The main objective of this study was to describe the perceived quality of life (QoL) in patients living with AIDS (PLWA) and their chosen coping strategies in a cohort of individuals managed with HAART.  This is a prospective cohort study conducted at the Medication Dispensing Unit of a university hospital (MDU-UH) located in southeastern Brazil. Study population comprised HIV/AIDS patients starting antiretroviral treatment at MDU. The final sample comprised 99 participants. Patients were followed up for 24 months from their recruitment. We used a face-to-face questionnaire to determine sociodemographic and behavioural variables. Quality of life (QoL) and coping strategies (CS) were measured through validated instruments.  Regarding the QoL dimensions, the general perception of QoL among these participants was considered good. Regarding CS, the adherent patients scored higher than the nonadherents.  The present study revealed that the perceived QoL can be maintained in individuals treated for HIV/AIDS. There is an association between high score of coping strategies and adherence to HAART. The improvement in the fight against HIV/AIDS can be attributed to the widespread use of highly active antiretroviral therapy (HAART) known as an effective HIV inhibitory medication therapy. HAART converted HIV infection from potentially fatal to the status quo of chronic disease, reducing the frequency of morbid episodes and hospitalizations, while also increasing the patient's survival , 2.However, the medication's toxicity level ranges from moderate to severe and they must be taken regularly throughout the patient's life, whereas therapy discontinuation leads to resistance by the virus and an increase in its quantity in the individual's body –5. ThereCommitment in the care process is a critical step for PLWHA newly initiated on HAART. Albeit effective, these drugs are not sufficient for the full and effective maintenance of viral suppression if the patient does not effectively take them continuously and adequately, a practice that is improbable in a scenario of low perceived QoL .Although bioclinical factors are important for antiretroviral therapy adherence, behavioural and social aspects of PLWHA must be considered. The therapeutic outcome in AIDS is not only a matter of pathogen versus host, development of new antiretroviral drugs, or adverse reactions; it is also a matter of cultural differences, social inequalities, poverty, stigmatization, and metaphorization of the disease –12.The complexity of the relationship between HIV, HAART, and QoL lies in the fact that while medication is necessary for viral suppression and to improve patients' quality of life in short and medium term, extended use of ART can lead to several adverse events that decrease QoL . In addiThere are few studies on the impact of HAART on the QoL of PLWHA in patients initiating antiretroviral therapy and, above all, on the influence of QoL and coping strategies on adherence to antiretroviral medication , 16, 17.n = 109) . The final sample comprised 99 participants.We conducted a prospective cohort study at the medication dispensing unit (MDU) of a university hospital (UH) located in southeastern Brazil. Patients were followed up for 24 months from their recruitment. The inclusion criteria were being older than 18 years, having started HAART in the study period at MDU, and being seen at the university hospital outpatient unit. We excluded from the sample patients who attended private clinics, inmates, and those incapable of fulfilling the proposed questionnaires or other instruments due to cognitive disablement. All eligible patients were invited to participate in the study. There were six dropouts at sample  was obtained from the laboratory test control system (SISCEL) and clinical information  obtained both directly and from the patient's medical record. The inclusion of asymptomatic patients was possible because the outpatient unit is a reference for providing health care to HIV-infected persons, receiving referrals from the entire state. Thus, patients screened for HIV infection during surgical procedures, blood donation, prenatal care, or treatment for sexually transmitted infections are frequently referred to the unit.Second, QoL was measured before the start of HAART. Both QoL and coping strategies (CS) were measured 12 months after the beginning of treatment using a translated and validated full version of WHOQOL-HIV BREF  and the The WHOQOL-HIV BREF contains 31 items divided into six domains: physical (D1), psychological (D2), level of independence (D3), social relationships (D4), environment (D5), and spirituality/religion/personal beliefs (D6). Participants selected their responses in a 5-point Likert scale, whereas high scores mean better perceived quality of life. The WCS consists of 45 items subdivided into four factors: problem-focused coping (PFC), emotion-focused coping (EFC), search for religious practices/fanciful thinking (SRP), and search for social support (SSS). Participants selected their responses in a 5-point Likert scale ranging from (1) never to (5) always. Overall scores for each strategy were obtained by averaging the scores of their respective items. Higher values indicate greater use of a certain coping strategy. Patients' HAART adherence was measured through the Brief Medication Questionnaire. The BMQ is divided into three groups of questions, called regime, belief, and recall, to be completed by the patient. The “regimen” group starts by asking the patient to list the medications they take by name, how many pills they take at a time, and so on. It is related to the patient's knowledge of their treatment, in addition to obtaining the account of how this medication was taken. Next, the “belief” group seeks to evaluate whether the patient believes that the treatment is indeed working and addresses the patient's concerns or doubts regarding their treatment, as well as whether it is generating any discomfort to the user. Finally, the “recall” group analyzes whether the patient has any problem remembering to take the medication correctly. For each answer that is not in conformity, or that is different from what is expected, the patient is evaluated with a score that is added up, establishing a score that classifies the patient in adherents or nonadherents . The BMQPatients who agreed on taking part in the study signed an informed consent form. This study was approved by the Research Ethics Committee of the Federal University of Espirito Santo, Health Sciences Center, under the protocol number 2008197.Background variables such as demographic, behavioural, clinical, and laboratory variables were presented as frequencies (n) and percentages (%). Differences in participants' QoL and CS score factors between the baseline and follow-up were assessed using the Wilcoxon Test.The comparison of quality of life and coping strategies in the patient's adherence profile was assessed using the Student's t-test for independent samples or the nonparametric Mann-Whitney test in case of normality not detected by the Kolmogorov-Smirnov test. The correlations between the scores of each factor of the ways of coping scale and the scores of each domain of the WHOQOL-HIV BREF questionnaire were assessed using the nonparametric Spearman test.p < 0.2 in the bivariate analysis (Chi-square or Fisher's Exact Test) were entered into the multivariate logistic regression backward stepwise model. The Hosmer-Lemeshow test was performed to assess model acceptance. The results were presented as adjusted odds ratio (aj. OR).To identify the factors that contributed to nonadherence in the group studied after two years of follow-up, all independent variables measured that had significance at the level of 3. Nearly all participants started their treatment with a therapeutic regimen based on DTG/TDF/3TC (dolutegravir/tenofovir disoproxil fumarate/lamivudine). Detailed characteristics of the included subjects are reported elsewhere  and in The majority were male (76.1%), 57.8% were nonheterosexual, 61.5% used alcohol, 78.9% did not use drugs, 81.7% had a viral load value over 1000 copies/ml, and 68.8% had more than 350 TCD4 cells/mmM = 14.9; DP = 3.3; Md = 16.0; IQR: 13.0–17.0). Except for the social relations QoL domain, all the other domains had an increase in their scores, comparing the beginning of treatment and 12 and 24 months of follow-up (p < 0.05). The general perception of QoL among these participants was considered good , with a significant increase in total quality of life scores at 12 and 24 months of follow-up (p < 0.001) compared with the beginning of treatment  = 16.7; standard deviation (SD) = 2.7; median (Md) = 18.0; interquartile range (IQR): 15.0–19.0) and lower values in social relationships domain  and emotion-focused  stood out as the most and least used strategies, respectively, by the participants after 24 months using antiretroviral therapy (ART). Comparing the coping strategies after 12 and 24 months of follow-up, only the search strategy for religious practices/fanciful thinking showed a significant increase in the measured scores  occurred negatively between emotion-focused coping strategy and QoL domain D2  and between emotion-focused coping strategy and QoL .According to p=0.021)  . For thip=0.021) , althougp=0.021) .The independent variables that remained in the final logistic regression model related to the factors of the WHOQOL-HIV BREF and the WCS were, respectively, the physical domain and the spirituality domain and the social support-seeking factor of the WCS. The increase of the spirituality domain score of the WHOQOL-HIV BREF represents risk of nonadherence in 1.4 times for each increased unit . In turn, the increase of the score in the social support-seeking factor of the WCS represented protection against nonadherence; that is, for each unit increased in the score of the factor, the chance of adherence increased by 75.7%  .The evaluation of the participants revealed a good and statistically significant general perception of QoL by these individuals throughout the 24 month period. When evaluating QoL measurements between different health conditions , it is expected that those with higher levels of illnesses report lower QoL scores .Across all possible QoL domains, participants scored higher on physical and level of independence, a result consistent with the studied sample, since 68.8% of the participants started treatment asymptomatic.p > 0.05). This domain has facets related to personal relationships, social support, social activity, and social inclusion, assessing aspects related to acceptance in society, satisfaction with sex life, personal relationships, and support from friends. This is perfectly expected considering that HIV is still stigmatized and excluding disease, which limits the social integration of those affected [The social relations QoL domain did not vary over time (affected , 23.At the end of two years of follow-up, 80.8% of them were adherent, reinforcing the role of adherence to HAART in viral suppression, maintenance of adequate clinical conditions, and improvement of quality of life of PLWHA. We attribute a significant increase in the total quality of life scores at 24 months of follow-up to the maintenance of virological suppression by the HAART, which allows improvement of physical condition enabling to carry out daily activities.At the end of the two year period, there was a significant increase in search for religious practices without altering the frequency of other coping strategies. Religious and spiritual practices are one of the most used strategies to manage the anguish and stress related to HIV-positive status . ReligioWhen using religion as a coping strategy, people can adopt a collaborative approach that consists of working together with their God to solve the problem, placing their expectations of resolution entirely in the capacities of a given deity . In the The emotion-focused coping strategy had a negative correlation with the D2 domain of QoL, representing agreement with the scores obtained in the evaluation of the study group in the 24 months of follow-up, since the focus on emotion was the least used strategy by these individuals. Moreover, we noted an increase in the measured scores of D2 comparing the measurements at the beginning with those after one and two years of treatment. Emotion-focused coping is an individual response that focuses on managing emotional responses to a stressful event .The responses of the WCS social support factor have in common the fact that they involve another person in their emission, meaning they are social interactions, which require the performance of another individual, with his support network . PreviouIn the process of adherence to antiretroviral therapy and its social representations for people living with HIV/AIDS, the family represents a support network of extreme importance for the continuity of adherence to drug treatment, constituting an agent of support to the process. Hence, nonadherence is an event determined by several factors, given their relationship with the person under treatment, the disease, the therapy, the health services, and social support .Indeed, adverse reactions to ARVs are a challenge for not only PLWHA adherence but also their socioeconomic status –35.Several systematic reviews addressing barriers to ART adherence in developed and developing countries have shown that fear of disclosing HIV-positive status, suspicion of being on treatment, and desire to avoid taking medications in public places, among others, negatively affect adherence . HoweverWe recognize that the study had some limitations. The first was the small sample size, which makes difficult to detect differences between the different categories. Therefore, some associations did not remain after 24 months of follow-up. The second is linked to the study scenario, conducted in real-life conditions for PLWHA. Even though this is advantageous because it reliably portrays the conduct of the treatment, it prevents stricter control over all variables, as in controlled clinical studies.Despite the limitations, the study succeeded in revealing the religious beliefs' negative influence on ART adherence process as well as the importance of the social support on the HIV care cascade.The participants revealed a good and statistically significant general perception of QoL. In general, coping strategies and medication adherence were not associated except for SSS.The increase in the WHOQOL-HIV BREF score in the spirituality domain represented an increased risk of nonadherence, suggesting a negative impact of this behaviour. In contrast, the coping strategy search for social support of the WCS favored adherence in the group studied.This study reinforces the importance of the influence of the social component in the process of adherence to ART. Thus, a multidisciplinary look at the individual newly initiated on HIV treatment for the continued maintenance of the antiretroviral treatment is clearly needed. It is essential to empower the patient, making them conscious of their role in the treatment process. If there is no cure for their disease, the patient must become aware that there is control over its progression. In this aspect, the act of dispensing the antiretroviral medication must be surrounded by care, especially by the pharmacist. Our results provide evidence to the health authorities responsible for policies regarding HIV infection care to emphasize the need for multidisciplinary teams, pharmacist empowerment, and valorization of strategies privileging self-caring and social support.


