To investigate the characteristics and outcomes of people who initiated different antiretroviral therapy (ART) regimens during the era of integrase strand transfer inhibitors (INSTIs).UK-based observational cohort study.UK Collaborative HIV Cohort study participants were included if they had started ART between 1 January 2012 and 30 June 2017. Virological failure was defined as the first of two consecutive plasma HIV RNA more than 50 copies/ml, at least 6 months after starting ART. Follow-up was censored at ART discontinuation, class switch or death. The risk of virological failure among those on INSTI, protease inhibitor or nonnucleoside reverse transcriptase inhibitor (NNRTI) regimens was compared using Kaplan–Meier and Cox regression methods.P = 0.0009; protease inhibitor group adjusted hazard ratio 2.70, 95% confidence interval 2.27–3.21, P less than 0.0001, likelihood ratio test P less than 0.0001.Of 12 585 participants, 45.6% started a NNRTI, 29.0% a protease inhibitor and 25.4% an INSTI regimen. Over a median follow-up of 20.3 months (interquartile range 7.9–38.9), 7.5% of participants experienced virological failure. Compared with those starting an NNRTI regimen, people receiving INSTIs or protease inhibitors were more likely to experience virological failure: INSTI group adjusted hazard ratio 1.52, 95% confidence interval 1.19–1.95, First-line INSTI regimens were associated with a lower risk of virological failure than protease inhibitor regimens but both groups were more likely to experience virological failure than those initiating treatment with a NNRTI. There is likely to be residual channelling bias resulting from selected use of INSTIs and protease inhibitors in specific clinical contexts, including in those with a perceived risk of poor adherence. P < 0.001) . Participant follow-up was censored because of a regimen change for 38.2% ; at 6 months after the last clinic date for 21.1% ; at death for 0.9% of the cohort  and at the end of the study period for 39.9% , P less than 0.0001. Overall, 13.6% (1717/12 585) of the cohort were deemed lost to follow-up, . Figure P < 0.0001). Figure P = 0.002). The older protease inhibitor lopinavir had a higher cumulative incidence than darunavir and atazanavir, though this was a small group and the difference was not statistically significant (log-rank P = 0.31). The three INSTI agents had a similar virological response during the study period, although dolutegravir and elvitegravir had shorter follow-up times than raltegravir (log-rank P = 0.28).The cohort was followed for a total of 26 067 person-years, during which time 7.5% (947/12 585) experienced virological failure. The median follow-up time on ART was 20.3 months, interquartile range 7.9–38.9 ; ethnicity ; HIV acquisition risk group ; baseline CD4+ cell count ; and baseline HIV RNA . There was a trend towards lower risk of virological failure in the latter years of the study period: HR 0.72  for the 2014/2015 period and HR 0.81  for the 2016/2017 period, compared with 2012/2013, likelihood ratio test P = 0.0007. There was no significant difference between the NRTI backbones tenofovir-emtricitabine and abacavir-lamivudine.Univariate Cox regression was used to examine the association between other exposure variables and virological failure. Factors with some evidence for an association with virological failure were sex [women more likely to experience virological failure than men: HR 1.45, 95% confidence interval (CI) 1.20–1.73, + cell count, HIV RNA, NRTI backbone and year of ART initiation, the INSTI and protease inhibitor groups had a higher risk of virological failure than the NNRTI group. INSTI compared with NNRTI: adjusted HR(aHR) 1.52, 95% CI 1.19–1.95, P = 0.0009 , protease inhibitor compared with NNRTI: aHR 2.70, 95% CI 2.27–3.21, P less than 0.0001 , likelihood ratio test P less than 0.0001. The intention-to-treat analysis, in which follow-up was not censored in the case of ART class switch, showed similar results for the INSTI and protease inhibitor groups and a higher cumulative incidence in the NNRTI group . Sensitivity analyses using different definitions of virological failure showed that the number of events decreased as the threshold for failure increased, but the relative effects of treatment group were largely unchanged , with no impact from transmitted resistance [+ cell count and the use of abacavir compared with tenofovir.The INSTI group had a 1.52 times greater risk of virological failure compared with NNRTI, even after adjusting for other covariates. There was a more marked difference in the protease inhibitor recipients who were 2.7 times more likely to experience virological failure. This may be because there were other factors related to poor adherence that were not measured or controlled for in this analysis. Univariate analysis suggested sex, ethnicity, HIV acquisition risk group, baseline CD4 failure ,28. The sistance . This stOne of the strengths of the current study is that it uses real-world data from a multicentre collaboration that is likely to be representative of people living with HIV in the United Kingdom, with findings that may be generalizable beyond the population that is typically recruited into randomized trials. Another advantage is that participants could switch agents within a class without their follow-up being censored, thus increasing the follow-up time to examine class effects. However, as with any observational study, our analysis may be affected by unmeasured confounding as the choice of ART class (and drugs within a class) for a given individual will be determined by many factors, including (but not limited to) information on any comorbidities present  or any concomitant medications prescribed. This information may not be available in observational databases and, as a result, it may be difficult to control for these factors. Clinicians will often favour a particular ART class depending on the clinical context, even when following established treatment guidelines. For example, protease inhibitor-containing regimens and some of the newer INSTIs may be preferentially used for individuals in whom there were concerns about adherence due to the perceived higher genetic barrier to resistance of these drugs. Significantly, one of the UK CHIC contributing centres has explored the indications for raltegravir use up to the end of 2012 in treatment-naive patients, and these included the need for a rapid reduction in viral load, for example during pregnancy; concerns about drug interactions with other medication, particularly in the context of mycobacterial coinfection; and tolerability issues such as relative contraindications to efavirenz use . This inSeveral other limitations should also be noted. In particular, UK CHIC participants were excluded if they had an undetectable viral load at ART initiation to avoid misclassification of those already receiving treatment. However, it was not possible to detect those previously treated who then present to a participating centre as ART-naive. It was surprising that 1912 people appeared to have an undetectable viral load at ART initiation, suggesting that many were already receiving ART but this information was missing from their UK CHIC record, and this group were excluded from the study. The inclusion of the newer INSTIs elvitegravir and dolutegravir, which were licensed by the European Medicines Agency in May and November of 2013 respectively, means that this study may inadvertently have included some clinical trial participants, whose responses would be likely to differ . AlthougIn the INSTI era, first-line ART regimens containing INSTI or protease inhibitor were associated with a greater risk of virological failure than those containing NNRTI and adjusting for potential confounders did not remove this effect. Poorer virological outcomes in these groups may be related to factors associated with suboptimal adherence that have not been captured by this analysis. There is likely to be residual channelling bias resulting from selected use of INSTIs and protease inhibitors in specific clinical contexts. Furthermore, these findings illustrate the changing clinical practice in the use of first-line regimens in the United Kingdom and could be used for benchmarking of virological response in future studies.Authors’ contributions: K.E.B., S.J., A.N.P., A.S., D.T.D. and C.A.S. designed the study; K.E.B., S.J. and C.A.S. performed the statistical analysis; A.P., A.U., M.G. and A.W. contributed data and clinical interpretation of results; K.E.B. wrote the original draft; all authors were involved in reviewing and editing the final draft.The UK CHIC study is funded by the UK Medical Research Council . The views expressed in this article are those of the researchers and not necessarily those of the Medical Research Council. K.E.B. is supported by a Wellcome Trust clinical research fellowship (award number 170461). The data were presented at European AIDS Clinical Society (EACS) conference, 25–27 October 2017, Milan, Italy.UK CHIC study membersSteering Committee: Jonathan Ainsworth, Sris Allan, Jane Anderson, David Chadwick, Duncan Churchill, Valerie Delpech, David Dunn, Richard Gilson, Mark Gompels, Phillip Hay, Teresa Hill, Margaret Johnson, Sophie Jose, Stephen Kegg, Clifford Leen, Fabiola Martin, Dushyant Mital, Mark Nelson, Chloe Orkin, Adrian Palfreeman, Andrew Phillips, Deenan Pillay, Frank Post, Jillian Pritchard, Caroline Sabin, Achim Schwenk, Anjum Tariq, Roy Trevelion, Andy Ustianowski, John Walsh.Central Co-ordination: University College London ; Medical Research Council Clinical Trials Unit at UCL, London .Participating Centres: Barts Health NHS Trust, London ; Brighton and Sussex University Hospitals NHS Trust ; Chelsea and Westminster Hospital NHS Foundation Trust, London ; Homerton University Hospital NHS Trust, London ; King's College Hospital NHS Foundation Trust, London ; Middlesbrough, South Tees Hospitals NHS Foundation Trust, ; Mortimer Market Centre, Central and North West London NHS Foundation Trust/Universtiy College London ; North Middlesex University Hospital NHS Trust, London ; Royal Free NHS Foundation Trust/Universtiy Collage London ; Imperial College Healthcare NHS Trust, London ; The Lothian University Hospitals NHS Trust, Edinburgh ; North Bristol NHS Trust ; Leicester, University Hospitals of Leicester NHS Trust ; Woolwich, Lewisham and Greenwich NHS Trust , St. George's Healthcare NHS Trust ; York Teaching Hospital NHS Foundation Trust ; Coventry, University Hospitals Coventry and Warwickshire NHS Trust ; Wolverhampton, The Royal Wolverhampton Hospitals NHS Trust ; Chertsey, Ashford and St.Peter's Hospitals NHS Foundation Trust ; Milton Keynes Hospital NHS Foundation Trust ; The Pennine Acute Hospitals NHS Trust ; Public Health England, London (V Delpech); i-Base (R Trevelion).S.J. has received speaker's fees from Gilead Sciences. A.P. reports grants and personal fees from ViiV, Gilead, Janssen, Merck, outside the submitted work; is Principal Investigator on a Test and Treat programme in Tanzania; and is part of a research group investigating new antiretroviral regimens in South Africa. A.U. has received speaker and advisory board fees from Abbvie (in other disease areas), BMS, Gilead, Janssen, MSD and Viiv; and has received grant support from Gilead and Abbvie (in other disease areas). M.G. has received grants from BMS and Gilead to attend CROI and World AIDS 2017; all HIV companies sponsor lunches at local meetings; and has received personal fees from Advisory board to Biocryst, grants from Novartis, grants from Allergy Therapeutics, outside the submitted work. A.W. has received honoraria, been an investigator on studies sponsored by or received research grants from Gilead Sciences, GSK, BMS, Janssen-Cilag, Merck and ViiV Healthcare. D.T.D. has received honoraria, not in connection with the submitted work, from ViiV Healthcare and Gilead Sciences. C.A.S. has received honoraria from Gilead Sciences, ViiV Healthcare and Janssen-Cilag for membership of Data Safety and Monitoring Boards, Advisory Boards and for preparation of educational materials. The remaining authors have no conflicts of interest.


