Risk of tuberculosis after achieving HIV virological suppression on antiretroviral therapy: a Danish nationwide prospective cohort study.

BACKGROUND: In countries with low tuberculosis (TB) burden, the risk of TB in people with HIV (PWH) once HIV virological suppression is achieved is not fully understood. METHODS: In a nationwide cohort, we included all adult PWH from the Danish HIV Cohort initiating antiretroviral therapy (ART) (1995-2017) without prior TB disease. We used Kaplan-Meier estimation and Poisson regression to calculate TB incidence rate (IR) after six months of ART, along with associated risk factors and mortality rates (MR). RESULTS: Among 6,849 PWH initiating ART (median follow-up 7.4 years), 84 developed TB (IR 1.4/1000 person-year [PY]), 54 of them beyond six months of ART initiation, IR 0.97/1000 PY (95%CI:1.17-1.79): 1.95 (95%CI:1.34-2.76) in non-Danish born, 0.36 (95%CI:0.21-0.62) in Danish-born without injection drug use (IDU), and 2.95 (95%CI:1.53-5.66) in Danish-born with IDU. Danish-born with suppressed viremia, and no IDU or known TB exposures had the lowest risk (IR 0.05/1000 PY).In the adjusted analysis, being non-Danish born (aIRR 4.27[95%CI:2.36-7.72]), IDU (aIRR 4.95[95%CI:2.55-9.62]), and previous AIDS-defining events (aIRR 2.05[95%CI:1.06-3.94]) raised TB risk, while suppressed HIV-RNA (aIRR 0.58[95%CI:0.34-0.99]) reduced it. The overall MR for HIV/TB co-infected post- ART was high, at 48.9/1000 PY (95%CI:30.4-78.7). CONCLUSIONS: The TB risk remains elevated in PWH beyond six months of ART initiation, especially among migrants, IDU, those without suppressed HIV-RNA, and individuals exposed to high TB endemic areas or with social risk determinants of health. Conversely, PWH without these risk factors have a TB risk similar to the general population and would not require targeted TB screening strategies.

Prevalence of people living with multidrug-resistant HIV and limited treatment options in Spain.

OBJECTIVES: Our aim was to determine the prevalence and characteristics of people with HIV on antiretroviral therapy (ART) with multidrug resistance (MDR; confirmed resistance to three or more [or resistance to two or more plus contraindication to one or more] core ART classes) and limited treatment options (LTOs) in Spain. METHODS: This was an observational, retrospective, multicentre, cross-sectional chart review study undertaken in five reference Spanish centres. Participants were people with HIV on ART with MDR and LTOs (detectable viral load [HIV-RNA >200 copies/mL], treatment-limiting drug-drug interaction [DDI], or intolerance precluding the use of one or more ART classes). Prevalence, demographic/clinical characteristics, and treatment options were assessed. Logistic regression analyses were used to identify MDR-associated variables. RESULTS: Of 14 955 screened people with HIV, 69 (0.46%) presented with MDR and 23 (0.15%) had LTOs. The population analysed was 73.9% male with a median age of 54.0 years; the median time since HIV diagnosis was 26.5 years, and median CD4+ cell count was 511.0 cells/µL. The only factor significantly associated with MDR (univariate analysis) was CD4+ cell count. Injection drug use was the most common transmission route. Comorbidities (mainly endocrine and cardiovascular disorders; 34.8% affecting HIV management) and concomitant treatments were frequent. No recent opportunistic infections were reported. Patients had been exposed to the following ART: nucleoside analogue reverse transcriptase inhibitors (100%), protease inhibitors (95.6%), non-nucleoside analogue reverse transcriptase inhibitors (87.0%), and integrase strand transfer inhibitors (82.6%). The available fully active drugs were dolutegravir (39.1%), bictegravir (30.4%), and raltegravir (21.7%). CONCLUSIONS: The prevalence of people with HIV with MDR and LTOs in Spain is very low, with approximately half of those studied not exhibiting virological suppression. Low CD4+ cell counts were associated with MDR. These findings may help address the impact and treatment needs of these patients and prevent clinical progression and transmission of MDR HIV.

