Oral Janus Kinase Inhibitors in Pediatric Atopic Dermatitis.

PURPOSE OF REVIEW: To analyze the efficacy and safety of Janus kinase inhibitors (JAKi) in the treatment of pediatric AD. RECENT FINDINGS: Adolescents with moderate and severe atopic dermatitis (AD) need systemic therapies, as stated several recent practice guidelines. (JAKi) have shown their efficacy in the treatment of adult AD, however, there is a lack of information concerning efficacy and safety of their use in pediatric AD. We found that the JAKi's abrocitinib (ABRO), baricitinib (BARI), and upadacitinib (UPA), are all an effective treatment option with a very fast onset of action for adolescents with moderate-to-severe AD. BARI was not effective in children between 2 and 10 years with moderate-to-severe AD. Fortunately, major safety issues with JAKi in adolescents with AD have not been documented in the trials, so far, contrasting with the reports in adults with AD, where these events have very rarely occurred. There are some reports of herpes zoster (HZ) infection in adolescents on JAKi, but it is not a major safety concern. Acne is a relatively common AE with UPA in adolescents; however, it is responsive to standard treatment. This review will help the clinician to choose among the JAKi according to the needs and clinical features of patients with moderate and severe AD. In the following years, with the advent of new biologicals and JAKi, these therapies will fall into place in each phase of the evolution of patients with AD.

Budget impact of upadacitinib in patients with moderate to severe rheumatoid arthritis in Argentina. / Impacto presupuestario de upadacitinib en pacientes con artritis reumatoide moderada a severa en Argentina.

OBJECTIVES.: To analyze the budget impact of upadacitinib (UPA) 15 mg + methotrexate (MTX) for the treatment of moderate-to-severe rheumatoid arthritis (RA) in patients with an inadequate response to conventional disease-modifying antirheumatic drugs (cDMARD-IR) from the perspective of social security and the private health sector in Argentina. MATERIALS AND METHODS.: A budget impact analysis model was developed for a hypothetical cohort of 100,000 adults with health insurance coverage who were diagnosed with RA over a 5-year time horizon. The model parameters were obtained through literature review and validated by local experts. The costs are expressed in 2024 US dollars (USD). RESULTS.: The introduction of UPA 15 mg + MTX for the treatment of moderate-to-severe RA and cDMARD-IR resulted in minimal increase, with a five-year total cumulative incremental cost of USD 1,855 for social security and USD 1,812 for the private health sector, representing 2% of the total budget. The acquisition cost of UPA was the most influential variable in the sensitivity analysis. CONCLUSIONS.: The introduction of UPA 15 mg + MTX for the treatment of moderate-to-severe RA and cDMARD-IR can provide an effective treatment option with a minimal increase in costs for the healthcare system in Argentina, which is especially important in developing countries where health system budgets are more limited. Providing evidence-based estimates is a valuable tool for informing healthcare policies and can help policymakers make informed decisions about the allocation of healthcare resources to improve patient outcomes while also managing costs.Motivation for the study. Rheumatoid arthritis (RA) is a disease that hasn't cure, so it's important to know the budget impact of treatment with upadacitinib (UPA) 15 mg + methotrexate (MTX) in patients with moderate to severe RA who didn't respond well to conventional antirheumatic drugs. Main findings. UPA + MTX would entail a minimal increase in costs for the healthcare system in Argentina, potentially making this effective treatment option more accessible to patients with RA. Access to this treatment can improve the outcome of patients with RA. Public health implications. In resource-constrained settings such as Argentina, providing evidence-based cost estimates can help healthcare managers allocate resources efficiently while improving patient outcomes. This study provides evidence to inform healthcare policies and decisions regarding the inclusion of UPA + MTX in treatment guidelines or formularies for RA management.

[Utilization of Upadacitinib in the treatment of Crohn's disease: a report on two clinical cases]. / Utilización de Upadacitinib en el tratamiento de la enfermedad de Crohn: reporte de dos casos clínicos.

Crohn's disease (CD) is a chronic, progressive inflammatory disease with complications that impact the well-being of patients. The therapeutic advances achieved in recent decades, especially through the advent of biological therapy, have allowed for a transformation in the approach and management of CD, thereby modifying the course of this disease. However, a significant number of patients do not experience a satisfactory response to these drugs or lose it during the course of the disease. In this scenario, a viable alternative is to switch medications. Upadacitinib, a novel Janus kinase inhibitor, has emerged as a promising strategy for the management of CD. We presented two cases of patients with CD refractory to conventional therapy and biological therapy, who responded successfully to treatment with upadacitinib.