In 2016, we conducted a systematic review to assess the feasibility of treatment monitoring for people living with HIV (PLHIV) receiving antiretroviral therapy (ART) in low and middle-income countries (LMICs), in line with the 90-90-90 treatment target. By 2020, global estimates suggest the 90-90-90 target, particularly the last 90, remains unattainable in many LMICs. This study aims to review the progress and identify needs for public health interventions to improve viral load monitoring and viral suppression for PLHIV in LMICs.A literature search was conducted using an update of the initial search strategy developed for the 2016 review. Electronic databases (Medline and PubMed) were searched to identify relevant literature published in English between Dec 2015 and August 2021. The primary outcome was initial viral load (VL) monitoring (the proportion of PLHIV on ART and eligible for VL monitoring who received a VL test). Secondary outcomes included follow-up VL monitoring , confirmation of treatment failure (the proportion of PLHIV who had two consecutive elevated VL results) and switching treatment regimen rates (the proportion of PLHIV who switched treatment regimen after confirmation of treatment failure).The search strategy identified 1984 non-duplicate records, of which 34 studies were included in the review. Marked variations in initial VL monitoring coverage were reported across study settings/countries (range: 12–93% median: 74% IQR: 46–82%) and study populations , children, adolescents/young people , and pregnant women ). Community-based models reported higher VL monitoring  compared to decentralised care at primary health facility . Suboptimal uptake of follow-up VL monitoring and low regimen switching rates were observed.Substantial gaps in VL coverage across study settings and study populations were evident, with limited data availability outside of sub-Saharan Africa. Further research is needed to fill the data gaps. Development and implementation of innovative, community-based interventions are required to improve VL monitoring and address the “failure cascade” in PLHIV on ART who fail to achieve viral suppression. In 2014, UNAIDS launched the 90-90-90 treatment target: by 2020, 90% of all people living with HIV (PLHIV) know their status, 90% of all people diagnosed with HIV infections receive antiretroviral therapy (ART) and 90% of all people on ART have suppressed viral load . On the In low and middle-income countries (LMICs), there has been an intense focus on scale-up of ART programs to increase treatment coverage in PLHIV through decentralisation of HIV services –9. GlobaIn 2016, we conducted a systematic review to assess the feasibility of ART monitoring for PLHIV in the context of decentralised HIV treatment and care in LMICs . The conDespite continuous gains in access to testing and treatment since 2015, the ambitious 90-90-90 treatment target, particularly the last 90, remains unattainable in many LMICs . ReachinThe study was designed and reported in accordance with the Preferred Reporting Item for Systematic Reviews and Meta-Analyses (PRISMA) statement . The iniPrimary outcome: Initial VL monitoring  and eligible for VL monitoring who receive a VL test for treatment monitoring purposes). Secondary outcomes include: (i) Follow-up VL monitoring ; (ii) Confirmation of treatment failure (the proportion of PLHIV on ART with two consecutive elevated VL results among those who received a follow-up VL test) and; (iii) Switching treatment regimen (the proportion of PLHIV on ART switching treatment regimen among those with confirmed treatment failure as defined in included studies). Prior to July 2021, WHO recommended that patients with elevated VL (≥ 1000 copies/ml) should be given enhanced adherence consultation (EAC) followed by a repeat VL test within 3–6 months of the initial VL. If the repeat VL remains greater than 1000 copies/ml, treatment failure is confirmed and patients should be switched to second-line ART [To be included in this review, studies must meet the following inclusion criteria: (1) was conducted in LMICs; (2) involved PLHIV receiving first-line ART and eligible for VL monitoring; (3) involved decentralised HIV treatment and care, defined as having treatment and treatment follow-up provided in non-hospital settings – primary health care facilities or community-based health care services; and (4) reported the primary outcome of interest. Only studies published in English were included.Data were extracted electronically using a pre-defined data extraction form. The following information was extracted: study details ; VL testing model; external funding and/or technical supports received and outcome of interests. Information on treatment regimen and VL threshold for definition of elevated VL and treatment failure were also extracted, if reported. Data on outcomes of interest are presented by time point or follow-up period as per the included studies. Outcomes by model of care  and subgroups of study population  are extracted (if reported) and presented to enable data comparison. Descriptive statistics were applied to describe the outcomes of interest across countries and study settings, study populations and models of care.The search strategy yielded 1984 records after removal of duplicates. Screening titles and abstracts identified 66 studies for full-text examination, of which 32 studies met the inclusion criteria and were included. Bibliography review identified two additional studies, making a total of 34 studies included in the review  countries, including South Africa –32, ZimbWide ranges of VL monitoring coverage in program settings were observed. Studies of adults/patients of all ages, children, adolescents (aged 0–19 years) and young people aged < 25) years), and pregnant women reported VL coverage of 25–96% (median: 67% interquartile range IQR: 50-84%), 2–94%  and 32–82% , respectively. Studies include community-based care models reported higher initial VL monitoring coverage  compared to decentralised care at primary health facility  ,Of 11 studies from South Africa, four were conducted in Cape Town, reporting relatively high VL coverage of 72–89% , 25–27. Of five studies in Asia, three were conducted in Myanmar using national HIV program data and reported a range of VL coverage from 34%  to 57% , 55. TwoThirteen studies provided data on the proportion of patients on ART receiving a follow-up VL test after an initial elevated VL (follow-up VL monitoring). Overall, the coverage for follow-up VL monitoring was lower than that of initial VL monitoring with nine out of 13 studies reporting gaps of 2–48% points  of the included studies were specifically designed to evaluate the implementation and/or reported the outcomes of VL monitoring program for PLHIV on ART. Most of these studies were published in 2019–2021. This represents a substantial increase in the number of studies focused on VL monitoring compared to our previous review , with onConsistent with findings from previous studies, the results of this review show that there are still significant gaps in VL monitoring across countries and regions. Studies that reported high VL monitoring coverage and use of VL results for patients’ management were conducted in settings with one or more of the following: (1) support from international donors and implementing partners; (2) innovative interventions and models of service delivery for decentralisation of HIV treatment and care, such as “hub and spoke”, “differentiated care” or “adherence club”; and (3) research clinics with free HIV services, including VL testing, for participants. From programmatic perspectives, whilst studies conducted in research or program contexts with external funding and technical supports may have limited generalizability, the finding that community-based models of care, implemented by local government or health authorities, can deliver high VL coverage is encouraging, and supports the continued scale-up of decentralisation of HIV treatment and care in LMICs.LMICs face immense financial and implementation challenges in provision of HIV treatment and routine VL monitoring for PLHIV on ART. External financial and technical supports with a multi-sector approach are crucial for the set-up and delivery of such services, particularly in decentralised settings where VL monitoring was historically unavailable . HoweverThere was also evidence of a narrow geographical focus for research on HIV treatment and VL monitoring programs with most of the data come from SSA countries. Even within SSA, almost all studies included in this review were conducted in Eastern and Southern Africa – the region with the second-highest point estimate of the proportion of people who are virally suppressed among all PLHIV , behind only high-income countries with well-developed health care systems in Western and Central Europe and North America  . This raOur findings suggest that research and targeted interventions are needed to improve VL monitoring coverage in vulnerable populations, including children, adolescents and young people, pregnant women and key populations (KPs) living with HIV.As HIV treatment programs expand in many LMICs, children and adolescents are a priority population for the scale-up of VL monitoring to improve quality of care and treatment outcomes . The staOur review highlights the lack of data on VL monitoring for KPs in real-world settings. Only two studies , 54 repoRoutine VL monitoring for PLHIV on ART is only meaningful if accompanied by the use of VL results for appropriate and timely clinical action. The findings of this review indicate suboptimal uptake of follow-up VL among patients with initial elevated VL ; high proportion of confirmed treatment failure among those patients who had a follow-up VL  and a low switching rate among those with confirmed treatment failure . These findings are of particular concern, because they could indicate inadequate EAC and/or a high level of treatment failure due to drug resistance that requires switching the ART regimen. It is known that prolonged treatment regimen failure significantly increases the risk of multiple drug-resistant mutations and compromises the efficacy of second-line ART in HIV-infected children , adults This review contributes to a growing body of literature highlighting the importance of VL monitoring and VL cascade analysis for planning, implementation and evaluation of HIV treatment programs in the era of “Test and Treat” –69. In dNew sampling technologies , 74 haveThis review had several limitations. Only peer-reviewed articles published in English were considered, meaning grey literature  with data on the outcomes of interest  was overlooked. The lack of data from geographic regions outside of SSA also raises a concern about bias and the generalizability of the findings. Another limitation is that some of the recently published studies report data collected 10–15 years ago which may not necessarily represent the recent uptake of VL monitoring. However, given the nature of the data reported from included studies ; these limitations are unlikely to affect the results and their interpretation substantially. Few studies reported a complete viral load cascade . Researchers are encouraged to report on the viral load cascade of patients failing first-line ART and patients on second-line ART to enable understanding of the magnitude of the problem and identify intervention strategies and resources required to meet the needs of these vulnerable patients.Since 2016, there has been marked growth in the peer-reviewed literature on VL monitoring and VL cascade in PLHIV in LMICs. Most studies were conducted in SSA with significant financial and technical support from international/bilateral donors and implementing partners. Available data suggest significant gaps in VL monitoring services across countries and geographic regions, highlighting the needs to strengthen health system capacity for effective and sustainable implementation of routine VL monitoring for PLHIV who receive ART at decentralised care settings in LMICs. Particular attention is needed to rectify the failure cascade to ensure that VL monitoring and follow-up clinical actions are taken for individuals on ART who fail to achieve viral suppression. To advance the global agenda towards ending the HIV epidemic by 2030, we must fill the data gaps outside SSA; support the development and implementation of targeted interventions to improve VL monitoring and the VL cascade among populations at high risk of unsuppressed VL but with poor access to HIV treatment and care.