Because inflammation is associated with mortality and has been linked to HIV transcription in lymphoid tissues during ART, it is necessary to address the long-term effects of switching 3-drug (3DR) to 2-drug regimens (2DR) on inflammation.Nested study in the Spanish AIDS Research Network. We selected PWH ART-naive initiating 3DR who achieved viral suppression in the first 48 weeks and either remained on 3DR or switched to 2DR . We assessed the trajectories on inflammatory markers during ART using multivariate piecewise mixed models.vs DTG).We analyzed 619 plasma samples from 148 patients , the median follow-up was 4.6 (IQR 3.2-6.2) years. There were no significant differences in baseline characteristics between groups. After adjusting for potential confounders, patients with 3DR experienced a slow decline of IL6, hs-CRP, sCD14, sCD163, and D-dimer over time. In contrast, compared to 3DR, switching to 2DR was associated with increases in IL-6 (p=0.001), hs-CRP (p=0.003), and D-dimer (p=0.001) after year 3 from virologic suppression. 2DR was associated with a higher risk of hs-CRP quartile increase  and D-dimer quartile increase . The adjusted biomarker trajectories did not reveal a distinct pattern according to the type of 2DR used (bPI In this study in virally suppressed individuals, maintaining 3DR was associated with a more favorable long-term inflammatory profile than switching to 2DR. The potential clinical implications of these findings on the development of non-AIDS events deserve further investigation. Levels of inflammatory biomarkers remain increased in people with HIV (PWH), even when antiretroviral therapy (ART) is started early , 2. ThisWhile the virologic efficacy and safety of current ART regimens are difficult to improve, a major challenge is to fully normalize the health of PWH. Non-virologic parameters associated with excess risk of mortality, such as increased bacterial translocation or inflammation , 10, areBecause inflammation is slow to change in virally suppressed individuals , studiesHere, we performed a nested study in the Spanish AIDS Research Network (CoRIS). We asked whether switching to 2DR is associated to a different long-term inflammatory profile compared to remaining on 3DR.nd, 2004, and December 28th, 2018, who were included in a prospective clinical cohort study with continuous enrollment and standardized data collection (We performed a nested study in the Cohort of the Spanish HIV Research Network (CoRIS)—a national ongoing prospective multicenter cohort of people with HIV (PWH), including 14,458 treatment-naïve adults recruited from 45 Spanish hospitals. We included ART naïve patients who initiated follow-up between January 2llection . CoRIS iWe selected ART naïve patients initiating 3DR from 2004 to 2008 with either boosted protease inhibitor (bPI)- or integrase strand transfer inhibitor (INSTI)-based combinations, who achieved virologic suppression in the first 48 ± 6 weeks of ART and who either remained on their selected 3DR or switched to 2DR consisting of lamivudine plus either a bPI or dolutegravir or of rilpivirine and dolutegravir, or to monotherapy (MT) with either lopinavir/ritonavir (LPV/r) or boosted darunavir (bDRV) after at least 48 weeks or virologic suppression. The decision to exclude non-nucleoside reverse transcriptase inhibitor (NNRTI)-based first-line ART was made to avoid the potential confounding effects of the third-drug used in 3DR in the comparison against 2DR or MT. Participants maintained virologic suppression until the last plasma sample available at the biobank and had available stored samples at the following timepoints: before ART initiation, after achieving virologic suppression, and at least two additional plasma samples with the treatment evaluated . Exclusion criteria were the presence of virologic failure during the first 48 weeks of ART and the diagnosis of AIDS and serious non-AIDS events  before ART initiation of during the first 48 weeks of ART. We defined virologic failure as two consecutive HIV RNA measurements >50 copies/mL, HIV RNA blips as a single HIV RNA measurement between 50 and 1000 copies/mL, and virologic failure with low-level viremia as two consecutive measurements between 50 and 1000 copies/mL.The Institutional Review Boards of the Carlos III Health Institute located in Madrid, Spain, the Ethics Committee at University Hospital Ramón y Cajal approved the study .Of the 14,458 individuals included in CoRIS, 7,655 had started ART with 3DR, 4,613 had at least one sample available in the first 96 weeks after achieving the virologic suppression, and 1,000 met the sample availability requirements. After virologic suppression, 705 individuals maintained their 3DR regimen and maintained the virologic suppression until the last available plasma sample. From the 4,613 individuals, 255 and 199 switched to 2DR and MT during follow-up, 196 and 88 maintained the selected regimen over time, 62 and 31 had at least one plasma sample stored under the same 2DR or MT treatment regimen, and 58 and 23 had enough plasma volume stored for the biomarker measurements. To meet the criteria of availability of at least two plasma samples on the evaluated regimen, we requested the centers participating in CoRIS to send an additional plasma sample to the biobank in those cases with only a single observation under the evaluated regimen or with a last sample sent long before the end of the follow-up.We measured levels of D-dimer, IL6, hs-CRP, IFABP, sCD14, and sCD163 in plasma as indicators of coagulation, inflammation, monocyte activation, and bacterial translocation using the commercial ELISA assays Human D2D (D-Dimer) ELISA Kit , Human Quantikine IL-6 HS ELISA , CRP ELISA , PicoKine ELISA for Human IFABP , Human CD14 Quantikine ELISA Kit (R&D Systems) and Human CD163 Quantikine ELISA Kit (R&D Systems), respectively, accordingly to manufacturers’ instructions. Each sample was assayed in duplicate in batches seeking an equal representation of the study groups and containing all samples from the same individual. Data was collected using a microplate luminometer with Gen5 Data Analysis Software .vs. MT comparisons are exploratory. Similarly, due to the smaller sample sizes we did not compute the statistical significance of the posthoc analyses segregating by the type of 2DR.We used IL-6 as the primary outcome variable for sample size calculation. We considered the IL-6 distribution data from a previous study in PWH.  AccordinAccording to the variable distribution, qualitative variables were reported as frequency distribution, whereas we described quantitative variables using medians with their interquartile ranges (IQR) or means with their standard deviations (SD). We fixed linear mixed models for the primary analysis to allow for correlation due to repeated measurements on the same subject. Interaction terms (time-versus-treatment group) were created to assess whether these changes differed significantly over time between the treatment groups. When the observed trajectories were not linear, we used piecewise linear mixed models to compare the slope parameters between treatment groups at the intervals defined by the inflection points. Because the median time to ART switch was three years from virologic suppression and there was an inflection point at this timepoint, we compared the slope parameters between treatment groups at year 0-3, and 3-8 from virologic suppression. To illustrate the predicted adjusted changes of inflammatory biomarkers, we plotted the values predicted by the piecewise models at the intervals between years 0, 1, 2, 3, 4, and 8, as previously performed in CoRIS for comparison of treatment effects on continuous variables . AnalyseWe assessed the probabilities of biomarker quartile increase over time in each group using multivariate logistic regression models, adjusted for the same covariates described above. We explored the crossed correlations between biomarkers by calculating Spearman’s Rho coefficients. Continuous outcome variables were log-transformed when necessary to satisfy model assumptions. We used Stata v. 17.0  for all statistical analyses.Of the 14,458 individuals included in CoRIS, 11,330 started ART with a combination of two nucleoside reverse-transcriptase inhibitor (NRTI) and either one NNRTI, one PI, or one INSTI; and 9,282 had achieved undetectable plasma HIV RNA in the first 48 ± 6 weeks of ART initiation.During the follow-up, 7,665 individuals remained on 3DR, 424 changed to 2DR, and 327 changed to MT. The general characteristics of the whole cohort are provided in The median follow-up was 4.3 years (IQR 3.0-6.2), and the median number of samples analyzed was 4 (IQR 3-11), accounting for 680 observations. The study sample was representative of a medium-aged population of individuals with HIV with a higher representation of men. During follow-up, there were 5 (5.6%) instances of virologic failure after the last available plasma sample with 3DR, 1 (1.6%) in 2DR, and 0 in MT (p=0.270), and 4 (1.1%) instances of low-level viremia with 3DR, 0 in 2DR and 0 in MT (p=0.166). The occurrence of severe non-AIDS events during follow-up was rare in the cohort, and no differences between groups were apparent . Subanalyses segregating the curves by the core agent used as 2DR (bPI or INSTI) indicated that the effect was not dependent on the type of 2DR used  but statistically significant correlations  cohort, type 1 myocardial infarction, type 2 myocardial infarction, and deep vein thrombosis were predicted by distinct inflammatory patterns .Despite the consistent link between inflammation and an excess risk of severe non-AIDS events and mortality , 25, theWe selected the inflammatory markers more robustly associated with the risk of severe non-AIDS events and mortality in HIV . Of noteThe major strengths of our study include the prospective collection of data and samples and the long follow-up, with a median of 5 years in the 2DR group, and the number of samples analyzed per patient, which allowed controlling for intra-individual variation. Both factors increased the power of our study to detect differences between groups. In addition, we only included 2DR with efficacy is supported by randomized controlled trials. Finally, because the rationale to expect an effect largely relies on tissue drug distribution, if any, an effect would be more apparent in an observational study than in a controlled trial, where ART adherence is expected to be higher.vs. MT comparison, but be interpreted as an exploratory sub-analysis. However, the patterns observed in the MT group were consistent with those observed with 2DR.Our study also has several limitations that prompt a cautious interpretation of our results. First, there is still a risk of unmeasured confounding as with any observational study. Given the large sample size and follow-up and the prospective nature of CoRIS, we could adjust the analyses for the major determinants of ART choice, but could not for other potentially relevant confounders such as the presence of comorbidities or treatments that could affect inflammation. However, no significant differences were found in the general characteristics of each cohort at baseline. The fact that many research groups participating in CoRIS have focused their research on 2DR could explain that the general characteristics of individuals in the 2DR group did not significantly differ from those in the 3DR group. In addition, our findings were independent of the immunovirological covariates analyzed . The higher number of episodes of virologic failure and low-level viremia occurring after the last available sample analyzed suggests that adherence was lower in individuals with 3DR, as expected in an observational study in which clinicians would be less likely to reduce the number of drugs in less adherent patients. In addition, the limited sample size determines that the detected effects could have been dependent of a small number of observations. Another source of potential bias is the immortal time bias, which is inherent to observational