Efficacy and Safety of Switching to the 2-Drug Regimen Dolutegravir/Lamivudine Versus Continuing a 3- or 4-Drug Regimen for Maintaining Virologic Suppression in Adults Living With Human Immunodeficiency Virus 1 (HIV-1): Week 48 Results From the Phase 3, Noninferiority SALSA Randomized Trial.

BACKGROUND: In TANGO, switching to dolutegravir/lamivudine (DTG/3TC) demonstrated long-term noninferior efficacy vs continuing tenofovir alafenamide-based regimens in treatment-experienced adults with HIV-1. The phase 3 SALSA study evaluated efficacy and safety of switching to DTG/3TC compared with continuing various 3-/4-drug current antiretroviral regimens (CARs). METHODS: Adults with HIV-1 RNA <50 copies/mL and no previous virologic failure were randomized (1:1, stratified by baseline third agent class) to switch to once-daily fixed-dose combination DTG/3TC or continue CAR (primary endpoint: proportion of participants with HIV-1 RNA ≥50 copies/mL at week 48; Snapshot, intention-to-treat-exposed population, 5% noninferiority margin). RESULTS: Overall, 493 adults (39% women; 39% aged ≥50 years; 19% African American/African heritage; 14% Asian) were randomized to switch to DTG/3TC (n = 246) or continue CAR (n = 247). At week 48, 1 (0.4%) participant in the DTG/3TC group and 3 (1.2%) in the CAR group had HIV-1 RNA ≥50 copies/mL (Snapshot), demonstrating noninferiority (adjusted difference, -0.8%; 95% CI, -2.4%, .8%). Zero participants met confirmed virologic withdrawal criteria; therefore, no resistance testing was performed. Drug-related adverse events were more frequent with DTG/3TC (20%) than CAR (6%) through week 48 but comparable post-week 24 (5% vs 2%, respectively). Proximal tubular renal function and bone turnover biomarkers improved with DTG/3TC. Both groups had generally minimal changes in lipids and inflammatory biomarkers. CONCLUSIONS: Switching to DTG/3TC was noninferior to continuing CAR for maintaining virologic suppression at week 48 with no observed resistance, supporting the efficacy, good safety, and high barrier to resistance of DTG/3TC. CLINICAL TRIALS REGISTRATION: www.clinicaltrials.gov, NCT04021290.

Plasma Human Immunodeficiency Virus 1 RNA and CD4+ T-Cell Counts Are Determinants of Virological Nonsuppression Outcomes With Initial Integrase Inhibitor-Based Regimens: A Prospective RESPOND Cohort Study.

BACKGROUND: There are conflicting data regarding baseline determinants of virological nonsuppression outcomes in persons with human immunodeficiency virus (HIV) starting antiretroviral treatment (ART). We evaluated the impact of different baseline variables in the RESPOND cohort. METHODS: We included treatment-naive participants aged ≥18 who initiated 3-drug ART, in 2014-2020. We assessed the odds of virological suppression (VS) at weeks 48 and 96 using logistic regression. Viral blips, low-level viremia (LLV), residual viremia (RV), and virological failure (VF) rates were assessed using Cox regression. RESULTS: Of 4310 eligible participants, 72% started integrase strand transfer inhibitor (INSTI)-based regimens. At 48 and 96 weeks, 91.0% and 93.3% achieved VS, respectively. At 48 weeks, Kaplan-Meier estimates of rates were 9.6% for viral blips, 2.1% for LLV, 22.2% for RV, and 2.1% for VF. Baseline HIV-1 RNA levels >100 000 copies/mL and CD4+ T-cell counts ≤200/µL were negatively associated with VS at weeks 48 (adjusted odds ratio, 0.51 [95% confidence interval, .39-.68] and .40 [.27-.58], respectively) and 96 and with significantly higher rates of blips, LLV, and RV. CD4+ T-cell counts ≤200/µL were associated with higher risk of VF (adjusted hazard ratio, 3.12 [95% confidence interval, 2.02-4.83]). Results were consistent in those starting INSTIs versus other regimens and those starting dolutegravir versus other INSTIs. CONCLUSIONS: Initial high HIV-1 RNA and low CD4+ T-cell counts are associated with lower rates of VS at 48 and 96 weeks and higher rates of viral blips, LLV, and RV. Low baseline CD4+ T-cell counts are associated with higher VF rates. These associations remain with INSTI-based and specifically with dolutegravir-based regimens. These findings suggest that the impact of these baseline determinants is independent of the ART regimen initiated.