Increasing access to viral load (VL) monitoring is essential to fight HIV epidemics. In remote settings in Vietnam, using dried blood spot (DBS) sampling for specimen collection could improve the situation. Here, people who inject drugs (PWID) represent many newly antiretroviral therapy (ART)-initiated patients. The goals of this evaluation were to evaluate if access to VL monitoring and the rate of virological failure differed between PWID and non-PWID.Prospective cohort study of patients newly initiated on ART in remote settings in Vietnam. DBS coverage at 6, 12 and 24 months of ART was investigated. Factors associated with DBS coverage were identified through logistic regression, as were factors associated with virological failure  at 6, 12 and 24 months of ART.Overall 578 patients were enrolled in the cohort, of whom 261 (45%) were PWID. DBS coverage improved from 74.7% to 82.9% between 6 and 24 months of ART (p = 0.001). PWID status was not associated with DBS coverage (p = 0.74), but DBS coverage was lower in patients who were late to clinical visits and in those in WHO stage 4 . The virological failure rate decreased from 15.8% to 6.6% between 6 and 24 months of ART (p<0.001). In multivariate analysis, PWID were more at risk of failure (p = 0.001), as were patients who were late to clinical visits (p<0.001) and not fully adherent (p<0.001).Despite training and simple procedures, DBS coverage was not perfect. DBS coverage was not associated with PWID status. Close management is required for effective routine HIV VL monitoring. PWID were more at risk of failure, as were patients who were not fully adherent and patients who were late to clinical visits. Specific interventions targeting these patients are needed to improve their outcomes. Overall, efforts in coordination and communication are essential to improve global HIV care.NCT03249493.Clinical Trial Number:  In one decade, antiretroviral therapy (ART) coverage greatly increased from 7.8 million people in 2010 to 27.4 million 73%) in 2020 % in 2020. In addiIn Vietnam, HIV prevalence in adults was 0.3% in 2019, but much higher in some key populations such as people who inject drugs (PWID) in whom it was 12.7% . It has This study aimed at describing different outcomes of HIV VL monitoring in HIV infected adults on ART in remote settings and evaluating if PWID have worse outcomes than the other patients (i.e. non-PWID). The goals were i) to describe DBS coverage for HIV VL monitoring; ii) evaluate the rate of virological success at 6, 12 and 24 months of ART and compare it between PWID and non-PWID, iii) evaluate use of the HIV VL monitoring algorithm in terms of availability of confirmatory DBS after failure.MOVIDA 2 is a prospective, observational, multicenter cohort study that aims to improve access to HIV VL monitoring, introducing the use of DBS, in HIV-infected adults followed in remote settings in Vietnam . It was The MOVIDA 2 study being observational, follow-up and care complied with national guidelines. Following the WHO [For HIV VL monitoring, the national algorithm, based on WHO guidelines, recommended HIV VL testing at 6 months of ART, 12 months of ART and then every 12 months afterward. At these timepoints, if the HIV VL was ≥1,000 copies/mL, the algorithm recommended providing adherence support and repeat HIV VL testing within 3 to 4 months from the initial measurement. If the confirmatory HIV VL was again ≥1,000 copies/mL, ART modification for a new ART line was recommended; otherwise, no ART modification was required.Adherence to ART was assessed at each clinical visit by self-reporting the number of missed ART doses in the last 4 days (ranging from none to four missed doses).At OPC level, DBS was used to collect blood specimen for HIV VL testing. Whole blood was collected by venous puncture, and immediately after collection, 70 μL of whole blood was dropped using a calibrated pipette onto each of the five spots of two Munktell TFN paper cards . The DBS cards were then left to dry on a rack at ambient temperature for a minimum of three hours, after which they were packed individually into a sealable plastic bag with three desiccants. The packed DBS cards were stored at ambient temperature until the transfer to the National Reference Laboratory of HIV Molecular Biology at the National Institute of Hygiene and Epidemiology (NIHE) in Hanoi (Vietnam). DBS were shipped once a week at ambient temperature, by postal service, directly from each OPC to the NIHE. However, some OPCs initially sent the DBS to an intermediate laboratory in the provincial capital which then transferred the DBS to Hanoi. This affected a limited number of OPCs for only a short time, and therefore a limited number of DBS.HIV VL testing on DBS was performed at the National Reference Laboratory of HIV Molecular Biology at the NIHE, where the technique used has previously been evaluated. VL was measured following the manufacturer’s recommendations with the Abbott RealTime HIV-1 assay  which is CE-marked and WHO pre-qualified for DBS. Briefly, one spot was taken out of the card and placed in a tube containing 1.3 mL of lysis buffer and then incubated for 30 minutes at 55°C. The tubes were then loaded into the Abbott m2000sp platform for RNA extraction. The extraction products were transferred to the Abbott m2000rt machine in which RNA was reverted to cDNA and where amplification/detection took place. The technique’s lower limit of detection was 839 copies/mL.Baseline characteristics were described between PWID and non-PWID using median and interquartile range (IQR) for continuous variables and frequency and proportions for categorical variables. Comparisons were made using student’s t-test for the continuous variables and chi-2 test for categorical variables.DBS coverage at 6, 12 and 24 months of ART was estimated as the proportion of patients still followed at these timepoints and in whom DBS had been collected, irrespective of DBS availability at previous timepoints. Patients were considered still followed if they attended a visit in the period ranging from 2 months prior to 4 months after the timepoint. Factors associated with DBS coverage were identified using mixed-effects logistic regression models to account for repeated measurements from the same patient.Virological failure at 6, 12 and 24 months of ART was defined as having a VL ≥1,000 copies/mL on DBS collected during the period ranging from 2 months prior to 4 months after the timepoint. The confirmatory HIV VL was never considered in this definition and were analyzed separately. Factors associated with virological failure at 6, 12 and 24 months of ART were identified using mixed-effects logistic regression models. In a sensitivity analysis, we restricted the selection to the 24 months of ART timepoint.In the statistical analyses described above, the period around the timepoints was considered to allow for variability in the timing of clinical visits and DBS collection, inherent to real-life conditions, and to describe what happens in real-life conditions.To evaluate use of the HIV VL monitoring algorithm, the proportion of patients in virological failure for whom a confirmatory DBS was collected was measured. Patients without confirmatory DBS because they died, were transferred or lost to follow-up (LTFU) were not considered. Factors associated with the availability of a confirmatory DBS were investigated using mixed-effects logistic regression models.The Vietnamese population consists in a large number of ethnic groups, not necessarily sharing the same language, the Kinh ethnic group being the main ethnic group in the country. In our analyses, we considered the ethnic group (Kinh versus the other ethnic minorities) to see if it impacted care and our health outcomes.In all analyses, late visit attendance was defined as being at least seven days late at a visit, at least once, within the 3 months preceding the evaluation timepoint. An alternative definition considered a delay of ten days. Non-adherence was self-reported and defined as having missed at least one drug intake in the last four days, to at least one of the attended visits within the 3 months preceding the evaluation timepoint. Body mass index (BMI) was categorized using the threshold defining severe to moderate underweight, underweight and overweight . WHO stage within the 3 months preceding the evaluation timepoint was categorized as asymptomatic HIV infection with some clinical manifestations (Stage 1–2), moderate symptomatic stage (Stage 3) or AIDS stage (Stage 4).In all analyses, factors associated with the outcomes with a p-value <0.20 in the univariate analysis were considered in the multivariate analysis. In the multivariate analyses, a backward stepwise procedure was used to identify factors independently associated with the outcome. However, PWID status, was added to the models irrespective of its p-value in the univariate analysis. A p-value <0.05 was considered statistically significant. All analyses were performed using Stata software .The study was reviewed and approved by the Institutional Review Board at the NIHE in Vietnam (02/QD-VSDTTU) and Institut Pasteur in France (2016-10/IRB/1). The protocol was submitted on the clinicaltrials.gov website (NCT03249493). All participants gave their written informed consent before the enrolling. Data processing was authorized by the French legal authority CNIL (DR-2017-046).From June 2017 to April 2018, 578 HIV-infected adults who initiated ART were enrolled in the cohort. All participants initiated ART with a combination of Lamivudine, Tenofovir and Efavirenz (3TC-TDF-EFV).Overall, 261/578 (45.2%) patients were former or current PWID . As prevTo globally assess routine HIV VL monitoring, we first quantified DBS coverage. In patients who were still followed, DBS coverage increased from 401/537 (74.7%) at 6 months of ART to 414/493 (84.0%) and 369/445 82.9%) at 12 and 24 months of ART, respectively , the effects of the other factors being unchanged.Out of the 1,184 DBS collected at 6, 12 and 24 months of ART, 9 (0.8%) were lost and never replaced and 31 (2.6%) were discarded from the analysis as the HIV VL result was undetectable but desiccants were showing signs of humidity or were absent, making the result questionable. The number of DBS discarded was 24, 2 and 5 at 6, 12 and 24 months of ART, respectively. Therefore, 373/537 (69.4%), 407/493 (82.6%) and 364/445 (81.8%) patients were virologically evaluated at 6, 12 and 24 months of ART, respectively.The proportion of patients in virological failure, defined at the threshold of 1,000 copies/mL decreased with time from 15.8% (59/373) at 6 months of ART to 6.6% (24/364) at 24 months of ART . In multIn an alternative multivariate analysis considering late visit attendance by ten days or more, being late showed an even stronger association (adjusted OR (95% CI): 3.49 (2.11–5.78); p<0.001) while the effects of the other factors were unchanged (data not shown).Restricting the analysis to the 24 months of ART timepoint, the only two factors that remained independently and significantly associated with higher risk of virological failure were PWID status and late visit attendance (data not shown).According to the national algorithm, patients in virological failure should receive adherence support and have another DBS collected within 3 to 4 months following the initial DBS. A confirmatory DBS was collected in 15/59 (25.4%), 36/58 (62.1%) and 14/24 (58.3%) patients who were in virological failure at 6, 12 and 24 months of ART, respectively . ExcludiIn patients with a confirmatory DBS, 11/15 (73.3%), 12/36 (33.3%) and 6/14 (42.8%) were in confirmed virological failure at 6, 12 and 24 months of ART, respectively. Overall, 52 patients were identified in virological failure