studies comparing treatment interventions. Because a subject had to survive to switch to 2DR, but not to remain on 3DR, if this bias existed, it would have underestimated the real difference. The number of virologic failures during follow-up was higher with 3DR, which also suggests that patients remaining on 3DR were on average less adherent than those switching to 2DR. Also, we lacked information that would have helped to interpret the results, such as ART adherence or weight gain, that are expected to affect inflammation. Last, because of the insufficient information obtained in the MT group, we lacked of statistical power to provide more accurate effect estimates. As a planned analysis, we decide to report the 3DR While our study fuels the debate on the potential differences of ART strategies on inflammation, our data should be interpreted only as exploratory of the long-term effects on inflammatory biomarkers of certain ART combinations. Even if our results are reproduced in other cohorts and controlled studies, it would still be important to analyze the impact of these differences on the risk of clinical events, for which very large studies would be needed. However, because several inflammatory markers are easy to measure and independently predict the risk of severe non-AIDS events and mortality –5, 26–28Due to ethical restrictions, some restrictions may apply. Study data requests should be addressed to the Spanish AIDS Cohort Research Network. Requests to access the datasets should be reasoned and directed to the corresponding authors. ceic.hrc@salud.madrid.org). Approval number 133-17. The patients/participants provided their written informed consent to participate in this study.The studies involving human participants were reviewed and approved by Comité de investigación clínica del Hospital Universitario Ramón y Cajal  as part of the Plan Nacional R + D + I and co-financed by the European Development Regional Fund ‘‘A way to achieve Europe’’ (ERDF). The RIS Cohort (CoRIS) is funded by the Instituto de Salud Carlos III through the Red Temática de Investigación Cooperativa en SIDA  as part of the Plan Nacional R+D+I and cofinanced by ISCIII-Subdirección General de Evaluacion and Fondo Europeo de Desarrollo Regional (FEDER)”. This work was supported by the Instituto de Salud Carlos III projects AC17/00019, PI18/00154, ICI20/00058, CIBER de Enfermedades Infecciosas, and Gilead Sciences (Investigator Sponsored Research ISR-17-10192). The funders had no role in the study design, data analysis, or in the interpretation of the resultsOutside the submitted work, SS-V reports personal fees from ViiV Healthcare, Janssen Cilag, Gilead Sciences, and MSD as well as non-financial support from ViiV Healthcare and Gilead Sciences and research grants from MSD and Gilead Sciences. JM-S, non-financial support from ViiV Healthcare, non-financial support from Jannsen Cilag, non-financial support from Gilead Sciences, outside the submitted work. JP reports grants from Instituto de Salud Carlos III during the conduct of the study; grants and personal fees from Gilead Sciences, personal fees from Janssen Cilag, personal fees from ViiV Health Care, personal fees from MSD, outside the submitted work. SM reports grants, personal fees and non-financial support from ViiV Healthcare, personal fees and non-financial support from Janssen, grants, personal fees and non-financial support from MSD, grants, personal fees and non-financial support from Gilead, outside the submitted work.The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.The reviewer PH declared a past collaboration with one of the authors SS-V to the handling editor.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Currently, the majority of new human immunodeficiency virus (HIV) infections are transmitted by individuals with untreated HIV. In this retrospective study, we examined associations between demographic factors, viral suppression, acquired immunodeficiency syndrome (AIDS) status (CD4 count <200), and adherence to clinical follow-up in individuals living with HIV. Of the 489 patients, 135 (27.6%) were females, 235 (48.1%) were over 50 years old, 191 (39.1%) had Medicaid, Medicare, or Ryan White Insurance, 25 (5.1%) had CD4 counts below 200, and 207 (42.3%) were adherent to their clinic appointments. In univariable logistic regression analysis, age and viral load detectability were significantly associated with patient adherence to their clinic appointment. In multivariable analysis, only age remained significantly associated with clinic appointment adherence . Patients 50 years old or younger were half as likely to be adherent to their clinic appointments than patients over 50 years old. Gender and insurance status were not associated with viral suppression or AIDS status. The results illustrate the need for increased age-specific outreach to improve clinical adherence in younger individuals. The US Department of Health & Human Services' (HHS') ending the HIV epidemic Plan for America intends to increase the human immunodeficiency virus (HIV) viral suppression rate from an estimated 53% in 2020 to 90% by 2030 . In addiThe last decade has seen significant advances in HIV prevention and treatment such as Undetectable=Untransmittable (U=U), pre-exposure prophylaxis, and effective single tablet regimens -5. HistoThe study was conducted at the HIV clinic of a tertiary care academic medical center. The center has a Ryan White program and is a referral source for a population of 1.8 million in the region. The study protocol and methods were approved by the Institutional Review Board (#18-03-FB-0044). Clinical and demographic data were collected retrospectively from patients who were seen at this HIV clinic during a two-year period , were between the ages of 18 and 89 years at the time of data retrieval (July 2020), and who were prescribed ART for at least six months. Patients were excluded if they were on ART for less than six months or if there was no information to determine their adherence to ART. ART adherence was determined by viral load measurements: patients were categorized as adherent if the viral load was <200 viral copies/mL or non-adherent if the viral load was ≥200 copies/mL. To determine the severity of the disease, patients were further categorized as those who had AIDS (CD4 count <200 cells/μl) and those who did not have AIDS (CD4 count ≥200 cells/μl). Only the most recent laboratory values were used for this study. Patients were categorized into two age groups: those 50 years of age or younger and those who were older than 50 years. Insurance status was categorized into public  or other (such as private insurance). Adherence to follow-up was defined as being seen in the HIV clinic every six months. Gender and age were used as reported in the medical records.Data were summarized as mean (standard deviation), median (interquartile range), and percentages as appropriate. The student’s t-test, chi-square test, or Fischer's exact test were used as appropriate to examine the relationship between adherence to ART and demographic or clinical variables. Univariable logistic regression was used to examine the effect size of each clinical and demographic variable on adherence to ART. Subsequently, we developed a single multivariable logistic regression model that includes all demographic and clinical variables to determine effect sizes in the presence of all variables. All analyses were conducted in Stata 16.1 , and a P<0.05 was considered significant.Of the 489 patients included in the study, 135 (27.6%) were females, 235 (48.1%) were older than 50 years, 191 (39.1%) had Medicaid, Medicare, or Ryan White Insurance, 25 (5.1%) had CD4 count <200, and adherence to the appointment was noted in 207 (42.3%). The mean (standard deviation) age of the participants was 47.9 (13.4) years and the CD4 count was 744 (362) cells/μl. Viral load was <200 copies/mL in 428 (87.5%) patients, 202 (41.3%) patients had non-detectable viral load, and the median (interquartile range) of detectable viral load was 66 (400) copies/mL (Table In univariable logistic regression analysis, age and viral load detectability were significantly associated with patient adherence to their clinic appointment Table . Each onIn this study, we found that age was an independent predictor of adherence to follow-up in HIV patients: older patients are more likely to adhere to their follow-up appointments than younger patients. Although viral load was also a factor in univariable analysis, it was no longer significant after adjustment for other variables. Adherence to clinical follow-up is important in the management of HIV, as is demonstrated by current guidelines. According to current guidelines, “retention in care” is defined as at least one medical visit every six months over the past two years . The HIVPotential causes for poor adherence to medical visits in younger HIV patients may include competing demands with work and childcare, lack of other medical co-morbidities, or symptoms that might drive seeking medical care, lack of transportation, substance use, and untreated mental health disease. Alternatively, survival bias may be a reason for the finding that older individuals were more likely to adhere to medical visit appointments. In other words, those who were not adherent to medical visits may not live long enough to be older - the proportion of HIV-related deaths was 48.6% among HIV patients aged 13-24 years and 30.0% among those aged ≥55 years .Importantly, decreased adherence to clinic visits does not necessarily mean a lack of viral load suppression. In the most recent “Prevalence-based HIV Care Continuum” for the United States, although only 50% of people diagnosed with HIV were retained in care, 57% of all individuals with HIV achieved viral load suppression . Our cliHistorically, studies have cited an increased loss of follow-up in younger patients with inadequate medication adherence in young people -18. HoweOur study had several limitations, including the use of a single institution site and a lack of data related to behavioral and/or medical comorbidities. Additionally, appointment adherence was classified dichotomously and the frequency of visits was not recorded as a continuous variable. We did not confirm whether patients were actually scheduled every six months and if so, whether the missed appointment reflected a cancellation by the clinic staff or other factors beyond the patient’s control. Measures of prescription adherence and effectiveness such as pick up of medication from the pharmacy and viral drug resistance were also not assessed. Moreover, younger populations may be recently diagnosed and therefore were expected to have a detectable viral load. However, in this study, individuals were only selected if they had been prescribed ART for six months, at which point, their viral loads are likely to be undetectable, reducing the effect of the aforementioned limitation . AdditioIn summary, our study identified younger individuals to be less likely to adhere to HIV follow-up appointments in comparison to their older counterparts. To meet the goals outlined in HHS’ Ending the HIV Epidemic, efforts to increase the engagement of young people in HIV care should be explored. Our study validates previous literature suggesting that clinical visit adherence is higher in older patients living with HIV. However, it also highlights that while retention in care is inversely associated with viral load suppression, a decrease in regular medical follow-up visits does not necessarily mean poor viremic control. Additional studies are needed to determine what factors lead both to a medical visit and medication adherence and to further explore the relationship between adherence to medical clinic visits and HIV viral load. Our study findings also raise important clinical implications for our current standards for retention in care, primarily further exploring whether some individuals with sustained viral load suppression on antiretrovirals may benefit from a decreased medical visit frequency.