Reversibility of Neuropsychiatric Adverse Events after Switching to Darunavir/Cobicistat or Doravirine in Men on INSTI-Based Regimen.

Integrase strand transfer inhibitors (INSTI) are associated with neuropsychiatric adverse events (NPAEs). The aim of this study was to evaluate improvements in NPAEs after switching an INSTI-based regimen to darunavir/cobicistat (DRV/c) or doravirine (DOR). Methods: A prospective cohort study was conducted to evaluate the reversibility of NPAEs via the Patient Health Questionnaire (PHQ-9), the Insomnia Severity Index (ISI), and the Hospital Anxiety and Depression Scale (HADS-A and D) in patients who started antiretroviral therapy with dolutegravir (DTG) or bictegravir (BIC). These patients were switched to DRV/c or DOR. Scales were compared at the moment of the switch and 12 weeks later. Results: We included 1153 treatment-naïve men, 676 (58.7%) with BIC and 477 (41.3%) with DTG. A total of 32 (2.7%) experienced NPAEs that led to discontinuation. Insomnia was found in 20 patients; depression via PHQ-9 in 21 patients, via HADS-D in 5 patients, and anxiety via HADS-A in 12 patients. All of them were evaluated by a psychiatrist at the moment of the symptoms; 7 (21.8%) started psychotropic drugs. After 12 weeks of follow-up, PHQ-9, ISI, HADS-A, and HADS-D decreased, with a p-value ≤ 0.05. Conclusions: NPAEs seem to improve after switching to a DRV/c- or DOR-based regimen after the first 4 and 12 weeks.

First case report of a perinatally HIV-infected infant with HIV resistance to dolutegravir associated with tenofovir/lamivudine/dolutegravir use in mothers.

Perinatally HIV-infected infants can be infected with a drug-resistant virus or select for drug resistance by exposure to sub-therapeutic levels of maternal antiretroviral drugs present in breastmilk or from sub-therapeutic infant prophylaxis. We report a case of dolutegravir resistance detected in a treatment-naive perinatally HIV-infected infant whose mother was receiving tenofovir/lamivudine/dolutegravir. This case was detected during a national survey of HIV drug resistance in Haiti amongst infants testing positive for HIV through the national early infant diagnosis program between April 2020 and March 2021. This unique case underscores the need for prompt management of high viral loads in pregnant and breastfeeding women and supports HIV drug resistance surveillance efforts targeted at antiretroviral therapy-naive infants born to mothers in low-and middle-income countries.

Dolutegravir in Mexico for special populations: A cost analysis perspective.

Integrase strand-transfer inhibitors (INSTI) are the latest class of antiretrovirals registered in Mexico. They include raltegravir (RAL), elvitegravir/cobicistat (EVG/c), dolutegravir (DTG) and bictegravir (BIC). Along with international guidelines, Mexico adopted the use of INSTI about two years ago as initial antiretroviral therapy (ART). This is partially due to the increase in the pre-treatment resistance to non-nucleoside reverse transcriptase inhibitors (NNRTI), mainly efavirenz (EFV). Furthermore, INSTI depict greater efficacy, safety and less drug-drug interactions than NNRTI and protease inhibitors (PI). DTG is a second generation INSTI with a high barrier to resistance. It is recommended in international and national guidelines in a wide variety of clinical scenarios for persons living with human immunodeficiency virus (HIV) (PLWHIV), including treatment-naïve, first-line NNRTI treatment failure, simplification switch in suppressed patients, pregnancy, women with childbearing potential, adolescents and children over 6 years of age. DTG is mostly metabolized by the liver UDP-glucuronosyltransferase, and exhibits low drug-drug interactions overall; on the other hand, it has an extremely low renal elimination, therefore may be used in PLWHIV with advanced kidney disease without dose modification. Tuberculosis is a common coinfection in Mexico that requires rifampin-based anti-tuberculosis therapy, which requires increasing DTG to double dosing (50 mg BID). In Mexico, DTG-based regimens are likely to be cost-effective in many scenarios, given its acquisition costs and the particularities of the HIV population and associated clinical conditions, including a relatively high proportion of the following: i) new HIV diagnoses presenting at acquired immunodeficiency syndrome (AIDS) stage; ii) high rate of tuberculosis coinfection; iii) frequent first-line NNRTI treatment failures; and iv) relatively high proportion of infected children and adolescents.