during follow-up and only one (1.9%) was switched to second-line ART.Médecins Sans Frontières in a 2016 report where, despite support, HIV VL coverage ranged from 32% to 91% [The MOVIDA study aimed at increasing access to HIV VL monitoring in remote settings using DBS, and to evaluate different aspects of HIV VL monitoring. Prior to the MOVIDA study, no routine HIV VL monitoring was implemented in the six provinces. All clinical and laboratory teams were trained to use DBS for routine HIV VL monitoring. Despite that training, regular contacts with the clinical teams for monitoring reasons , and simple procedures for sample collection, storage and transfer, DBS coverage was not 100%. However, DBS coverage increased with time to reach 83.8% and 81.8% at 12 and 24 months of ART, respectively. Sub-optimal coverage was also reported by others, including % to 91% . We alsoIn multivariate analysis, disparities were observed between provinces in terms of DBS coverage. This probably illustrates differences between clinical sites, but limited sample sizes in each OPC did not allow investigations at that level. Differences between clinical sites could be explained by the involvement of clinical staff, management at the OPC or workload. We did not, however, record the total number of patients followed at each site to investigate its potential impact. It is also likely that, in some OPCs, staff turnover led to lower DBS coverage.Interestingly, late clinical visit attendance was associated with lower DBS coverage. Patients’ attitude towards their care could have influenced the health workers’ decision to collect a DBS or not. Patients in WHO stage 4 were less likely to have DBS collected, even though they would greatly benefit from HIV VL monitoring. Although this should be confirmed by a dedicated socio-anthropological qualitative study, one could wonder if these results reflect prejudice from clinical staff against patients who show signs of failure and are believed to be non-adherent to ART. On the other hand, while it has been shown that PWID often experience lower and delayed access to care , 15, thePrevious studies reported that workload and complexity of the process to obtain results limited access to HIV viral load monitoring . In VietAt some point, some patients saw their DBS lost. Unfortunately, in most cases, the clinical team did not realize that no HIV VL result was returned to these patients, and therefore no new samples were collected. A small proportion of DBS (2.6%) showed quality defects. The NIHE laboratory informed the OPC about the defect observed but this did not translate into a request for new DBS to be collected. Consequently, patients never received their HIV VL result. This is worrying as it could create distrust in the care system and ultimately affect their adherence to ART but also compromise patient outcomes. Therefore, these gaps in DBS tracking should be addressed to improve the overall HIV monitoring system.The proportion of patients in virological failure significantly decreased from 15.8% at 6 months of ART to 6.6% at 24 months of ART. The decrease in the proportion of patients in virological failure is likely partly explained by the healthy survivor effect. Indeed, more adherent patients are more likely to remain in care, hence leading to lower proportion of patients with high HIV VL. The result at 24 months of ART was consistent with previous cross-sectional surveys in Vietnam which showed >90% success in patients on ART for >24 months , 19.PWID were at increased risk of virological failure. This was also evidenced in an earlier study conducted in Hanoi . It has Médecins Sans Frontières in its programs [National guidelines, inspired by WHO guidelines, recommend adherence intervention followed by a new HIV VL measurement to confirm or invalidate virological failure. The proportion of patients in failure, for whom a confirmatory DBS was collected, improved with time from 25.4% at 6 months of ART to 60% at 12 and 24 months of ART. Our results are consistent with what was observed by programs . Again, Worryingly, only 1 out of 52 patients in failure was switched to second line. This figure, consistent with previous findings , shows t3, however, who should have faster ART initiation and compulsory screening for other diseases such as Cryptococcus and Tuberculosis. Consequently, it did not allow us to describe the extent of late ART initiation. Some bias might influence the interpretation of VL suppression. For instance, adherence should be interpreted with caution because it was self-reported and subject to desirability bias. However, the fact that those who self-reported being non-adherent were also more often in virological failure suggests that the information provided is very relevant.This study has some limitations. The population enrolled was essentially men, partly because 45% of our study population consisted of PWID. However, the over-representation of men in Vietnamese HIV programs has been reported by others –20, 25 aDespite training and simple procedures, DBS coverage was not perfect, suggesting the need to invest in close management for effective routine HIV VL monitoring. PWID were more at risk of failure, as were late presenters and patients who reported not being fully adherent. Interventions targeting these patients are needed to improve their outcomes.S1 TableART: antiretroviral therapy; VL: viral load; LTFU: lost to follow-up *these events occurred before a blood sample for confirmatory VL testing at M6 was collected **this event occurred after the confirmatory VL at M6 was measured but before a blood sample for VL testing at M12 was collected.(DOCX)Click here for additional data file.


Viral suppression was balanced between the two arms . At month 6 post study entry (primary endpont), 64% of the women retained in care were virally suppressed, 54% intervention vs. 76% control arm . At month12 post study entry (secondary endpoint), 69% of the women retained in care were virally suppressed, 67% intervention vs. 71% control arm women . More intervention women completed all scheduled sessions by month 6. Control group women were more likely to be virally suppressed at both timepoints. Only 25% had treatment switch by 12 months. Despite intense adherence support and viral load monitoring, sustained viral suppression remained elusive in women identified at risk of viral failure. These findings highlight the continued need for effective adherence intervention for women with unsuppressed HIV viral loads, efficient treatment switch strategies, as well as drug level monitoring.We piloted the combined effectiveness of point-of-care viral load monitoring plus motivational enhanced adherence counseling (intervention) compared with routine care (control) in women identified at risk of virologic failure in the PROMOTE study in Zimbabwe. In an unblinded randomized study, consenting women with last viral load ≥200 copies/ml and/or pill count outside 90–110% range were randomized 1 : 1 to receive the intervention or continue routine care, comprising laboratory-based VL monitoring and standard EAC, from trained nurses and counsellors. Viral load was measured 0, 3, 6, and 12 months after enrolment. We compared viral suppression <200 copies/ml at 6 and 12 months between the arms through Fisher's exact test and sought associated factors by logistic regression with a 95% confidence interval (CI). Between December 2018 and July 2019, 50 women were enrolled (25 intervention and 25 controls) and followed until November 2020. At entry, 60% of the women were virally suppressed, 52% intervention  Increasing access to antiretroviral therapy (ART) has led to significant success in the fight against the human immunodeficiency virus (HIV) pandemic, yet low adherence to life-long ART continues to undermine its effectiveness in preventing vertical HIV transmission. Previous research in sub-Saharan Africa suggests that ART adherence is particularly challenging during the peripartum period –3. EnhanHIV viral load (VL) testing became the gold standard for HIV treatment monitoring and confirmation of treatment failure in 2013 . In addiIn 2014, Zimbabwe adopted the 2013 World Health Organization (WHO) ART guidelines, which included life-long treatment for pregnant women with HIV (Option B+), with an aim to achieve the 90-90-90 UNAIDS goals by 2018 . While tTo improve adherence monitoring and treatment outcomes in women on life-long ART, this study sought to assess the effect of POC HIV VL monitoring and motivational EAC (mEAC) compared with routine care on virological suppression rates in women with elevated HIV VL and at risk of elevated VL in the PROMOTE study in Zimbabwe. We aimed to assess whether adherence counseling sessions that use facets of the information, motivation, and behavior (IMB) model combined with real-time viral load feedback through POC testing are more effective in providing adherence skills required to achieve viral suppression at 6 months and maintain long-term adherence to ART measured at 12 months after intervention.It was a randomized (1 : 1), unblinded, implementation science pilot study nested within the PROMOTE observational cohort being followed at three clinics in Zimbabwe .Women targeted for enrolment in this study were study participants at PROMOTE sites in Zimbabwe, living with HIV and experiencing elevated VL (≥200 copies/ml) at a previous PROMOTE study visit or considered at risk of virologic failure. At-risk criteria were defined as VL ≥ 50 copies/ml for three consecutive visits at least 6 months apart or abnormal pill count . Women were included if they were willing and able to provide informed consent to enrol in this substudy, had initiated an ART regimen at least six months prior to enrolment, were enrolled at a participating research site, and met the elevated VL or at-risk criteria. Women were excluded if they had plans to move out of the research area within one year.The study took place at the three PROMOTE study sites in Zimbabwe, two located in Chitungwiza, a dormitory city located about 30 km away from Zimbabwe's capital city of Harare, with a total of 354 women in the PROMOTE study, and one in Harare with 94 women. Participants included in this study were a subset of former participants from the multicountry IMPAACT PROMISE randomized trial (IMPAACT 1077BF) (NCT01061151) , 23 and ART initiated by these ART-naïve women during the PROMISE study for the purpose of preventing vertical HIV transmission during the pregnancy and breastfeeding period when they did not meet the criteria for initiating ART at that time is described elsewhere , 23. TheIn the national program, people living with HIV who were on ART had routine VL testing at 6 months after ART initiation, and annually thereafter if considered stable, i.e., VL < 1000 copies/ml and no opportunistic infections. VL testing was done on dried blood spots or plasma samples at centralized referral laboratories. Patients with elevated VL > 1000 copies/ml were switched to second line treatment following a second VL > 1000 copies/ml with EAC sessions having been conducted, or where there was evidence of immunologic or clinical failure without a repeat VL result. Pregnant and breastfeeding women on ART had their first ANC VL either 3 months after ART initiation if ART naïve or at the first antenatal clinic (ANC) visit if already on ART. If the woman had an elevated VL > 1000 copies/ml, EAC was conducted with a repeat VL after one month. Pregnant and breastfeeding women were prepared for treatment switch if repeat VL remained elevated above 1000 copies/ml. Women in the PROMOTE study had access to these services while being followed up on the study.Research records from 448 women enrolled in the PROMOTE study in Zimbabwe were reviewed. Participants