Significant improvement in renal function was noted . At the end of the follow-up, conversion resulted in an overall decrease in non-adherence of 53.3% (p = 0.0001) and an improvement in QoL was reported by 76.2% of patients. Thus, 1:1 conversion from immediate to prolonged-release Tacrolimus is safe, feasible and efficient, avoiding under-therapeutic and toxic peak concentrations, improving renal function, adherence to immunosuppression and overall patient QoL.Immunosuppression non-adherence is a major cause of graft failure after liver transplantation. The aim of this study was to evaluate practice surrounding conversion from immediate-release to prolonged-release Tacrolimus formulation and to assess patient adherence and quality of life (QoL). One hundred and seven adult liver transplant recipients, receiving immediate-release Tacrolimus for a minimum of 6 months, were converted to prolonged-release formulation, based on a dose ratio of one (1:1). The median follow-up was 120  months. Tacrolimus dosage and blood level, liver and renal function, lipid and glucose profiles were recorded. In addition, questionnaires were submitted to evaluate adherence and QoL following conversion. No rejection was recorded. The median serum Tacrolimus blood level decreased over 1 month (5.80,  vs. 3.8 ;   However, immunosuppression (IS) has several side-effects including renal failure, infections, cardiovascular diseases, metabolic disorders and gnancies -4. In adgnancies -7, whichgnancies -10. Thergnancies -13. Thergnancies , 15. Furgnancies , 17.®; Astellas Pharma US, Inc., Deerfileld, IL, USA), administered twice daily to maintain stable blood levels, a prolonged-release  formulation was licensed in Europe in 2007 for the prevention and treatment of graft rejection. Conversion from IR to PR-Tac has been studied in maintenance LT recipients (Tac is frequently used in liver transplantation (LT). In addition to the immediate-release formulation , C/D intra-patient variability following conversion from IR to PR-Tac, based on a dose ratio of 1 (1:1).This is a prospective, single arm study and patients were followed up at one, six, 12, 60 and 120 months between December 2010 and March 2021 in our hospital.All adult patients, who underwent LT, who were on IR-Tac-based IS regimen for at least 6 months, with stable liver function test (LFT) and serum creatinine levels <2.0 mg/dl were enrolled in this study.Patients were excluded in case of pregnancy, breastfeeding, malignancy, severe systemic infection requiring any therapy that could modify Tac pharmacokinetics, or the use of any other investigational drugs.In general, the IS therapeutic protocol of our centre requires that corticosteroids are not used unless the patient has autoimmune pathologies. In patients with stable liver function, Tac monotherapy is usually achieved 1 year after the transplantation .The conversion from IR-Tac to PR-Tac started as soon as the new formulation was available in our hospital. All patients enrolled in the study were switched to PR-Tac, individually, during a 2 months period, and they were followed-up for at least 10 years. The starting dose of PR-Tac was exactly the same as the dose of IR-Tac taken by the patient at the time of conversion (1: 1).Tac levels were measured in our central laboratory using a high-performance liquid chromatography-mass-spectrometry procedure . PatientAt follow-up, physical examination and measurement of vital signs were performed, contingent adverse events were noted, and laboratory test results were checked. Arterial hypertension was defined as systolic blood pressure >140 and/or diastolic >90 mm Hg at two subsequent visits or when antihypertensive treatment was prescribed. Diabetes mellitus was defined as fasting glucose >126 mg/dl at two subsequent visits or when hypoglycemic treatment was used. Dyslipidemia was defined as cholesterolemia >220 mg/dl and/or triglyceridemia >200 mg/dl at two subsequent visits or when using hypolipidemic treatment.LFTs including aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl-transferase and bilirubin were performed at each clinic. Elevated transaminases, defined as twice the upper limit of our laboratory cut-off , triggered closer surveillance and a liver biopsy when LFT abnormalities persisted . Graft lAdherence was assessed using the ‘‘Basel Assessment of Adherence Scale to Immunosuppressives”  (BAASIS)de novo questionnaire (unpublished data) was developed to address those aspects of the IS regimen that influence patient care and the general perception of good or poor QoL in patients taking PR-Tac versus IR-Tac. The questionnaire was designed to be short, simple and easy to understand, to ensure a high completion rate with minimal missing data. The questionnaire, filled in anonymously by patients, collected demographic information , and included three additional questions. Demographics were collected to facilitate the interpretation of the data at the end of the study. The first question was completed in the pre-conversion phase and queried the possible difficulty of taking multiple daily doses of drugs using a binary response option (YES/NO). The response was followed by a four-point Likert scale measuring the degree of difficulty, with two positive  and two negative  quantitative responses. At 12 and 120 months, questions two and three were administered. The second question assessed the possible satisfaction of the new drug regimen using a binary response option (YES/NO). The third question evaluated the perception of an improvement in QoL following the intake of the single-dose drug with a four-point Likert scale measuring the degree of improvement with two positive  and two negative  quantitative responses.A A positive response to the first question assumed dissatisfaction with taking multiple daily drugs, which was confirmed by positive responses on the Likert scale. Positive responses to questions 2 and 3 indicated satisfaction with the new therapeutic regimen and increased perception of QoL.Data were presented as means (standard deviation), medians , or frequencies (percentage) as appropriate. For adherence data, categorical variables collected during follow-up were compared to baseline values using Fisher’s exact-test, while continuous data were compared to baseline values using the paired Student’s t-test. To simultaneously subject-wise as well as time-related changes, and possible interactions between them, all other variables were analyzed using multivariate linear mixed models modelling timepoints as a repeated within-subject factor and employing an unstructured estimate of the covariance matrix. As opposed to general linear models, mixed models have the advantage of being able to account for heterogeneous distances between timepoints, missing data as well as unequal variances and covariances. To account for possible confounding due to inter-patient variability, all models included gender, categorized disease etiology, time between therapy inception and conversion, and Tac blood levels (primary endpoint only) as covariates of interest.p < 0.05) overall effect of time was found, pairwise comparisons between timepoints were performed and corrected for multiple comparisons across pairs of timepoints using the Dunn–Šidák procedure.Whenever a statistically significant  years were enrolled into the study. The median time from LT to study enrolment was 55  months. Patient characteristics are summarized in de novo intestinal adenocarcinoma and subsequently switched to mTOR-inhibitor monotherapy.At enrolment, 74 patients (69%) were on IR-Tac monotherapy. Median Tac daily dose was 2.0  mg and similar values were reported within the first 12-month after conversion. Eight-six out of 107 (81.9%) patients continued with the same Tac dosage after 1 year and the dosage was decreased in six patients (5.7%), increased in 11 patients (10.5%) and two (1.9%) patients were withdrawn from PR-Tac: the first patient due to frequent episodes of hypertension, diarrhea and vertigo and reconverted to IR-Tac; the second one due to n = 4) or malignancy  and esophagus cancer (n = 2))  patients were still on the PR-Tac IS regimen: 56 patients (52.3%) were maintained on the same dosage as baseline; 24 patients (22.4%) had their dosage decreased and 11 patients (10.3%) increased. Six (5.6%) were converted to a different IS drug between 12th and 120th month. Three patients (2.8%) initiated single drug treatment with mycophenolate mofetil due to blood hypertension at 28, 56 and 68 months respectively. Three patients (2.8%) were converted to mTOR-inhibitor due to HCC recurrence, breast cancer and colon adenocarcinoma at 58, 89 and 112 months, respectively. A total of eight (7.4%) patients died due to a cardiovascular accident ((n = 2)) .p < 0.0001) at baseline and 1 month after conversion, respectively. When the LFTs remained stable no dose adjustments were considered. In patients without dose adjustments, the median Tac blood levels remained 2.0 mg  We found a significant effect of the timepoint factor (p < 0.0001) on Tac blood levels, which in post-hoc comparison appeared to be associated with the following differences: baseline vs. 1, 6, 60 and 120 months ; 1-month vs. 6, 60 and 120 months ; 6 months vs. 12, 60 and 120 months   ng/ml and 3.80  ng/ml respectively (= 0.001) .No patient experienced clinical or biopsy-proven acute rejection (BPAR) after conversion. The 10-year survival was 92.6%.p < 0.0001) on eGFR (p < 0.0001); baseline>1 month (p < 0.0001); baseline>6 months (p = 0.049); month 1<6, 12, 60 and 120 .There was no statistically significant effect for the timepoint factor on liver function. Even the comparison of glucose levels and cholesterol and triglycerides values between the pre and post conversion periods was not statistically significant. We found a significant effect of the timepoint factor . Sixty-six patients (61.7%) declared at baseline that they had possibly missed two consecutive drug doses, which dropped to 12  and 22  patients at 12 and 120 months, respectively. Sixty-three patients (58.9%) did not respect the therapeutic intake time at baseline but this decreased to 15  and 25  patients at 12 and 120 months, respectively. Five patients (4.7%) admitted to taking lower drug dosages than medically prescribed, which dropped to three  and no  patients at 12 and 120 months, respectively.The BAASIS questionnaire addressed different aspects of adherence, with the aim of identifying those areas where adherence has significantly increased. At baseline, 84 (78.5%) patients reported forgetting to take at least one drug dose in the previous 4 weeks, whereas this dropped to 24 (22.4%) and 27 (25.2%) patients at 12 and 120 months, respectively (p = 0.0009) and 120 months   at baseline and were significantly higher at 12 months  .n = 69; 65.7%) and 120 months . Filter questions showed that 40 (60.6%), 49 (71.0%) and 45 (73.8%) of patients found it very difficult to take more than one type of drug at baseline, 12 months and 120 months, respectively. Twenty-six (39.4%), 20 (72.4%) and 48 (78.7%) patients found it very difficult to take one or more doses of the same drug at baseline, 12 months and 120 months, respectively. Thirty (45.4%), 67 (97.1%) and 60 (98.4%) patients found it very difficult to take drugs at different times at baseline, 12 months and 120 months, respectively.The three separate questions regarding QoL were completed by all participants at baseline. At baseline 66 (61.7%) patients indicated that they experienced difficulty with taking multiple doses of immunosuppressants daily, which was similar after 12 months (The second item addressed the degree of satisfaction with the PR-Tac therapeutic regimen. The data showed that 98 (93.3%) and 79 (86.8%) patients were very satisfied at 12 and 120 months, respectively. The third item asked if there had been an improvement in QoL after conversion. Eighty (76.2%) and 75 (82.4%) patients confirmed that their QoL had improved at 12 and 120 months respectively, with the filter question showing that 82.5% and 86.8% felt that QoL had very much improved at 12 and 120 months, respectively .p < 0.000001) . After one and 12 months, the ratio decreased to 1.87  and 2.03 , respectively and remained stable during the follow up  .p < 0.0001) associated with the following differences: 12 months vs. baseline, 1, 6, 60, 120 months , 6 months vs. baseline, 1, 12, 60, 120 months , 1 month vs. baseline, 6, 12, 60, 120 months , 120 months vs. baseline, 1, 6, 12, 60 months . In addition, we compared 10 consecutive pre-conversion timepoints to 10 consecutive post-conversion measurements to evaluate the change of Tac blood levels and dose in a long-term observation: the mean C/D ratio was significantly higher pre-conversion compared to post conversion , while the coefficient of variation of the C/D ratio was significantly lower pre-conversion compared to post-conversion (2.12 versus 1.19: p = 0.003).We observed a significant effect of the timepoint factor  was seen, with a retrospective comparison showing the following differences at baseline vs. 1 month (p < 0.0001), baseline vs. 6 months (p = 0.049), month 1 vs. 6, 12, 60, and 120 . There were no new cases of posttransplant diabetes or glucose intolerance or any increase in adverse events associated with Tacrolimus use after conversion to PR-Tac.With normal aging, nephron loss occurs and is detectable to some extent by the age-related decrease in eGFR , 30. Sev2/year , 32. In 2/year , 33. HowIt can be hypothesized that extended-release Tac may influence drug absorption and avoid drug peaks whilst maintaining adequate drug blood levels to avoid rejection.Self-reporting adherence instruments having a tendency to overestimate adherence and under-report non-adherence due to increased awareness and pleasing the physician. However, BAASIS is considered a valid tool as it uses a rigorous definition of non-adherence, classifying a patient as non-adherent in case of positive answer to any of the four questions to be given. Non-adherence at study entry was considerably high especially regarding the evening dose, which has also been found by previous studies ,34. At tAdherence rates improved significantly between baseline and the end of the study in terms of missing one or more doses, violating drug timing and autonomous prescription modification. Patients themselves felt more adherent at the end of the study with 97% of patients defining themselves as “adherent” at 120 months compared with 90% at baseline. Patients reported having difficulty taking more than one IS drug in 61.7% of cases before conversion, not knowing about PR-Tac, subsequently, 93.3% defining the PR-Tac regimen as “very satisfactory.” During medical interviews, 68% referred the evening dose as being the most difficult to self-administer for perceived interference with social life and sense of freedom. This has radically changed following conversion to PR-Tac.de novo questionnaire, drawn up and validated in collaboration with the Center for Psychology of our hospital, is due to the fact that in the literature, in our opinion, there were no validated questionnaires that had the characteristics, suitable for a complete evaluation of our patients which would allow us to obtain such complete results and which went hand in hand with the BAASIS, used for the assessment of adherence. The fact that no patient enrolled, with the sole constraint of taking IR-Tac for at least 6 months before signing the informed consent to the study, was for us surprising evidence of the excellent relationship of trust that we establish every day with all the people we follow in our post-transplant clinic and further confirmation of the patients’ desire to seek “simpler” therapy regimens to follow.Freedom of choice relating to time of drug administration directly impacted on perception of improvement in QoL for the majority of patients. QoL improvement was reported in over 82.4% of patients in our study following conversion. The reason why we decided to use a Despite the absence of a control group that may evidence bias, we have considered the group itself before conversion as satisfactory for comparison.p = 0.008) higher pre-conversion as compared to post conversion, while the coefficient of variation of the C/D ratio was significantly (p = 0.003) lower pre-conversion compared to post-conversion, indicating greater stability post-conversion compared to pre-conversion.There is significantly less intrasubject variability in exposure after conversion to PR-Tac: the mean C/D ratio was significantly (In conclusion, our study demonstrates that 1:1 conversion from IR-TAC to PR-TAC is safe, feasible, efficient, and well-tolerated. Hepatic and renal function was closely monitored and no major dose adjustment to correct low Tac blood levels were required. Stable LT patients can be successfully switched from IR-Tac to PR-Tac formulation without risk of acute rejection even in the short term. A simplified formulation of Tac can improve patient adherence and their QoL. Improvement of renal function is probably due to lower Tac blood level exposure.


In 2019, about 1.7 million adolescents between the ages of 10 and 19 years were living with HIV worldwide, of which 170 000 were newly infected with HIV in 2019. South Africa has the highest number of persons living with HIV. Although there has been major improvement in access to antiretroviral therapy (ART), it is still unclear what proportion of adolescents (aged 10–19 years) are virally suppressed in the provinces of South Africa.To determine the prevalence of and the factors associated with viral suppression among adolescents (10–19 years) on ART in the Thabo Mofutsanyane District Municipality of the Free State province of South Africa.A retrospective cross-sectional analysis of demographic, clinical and treatment-related information that were extracted from an electronic database was conducted using Statistical Package for the Social Sciences version 26.n = 4520) of adolescents living with HIV who were on ART achieved viral suppression (< 1000 copies/mL), only 9.5% (n = 430) were fully suppressed at < 50 copies/mL. In multivariate analysis, the odds of being virally suppressed reduced with increasing age at ART initiation. Adolescents with CD4 counts greater than 500 cells/mm3 at baseline had a higher odds ratio of viral suppression . The odds of viral suppression were significantly lower among those not retained in care .The median duration on ART was 6.58 years. Although 78% (Tailored interventions should be developed to improve viral suppression among adolescents on ART. In 2019, there were approximately 1.5 million adolescents living with HIV (ALHIV) in sub-Saharan Africa; roughly 88% of the total global number.14Despite the high frequency worldwide of suboptimal viral suppression levels among adolescents on ART, the group is often overlooked because programmatic reporting rather focuses on other groups: paediatric (0–14 years) and adult (15 years and older). Furthermore, there is an insufficient number of studies of viral load suppression (VLS) using secondary data derived from adolescents in public health settings. An analysis of the factors that affect viral suppression among ALHIV is critical to the development, at the local level, of adolescent interventions and the achievement of the final 95% goal of the Joint United Nations Programme on HIV/AIDS (UNAIDS) 95-95-95 targets.The objectives of the current study were to determine demographic, clinical and treatment characteristics associated with VLS among ALHIV on ART in the Thabo Mofutsanyane District Municipality of the Free State province of South Africa.A retrospective, quantitative cross-sectional study was conducted to determine the factors associated with VLS among adolescents.n = 100 361)15 and, with regard to incidence rates, ranks second highest in the province, with 10.6 new infections per 100 000 population.16 It was against this background that the aim of this study was to determine factors associated with viral suppression among adolescents on ART in this district.In the Free State province, the Thabo Mofutsanyane District has the highest number of HIV cases (n = 4553) in 2019. The study sample included those who were on ART for a minimum of 6 months and who had at least one documented viral load (VL) on ART in the last 12 months (n = 4475).The study population consisted entirely of adolescents, aged 10–19 years, on ART and living in the Thabo Mofutsanyane District Municipality of the Free State province , after determining the population of HIV-infected adolescent patients initiated on ART from all the facilities in the study region. TIER.Net is a commonly used electronic database in public health facilities in South Africa and monitors the baseline clinical care and treatment of HIV patients.18Demographic variables included gender, current age and age at ART initiation. Clinical characteristics included the World Health Organization (WHO) clinical stage, the CD4 count, pregnancy, a history of tuberculosis and the use of Isoniazid Preventive Therapy and Cotrimoxazole, all at baseline (at ART initiation). The duration of ART was included. Information on retention in care was used to distinguish between those in care; those registered as dead, transferred out