Who is lost to follow-up in HIV care? Assessment of care retention over time and the impact of COVID-19. Longitudinal analysis of the PISCIS cohort.

INTRODUCTION: People living with HIV who are lost to follow-up have a greater risk of health deterioration, mortality, and community transmission. OBJECTIVE: Our aim was to analyse both how rates of loss to follow-up (LTFU) changed between 2006 and 2020 and how the COVID-19 pandemic affected these rates in the PISCIS cohort study of Catalonia and the Balearic Islands. METHODS: We analysed socio-demographic and clinical characteristics of LTFU yearly and with adjusted odds ratios to assess the impact of these determinants on LTFU in 2020 (the year of COVID-19). We used latent class analysis to categorize classes of LTFU based on their socio-demographic and clinical characteristics at each year. RESULTS: In total, 16.7% of the cohort were lost to follow-up at any time in the 15 years (n = 19 417). Of people living with HIV who were receiving follow-up, 81.5% were male and 19.5% were female; of those who were lost to follow-up, 79.6% and 20.4% were male and female, respectively (p < 0.001). Although rates of LTFU increased during COVID-19 (1.11% vs. 0.86%, p = 0.024), socio-demographic and clinical factors were similar. Eight classes of people living with HIV who were lost to follow-up were identified: six for men and two for women. Classes of men (n = 3) differed in terms of their country of birth, viral load (VL), and antiretroviral therapy (ART); classes of people who inject drugs (n = 2) differed in terms of VL, AIDS diagnosis, and ART. Changes in rates of LTFU included higher CD4 cell count and undetectable VL. CONCLUSIONS: The socio-demographic and clinical characteristics of people living with HIV changed over time. Although the circumstances of the COVID-19 pandemic increased the rates of LTFU, the characteristics of these people were similar. Epidemiological trends among people who were lost to follow-up can be used to prevent new losses of care and to reduce barriers to achieve Joint United Nations Programme on HIV/AIDS 95-95-95 targets.

Integrase resistance emergence with dolutegravir/lamivudine with prior HIV-1 suppression.

OBJECTIVES: Integrase resistance has not been reported with co-formulated dolutegravir/lamivudine in clinical trials or real-life cohorts. We aim to report, to the best of our knowledge, the first case of selection of the key integrase mutation R263K in a subject treated with this regimen started as a switch strategy with undetectable plasma HIV-1 viraemia. METHODS: Clinical case report. RESULTS: A patient with long-term suppressed HIV-1 viraemia (<50 copies/mL) with no known risk factors for virological failure and never exposed previously to an integrase inhibitor developed virological failure (consecutive plasma HIV-1 RNA 149 and 272 copies/mL) with 322 CD4 cells/mm3 despite good treatment adherence. He was receiving the anticonvulsant clobazam, considered to have a potential weak interaction with dolutegravir, unlikely to require a dose adjustment. Plasma HIV-1 genotypic deep sequencing (Vela System) revealed the emergence of R263K (79.6%) and S230N (99.4%) mutations in the integrase region (intermediate resistance to dolutegravir, score = 30 Stanford HIVDB 9.0). The reverse transcriptase and protease regions could not be amplified due to low viral loads. PBMC DNA deep sequencing performed some months later revealed mutations M184I (14.29%) and M230I (6.25%) in the reverse transcriptase and G163R (9.77%) and S230N (98.8%) in the integrase. R263K was only found at extremely low levels (0.07%). CONCLUSIONS: This case illustrates that integrase resistance can emerge in patients treated with co-formulated dolutegravir/lamivudine and raises awareness of the need to carefully consider and monitor drug-drug interactions, even when regarded as having a low potential, in subjects treated with dolutegravir/lamivudine.

Mortality and immunovirological outcomes in patients with advanced HIV disease on their first antiretroviral treatment: differential impact of antiretroviral regimens.