meeting the eligibility criteria were selected for the substudy entry and approached by study personnel at a scheduled PROMOTE study visit.After providing informed consent to enrol into the substudy, eligible women were enrolled and randomized 1 : 1 to receive either motivational EAC (mEAC) and POC VL testing (intervention arm) or standard of care (SOC) VL monitoring and EAC (control arm). Following randomization, blood samples for VL monitoring were collected by trained nurses at study entry and at months 3, 6, and 12 after enrolment. As no testing machines were housed at the clinics where the study was conducted, samples for both arms were sent to the University of Zimbabwe Clinical Trials Research Centre (UZ-CTRC) Central Laboratory, where testing was done using the Gene Xpert® for POC tests and the Abbott® for SOC tests by trained laboratory scientists. The Gene Xpert Qual Assay used for POC testing was validated against the qualitative COBAS® AmpliPrep/COBAS® TaqMan® HIV-1 Test version 2.0 at BARC Laboratory in South Africa prior to study implementation . VL resuWomen who fell pregnant during the study could continue study participation as the benefits derived from the interventions included reduced transmission to the infants and better health outcomes for the mother and the baby.The primary outcome of interest was the proportion of women with viral suppression at 6 months and sustained at 12 months poststudy entry. Viral suppression was defined as VL < 200 copies/ml at each of the two timepoints. The characteristics of women who continued to have VL ≥ 200 copies/ml (unsuppressed VL) were also determined at both time points. For our secondary outcomes, we determined if pill count eligibility criteria use was a good predictor of virologic failure, and whether the use of POC VL testing improved HIV VL result delivery to participants.Based on Pocock's formula, 25 participants were selected for each study arm, with an additional 3 (∼10%) to allow for loss to follow-up or reasons prohibiting intervention, providing 80% power to detect a 28% increase in the proportion of women who achieve the primary outcome of viral suppression at 6 months.A randomization list was generated by a trained data manager at one of the three study sites using Microsoft Excel. Continuous numbers between 0 and 1 were generated using the = RAND  function on a list of randomization arms, noted as Arm 1 (intervention) or Arm 2 (control). A list of study participant identification numbers linking the treatment assignments was generated for the study and the randomization list applied to the arms. Participants were enrolled at their respective sites and assigned the next available arm on the list consecutively by the data manager responsible for generating the list, with data teams from each site requesting a treatment assignment at the point of participant enrolment.Sociodemographic-, medical-, laboratory-, and drug-related data routinely collected for the PROMOTE study was extracted from the PROMOTE dataset. Additionally, a structured data form was designed to capture the study-specific viral load data and results of the implementation process. These forms were completed by trained study staff in real time, reviewed for completeness and accuracy, and captured into the online study database. Participants were considered lost to follow-up if they missed two or more visits, including the month 12 visit, or a visit was noted as missed if one was missed, including the month 12 visit.Quantitative data was analyzed using STATA, Version 15.1, Stata Corp, 4905 Lakeway Drive, College Station, Texas 77845, USA,  to estimp value <0.05 for independent and dependent variables, respectively. For continuous data, a regression analysis was done to estimate the association between variables and randomization or viral suppression. The characteristics of the women who continued to have a viral load ≥200 copies/ml despite the intervention provided were analyzed using bivariate and multivariate logistic regression to determine the odds ratio (OR) and adjusted odds ratio (aOR) with 95% CI, respectively, at months 6 and 12. Variables used for aOR determination were selected based on prior literature [For categorical data, Fisher's exact and McNemar tests were used to test for association between variables and randomization or viral suppression using the 95% confidence interval (CI) with a difference being noted if terature . Pill coThe study was conducted in compliance with local regulatory requirements and in accordance with Good Clinical Practice (GCP) principles laid out by the International Conference on Harmonization (ICH) and the Declaration of Helsinki. The study was approved by the Medical Research Council of Zimbabwe (MRCZ)  and the Joint Research Ethics Committee (JREC) for the University of Zimbabwe Faculty of Medicine and Health Sciences, and Parirenyatwa Group of Hospitals . Written informed consent was obtained from the women for their participation prior to the conduct of the study.Between December 2018 and July 2019, 448 women were screened from the PROMOTE study in Zimbabwe. 157 (35%) participants were eligible for entry into the substudy, with 410 (91.5%) being virally suppressed . From thp value >0.05).p value 0.387) . Five participants missed their month 6 visit. At month 12, 42 (84%) of the participants were retained in care. 29 (69%) were virally suppressed, 14 of 21 (67%) in the intervention arm and 15 of 21 (71%) in the control arm . Two participants were considered lost to follow-up, while 6 missed the month 12 visit.At study entry, 30 (60%) of the women were virally suppressed, 13 (52%) in the intervention and 17 (68%) in the control arm (e 0.387) . At montWe considered the site of participation, randomization, age, duration of treatment, marital status, travel time to clinic, depression score above 4, mean pill count at screening, HIV disclosure, pregnancy intention at last pregnancy, breastfeeding status, level of education, and employment status at enrolment -3. At moThere was a marginal change in the odds of viral suppression for participants in the intervention arm compared to those in the control arm after adjusting for age, duration on treatment, and disclosure status to the partner using multiple regression  .At month 12, the odds of viral suppression decreased by a factor of 0.80 in the intervention arm compared with participants in the control arm (CI 0.22–2.97). Viral suppression decreased by a factor of 0.92 and 0.55 with each 1-year increase in age and duration on treatment, respectively. There was a 1.2-fold increase in viral suppression with HIV status disclosure, while suppression decreased by a factor of 0.35 with treatment switch . After aThere was an association between participants eligible by pill count and viral load suppression at 6 months and 12 months poststudy entry. Participants who were eligible for enrolment based on pill count were likely to be virally suppressed by 98% at month 6  , and 86%Participants with VL ≥ 200 copies/ml at entry or month 3 were required to attend three EAC or mEAC sessions before the next VL blood sample was taken at month 3 or 6, respectively. Of the 20 participants with VL ≥ 200 copies/ml at enrolment, 15 (75%) had all three EAC sessions with a follow-up VL test (full intervention) at month 3 visit. In the control arm, 4 (50%) of the 8 participants received the full intervention by month 3 visit, and in the intervention arm, 11 (92%) of the 12 participants received the full intervention. At month 6, nine of the 11 participants (91%) not suppressed (VL ≥ 200 copies/ml) at month 3 received the full intervention by the month 6 visit. In the control arm, 3 (60%) of the 5 participants not suppressed at month 3 visit received the full intervention at month 6, while in the intervention arm, all 6 (100%) of the participants with unsuppressed VL at month 3 received the full intervention .Of the 192 EAC visits required from study entry up to the month 12 visit, 155 (81%) of the participants with VL ≥ 200 copies/ml managed to complete their required EAC sessions. Of the 155, 56 VL visits were conducted, and 10 results showed viral suppression, 5 at month 3, 2 at month 6, and 3 at month 12 visit .Participants were required to attend three VL testing visits at months 3, 6, and 12 poststudy entry. From a total of 150 required VL visits, 126 (84%) viral load visits were conducted, with 86 (68%) of the 126 VL results obtained showing viral suppression. Ten participants had a sustained VL ≥ 200 copies/ml from study enrolment through to the month 12 visit .Visit burden at month 6 was assessed for both women with suppressed and unsuppressed VL . ParticiFourteen (28%) participants had their treatment switched by the month 12 visit, 7 (50%) in each arm. Ten were switched as part of the change in national treatment guidelines from Efavirenz (EFV)-based ART to Dolutegravir (DTG)-based ART, while four were switched because of treatment failure. Of the 10 having regimen switch because of a change in national guidelines, one had elevated VL at month 6 and became virally suppressed by month 12 visit. Of the four participants switched because of treatment failure, one participant was switched at the month 2 visit and became virally suppressed by month 3 visit before missing the month 6 visit and ultimately being lost to follow up by the month 12 visit. The new regimen was not documented.Of the 16 women with VL ≥ 200 copies/ml at month 6, three (19%) had the ARV treatment switch to second line treatment because of virologic failure. The timing of treatment switch varied with one participant being switched at the month 6 visit, the second between 91 and 180 days, and the third was switched more than 180 days after the month 6 visit. All three participants were switched from TDF/3TC/EFV to second line treatment consisted of either Abacavir (ABC) (two participants) or Zidovudine (AZT) (one participant) plus Lamivudine (3TC) backbone, with ritonavir boosted Atazanavir (ATVr). Of these three, only two presented for the month 12 visit.In this pilot study aimed at achieving viral suppression using a VL cut-off limit of <200 copies/ml, IMB-modeled motivational EAC sessions with POC VL testing did not reduce the proportion of women with unsuppressed VL at 6 months and 12 months poststudy entry. Apart from being eligible based on pill count, there were no characteristics that were significantly associated with suppressed VL at both 6 months and 12 months poststudy entry. Pill count did not predict virologic failure, as participants who were eligible based on pill count were more likely to be suppressed at both month 6 and 12 poststudy entry. POC VL result delivery achieved better outcome in terms of full EAC delivery. Result delivery for the intervention arm was not on time for more than half the participants.Different studies have reported various suppression rates with different VL cut-off limits being used, indicating the need to review the VL limit used in care as low-level viremia continues to be associated with transmission at different levels , 16, 28.We looked at treatment switch following unsuppressed viral load up to 6 months poststudy entry, as part of a strategy to achieve viral suppression following virologic failure. This study noted a treatment switch rate of 25% among those participants needing a regime change, raising the need to explore further why participants were not accessing treatment switch when required. In 2019, the WHO updated its guidelines to shift from EFV-based ART to DTG, combined with two nucleoside reverse-transcriptase inhibitors (NRTIs) as first-line treatment because of the evidence of higher viral suppression and lower risk of discontinuing treatment and developing HIV drug resistance