and those lost to follow-up, as per national ART guidelines.P < 0.05. Multivariate logistic regression identified factors independently associated with viral suppression and presented as adjusted odds ratios (AOR) with 95% confidence intervals (95% CI).Extracted data were entered into an Excel spreadsheet, cleaned and thereafter imported into Statistical Package for the Social Sciences (SPSS) version 26  for analysis. Descriptive frequency tables were created for categorical variables outlining the number of adolescents in the various categories and the proportions, using percentages. Continuous data were also presented either as means with standard deviations or as medians with interquartile ranges (IQR). Bivariate analysis was used to determine the significance and strength of associations between VLS, at < 1000 copies RNA/mL, and the exposure variables as indicated above. Statistical significance was tested using the chi-square test with significance set at n = 3083) and were female . The median age at ART initiation in this cohort was 8 years (IQR: 5–12), and the median CD4 count at ART initiation was 285 cells/mm3 (IQR: 103–490). The median duration of treatment was 6.6 years (IQR: 3.58–8.75).The median age of adolescents in this study was 15 years (IQR: 13–18 years). Most were between 15 and 19 years ; followed by Stavudine/Lamivudine/Efavirenz (S3E)  and Tenofovir/Emtricitabine/Efavirenz (TFE) . At the time of data extraction, 46.1% (n = 2084) were on A3E, with 7.5% (n = 340) on Abacavir/Lamivudine/Lopinavir/ritonavir (A3L), and 23.7% (n = 1070) on TFE.Approximately half were initiated on Abacavir/Lamivudine/Efavirenz (A3E)  were in care; while 16.3% (n = 736) had transferred, 11.6% (n = 523) were lost to follow-up and 2.1% (n = 94) had died.At the time of the study, 70.1% (n = 3107) were categorised as transiently suppressed (50–999 RNA copies/mL); while only 9.5% (n = 430) were fully suppressed (< 50 RNA copies/mL) and 21.8% (n = 983) were unsuppressed (≥ 1000 RNA copies/mL).Most participants  and age at ART initiation (P < 0.001) . World Health Organization stage IV had the highest viral suppression , followed by WHO stage I .In bivariate analysis, viral suppression was significantly associated with current age (< 0.001) . There wP = 0.003), duration on ART (P = 0.045), ART regimen at baseline (P < 0.001) and current ART regimen (P < 0.001) were also significantly associated with viral suppression.Furthermore, clinical factors such as history of tuberculosis (P = < 0.001).Adolescents who were retained in care had higher viral suppression rates compared to those who were not retained  were 77% more likely to be virally suppressed compared to adolescents who had a CD4 count < 200 cells/mm3.A higher CD4 count at baseline was associated with higher odds of viral suppression, and adolescents who had a CD4 count > 500 cells/mm3 However, in the Eastern Cape and Mpumalanga, in settings reflecting conditions similar to those reported in the current paper, 71% of adolescents in the Eastern Cape and 74% of those in Mpumalanga were virally suppressed in the past 12 months.20 Our study extends the evidence in support of an optimised adolescent HIV care cascade for all South African ALHIV across all healthcare facilities.21Our findings indicate that the progression of adolescents on ART in the Thabo Mofutsanyane District Municipality of the Free State province to the final ‘95’ of viral suppression in the UNAIDS 95-95-95 treatment trajectory, remains low at 78%. Our finding is lower than that reported in a meta-analysis by Zanoni et al., of South African adolescents and young adults on ART, where 81% were virally suppressed (< 1000 copies RNA/mL).3 – 350 cells/mm3) appear to have better virological outcomes than those who commence with more severe immunodeficiency (CD4 count < 200 cell/mm³).25 However, other studies found that higher CD4 counts were not associated with viral suppression.28 Thus, further qualitative research is needed to explain the association of initiating ART when symptomatic  and subsequent health behaviours (adherence and engagement in care) impact viral suppression.Our study confirms the association between baseline CD4 count levels and viral suppression. We found that adolescents in our analysis follow the pattern reported elsewhere, where people commencing ART with less advanced immunodeficiency , with sexual and reproductive health services and support groups in addition to ART, has been reported by Lamb et al. to significantly lower attrition rates.32 Moreover, Massavon et al. reported that higher retention in care rates are achieved in community home-based care services (94.0%) than in facility-based/family-centred care services (84.7%).33Prolonged retention in care is associated with optimal adherence and the reduced likelihood of high VL in patients on ART.An important limitation of this study has been missing information from routine records. This may have affected the analysis of variables associated with viral suppression. The study also involved retrospective extraction of data from a database, restricting us to routinely collected variables. This limited the extent to which other variables could also be explored, such as social, cultural and economic factors that can also affect viral suppression. Specifically, it is noted that there may be considerable differences in adolescents that are infected perinatally versus behaviourally. Unfortunately, this point was not part of our routine data and we were not able to test for a difference. A standard VL result of 124 copies/mL is captured in TIER.Net for persons with a laboratory result reported as ‘lower than the detectable level’, rather than as an actual value.Cross-sectional studies do not allow causality to be established and, in particular, with regard to VL testing, these events were not co-incident with several co-variates recorded in the study, for example, the WHO stages and the occurrence of tuberculosis. The significance of such factors in relation to viral suppression could not reliably be determined in this study. Further, we note the limitation that retention in care status was not assessed at the same time as VLS. Therefore, the significant association between retention in care and VLS should be interpreted with caution. Notwithstanding, there are several studies that support this association – therefore this result is likely to be valid.14 Routine monitoring of viral load results should be enhanced to detect possible VL failure earlier, so that timely interventions can be put in place. Further qualitative research is recommended to explore explanations for failure to achieve viral suppression.Viral suppression of adolescents on ART in the Thabo Mofutsanyane District at 78% is below the target of 95% set by UNAIDS, and there is an urgent need for interventions to improve individual behaviour, such as the earlier initiation on ART and retention in care, that would lead to improved rates of viral suppression. It is further disconcerting that when considering the higher threshold of viral load < 50 copies/mL as fully suppressed, only 9.5% achieved this rate. This finding does not bode well for achieving global efforts to reach 95-95-95 results by 2030, as propagated by UNAIDS.


The change in lipid panels at the end of the medication use evaluation endpoint was a decrease in total cholesterol, LDL, HDL, and triglycerides of −2.5, −0.1, −0.6, and −9 mmol/L, respectively. There was no clinically meaningful difference in kidney function as measured by eGFR or Scr, nor was there any clinically meaningful difference in lipid panels in patients switched from TDF to TAF-containing ART. Our observations suggest that the favorable impact of TAF on kidney function is sustained for at least 44 months after conversion from TDF. Tenofovir is one of the most widely used medications for HIV treatment and is administered as either tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide (TAF). Use of TAF is preferred as it is associated with fewer negative impacts on renal function; however, long-term follow-up beyond 96 weeks is limited. A retrospective chart review of patients ≥18 years who received TDF-containing anti-retroviral therapy (ART) for ≥6 months and then switched to a TAF-containing regimen between 1 December 2015 and 1 January 2020 is presented. The primary objective was to evaluate changes in kidney function as measured by eGFR and Scr. The secondary objective was to evaluate changes in lipids. Among the 142 patients identified, the median age was 66 years old with a median follow-up of 3.6 years. The change in kidney function was a median increase in Scr of 0.1 mg/dL and a decrease in eGFR of −8 mL/min/1.73 m Tenofovir is one of the most widely used medications for HIV pre-exposure prophylaxis (PrEP), HIV treatment, and hepatitis B treatment. Tenofovir is an acyclic nucleotide diester analog of adenosine monophosphate, which is administered orally as TDF or tenofovir alafenamide (TAF) . Both ar2. However, if TDF must be used in this setting, the manufacturer recommends the dose be adjusted when the eGFR falls below 50 mL/min/1.73 m2. Adjusting the dose or switching to a less nephrotoxic agent is of clinical importance given that TDF-induced nephrotoxicity was reported in nearly 15 percent of patients treated with TDF for 2–9 years [TDF can lead to kidney impairment characterized by increases in serum creatinine, proteinuria, glycosuria, hypophosphatemia, and acute tubular necrosis . The mai–9 years . A studyTAF is a prodrug that is absorbed more quickly than TDF and produces higher levels of the active drug, known as tenofovir diphosphate, in cells . PharmacPrevious studies have established that switching to TAF was associated with increases in eGFR of 1.5 mL/min if the baseline eGFR was 60–89 mL/min, and 4.1 mL/min if <60 mL/min . In contThe primary objective of this medication use evaluation is to evaluate the change in kidney function as measured by eGFR and Scr in patients switched from TDF to TAF-containing ARV regimens. The secondary objective is to evaluate the change in lipids in patients switched from TDF to TAF-containing ARV regimens.Pharmacists conducted an electronic chart review of patients ≥18 years with HIV who received TDF-containing ART for ≥6 months and then switched to a TAF-containing regimen at any point between 1 December 2015 and 1 January 2020. Patients who did not directly switch from TDF to TAF, had an interruption in ART > 1 month, or did not have a Scr and eGFR value > 9 months after the switch date were excluded. ® AmpliPrep/COBAS® TaqMan® HIV-1 Test . Collected demographic information