OBJECTIVES: To assess the clinical and immunovirological outcomes among naive patients with advanced HIV presentation starting an antiretroviral regimen in real-life settings. METHODS: This was a multicentre, prospective cohort study. We included all treatment-naive adults with advanced HIV disease (CD4+ T cell count < 200 cells/mm3or presence of an AIDS-defining illness) who started therapy between 2010 and 2020. The main outcomes were mortality, virological effectiveness (percentage of patients with viral load of ≤50 copies/mL) and immune restoration (percentage of patients with CD4+ T cell count above 350 cells/mm3). Competing risk analysis and Cox proportional models were performed. A propensity score-matching procedure was applied to assess the impact of the antiretroviral regimen. RESULTS: We included 1594 patients with advanced HIV disease [median CD4+T cell count of 81 cells/mm3and 371 (23.3%) with AIDS-defining illness] and with a median follow-up of 4.44 years. The most common ART used was an integrase strand transfer inhibitor (InSTI) regimen (46.9%), followed by PI (35.7%) and NNRTI (17.4%), with adjusted mortality rates at 3 years of 3.1% (95% CI 1.8%-4.3%), 4.7% (95% CI 2.2%-7.1%) and 7.6% (95% CI 5.4%-9.7%) (P = 0.001), respectively. Factors associated with increased mortality included older age and history of injection drug use, whilst treatment with an InSTI regimen was a protective factor [HR 0.5 (95% CI 0.3-0.9)]. A sensitivity analysis with propensity score procedure confirms these results. Patients who started an InSTI achieved viral suppression and CD4+ T cell count above 350 cells/mm3significantly earlier. CONCLUSIONS: In this large real-life prospective cohort study, a significant lower mortality, earlier viral suppression and earlier immune reconstitution were observed among patients with advanced HIV disease treated with InSTIs.

Impact of tenofovir on SARS-CoV-2 infection and severe outcomes among people living with HIV: a propensity score-matched study.

BACKGROUND: Reports on the impact of some antiretrovirals against SARS-CoV-2 infection and disease severity are conflicting. OBJECTIVES: We evaluated the effect of tenofovir as either tenofovir alafenamide/emtricitabine (TAF/FTC) or tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) against SARS-CoV-2 infection and associated clinical outcomes among people living with HIV (PLWH). METHODS: We conducted a propensity score-matched analysis in the prospective PISCIS cohort of PLWH (n = 14 978) in Catalonia, Spain. We used adjusted Cox regression models to assess the association between tenofovir and SARS-CoV-2 outcomes. RESULTS: After propensity score-matching, SARS-CoV-2 diagnosis rates were similar in TAF/FTC versus ABC/3TC recipients (11.6% versus 12.5%, P = 0.256); lower among TDF/FTC versus ABC/3TC recipients (9.6% versus 12.8%, P = 0.021); and lower among TDF/FTC versus TAF/FTC recipients (9.6% versus 12.1%, P = 0.012). In well-adjusted logistic regression models, TAF/FTC was no longer associated with reduced SARS-CoV-2 diagnosis [adjusted odds ratio (aOR) 0.90; 95% confidence interval (CI), 0.78-1.04] or hospitalization (aOR 0.93; 95% CI, 0.60-1.43). When compared with ABC/3TC, TDF/FTC was not associated with reduced SARS-CoV-2 diagnosis (aOR 0.79; 95% CI, 0.60-1.04) or hospitalization (aOR 0.51; 95% CI, 0.15-1.70). TDF/FTC was not associated with reduced SARS-CoV-2 diagnosis (aOR 0.79; 95% CI, 0.60-1.04) or associated hospitalization (aOR 0.33; 95% CI, 0.10-1.07) compared with TAF/FTC. CONCLUSIONS: TAF/FTC or TDF/FTC were not associated with reduced SARS-CoV-2 diagnosis rates or associated hospitalizations among PLWH. TDF/FTC users had baseline characteristics intrinsically associated with more benign SARS-CoV-2 infection outcomes. Tenofovir exposure should not modify any preventive or therapeutic SARS-CoV-2 infection management.