compared with EFV-based regimens among treatment-naive adults . Other aVarious factors have been associated with unsuppressed viral load in different settings , 27, 33.Pill count was used as one of the eligibility criteria to assess if a pill count out of the range of 90–110% was associated with future virologic failure. The results indicate that the pill count was close to 100% for those assessed, and those who were eligible based on pill count were more likely to remain suppressed. Atuhaire et al. assessed self-report and not pill count as a possible proxy for virologic failure  and noteThe WHO have dropped the threshold for action from 1000 copies/ml with EAC now due with detectable VL (≥50 copies/ml), whilst also advocating for POC VL testing to reduce result TAT and provide real-time feedback to women on ART . In thisResult TAT was an important factor in monitoring viral response because of the early detection and reporting of virologic failure and action on results. In the intervention arm, result delivery on the day of testing (Day 0) was very challenging with less than half of the participants receiving the result on the same day of test. It was because of the POC testing machine being located off site and at the central laboratory. The study had access to one testing machine only, which was shared across the three research sites and among other studies. It resulted in near-POC services being provided with results being sent to sites via telephone or e-mail once ready or printed copies being sent the day following the visit to ensure that the participant received the result as soon as possible. Because of the effort to get results to sites as soon as possible, participants in the POC arm received their results for a median of 25.5 days of testing, compared with 130 days median in the control arm. There is, therefore, value in utilizing regionalized testing machines as the result TAT was still reduced with participants having earlier access to results with the less complex 2-hour VL testing platform.There was a trend observed toward higher completion of the mEAC cycle in the intervention arm compared to the control arm participants, indicating that the three elements of the intervention are highly relevant to the current efforts to adapt WHO 2021 treatment guidelines locally and across the region . A studyThis study's findings begin to outline implementation considerations for treatment experienced perinatal women that need additional focus and modification of current practice. Policy should consider using POC testing to ensure rapid result delivery and intervention in women with unsuppressed HIV VL.As gaps remain in the effort to achieve viral suppression through adequate counseling and treatment switch strategies, there is a need to explore increased access to drug level monitoring and resistance testing to ascertain sooner the reasons for poor viral suppression in women who have been on ART for a prolonged period. Reasons for failure to switch treatment timeously also need exploring as there is an increased risk of development and transmission of drug resistance virus. There are still other factors that impact adherence to ART that were not explored in this study, including the impact of individual compared to group adherence counseling, person delivering the intervention, and children under 5 years being cared for by the woman. These factors have been associated with unsuppressed VL in some studies and could be considered a contributor in this cohort of women.Because of the small sample size used in this study, we were not able to detect significant differences in interventions and comprehensively conclude on the characteristics predictive of future virologic failure in women on life-long ART. The results are also limited in being generalizable as the cohort of women selected for this study were in follow-up in an ongoing research study with compensation for attending visits for at least three years. The study was also not able to measure fidelity in intervention delivery as each participating site delivered both interventions to their participants. There is a risk of intervention contamination as a counsellor could easily administer an incorrect intervention or viral load test being requested on the wrong platform resulting in delays in the POC arm. The interventions in both arms were also delivered as a comprehensive package. Hence, we were not able to detect the effect of each component of the intervention on viral suppression.Adherence support and rapid intervention in unsuppressed viral load are vital in women on life-long ART as viral suppression remained low in this cohort of treatment experienced women. The use of POC is recommended to improve result delivery. More research is required to explore strategies that will improve adherence to ART in this cohort. The use of more impactful motivational EAC with limited contact time could be explored. The availability of qualitative data can also help tease out relevant intervention strategies that may be more effectively implemented.


In sub-Saharan Africa, data on virologic outcomes of young people living with HIV (YLWH) enrolled on antiretroviral therapy (ART) remains scarce. In this study, we describe the prevalence of HIV virological non-suppression (VNS) and its associated factors among YLWH aged 18–24 years from the Kenyan coast.Data were analyzed for 384 YLWH who participated in a larger cross-sectional study conducted between November 2018 and September 2019 in two counties at the Kenyan coast (Kilifi and Mombasa). Descriptive statistics were used to summarize sample characteristics and logistic regression was used for statistical modeling of factors associated with VNS. In this study, VNS was defined as plasma viral load ≥ 1000 copies/mL.32.0% : 27.5, 36.9%). In the multivariable logistic regression analysis, being from a largely rural setting (adjusted Odds Ratio (aOR) 1.73, 95% CI 1.10, 2.71; p = 0.02), underweight  and low self-reported ART adherence  were significantly associated with higher odds of VNS in YLWH.Among these YLWH with a mean age of 20.7 years (SD = 2.2); 55.5% females, the overall prevalence of VNS was In this study, high levels of VNS were observed among YLWH and this was significantly associated with rural residency, nutritional and ART adherence problems. ART adherence counselling and nutritional support and education should be intensified in this setting targeting YLWH residing mostly in rural areas. Given the high frequency of VNS, there is need to closely monitor viral load and profile HIV drug resistance patterns in youths from the Kenyan coast with confirmed virologic failure. The latter will help understand whether drug resistance also contributes to poor viral suppression in addition to, or exclusive of suboptimal ART adherence. Globally, 3.4 million young people aged 15–24 years were living with HIV by 2019 . In KenyThe advent, increasing access and continued adherence to antiretroviral therapy (ART) has transformed the management of HIV from a fatal disease to now a manageable chronic condition . A key gStudies from different geographical settings—mostly in the West—have investigated virologic suppression status among YLWH on ART. In general, suboptimal level of viral suppression among these youths is evident. In a global review of virological outcomes of YLWH , the preInvestigations of the factors associated with VNS among YLWH are generally scarce, more so in SSA. Most of the existing studies are limited in terms of consensus and some studies present contradictory findings, albeit because of contextual differences. For instance, long duration on ART was found to be significantly associated with lower odds of VNS among Cambodian youths , while aData on virologic outcomes of YLWH enrolled on ART in SSA is limited. In particular, knowledge about the factors associated with VNS in this sub-population is not widely documented. In Kenya, we are aware of a recent study investigating VNS among YLWH 10–24 years old  but thisThis work is part of data collected from a larger cross-sectional study conducted between November 2018 and September 2019 along the Kenyan coast. The details of the methodology have been described previously . Below, Study participants were YLWH recruited through consecutive sampling from 20 geographically diverse HIV-clinics in two counties at the Kenyan coast . Kilifi County is largely a rural setting with an estimated population of 1.5 million people . HIV preEligibility criteria in the larger study included: age range of 18–24 years, a confirmed HIV-positive status, being on ART and providing informed consent for participation. YLWH were identified from existing clinic records, contacted, and invited for study briefs at a day coinciding with the monthly teen support group meetings. Those who could not be reached via available mobile contacts or without contact details were traced during their next scheduled clinic appointment dates. Bookings for study interviews were done after consenting participants had been taken through the study in details by research assistants present at the time of the meeting. Eligible for the present analysis were young people on ART for at least 6 months  utilizing about 1200 µL of plasma. All the remaining plasma were individually labelled and archived at − 80 °C for future investigations that will involve ART plasma concentration and HIV drug resistance genotyping. In the event the viral load test failed on the first attempt, an extra 1200µL of archived plasma was retrieved for a repeat run. In this study, YLWH were categorized as having VNS if their plasma viral load was ≥ 1000 copies/mL in line with WHO recommendations . All theThe sociodemographic form captured participant’s age, sex, educational level, employment status, religion, relationship status, area of residence, living status of parents and whom they currently lived with. The asset index form gathered information about individual or family ownership of disposable items as a proxy indicator of socioeconomic status.This form captured data on whether participants currently smoked cigarette, chewed khat or used alcohol using a yes/no response option via audio computer-assisted self-interview (ACASI). Self-report information sought from YLWH included disclosure of their HIV status, their level of satisfaction with current care and their view on accessibility of their current point-of-care. YLWH were also asked whether they experienced any current ART side effects or an opportunistic infection, as informed by their clinician.This included data on participant current ART regimen and duration they have been on ART, WHO clinical staging of HIV, height and weight (recorded during the most recent clinic visit) for body mass index (BMI) computation, categorized as underweight (BMI < 18.5), normal (BMI of 18.5–24.9), overweight (BMI of 25.0–29.9) and obese (BMI ≥ 30.0). Participants were managed based on local guidelines on use of antiretroviral drugs for treating and preventing HIV infection .the 9-item patient health questionnaire (PHQ-9) [A locally validated version of  (PHQ-9) , adminis (PHQ-9) , a cut-o (PHQ-9) , indicatThe brief 12-item HIV stigma scale [ma scale , adminisThe 4-item Morisky, Green and Levine Medication Adherence Scale (MGLS) [e (MGLS)  was used2) test and independent Student’s t-test were used to compare group differences for categorical and continuous variables, respectively. Proportions as percentages were used to estimate the prevalence of VNS. Univariate logistic regression analysis was used to assess the crude association between exposure variables  and the outcome variable (VNS). All variables with p < 0.25 from univariate analyses were taken forward to the multivariable logistic regression analysis