included age, race, ethnicity, sex, chronic kidney disease diagnosis, diabetes mellitus diagnosis, and hypertension diagnosis. ART data collected consisted of the date started on the ART regimen containing TDF, the date stopped the ART regimen containing TDF, the duration of therapy on the ART regimen containing TDF, the date started the ART regimen containing TAF, the date stopped the ART regimen containing TAF (in the event TAF was discontinued), viral load while on TDF within 6 months prior to the switch date , viral load > 6 months after switch date, CD4+ count while on TDF within 6 months prior to the switch date , and CD4+ count > 6 months after the switch date. Viral load of HIV was determined using COBASKidney function values collected consisted of an Scr value while on TDF within 6 months prior to the switch date , any available Scr values at 6 ± 1 month, 9 ± 1 month, 12 ± 1 month, 18 ± 1 month, 24 ± 1 month, and 36 ± 1 month after the switch date, eGFR while on TDF within 6 months prior to the switch date , and any available eGFR at 6 ± 1 month, 9 ± 1 month, 12 ± 1 month, 18 ± 1 month, 24 ± 1 month, and 36 ± 1 month after the switch date. Finally, lipid profiles collected consisted of total cholesterol, LDL, and TG while on TDF within 6 months prior to the switch date , and total cholesterol, LDL, and TG > 6 months after the switch date. Descriptive statistics were used to analyze the results. A total of 142 patients were identified who were ≥18 years and received TDF-containing ART for ≥6 months and then switched to a TAF-containing regimen at any point between 1 December 2015 and 1 January 2020. The median age was 66 years old with 63% identifying as Black or African American and 27% identifying as Hispanic or Latino. Of these patients, 48% had hypertension, 22% had diabetes mellitus, and 9% had chronic kidney disease. A complete list of baseline characteristics is found in Of the TDF containing pre-switch regimens, 27% were Atripla (Efavirenz/Emtricitabine/TDF), 19% were Complera (Emtricitabine/Rilpivirine/TDF), 22% were Stribild (Elvitegravir/Cobicistat/Emtricitabine/TDF), 3% were TDF 300mg tablets, and 29% were Truvada (Emtricitabine/TDF). Of the TAF post-switch regimens, 6% were Biktarvy (Bictegravir/Emtricitabine/TAF), 15% were Descovy (Emtricitabine/TAF), 42% were Genvoya (Elvitegravir/Cobicistat/Emtricitabine/TAF), and 36% were Odefsey. 2. The median baseline viral load was <20 copies/mL, and the median CD4+ count was 517 cells/mm3. Baseline lipid profiles showed the median total cholesterol was 176 mmol/L, the median LDL cholesterol level was 98.8 mmol/L, the median HDL cholesterol level was 45 mmol/L, and the median triglyceride level was 136 mmol/L. A complete list of baseline characteristics is further summarized in The average duration of therapy on a TDF-containing regimen was 6.5 ± 3.6 years, and the average duration of therapy on a TAF-containing regimen was 3.8 ± 1.0 years. Baseline kidney function parameters before the switch in therapy showed a median Scr of 1.08 mg/dL and an average eGFR of 84.2 ± 23.2 mL/min/1.73mBaseline median kidney function, lipid panels, HIV viral load, and CD4+ count were compared to the post-switch values. Post-switch values were the last documented values after the 36 ± 1 month interval. The median post-switch time was 44 months. 2 and 8 mL/min/1.73m2, respectively. Scr also increased in these groups by 0.2 mg/dL and 0.1 mg/dL, respectively, whereas the other TDF-containing ART groups had no change in Scr. Patients transitioned onto Odefsey (Emtricitabine/Rilpivirine/TAF) and Biktarvy (Emtricitabine/Bictegravir/TAF) had the sharpest decline in kidney function relative to the other TAF regimens with a decrease in eGFR of 11 mL/min/1.73m2 and 9 mL/min/1.73m2, respectively. The sample size was too small to create clusters focusing on one specific TDF-containing ART regiment to one specific TAF-containing ART.Median change in kidney function from baseline across the 6 ± 1 month, 9 ± 1 month, 12 ± 1 month, 18 ± 1 month, 24 ± 1 month, 36 ± 1 month, and 44-month intervals was subsequentially grouped by initial TDF regimen as seen in 2 per year in elderly subjects [Switching from TDF-containing ART to TAF-containing ART did not appear to result in a clinical impact patient on kidney function or lipid panels over a median of 44 months of observation. There are several potential explanations for these findings. First, aging is a naturally developing biological process associated with gradual structural changes and functional loss of most systems and is often characterized by declining capacity and increasing morbidity . As one subjects . Regardl2. Switching to a TAF-containing regimen did not lead to a significant change in eGFR . While our medication use evaluation corroborates with these findings, it adds to the clinical picture a much older cohort with a median age of 66 years versus this study’s median age of 44 years. Likewise, this study had a majority of patients in the cohort that were on a regimen containing one of dolutegravir, cobicistat, or rilpivirine, all of which have been shown to inhibit creatinine secretion from the proximal kidney tubule, without affecting glomerular filtration rate. Their sample size of 79 did not allow for an exploration of the effect of other agents in the ART regimens. This is of particular importance in real-world clinical settings given there is likely to be more heterogeneity in ART regimens than in clinical trials. Nonetheless, with a slightly larger sample size of 142 patients, our medication use evaluation was able to create clusters based on which TDF or TAF-containing ART patients were on. While we found patients who transitioned off Atripla (Efavirenz/Emtricitabine/TDF) had the sharpest decline in eGFR relative to the other TDF-containing regimens and patients who transitioned onto Descovy (Emtricitabine/TAF) had the sharpest decline in eGFR relative to the other TAF-containing regimens, we cannot conclude these specific agents have a worse kidney profile than the others given that the sample size was too small to track specific clusters taking into account the TDF and TAF-containing regimen as an individual cluster. These findings have been corroborated in previous studies. One retrospective analysis was performed of a cohort from a publicly funded sexual health clinic in Sydney, Australia . A totalAnother single-arm, open-label phase 3 study performed at 70 outpatient centers in the United States, Thailand, the United Kingdom, Australia, Spain, France, the Dominican Republic, Mexico, and the Netherlands enrolled virologically suppressed HIV-1-infected subjects with estimated CrCl 30–69 mL/min in a single-arm, open-label study to switch regimens to Stribild  . The priTreatment with TDF has consistently been associated with a lower increase in lipids compared with other regimens in treatment-naive patients . In randWith HIV shifting into chronic disease state management, the control of comorbid conditions is essential for improving patient care. Patients with HIV are at increased risk for both cardiovascular disease and kidney disease, which are both associated with an increased risk of mortality ,18,19. OThis medication use evaluation has several limitations. As a retrospective chart review, findings are dependent on the assumption of accurate documentation. First, the patient’s “Active Problem” list was used to collect data regarding patients’ baseline disease states. Of note, CKD is defined based on the presence of either kidney damage or decreased kidney function for three or more months, irrespective of the cause. It is commonly underreported in this “Active Problem” list given the complexity of the diagnosis. While eGFR was collected at baseline and could infer CKD diagnosis, this medication use evaluation did not collect data on albuminuria, proteinuria, or proximal kidney tubular function to further confirm and more accurately report a CKD diagnosis. As such, our cohort may have a higher rate of CKD status, and it has been found that pre-switch eGFR was a significant predictor of the magnitude of eGFR change after the switch in regimens. Secondly, our sample size is small; however, our observations were largely in elderly and Black patients, two populations that are often under-represented in clinical trials. While no definitive conclusions can be made from a group of this size, these observations help provide insight into diverse populations and can hopefully be built upon by future research. An additional limitation to this medication use evaluation is the small representation of women, who made up only 2% of our cohort. Given that low body weight, especially in women, is a risk factor for poor kidney outcomes, it is unclear whether these findings can be extrapolated to female patients. Additionally, we did not collect information on Hepatitis B co-infection, use of statin medications, or changes in weight. Statins and weight changes can directly impact a patient’s lipid panels, which could have influenced our findings. Lastly, the patient’s concomitant medications were not collected. Specifically, mediation classes such as angiotensin-converting enzyme inhibitors (ACE-I), angiotensin receptor antagonists (ARB), and sodium-glucose cotransporter 2 (SGLT2) inhibitors can have a beneficial impact on the progression of kidney disease. Additionally, the use of therapies targeting the lipid profile such as statins, ezetimibe, and fenofibrates could have impacted changes in patient labs over this extended time period.Our observations suggest that prolonged use of TAF-containing ART regimens was associated with a decline in eGFR similar to what we would expect to occur naturally from age-related changes alone. These findings support the recommendation of the European society guidelines that patients receiving TDF with an eGFR >60 mL/min should be considered for a switch if their eGFR has declined by 5 mL/year for three or more years and/or their eGFR has decreased >25% from baseline. They also support the National Institutes of Health (NIH) guideline’s recommendation that TDF should be used with caution or avoided in patients with baseline kidney disease as prolonged use of TAF does not appear to be associated with an enhanced decline in eGFR. As such, patients with risk factors for worse kidney outcomes such as advanced HIV disease, longer treatment history, low body weight , pre-existing kidney impairment, or concomitant use of pharmacokinetically-enhanced regimens that can increase TDF concentrations should be transitioned to a TAF-containing ART or monitored closely if there is a refusal to switch regimens.