Predictors of low-level HIV viraemia and virological failure in the era of integrase inhibitors: A Spanish nationwide cohort.

OBJECTIVES: To pinpoint factors associated with low-level viraemia (LLV) and virological failure (VF) in people living with HIV in the era of high-efficacy antiretroviral treatment (ART) and widespread use of integrase strand transfer inhibitor (INSTIs)-based ART. METHODS: We included adults aged > 18 years starting their first ART between 2015 and 2018 in the Spanish HIV/AIDS Research Network National Cohort (CoRIS). Low-level viraemia was defined as plasma viral load (pVL) of 50-199 copies/mL at weeks 48 and 72 and VF was defined as pVL ≥ 50 copies/mL at week 48 and pVL ≥ 200 copies/mL at week 72. Multivariable logistic regression models assessed the impact on LLV and VF of baseline CD4 T-cell count, CD4/CD8 T-cell ratio and pVL, initial ART classes, age at ART initiation, time between HIV diagnosis and ART initiation, gender and transmission route. RESULTS: Out of 4186 participants, 3120 (76.0%) started INSTIs, 455 (11.1%) started boosted protease inhibitors (bPIs) and 443 (10.8%) started nonnucleoside reverse transcriptase inhibitors (NNRTIs), either of them with two nucleos(t)ide reverse transcriptase inhibitors (NRTIs). Low-level viraemia was met in 2.5% of participants and VF in 4.3%. There were no significant differences throughout the years for both virological outcomes. Baseline HIV-1 RNA > 5 log10 copies/mL was the only consistent predictor of higher risk of LLV [adjusted odds ratio (aOR) = 9.8, 95% confidence interval (CI): 2.0-48.3] and VF (aOR = 5.4, 95% CI: 1.9-15.1), even in participants treated with INSTIs. CONCLUSIONS: The rates of LLV and VF were low but remained steady throughout the years. Baseline HIV-1 RNA > 5 log10 copies/mL showed a persistent association with LLV and VF even in participants receiving INSTIs.

The association between hepatitis B virus infection and nonliver malignancies in persons living with HIV: results from the EuroSIDA study.

OBJECTIVES: The aim of this study was to assess the impact of hepatitis B virus (HBV) infection on non-liver malignancies in people living with HIV (PLWH). METHODS: All persons aged ≥ 18 years with known hepatitis B virus (HBV) surface antigen (HBsAg) status after the latest of 1 January 2001 and enrolment in the EuroSIDA cohort (baseline) were included in the study; persons were categorized as HBV positive or negative using the latest HBsAg test and followed to their first diagnosis of nonliver malignancy or their last visit. RESULTS: Of 17 485 PLWH included in the study, 1269 (7.2%) were HBV positive at baseline. During 151 766 person-years of follow-up (PYFU), there were 1298 nonliver malignancies, 1199 in those currently HBV negative [incidence rate (IR) 8.42/1000 PYFU; 95% confidence interval (CI) 7.94-8.90/1000 PYFU] and 99 in those HBV positive (IR 10.54/1000 PYFU; 95% CI 8.47-12.62/1000 PYFU). After adjustment for baseline confounders, there was a significantly increased incidence of nonliver malignancies in HBV-positive versus HBV-negative individuals [adjusted incidence rate ratio (aIRR) 1.23; 95% CI 1.00-1.51]. Compared to HBV-negative individuals, HBsAg-positive/HBV-DNA-positive individuals had significantly increased incidences of nonliver malignancies (aIRR 1.37; 95% CI 1.00-1.89) and NHL (aIRR 2.57; 95% CI 1.16-5.68). There was no significant association between HBV and lung or anal cancer. CONCLUSIONS: We found increased rates of nonliver malignancies in HBsAg-positive participants, the increases being most pronounced in those who were HBV DNA positive and for NHL. If confirmed, these results may have implications for increased cancer screening in HIV-positive subjects with chronic HBV infection.

Clinical outcomes after IL-6 blockade in patients with COVID-19 and HIV: a case series.