Phase III trials of JAK1 selective inhibitors in rheumatoid arthritis.

Upadacitinib and filgotinib, two JAK1 selective drugs have undergone extensive phase III clinical trials in RA and have demonstrated rapid improvements in disease activity, function and patient reported outcomes. Six global phase III randomized controlled clinical trials (SELECT phase III program) evaluated the efficacy and safety of upadacitinib and four clinical phase III trials (the FINCH program) evaluated the efficacy and safety of filgotinib. This article is a critical review of all these studies with focus on the therapeutic efficacy in RA. The aim is to display the data that could allow the approval of these new drugs for the treatment of RA (upadacitinib has been already approved in most of the markets around the world).

Dolutegravir and pregnancy outcomes in women on antiretroviral therapy in Brazil: a retrospective national cohort study.

BACKGROUND: Dolutegravir has been widely available in Brazil since 2017. Following the signal that infants born to women with dolutegravir exposure at conception in Botswana had a higher risk of neural tube defects (NTDs), public health leaders initiated a national investigation to evaluate periconception dolutegravir exposure among all pregnant Brazilian women with HIV and its potential association with risk of NTDs, stillbirth, or miscarriage before 22 weeks (also called spontaneous abortion). METHODS: In this retrospective, observational, national, cohort study, we identified all women with pregnancies and possible dolutegravir exposure within 8 weeks of estimated date of conception between Jan 1, 2017, and May 31, 2018, and approximately 3:1 matched pregnant women exposed to efavirenz between Jan 1, 2015, and May 31, 2018, using the Brazilian antiretroviral therapy database. We did detailed chart reviews for identified women. The primary outcomes were NTD and a composite measure of NTD, stillbirth, or miscarriage. NTD incidences were calculated with 95% CI. The composite outcome was examined with logistic regression using propensity score matching weights to balance confounders. FINDINGS: Of 1427 included women, 382 were exposed to dolutegravir within 8 weeks of estimated date of conception. During pregnancy, 183 (48%) of 382 dolutegravir-exposed and 465 (44%) of 1045 efavirenz-exposed women received folic acid supplementation. There were 1452 birth outcomes. There were no NTDs in either dolutegravir-exposed (0, 95% CI 0-0·0010) or efavirenz-exposed groups (0, 95% CI 0-0·0036). There were 23 (6%) stillbirths or miscarriages in 384 dolutegravir-exposed fetuses and 28 (3%) in the 1068 efavirenz-exposed fetuses (p=0·0037). Logistic regression models did not consistently indicate an association between dolutegravir exposure and risk of stillbirths or miscarriages. After study closure, two confirmed NTD outcomes in fetuses with periconception dolutegravir exposure were reported to public health officials. An updated estimate of NTD incidence incorporating these cases and the estimated number of additional dolutegravir-exposed pregnancies between Jan 1, 2015 and Feb 28, 2019, is 0·0018 (95% CI 0·0005-0·0067). INTERPRETATION: Neither dolutegravir nor efavirenz exposure was associated with NTDs in our national cohort; incidence of NTDs is probably well under 1% in dolutegravir-exposed HIV-positive women but still slightly above HIV-uninfected women (0·06%) in Brazil. FUNDING: The Brazilian Ministry of Health and the United States' National Institutes of Health.

Dolutegravir: Virologic response and tolerability of initial antiretroviral regimens for adults living with HIV.

The integrase inhibitor dolutegravir was included in initial antiretroviral therapy in Brazil in January 2017. Studies have demonstrated that the efficacy and safety of antiretrovirals have improved with the introduction of new classes of antiretrovirals, such as integrase inhibitors. This study aimed to estimate the frequency of individuals with a virologic response by week 24 of antiretroviral treatment and to describe the adverse events of the regimen containing dolutegravir. This was a cohort of people living with HIV followed up at a referral hospital. Patients were included who had initiated their first treatment between January and August 2017. Data were obtained from medical records, the Drug Logistics Management System and from the Laboratory Tests Control System. Two hundred and twenty-two patients were included for the tolerability analysis and one hundred and thirty-seven for the virologic response analysis. The mean age was 34 years, the median time between diagnosis and initiating treatment was 1.9 months and the median time on antiretroviral therapy was 13.2 months. The frequency of adverse events was 10% (95% CI: 7% to 15.2%), of these, amongst the most frequent events, 91% presented gastrointestinal effects, and 47.8% neuropsychiatric. By week 24 the estimated incidence of virologic response was 89.1% (95% CI: 83% to 93.5%), with an increase during the first 6 months in the number of T-CD4 lymphocytes of 50.7 cells/mm 3 (95% CI: 42 to 59.3). Initial antiretroviral regimens containing dolutegravir were well tolerated and effective in viral suppression during the first 24 weeks after initiating treatment. The occurrence of adverse events was low, either mild or moderate.

