and efficient sample transport networks. All the laboratories in these 7 countries participated in continuous quality improvement activities and were either working towards or received international accreditation (data not shown).The number of PLHIV and ART patients in the seven countries markedly increased between January 2016–June 2018, increasing the demand for VL testing. Kenya had the greatest number of ART patients with 969,433 (approximately 64.6% of PLHIV) and 1,069,451 (66.8% of PLHIV) in 2016 and 2018, respectively. The smallest volume of ART patients was in Lesotho  in 2016, and in Namibia  in 2018 . LesothoIn 2016, the number of ART patients with one or more VL tests ranged from 22,996 (Lesotho) to 725,339 (Kenya). Comparing 2017 to 2016, Malawi, Namibia and Kenya demonstrated 12.3%, 17.6%, and 18.8% increases, respectively, in ART patients with one or more VL test. Increases of 41.9%, 173.3%, 188.3% and 243.1% were observed for Uganda, Côte d’Ivoire, Lesotho and Tanzania, respectively . By the In 2016, the proportion of VL tests demonstrating viral suppression was greater than 85% in 4  of the 7 countries, ranging from 86.5% (Kenya) to 88.9% (Uganda) . Côte d’In 2016, the mean TAT from specimen collection to return of VL results to the referring clinic ranged from 4 days (Namibia) to 42 and 41.5 days in Malawi and Côte d’Ivoire, respectively . By JuneThe 2016 WHO recommendations for universal access to ART for all PLHIV prompted countries to improve their infrastructure, and increase the capacity of laboratories and health care facilities to respond to the increase in demand for ART and VL testing . From JaBy mid-year 2018 all countries except Côte d’Ivoire achieved >85% VL suppression rates for patients on ART who received a VL test, suggesting successful treatment outcomes for the majority of PLHIV on ART. Of the 7 countries, 5 completed Population-based HIV/AIDS Impact Assessments surveys  during November 2015 to December 2017  and wereTAT for VL results is critical for the timely management of patients. TAT improved for most countries between January 2016 and June 2018. Despite TAT improvements, there are still opportunities to optimize VL testing networks and improve the laboratory-clinic interface. Routine extended TATs of ≥ 2 weeks suggest additional strengthening of specimen transport systems may be necessary. Facilities lacking electronic results and relying on the return of paper based VL results generally face challenges with the timely return of results to patients. Lesotho was the only country observed to have a decline in TAT by > 2 weeks from 28 days in 2016 to 56 days in over the study period. The reasons for the delayed TAT in Lesotho include intermittent backlogs of VL testing due to frequent equipment breakdown, and expansion of sample collection from remote areas often leading to batching prior to VL testing. These problems highlight persistent weaknesses in VL testing networks and service delivery within the VL cascade. Focused attention and effort is needed for continuous TAT improvement through the review and streamlining of laboratory and clinical workflows, and resolving challenges with specimen types (DBS and plasma) bearing in mind the distance and time to centralized laboratory testing . FurtherThere are several limitations with our study. First, it is unclear if less than optimal viral suppression may be related to targeted VL load testing for suspected treatment failures as opposed to routine VL testing. Among VL results, we were not able to distinguish those reflecting repeat testing for patients who had already achieved VL suppression. Demographic information of patients on ART was limited, and we were unable to disaggregate VL suppression data by gender and age. While the data template requested that VL test results reported from the laboratory information system be de-duplicated by patient, we were unable to ensure that de-duplication occurred due to known gaps in unique patient identifiers and challenges obtaining patient-level data in SSA countries. Despite the challenges, there has been great progress in VL scale-up across the 7 SSA countries assessed in this study.The knowledge and experience gained since the inception of VL testing have been critical in the identification of specific challenges at both health facility site and national levels. To accelerate the efficient scale-up of VL testing, sample transport systems may be strengthened, especially in rural and hard-to-reach areas . SpecifiIn conclusion, as countries strive to reach the 95-95-95 fast track UNAIDS targets by 2030, there will be an increase in HIV diagnoses and individuals accessing optimized ART, requirements for routine VL monitoring and need for efficient systems to support sustained community viral suppression and the goals of achieving epidemic control . Innovat