BACKGROUND: In hospitalized people with HIV (PWH) there is an increased risk of mortality from COVID-19 among hospitalized PWH as compared to HIV-negative individuals. Evidence suggests that tocilizumab-a humanized monoclonal interleukin (IL)-6 receptor inhibitor (IL-6ri) antibody-has a modest mortality benefit when combined with corticosteroids in select hospitalized COVID-19 patients who are severely ill. Data on clinical outcomes after tocilizumab use in PWH with severe COVID-19 are lacking. CASE PRESENTATION: We present a multinational case series of 18 PWH with COVID-19 who were treated with IL-6ri's during the period from April to June 2020. Four patients received tocilizumab, six sarilumab, and eight received an undocumented IL-6ri. Of the 18 patients in the series, 4 (22%) had CD4 counts < 200 cells/mm3; 14 (82%) had a suppressed HIV viral load. Eight patients (44%), all admitted to ICU, were treated for secondary infection; 5 had a confirmed organism. Of the four patients with CD4 counts < 200 cells/mm3, three were treated for secondary infection, with 2 confirmed organisms. Overall outcomes were poor-12 patients (67%) were admitted to the ICU, 11 (61%) required mechanical ventilation, and 7 (39%) died. CONCLUSIONS: In this case series of hospitalized PWH with COVID-19 and given IL-6ri prior to the common use of corticosteroids, there are reports of secondary or co-infection in severely ill patients. Comprehensive studies in PWH, particularly with CD4 counts < 200 cells, are warranted to assess infectious and other outcomes after IL-6ri use, particularly in the context of co-administered corticosteroids.

Characteristics, Comorbidities, and Outcomes in a Multicenter Registry of Patients With Human Immunodeficiency Virus and Coronavirus Disease 2019.

BACKGROUND: People living with human immunodeficiency virus (HIV) may have numerous risk factors for acquiring coronavirus disease 2019 (COVID-19) and developing severe outcomes, but current data are conflicting. METHODS: Health-care providers enrolled consecutively, by nonrandom sampling, people living with HIV (PWH) with lab-confirmed COVID-19, diagnosed at their facilities between 1 April and 1 July 2020. Deidentified data were entered into an electronic Research Electronic Data Capture (REDCap) system. The primary endpoint was a severe outcome, defined as a composite endpoint of intensive care unit (ICU) admission, mechanical ventilation, or death. The secondary outcome was the need for hospitalization. RESULTS: There were 286 patients included; the mean age was 51.4 years (standard deviation, 14.4), 25.9% were female, and 75.4% were African American or Hispanic. Most patients (94.3%) were on antiretroviral therapy, 88.7% had HIV virologic suppression, and 80.8% had comorbidities. Within 30 days of testing positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 164 (57.3%) patients were hospitalized, and 47 (16.5%) required ICU admission. Mortality rates were 9.4% (27/286) overall, 16.5% (27/164) among those hospitalized, and 51.5% (24/47) among those admitted to an ICU. The primary composite endpoint occurred in 17.5% (50/286) of all patients and 30.5% (50/164) of hospitalized patients. Older age, chronic lung disease, and hypertension were associated with severe outcomes. A lower CD4 count (<200 cells/mm3) was associated with the primary and secondary endpoints. There were no associations between the ART regimen or lack of viral suppression and the predefined outcomes. CONCLUSIONS: Severe clinical outcomes occurred commonly in PWH with COVID-19. The risks for poor outcomes were higher in those with comorbidities and lower CD4 cell counts, despite HIV viral suppression. CLINICAL TRIALS REGISTRATION: NCT04333953.

Clinical Outcomes of 2-Drug Regimens vs 3-Drug Regimens in Antiretroviral Treatment-Experienced People Living With Human Immunodeficiency Virus.