Evaluating upadacitinib for the treatment of rheumatoid arthritis.

INTRODUCTION: The introduction of JAKs inhibitors for the treatment of rheumatoid arthritis represents a promising new era in the management of the disease. New compounds under investigation, like upadacitinib, with greater selectivity for JAK1 inhibition have recently been approved for the treatment of adults with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to conventional synthetic disease-modifying antirheumatic drugs. AREAS COVERED: Herein, the authors review the pharmacological data, the therapeutic efficacy, and safety data of upadacitinib before providing the reader with their critical evaluation and future perspectives. EXPERT OPINION: Upadacitinib was able to accomplish all the primary and secondary end points in most of the trials, with a safety profile that is similar to the other JAK inhibitors. It has also demonstrated superiority over a tumor necrosis factor inhibitor and data on new indications is also favorable. Upadacitinib is a promising new drug for the treatment of rheumatoid arthritis. GLOSSARY: Adalimumab: ADA; American College of Rheumatology: ACR; Assessment of Spondylarthritis International Society 40: ASAS40; Ankylosis Spondylitis: AS; Area under the Curve: AUC; Biological Disease-modifying arthritis drugs: bDMARDs; Clinical disease activity index: CDAI; C Reactive Protein: CRP; Conventional Synthetic Disease-modifying arthritis drugs: csDMARDs; Deep Venous Thrombosis: DVT; Disease arthritis score: DAS.

New Drugs 2020, part 2.

This article reviews seven drugs recently approved by the FDA, including indications, precautions, adverse reactions, and nursing considerations.

Durable Efficacy of Dolutegravir Plus Lamivudine in Antiretroviral Treatment-Naive Adults With HIV-1 Infection: 96-Week Results From the GEMINI-1 and GEMINI-2 Randomized Clinical Trials.

BACKGROUND: The 2-drug regimen dolutegravir + lamivudine was noninferior to dolutegravir + tenofovir disoproxil fumarate/emtricitabine in achieving HIV-1 RNA <50 copies/mL in treatment-naive adults in the 48-week primary analysis of the GEMINI trials. We present results from the prespecified 96-week secondary analyses. SETTING: One hundred eighty-seven centers in 21 countries. METHODS: GEMINI-1 and GEMINI-2 are identical, double-blind phase III studies. Participants with screening HIV-1 RNA ≤500,000 copies/mL were randomized 1:1 to once-daily dolutegravir + lamivudine or dolutegravir + tenofovir disoproxil fumarate/emtricitabine. RESULTS: At week 96, dolutegravir + lamivudine (N = 716) was noninferior to dolutegravir + tenofovir disoproxil fumarate/emtricitabine (N = 717) in achieving HIV-1 RNA <50 copies/mL (Snapshot algorithm; -10% noninferiority margin) in the pooled analysis (proportion of responders, 86.0% vs 89.5%, respectively; adjusted treatment difference [95% CI], -3.4% [-6.7 to 0.0007]), GEMINI-1 (-4.9% [-9.8 to 0.03]), and GEMINI-2 (-1.8% [-6.4 to 2.7]). Proportions of participants in the HIV-1 RNA ≥50 copies/mL Snapshot category were largely unchanged from week 48 to 96. Eleven participants taking dolutegravir + lamivudine and 7 taking dolutegravir + tenofovir disoproxil fumarate/emtricitabine met confirmed virologic withdrawal criteria through week 96; none had treatment-emergent resistance mutations. Dolutegravir + lamivudine had a lower rate of drug-related adverse events than dolutegravir + tenofovir disoproxil fumarate/emtricitabine (19.6% vs 25.0%; relative risk ratio, 0.78; 95% CI: 0.64 to 0.95). Renal and bone biomarker changes favored dolutegravir + lamivudine. CONCLUSIONS: Consistent with 48-week data, dolutegravir + lamivudine demonstrated long-term, noninferior efficacy vs dolutegravir + tenofovir disoproxil fumarate/emtricitabine without increased risk of treatment-emergent resistance, supporting its use in treatment-naive HIV-1-infected individuals.