which was used to investigate factors independently associated with VNS. Backward stepwise logistic regression models were fit in the multivariable model building process, removing all variables with p > 0.05 (one at a time). Collinearity diagnostics were performed for the final multivariable model, with no multicollinearity problems identified based on interpretation of the variance inflation factor. A p-value > 0.05 in the Hosmer–Lemeshow goodness of fit test was considered a well-fitting final logistic regression model. For all tests of hypothesis, a two-tailed p-value of < 0.05 was considered statistically significant, with a confidence interval of 95% used to report on the precision of the reported estimates.All analyses were conducted in STATA version 15.0 . Basic descriptive statistics  were used to summarize sample characteristics by group viral suppression status . Chi-squared : 27.5, 36.9%). The prevalence of VNS was significantly higher among YLWH from the rural setting compared to those from the urban setting, 37.8%  vs 26.5% ; p = 0.02.Figure The univariate logistic regression analysis showed that being from a rural setting, underweight, low self-reported ART adherence, presence of a current opportunistic infection and disclosure of HIV status significantly increased the odds of VNS Table . Lack ofaOR 1.73 95% CI 1.10, 2.71; p = 0.02), underweight  and low self-reported adherence to ART  were significantly associated with higher odds of VNS. Hosmer–Lemeshow goodness of fit statistic for the final regression model was X215) of these youths were virally non-suppressed and this was significantly associated with rural residence, being underweight and low ART adherence. Other studies investigating VNS among YLWH in SSA and beyond report varying prevalence estimates, some similar to what we observed, for instance estimates of 26% reported by a study conducted in Ethiopia , 39% in Across the above studies documenting VNS prevalence, of note is the differences in the threshold applied when defining VNS and the recruited age groups of YLWH which may account for the variation in prevalence estimates. For instance, the South African  and TanzAs would be expected and consistent with previous findings , 39, 40,To the best of our knowledge, this is the first study from SSA to report a significant association between low BMI  and higher odds of VNS among YLWH. Similar associations have been reported in studies involving the general adult population with HIV –53. ContIn this study, rural residency was significantly associated with nearly twofold higher odds of VNS. This finding is difficult to compare within the literature of virologic outcomes in YLWH; we are not aware of any study that reports this kind of association. However, the finding is supported by an investigation from Ethiopia involving adults living with HIV . Living We did not observe any significant associations between VNS and demographic variables of age and sex. In contrast, other studies have found significant association between VNS and youth age –24 or seHIV-related stigma has been associated with higher odds of VNS in YLWH  but thisThe findings reported in this study should be interpreted in the context of several study limitations. First, the cross-sectional analyses do not allow for any causal inference. Second, we did not include underlying HIV drug resistance in the analyses, and this could also be a cause of VNS . Future A considerable proportion of YLWH in this study were virally non-suppressed. In this setting, rural residency, being underweight and poor ART adherence are important indicators associated with VNS that necessitate intensified adherence counselling and nutritional support and education which should target YLWH mostly from rural areas. Given the high frequency of VNS, there is need to closely monitor viral load and profile HIV drug resistance patterns in youths from the Kenyan coast with confirmed virologic failure. The latter will help understand whether drug resistance also contributes to poor viral suppression in addition to, or exclusive of suboptimal ART adherence but also inform the need for ART regimen switching.


Late HIV diagnosis (i.e CD4≤350 cells/µL) is associated with poorer outcomes. However, determinants of long-term mortality and factors influencing immune recovery within the first years after antiretroviral treatment (ART) initiation are poorly defined.From PISCIS cohort, we included all HIV-positive adults, two-year survivors after initiating ART between 2005–2019. The primary outcome was all-cause mortality according to the two-year CD4 count. We used Poisson regression. The secondary outcome was incomplete immune recovery . We used logistic regression and propensity score matching.We included 2,719 participants (16593·1 person-years): 1441 (53%) late presenters (LP) and 1278 non-LP . Overall, 113 patients (4·2%) died. Mortality was higher among LP with two-year CD4 count 200–500 cells/µL (aMRR 1·95[95%CI:1·06-3·61]) or <200 cells/µL (aMRR 4·59[2·25-9·37]).p = 0·48). The stronger factor influencing immune recovery was the CD4 count at ART initiation. First-line integrase-inhibitor-(INSTI)-based regimens were associated with reduced mortality compared to other regimens (aMRR 0·54[0·31-0·93]) and reduced risk of incomplete immune recovery in LP (aOR 0·70[0·52-0·95]).Conversely, no differences were observed in participants with two-year CD4 counts >500 cells/µL, regardless of being initially LP or non-LP (aMRR 1·05[0·50-2·21]). Mortality rates within each two-year CD4 strata were not affected by the initial CD4 count at ART initiation (test-interaction, Two-year immune recovery is a good early predictor of long-term mortality in LP after surviving the first high-risk 2 years. Nearly half experienced a favorable immune recovery with a life expectancy similar to non-LP. INSTI-based regimens were associated with higher rates of successful immune recovery and better survival compared to non-INSTI regimens.Southern-Denmark University, Danish AIDS-foundation, and Region of Southern Denmark. Three cohort studies and two randomized controlled trials (RCT) have indicated that integrase strand transfer inhibitors (INSTI)-based regimens might offer a benefit in immune recovery compared to other ART regimens. However, these cohort studies included both late and non-late presenters, and the last is under-represented in RCT. Knowledge on determinants of long-term mortality and immune recovery in late presenters is scant.Our results provide new evidence that ART initiation with an INSTI-based regimen is associated with a more favorable immune response in late presenters and with improved long-term survival especially compared to protease inhibitors.Besides, PLWH surviving the first two years after ART initiation and reaching a CD4 cell count threshold above 500 cells/μL achieved similar survival rates to non-late presenters, irrespective of their baseline CD4 count at ART initiation. Thus, ART-associated immune recovery at two years was a good early predictor of long-term mortality.The long-term survival prognosis for late presenters can be assessed upon immune recovery seen two years after ART initiation. Those achieving an early favorable response improve their life expectancy to the same level as non-late presenters, thus narrowing the gap between late and non-late presenters. INSTI-based ART is associated with a more favorable immune response and significantly improved survival, supporting the growing body of evidence in clinical trials. Based on all knowledge available, health care programs should consider using two-year CD4 cell counts after ART initiation as an early prognostic factor for long-term survival in late presenters. Also, INSTI-based regimens should be considered the preferred treatment choice, particularly in late HIV presenters.Alt-text: Unlabelled boxHIV-associated morbidity and mortality have decreased dramatically since the introduction of antiretroviral therapy (ART) in 1996. Today, people living with HIV (PLWH) timely diagnosed and starting treatment with CD4 counts ≥350 cells/μL have life expectancies close to the general population.,,,This late HIV diagnosis significantly reduces life expectancy while increasing the frequency of HIV-related comorbidities,,Various observational studies of late presenters (LP) have reported high mortality rates within the first year after ART initiation, mainly due to advanced AIDS-defining conditions present at that time, which tends to decrease after this period.This study explores the performance of an early predictor for long-term survival after ART initiation, skipping this initial high-risk time. Furthermore, the influence of the first-line ART on the clinical trajectories of LP is poorly understood. Various studies have described that first-line ART with integrase strand-transfer inhibitor (INSTI)-based regimens could be associated with an improved immune response with greater CD4 gain.In this prospective multicentre, ongoing cohort of PLWH in our area, we aimed to investigate whether CD4 cell counts 2 years after ART initiation was a good early predictor of long-term survival in LP compared with a non-LP group with an optimal two-year immune response and explored determinants of survival in these patients, including the potential impact of INSTI as first-line regimen. Furthermore, we assessed the predictors of adequate immune recovery within this period.This is a multicentre, prospective, population-based longitudinal analysis conducted in Catalonia, an autonomous region located in north-easter Spain. On January 1, 2021, Catalonia had a population of 7·7 million citizens and an estimated HIV prevalence among the adult population of 0·4%.th revision (ICD-10).Data were retrieved from the PISCIS Cohort project  and PADRIS . For this study, only data from the Catalan PISCIS cohort were used. Briefly, PISCIS is an ongoing, prospective, multicentre, population-based cohort ongoing from 1998 that includes all PLWH aged ≥16 years followed in one of the 16 collaborating hospitals from Catalonia, representing 84% of all diagnosed PLWH.The PISCIS cohort has been approved by the ethics committee of the coordinating centre, and patient data extraction is allowed by the 203/2015 Decree from the Catalan Health Department. PISCIS data is owned by each individual patient, and data is eliminated if requested by the hospital or by a patient. All data is pseudo-anonymized before arriving at the coordinating center, and confidentiality is guaranteed in accordance with the provisions of the Regulation (EU) 2016/679 of the European Parliament and of the Council of 27 April 2016 on the protection of natural persons regarding the processing of personal data and on the free movement of such data and the new national Organic Law 3/2018 of December 5 on Protection of Personal Data and Digital Rights.PISCIS cohort for treatment naïve PLWH ≥18 years, who initiated ART between January 1, 2005, and June 30, 2019. Of these, we included all 2-year survivors with active follow-up and available CD4 cell count at both timepoints, ART initiation and two years after treatment start.We screened the Patients were classified according to the CD4 cell count at ART initiation into late HIV presenters  and non-LP . LP were further stratified according to their CD4 count at two different time points: at ART initiation  and at 2 years after ART initiation . Non-LP were also stratified according to their immune recovery two years after ART initiation (≤500 cells/μL and >500 cells/μL).The primary outcome was time to all-cause mortality, setting the baseline time at two years after ART initiation. We chose a two-year time-point expecting to get rid of the bias introduced in the analysis by initial mortality related to