BACKGROUND: Limited data exist that compare clinical outcomes of 2-drug regimens (2DRs) and 3-drug regimens (3DRs) in people living with human immunodeficiency virus. METHODS: Antiretroviral treatment-experienced individuals in the International Cohort Consortium of Infectious Diseases (RESPOND) who switched to a new 2DR or 3DR from 1 January 2012-1 October 2018 were included. The incidence of clinical events (AIDS, non-AIDS cancer, cardiovascular disease, end-stage liver and renal disease, death) was compared between regimens using Poisson regression. RESULTS: Of 9791 individuals included, 1088 (11.1%) started 2DRs and 8703 (88.9%) started 3DRs. The most common 2DRs were dolutegravir plus lamivudine (22.8%) and raltegravir plus boosted darunavir (19.8%); the most common 3DR was dolutegravir plus 2 nucleoside reverse transcriptase inhibitors (46.9%). Individuals on 2DRs were older (median, 52.6 years [interquartile range, 46.7-59.0] vs 47.7 [39.7-54.3]), and a higher proportion had ≥1 comorbidity (81.6% vs 73.9%). There were 619 events during 27 159 person-years of follow-up (PYFU): 540 (incidence rate [IR] 22.5/1000 PYFU; 95% confidence interval [CI]: 20.7-24.5) on 3DRs and 79 (30.9/1000 PYFU; 95% CI: 24.8-38.5) on 2DRs. The most common events were death (7.5/1000 PYFU; 95% CI: 6.5-8.6) and non-AIDS cancer (5.8/1000 PYFU; 95% CI: 4.9-6.8). After adjustment for baseline demographic and clinical characteristics, there was a similar incidence of events on both regimen types (2DRs vs 3DRs IR ratio, 0.92; 95% CI: .72-1.19; P = .53). CONCLUSIONS: This is the first large, international cohort to assess clinical outcomes on 2DRs. After accounting for baseline characteristics, there was a similar incidence of events on 2DRs and 3DRs. 2DRs appear to be a viable treatment option with regard to clinical outcomes. Further research on resistance barriers and long-term durability of 2DRs is needed.

Redefining therapeutic success in HIV patients: an expert view.

Thanks to advances in the field over the years, HIV/AIDS has now become a manageable chronic condition. Nevertheless, a new set of HIV-associated complications has emerged, related in part to the accelerated ageing observed in people living with HIV/AIDS, the cumulative toxicities from exposure to antiretroviral drugs over decades and emerging comorbidities. As a result, HIV/AIDS can still have a negative impact on patients' quality of life (QoL). In this scenario, it is reasonable to believe that the concept of therapeutic success, traditionally associated with CD4 cell count restoration and HIV RNA plasma viral load suppression and the absence of drug resistances, needs to be redefined to include other factors that reach beyond antiretroviral efficacy. With this in mind, a group of experts initiated and coordinated the RET Project, and this group, using the available evidence and their clinical experience in the field, has proposed new criteria to redefine treatment success in HIV, arranged into five main concepts: rapid initiation, efficacy, simplicity, safety, and QoL. An extensive review of the literature was performed for each category, and results were discussed by a total of 32 clinicians with experience in HIV/AIDS (4 coordinators + 28 additional experts). This article summarizes the conclusions of these experts and presents the most updated overview on the five topics, along with a discussion of the experts' main concerns, conclusions and/or recommendations on the most controversial issues.

Strategies to reengage patients lost to follow up in HIV care in high income countries, a scoping review.

BACKGROUND: Despite remarkable achievements in antiretroviral therapy (ART), losses to follow-up (LTFU) might prevent the long-term success of HIV treatment and might delay the achievement of the 90-90-90 objectives. This scoping review is aimed at the description and analysis of the strategies used in high-income countries to reengage LTFU in HIV care, their implementation and impact. METHODS: A scoping review was done following Arksey & O'Malley's methodological framework and recommendations from Joanna Briggs Institute. Peer reviewed articles were searched for in Pubmed, Scopus and Web of Science; and grey literature was searched for in Google and other sources of information. Documents were charted according to the information presented on LTFU, the reengagement procedures used in HIV units in high-income countries, published during the last 15 years. In addition, bibliographies of chosen articles were reviewed for additional articles. RESULTS: Twenty-eight documents were finally included, over 80% of them published in the United States later than 2015. Database searches, phone calls and/or mail contacts were the most common strategies used to locate and track LTFU, while motivational interviews and strengths-based techniques were used most often during reengagement visits. Outcomes like tracing activities efficacy, rates of reengagement and viral load reduction were reported as outcome measures. CONCLUSIONS: This review shows a recent and growing trend in developing and implementing patient reengagement strategies in HIV care. However, most of these strategies have been implemented in the United States and little information is available for other high-income countries. The procedures used to trace and contact LTFU are similar across reviewed studies, but their impact and sustainability are widely different depending on the country studied.