Potential impact of the antirheumatic agent auranofin on proviral HIV-1 DNA in individuals under intensified antiretroviral therapy: Results from a randomised clinical trial.

Antiretroviral therapy (ART) is typically composed of a combination of three antiretroviral drugs and is the treatment of choice for people with human immunodeficiency virus type 1/acquired immune deficiency syndrome (HIV-1/AIDS). However, it is unable to impact on viral reservoirs, which harbour latent HIV-1 genomes that are able to reignite the infection upon treatment suspension. The aim of this study was to provide an estimate of the safety of the disease-modifying antirheumatic agent auranofin and its impact on the HIV-1 reservoir in humans under intensified ART. For this purpose, an interim analysis was conducted of three of the six arms of the NCT02961829 clinical trial (five patients each) with: no intervention, i.e. continuation of first-line ART; intensified ART (ART + dolutegravir and maraviroc); and intensified ART plus auranofin. Auranofin treatment was found to be well tolerated. No major adverse events were detected apart from a transient decrease in CD4+ T-cell counts at Weeks 8 and 12. Auranofin decreased total viral DNA in peripheral blood mononuclear cells compared with ART-only regimens at Week 20 (P = 0.036) and induced a decrease in integrated viral DNA as quantified by Alu PCR. Despite the limited number of patient-derived sequences available in this study, phylogenetic analyses of nef sequences support the idea that auranofin may impact on the viral reservoir. [ClinicalTrials.gov ID: NCT02961829].

DOLAMA study: Effectiveness, safety and pharmacoeconomic analysis of dual therapy with dolutegravir and lamivudine in virologically suppressed HIV-1 patients.

Dolutegravir (DTG) has shown effectiveness in combination with rilpivirine in with experience of antiretroviral therapy (ART) and with 3TC in naïve patients (GEMINI trial). The main objectives of this real-life study were to analyze the effectiveness and safety of 3TC plus DTG in virologically suppressed HIV-1 patients and to conduct a pharmacoeconomic analysis.We conducted an observational, retrospective and multicenter study of HIV+ patients pretreated for at least 6 months with ART that was then simplified to 3TC + DTG for any reason. We gathered data on viral loads (VLs) during exposure to the DT, calculating the rate with VL < 50 copies/mL at week 48, and on associated adverse effects.The 177 HIV+ patients were collected, 77.4% male, with average age of 48.5 years and mean count of 252.2cell/µL CD4+ nadir lymphocytes; 96.6% had VL < 50 copies/mL and 674 cells/µL CD4+ lymphocytes. Median time since HIV diagnosis was 15 years, and median ART duration was 13 years, and 34.5% of patients were on mono- or dual-therapy before the switch. At week 48, 82.4% of patients had VL < 50 cop/µL using an intention-to-treat (ITT) analysis, 89.6% according to mITT, and 96.7% according to Per-Protocol analysis. 3.3% patients had virological failure (VF). These effectiveness data and costs were compared with those for 2 reference triple therapies (DTG/ABC/3TC and EVG/cobi/FTC/TAF) in a cost minimization analysis, showing cost savings with administration of DTG+3TC (2741 &OV0556;/year vs DTG/ABC/3TC and 4164 &OV0556;/year vs EVG/cobi/FTC/TAF) and in a cost-effectiveness analysis, finding the DT to be the most cost-effective approach (ICER = -548 vs DTG/ABC/3TC and ICER = -4,627&OV0556; vs EVG/cobi/FTC/TAF)The combination of 3TC with DTG appears to be a safe and effective option for the simplification of ART in pretreated and virologically stable HIV-positive patients, being cost-effective and offering the same effectiveness as the triple therapy it replaces.

Resistance to HIV integrase strand transfer inhibitors in Argentina: first interim survey.