baseline conditions in this cohort of PLWH with advanced HIV infection. The outcome was assessed for the different groups of LP based on the CD4 count immune recovery two years after ART initiation; non-LP with CD4 >500 cells/μL two years after ART initiation was used as the reference population.The secondary outcome was incomplete immune recovery two years after ART initiation, defined as CD4 cell count ≤500 cells/μL. This was assessed in a nested case-control study design.Continuous variables were described as the median and the interquartile range (IQR), whereas categorical variables were presented as the frequency and percentage over available data. Missing data were not imputed because the essential variables for the analysis  were among the selection criteria for the study population. We used the chi-squared test, the t-test, and the Mann–Whitney U test to compare variables between late and non-LP. For polycothomous categorical variables with a statistically significant chi-square test of homogeneity, we further provided a significance test of the difference between proportions across categories of the variable between LP and non-LP.The survival analysis considered all-cause death, loss-to-follow-up, or end of the observation period, whichever occurred first, between the 2-year time point after the date of ART initiation to June 30, 2021. The cumulative survival of PLWH in the different groups of two-year CD4 cell count was compared using the Log-rank test. We used a Poisson regression analysis to control for the following potential confounders and to explore for prognostic factors for survival: age, gender, HIV risk group (men who have sex with men (MSM), heterosexual men, women, history of injection drug use (IDU), and other/unknown), region of birth , two-year CD4 cell count recovery , two-year HIV viral load (>200 vs ≤ 200 copies/mL), modified Charlson comorbidity index (CCI) at two years after ART initiation, prior AIDS-defining disease at two years after ART initiation, time-updated calendar period .We conducted a sensitivity analysis using propensity score matching  for gender, age, CD4 cell count, modified CCI, and AIDS-defining event, all at ART initiation, to assess the impact of initiation of INSTI as first- line regimen on long-term mortality. The application of these probabilities to the study population created a subpopulation in which these potential confounders were more equally distributed across both groups. The same analysis was performed for the whole database population of individuals who initiated ART, regardless of survival in the first two years or availability of CD4 counts at 2 years after ART.To identify risk factors in the group of LP associated with incomplete immune recovery 2 years after ART initiation (defined as CD4 cell count ≤500 cells/μL), we performed a logistic regression analysis with propensity score matching on age (continuous), gender, CD4 cell count at ART initiation ) and modified CCI. We assessed the following covariates at ART initiation: age, gender, CD4 cell count, INSTI as first ART regimen, modified CCI, AIDS-defining event within 90 days after ART initiation. We provide the odds ratio (OR) and a 95% CI.All analyses were conducted using the STATA software .This work was supported by scholarships from the University of Southern Denmark, the Danish AIDS foundation, and Public Regional Funds from the Region of Southern Denmark. The study was investigator-driven and thus independent of any pharmaceutical company. The funding sources were not involved in study design, data collection, analyses, report writing, or decision to submit the paper.From the PISCIS cohort, we identified 4036 PLWH starting ART between 2005 and 2019. Of them, 2719 (67·4%) were eligible for the analysis, giving rise to 16593·1 person-years of follow-up (median follow-up 5·8 years [IQR 3·2-8.9]) . Table Sp<0·001). Among LP, 27% initiated ART with a CD4 cell count <100 cells/µL, 21·8% with 100–199 cells/µL and 51·6% with 200–350 cells/µL, and 13·2% had an AIDS-defining event at baseline. Six hundred thirty-seven (44·2%) of late presenters achieved CD4 cell counts >500 cells/µL two years after ART start. The comparator population of non-LP with two-year CD4 cell count >500 cells/µL (n =1145) had a median two-year CD4 count of 837 (IQR: 697-1030).p = 0·48) .Overall, 113 (4·2%) died during the study period . Compared with non-LP with two-year CD4 count >500 cells/µL (reference population), LP with two-year CD4 count ≤500 cells/µL had higher mortality . Conversely, no significant differences were observed between the adjusted MR of non-LP and LP with two-year CD4 count >500 cells/µL (1·05 [0·50-2·21]) (versus non-INSTI regimens (0·48 [0·25-0·90]) (Table S5). We did a second sensitivity analysis including all individuals starting ART regardless of survival the first two years or availability of CD4 cell count two years after ART. In line with the previous analysis, the sensitivity analysis showed that INSTI-based first-line regimens were associated with a survival benefit when compared to protease inhibitor (PI) (0·41 [0·23-0·72]) but not versus non-nucleoside reverse transcriptase inhibitors (NNRTI (0·88 [0·48-1·61]), Table S5).INSTI-based regimens as first-line ART were associated with lower mortality than non-INSTI regimens (0·54 [0·31-0·93]). There was an improved survival trend when considering LP and non-LP separately, but it was not statistically significant . However, the sensitivity analysis with propensity score matching, conducted to address the potential channeling bias, did show a significant benefit of INSTI n =349), with similar results . The long-term survival analysis comparing non-LP achieving CD4 cell count >500–699 and those with ≥700 cells/µL did not reveal significant differences between groups (0·57 [0·21-1·51]) (Tables S6 and S7).The log-rank test revealed significant differences between survival curves for all-cause mortality . HoweverIn this population-based prospective cohort study with 2719 PLWH initiating their ART between 2005 and 2019 and surviving the first two years, 53% of them were diagnosed at a late stage . Despite this delayed ART initiation in these patients presenting late to care, 44% achieved an optimal immune recovery with a CD4 cell count >500 cells/µL at two years. LP achieving two-year CD4 cell count >500 cells/µL had comparable long-term mortality rates to non-LP, irrespective of their initial CD4 cell count. CD4 cell count recovery two years after ART initiation was a useful early predictor of long-term mortality. Exposure to an INSTI-based ART regimen in the first two years was associated with a significantly better two-year immune recovery and better long-term survival. A lower CD4 cell count, older age, and worse CCI score at ART initiation significantly increased the risk for incomplete two-year immune recovery.,,,,Although LP have an overall increased mortality, earlier studies have shown that the risk of death and/or AIDS is highest in the first year after HIV diagnosis and decreases hereafter.,Our findings in immunological non-responders are in accordance with results from the COHERE cohort,,,,,Several studies have described a better CD4 count recovery in patients exposed to INSTI-based regimens, mainly versus efavirenz-based regimens.25To our knowledge, this is the first study to identify the exposure to INSTI-based regimen first-line ART with a significantly higher probability of reaching a successful immune recovery with a significant impact on long-term mortality in LP. Nonetheless, the strongest independent risk factor for incomplete immune recovery was lower CD4 cell count at ART initiation, reinforcing the importance of timely HIV diagnosis.Our study is strengthened by the prospective, population-based, multicentre HIV-cohort design, including 84% of all PLWH followed in Catalonia, and the long-term observation time. We had access to high-quality, real-world health data generated by the public health system providing additional information on comorbidities and mortality. We compared a fully characterized group of LP regarding their CD4 count at ART initiation and two-years after with non-LP with optimal immune response ) also including more recent calendar years and treatments. A propensity score matching helped us to obtain more comparable treatment risk groups in the cohort regarding INSTI-exposure, reducing possible channeling bias.n =20), so including these in the group of LP would not have significantly change the results. Second, we excluded 817 individuals from the analysis because initial (n =223) or two-year CD4 counts (n =708) were not available. Of the last group, 41% (n =281) corresponded to individuals whose two-year blood samples had to be collected during the COVID-19 pandemic years 2020-2021, where hospital closure for non-COVID-19 patients prevented access to perform these blood analyses. Of those missing CD4 cell count at ART initiation, most  belonged to the initial calendar period 2005-2009. Thirty-one (3·8%) of the excluded individuals died after ART initiation with a high proportion having a history of IDU (58%). This population differs from our overall study population being probably more prone to non-adherence to care and ART. Overall, these differences in the excluded population represent small absolute numbers and it is unlikely that it would have affected our results. Third, the availability and prescribing practices of INSTI have varied over time. We added calendar time to our models to adjust for these differences over time. However, we cannot rule out bias, especially residual channelling bias. When assessing the risk of incomplete immune recovery (two-year CD4 cell count ≤ 500 cells/μL) in LP we found 30% lower odds when initiating ART with an INSTI-based regimen. This trend was maintained when we also adjusted for calendar time, however, the results did not reach statistical significance, possibly due to lack of power. Other residual confounders such as viral resistance, lifestyle factors, or comorbidities other than the ones included were not examined, though these factors would be unlikely to have a significant impact on the results. Forth, the size of the study cohort is little with regard to a rare event like death, so risk of type II errors cannot be excluded. Finally, the lack of access to cause of death information is a limitation for the detailed interpretation of the mortality figures.On the other hand, some limitations must be considered. First, the definition of LP in our study included only CD4 cell count at ART initiation ≤ 350 cells/μL and not AIDS-defining events as we focused in CD4 responses. However, few non-LP experienced an AIDS-defining event , the coordinating centre of the PISCIS cohort study and from each of the collaborating hospitals upon request. Requests can be made via raquel@bisaurin.org).The study protocol, the statistical codebook and dofiles for the analysis can be requested from RMI (www.icmje.org/coi_disclosure.pdf and declare: no support from any organization for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.All authors have completed the ICMJE uniform disclosure form at RMI has received consulting honoraria and/or research grants from GSK, MSD, and Lundbeck, outside the submitted work. RMI has received payment for travel and congress assistance from MSD, outside the present work.JMM has received consulting honoraria and/or research grants from AbbVie, Angelini, Contrafect, Cubist, Genentech, Gilead Sciences, Jansen, Lysovant, Medtronic, MSD, Novartis, Pfizer, and ViiV Healthcare, outside the submitted work.JML has received payments or honoraria for lectures, presentations or speaker's bureaus from Janssen-Cilag, Gilead Sciences, and ViiV Healthcare, outside of the present work.