To analyze the perinatal outcomes of Perinatally acquired HIV Infection (PHIV) in pregnant women.This retrospective cohort study included singleton pregnancies in Women Living with HIV (WLH) between 2006 and 2019. Patient charts were revised, and maternal characteristics, type of HIV infection , Antiretroviral Therapy (ART) exposure, and obstetric and neonatal outcomes were assessed. The HIV-related aspects considered were: Viral Load (VL), CD4+ cell count, opportunistic infections, and genotype testing. Laboratory analyses were performed at baseline (first appointment) and 34 weeks of gestation.p < 0.001), had less frequently stable partnerships (p < 0.001), had more commonly serodiscordant partners (p < 0.001), had a longer time on ART (p < 0.001), and had lower rates of undetectable VL at baseline (p = 0.046) and at 34 weeks of gestation (p < 0.001). No association was observed between PHIV and adverse perinatal outcomes. Among patients with PHIV, third trimester anemia was associated with preterm birth (p = 0.039). Genotype testing was available only for 11 patients with PHIV, who presented multiple mutations related to ART resistance.There were 186 WLH pregnancies, and 54 (29%) patients had PHIV. Patients with PHIV were younger (PHIV did not seem to increase the risk of adverse perinatal outcomes. However, PHIV pregnancies have a higher risk of viral suppression failure and exposure to complex ARTs. The number of people living with HIV has increased worldwide. Recent worldwide data estimated that 37.6 million persons were living with HIV, and there were 1.5 million new cases in 2020.,,Perinatally acquired HIV (PHIV) accounts for approximately 1% of HIV cases in Brazil.,,Available studies suggest that obstetric care of PHIV pregnant women may be challenging due to lower rates of viral suppression, higher rates of viral resistance, and exposure to complex, multidrug ART.A few studies have assessed the outcomes of PHIV in pregnant women with controversial results on birth weight and preterm birth.This retrospective cohort study comprised singleton WLH pregnancies followed up at our obstetrics department  between 2006 and 2019.A database search was conducted to identify all cases of WLH evaluated in our department during the study period. Cases of multiple pregnancies, loss to follow-up, delivery at other hospitals, absence of prenatal care, unawareness of HIV diagnosis before delivery, and unavailability of hospital charts were not included.Patient charts were revised, and data regarding maternal demographic characteristics, HIV infection, ART exposure, and obstetric and neonatal outcomes were assessed. HIV-related aspects considered were the type of transmission , time of diagnosis, Viral Load (VL), CD4+ cell count, signs of immunodeficiency  cases.The perinatal outcomes assessed included gestational age at delivery, preterm birth, low birth weight (< 2500 g), gestational diabetes, preeclampsia, fetal growth restriction, preterm labor, abnormal fetal well-being, and HIV Mother-To-Child Transmission (MTCT).Throughout the study period, there were different guidelines for caring for pregnant WLH. Follow-up of this group of patients comprised regular prenatal appointments, first and second-trimester morphology scans, and regular assessment of fetal growth and wellbeing. All patients were prescribed ART, which consisted of three active antiretroviral drugs. The patients were assisted by a multidisciplinary team consisting of obstetricians, infectologists, psychologists, and social workers.Historically, local practices regarding pregnant WLH tended toward elective cesarean delivery, irrespective of VL. Such policies have changed, and vaginal births have recently been encouraged. During the study period, zidovudine intrapartum prophylaxis and neonatal zidovudine syrup were routinely recommended to all the patients. Breastfeeding was contraindicated.naïve pregnant women. Data on genotype testing were assessed retrospectively, based on available test results on patients’ charts and the “Brazilian National Network of CD4+/CD8+ Lymphocyte Count and Viral Load” (SISCEL).Indications for genotype testing during the study period included virological failure and, most recently, ART-t-test and Mann-Whitney U test were used to compare continuous variables presenting parametric and non-parametric distribution, respectively. McNemar's test was used to analyze paired nominal data (change in VL status). Unconditional logistic regression was applied to estimate Odds Ratios (ORs) and 95% Confidence Intervals (95% CIs). Statistical significance was set at p-value < 0.05. The data were analyzed using SPSS Statistics for Windows .Categorical data were presented as frequencies. Kolmogorov-Smirnov test and the values of kurtosis and skewness were employed to assess the distribution of numerical data. Variables presenting normal distribution were expressed as a mean and standard deviation; variables with non-normal distribution were expressed as median and interquartile range. Fisher's exact test and Chi-Square test were used to compare categorical variables. Student's This study was in accordance with the Helsinki Declaration. The study was approved by the ethics committee of Hospital das Clínicas FMUSP, São Paulo, Brazil .During the study period, 241 WLH pregnancies were registered in our obstetrics department. Fifty-five pregnancies did not meet the inclusion criteria and therefore were excluded from the analysis. Sixteen patients had their prenatal follow-up elsewhere, 14 did not have any prenatal appointment, 10 had twin pregnancies, one delivered at another hospital, one patient had an HIV diagnosis at the time of delivery, and 13 cases’ hospital charts were unavailable. Thus, 186 WLH pregnancies were included, corresponding to 161 subjects: 24 women with two pregnancies during the study period and one with three pregnancies.The demographic characteristics of the study population and prenatal, delivery, and neonatal information are presented in p < 0.001), had less frequent stable partnerships , and had more commonly serodiscordant partners   and smoking  . The PHIp < 0.001) and lesser rates of undetectable VL at the first prenatal appointment  and at 34 weeks of gestation . A change in the detectable baseline to undetectable VL at 34 weeks was observed in the BHIV group (p < 0.001) but failed to occur in the PHIV group (p = 0.267). However, the PHIV and BHIV groups had similar rates of baseline CD4+ cell count < 200 mmp = 0.348), opportunistic infections before pregnancy  and throughout gestation , and clinical hospital admissions .PHIV patients had a longer time on ART  and PI , including darunavir . ART comprising more than 3 drugs was more common in the PHIV group . Non-Nucleoside Reverse Transcriptase Reverse Inhibitors (NNRTI) were more frequent in the BHIV group (p = 0.001).ART regimens were markedly different among the groups. Compared with the BHIV group, PHIV patients’ ART comprised more frequently raltegravir . In this subgroup of patients, third-trimester anemia was associated with detectable VL at 34 weeks (p = 0.001), baseline and 34-week CD4+ cell counts , and trimethoprim-sulfamethoxazole intake (p < 0.001). There were no significant associations between third-trimester anemia and antiretroviral drugs (Supplementary Table 1).Patients with PHIV had a higher rate of third-trimester anemia  (Supplementary Table 2).Perinatal outcomes are shown in Genotype testing was available for only 11 pregnant women, and three cases did not present drug resistance. The genotype test results for patients with PHIV are summarized in The present study is the largest single-center cohort study of PHIV pregnancies to date. Preterm birth and low birth weight were the most frequent events in the general study population . Nevertheless, there was no association between the type of maternal HIV transmission and perinatal outcome.,Adverse perinatal outcomes have been described in previous small studies on PHIV pregnancies. Kenny et al. reported preterm birth in 14% of adolescent PHIV patients in the UK, a prevalence two times higher than that observed among teenagers in the same period of time.Conversely, Lazenby et al. recently assessed a multicentric cohort of 41 PHIV gestations and found higher birth weight in the PHIV group, in addition to similar rates of live birth, low birth weight, MTCT, and neonatal intensive care admissions between the PHIV and BHIV groups.,,The present findings suggest that PHIV does not increase the odds of preterm birth, low birth weight, fetal growth restriction, fetal loss, or maternal risks of preeclampsia, gestational diabetes, and hospital admission. These findings are consistent with those of other recent retrospective case-control studies on PHIV pregnancies.Compared with BHIV patients, the PHIV population had a higher prevalence of third-trimester anemia, which was associated with an increased risk of preterm birth. Anemia has been described as a frequent complication of WLH pregnancies, ranging from 37% to 64%;The management of ART seemed to be more complex in our PHIV group than in the BHIV group. PHIV pregnancies were more frequently exposed to antiretroviral drugs, ART combinations comprising >3 drugs, and alternative drugs, such as raltegravir and darunavir. Currently, the Brazilian HIV guidelines consider raltegravir-based ART as the first option for pregnant women;Although there were higher rates of detectable VL and failure to suppress viral infection among our PHIV patients, this group presented neither an increased risk of MTCT nor a higher prevalence of immunodeficiency signs, such as opportunistic infections and CD4+ cell count <200 mm,,10,,3; however, they found similar baseline CD4+ cell counts and VL in PHIV and BHIV pregnancies.ART in PHIV patients tends to be more challenging since these patients have longer periods on ART and multiple expositions to antiretroviral drugs.,,,,Low ART adherence is a plausible cause of reduced viral suppression in PHIV patients.In this regard, the lack of ART adherence and subsequent lack of viral suppression among PHIV patients might be related to the socio-demographic aspects of such a population. In the present findings, PHIV pregnant women were younger, had fewer stable partnerships, and more commonly had serodiscordant partners. Although not statistically significant, pregnancies were unplanned in 96% of patients with PHIV. Colombini et al. reviewed studies on ART adherence during pregnancy and suggested that HIV-related stigma, fear of disclosure of HIV diagnosis, young maternal age, low income, and lack of partnership may be associated with low ART adherence.Another plausible reason for lower viral suppression in patients with PHIV is viral resistance to ART. Although genotype testing was available only for a small sample of our PHIV population, multiple antiretroviral resistance mutations were confirmed in 73% of the tested cases, and five patients had multiclass resistance to NRTI, NNRTI, and PI. The present results might have a selection bias since genotype testing was only performed in cases with virological failure and risk of viral resistance. Nonetheless, previous studies reported an association between PHIV and ART resistance. Teixeira et al. analyzed a Brazilian cohort of 232 pregnant WLH and found that 15% of the population had at least one antiretroviral resistance.In conclusion, PHIV did not seem to increase the risk of adverse perinatal outcomes. However, PHIV pregnancies have a higher risk of viral suppression failure and exposure to complex ART. Such patients should be followed up by an experienced multidisciplinary team familiar with the management of viral resistance. Social issues regarding PHIV pregnancies should also be considered to reduce risks and vulnerability. Larger and multicenter studies are necessary to properly address PHIV-related perinatal risk.Osmundo Junior GS was responsible for study conception and design, data collection, analysis, interpretation, and manuscript drafting. Costa RA participated in the analysis and revision of the manuscript for intellectual content. Ruocco RMA and Francisco RPV reviewed the manuscript and contributed to relevant discussions. All the authors approved the final version of the manuscript.This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectorsThe authors declare no conflicts of interest.


The pediatric HIV follow-up is challenging, and treatment indicators are markedly distant from UNAIDS goals. In this study, we describe the 2019 Brazilian HIV cascade according to age categories and sociodemographic variables and address temporal trends between 2009-2019.+ T cell count ≥350 cells/mm3 or a first ART dispensation ≤30 days after the first CD4+ T cell measurement) and detectable HIV viral load (>50 copies/mL) was assessed in univariable and multivariable analysis adjusted for gender, race, and Social Vulnerability Index (SVI). Temporal trends in timely ART initiation and viral suppression were evaluated graphically.We obtained data from the Brazilian Ministry of Health monitoring database. Cascade outcomes included retention in care, antiretroviral use, and viral suppression. The effect of age on timely initiation of antiretroviral treatment Among 771,774 people living with HIV (PLHIV), those from youngest age categories had poorer indicators in the care cascade . PLHIV in younger age groups, those with higher SVI, and those declaring black and native Brazilian race/ethnicity, had higher odds of having detectable viral load and delayed ART initiation (Table 1).Social aspects are also associated with worse outcomes. Although children living with HIV tend to start ART with higher CD4Continuum of care in Brazil, 2019Retention in care, antiretroviral use and viral load suppression in people living with HIV under care in the Brazilian Unified Health System in 2019, overall and by age category .Temporal trends, Brazil (2009-2019)Temporal trends of timely initiation of ART based on a CD4+ T cell count ≥500m/mm3 (panel A), timely initiation of ART based on a first ART dispensation ≤30 days after the first CD4+ T cell count measurement (panel B) and viral load suppression (panel C) overall and according to age categories between 2009 and 2019 in Brazil.Our results highlight the challenge faced by children and adolescents living with HIV to achieve UNAIDS goals. Lower access to ART among children is a central barrier to improve pediatric care.All Authors: No reported disclosures.