OBJECTIVE: No data on resistance to HIV integrase strand transfer inhibitors (InSTIs) in Argentina are available as access to these drugs and to integrase genotypic resistance test is limited. We aimed to evaluate the clinical profile of patients who underwent an integrase genotypic resistance test, prevalence of InSTI resistance mutations and predicted efficacy of raltegravir, elvitegravir and dolutegravir in our country. METHODS: Retrospective multicentric pilot survey from January 2011 to November 2017 of InSTI-failing patients assisted at two private and one public healthcare institutions located in Buenos Aires city, Argentina. RESULTS: Sixty seven patients were included. Patients had a median of 5 (4-7) prior treatments. All patients had InSTI-containing regimens (median exposure of 22.5 months); 94% were under raltegravir therapy and 71.9% had InSTI-resistance mutations. Predominant major mutations were N155H (35.1%), Q148H/R (15.8%) and G140A/S (14%). Considering Stanford HIVdb program, extremely low and identical activity of raltegravir and elvitegravir was described while dolutegravir remained either partially or fully active in 97.7% of patients. CONCLUSIONS: Integrase resistance test was prescribed almost exclusively in heavily pretrated raltegravir-exposed patients. The three main mutational pathways were described, with a predominance of N155H. Despite almost null susceptibility and extensive cross resistance was shown among raltegravir and elvitegravir, dolutegravir remains active in the majority of patients.

Comparative effectiveness of first-line antiretroviral therapy: results from a large real-world cohort after the implementation of dolutegravir.

OBJECTIVE: We aimed to assess the effectiveness of first-line antiretroviral therapy (ART) regimens in achieving viral suppression at 12 months, from 2014 to 2017 in Brazil. DESIGN: A retrospective cohort study utilizing programmatic data from the Brazilian HIV Program. METHODS: Adults (aged 15-80 years) who started ART from January 2014 to July 2017 and had a viral load 365 (±90) days after treatment initiation were included. Associations with achieving viral suppression (<50 copies/ml) at 365 (±90) days were assessed using logistic regression. Our main study variable was ART regimen, and covariates included year of ART initiation, sex/exposure group, age, education, race, region, baseline CD4 and viral load counts, and adherence measured by pharmacy refill data. We performed both intent-to-treat and per-protocol analogous analyses. RESULTS: Out of 107 647 ART-naive patients, 71.5% initiated with tenofovir/lamivudine/efavirenz (TLE) and 10.5% with tenofovir/lamivudine/dolutegravir (TLD). Median age and CD4 cell counts were 34 [interquartile range (IQR) 26-46] and 379 cells/µl (IQR 190-568), respectively; 68.0% were men. Viral suppression by 12 months was 84.0% [95% confidence interval (95% CI) 83.7-84.2] with TLE and 90.5% (95% CI 90.0-91.0) with TLD, and below 80% for protease-inhibitor-based regimens. In the multivariable intent-to-treat-analogous analysis, controlling for cofactors related to viral suppression including adherence, the adjusted odds ratio (aOR) for TLD's viral suppression relative to TLE was 1.56 (95% CI 1.40-1.75). Findings were robust to secondary per-protocol analogous and sensitivity analysis. CONCLUSION: Our results showed the superiority of dolutegravir- over efavirenz- and protease-inhibitor-based regimens in suppressing viral replication in a real-word cohort of HIV-positive adults. This superiority was not driven by higher levels of adherence with dolutegravir-based regimens.

The Brazilian experience of implementing the active pharmacovigilance of dolutegravir.

In 2017, the Ministry of Health Brazilian started using dolutegravir (DTG) 50 mg to all people living with HIV who began antiretroviral therapy (ART) or rescue regimens. Although DTG is thought to have better tolerability levels and a lower possibility of causing adverse reactions, it is necessary to continuously evaluate the safety profile of the drug in the population. Therefore, an active pharmacovigilance project for DTG was implemented. The objective of this study was to describe the Brazilian experience of implementing pharmacovigilance and the results obtained during the period between April and December 2017.Active pharmacovigilance was implemented through patient interviews and an online questionnaire developed in the Medication Logistics Control System (SICLOM).Of the total number of people on DTG in Brazil (79,742) 90.33% participated in the project, and 2.24% of those who participated reported adverse reactions to the drug; of those who reported adverse reactions, 73.86% were on first-line ART regimens, and 26.13% were on third-line regimens. The mean age of the patients who had adverse reactions to DTG was 39 years; 68.79% were male, and 31.21% were female. Of the adverse reactions reported, 50.39% were considered persistent. The 3 most frequent reactions were nausea (13.34%), diarrhea (9.83%), and headaches (9.23%).The Brazilian experience with this project has been deemed successful by federal and local managers, and the online tool to collect data has proved to be an important strategy for the pharmacovigilance of DTG as well as that of other drugs.