Routine Screening of Anal Cytology in Persons With Human Immunodeficiency Virus and the Impact on Invasive Anal Cancer: A Prospective Cohort Study.

BACKGROUND: The efficacy of screening programs to prevent anal cancer in persons with human immunodeficiency virus 1 (HIV-1) is unclear. METHODS: To examine the impact of a screening program to detect anal cancer precursors on the incidence of cases of invasive anal squamous-cell carcinoma (IASCC) in persons with HIV-1, we performed a single-center, retrospective analysis of a prospective cohort of outpatients with HIV-1 attending a reference HIV unit from January 2005 onward. All participants were invited to participate in a continued structured screening program for anal cancer prevention. We estimated the incidence of IASCC and performed a comparative analysis between subjects enrolled in the screening program (screening group) and those who declined to participate (nonscreening group). To reduce any selection bias, a propensity score analysis was applied. RESULTS: We included 3111 persons with HIV-1 (1596 men-who-have-sex-with-men [MSM], 888 men-who-have-sex-with-women [MSW], 627 women; mean age, 41 years), with a median follow-up of 4.7 years (14 595 patient-years of follow-up); 1691 (54%) participated in the screening program. Ten patients were diagnosed with IASCC: 2 (MSM) in the screening group and 8 (4 MSM, 2 MSW, and 2 women) in the nonscreening group. The incidence rates of IASCC were 21.9 (95% confidence interval [CI], 2.7-70.3) and 107.0 (95% CI, 46.2-202.0) per 100 000 person-years, respectively. After a propensity score adjustment, the difference was significant in favor of the screening group (hazard ratio, 0.17; 95% CI, .03-.86). CONCLUSIONS: The number of cases of IASCC was significantly lower in persons with HIV engaged in an anal cytology screening program. These results should be validated in a randomized clinical trial.

Efficacy, safety, and tolerability of dolutegravir-rilpivirine for the maintenance of virological suppression in adults with HIV-1: phase 3, randomised, non-inferiority SWORD-1 and SWORD-2 studies.

BACKGROUND: Lifelong HIV antiretroviral therapy (ART) has prompted an interest in two-drug regimens to minimise cumulative drug exposure and toxicities. The safety, tolerability, and efficacy of dolutegravir and rilpivirine suggest potential compatibility and effectiveness as a two-drug regimen. We aimed to investigate this two-drug regimen in a phase 3 study. METHODS: We identically designed SWORD-1 and SWORD-2, which were open-label, parallel-group, multicentre, phase 3, randomised, non-inferiority studies in 12 countries evaluating efficacy and safety of once-daily dolutegravir 50 mg plus rilpivirine 25 mg versus current ART regimen (CAR). We included participants aged 18 years or older who were on first or second ART with stable plasma HIV-1 RNA (viral load <50 copies per mL) for 6 months or longer at screening. We randomly assigned participants (1:1) with stratification by third-agent class, age, and planned participation in a bone mineral density substudy. The primary endpoint was proportion of participants with viral load lower than 50 copies per mL at week 48 among those individuals who received one or more doses of study medication. Investigators monitored adverse events to assess safety. These trials are registered with ClinicalTrials.gov, numbers NCT02429791 (SWORD-1) and NCT02422797 (SWORD-2). FINDINGS: We screened for participants from April 14, 2015, to Oct 15, 2015, for SWORD-1 and from April 21, 2015, to Sept 25, 2015, for SWORD-2. We randomly assigned 516 participants to dolutegravir-rilpivirine and 512 to continue with CAR. At week 48 (last patient visit was Nov 22, 2016), in the pooled analysis of the intention-to-treat population, 95% of participants had viral loads lower than 50 copies per mL in each group (486 of 513 in the dolutegravir-rilpivirine group vs 485 of 511 in the CAR group), with an adjusted treatment difference of -0·2% (95% CI -3·0 to 2·5) and showed non-inferiority with a predefined margin of -8%. 395 (77%) of 513 participants in the dolutegravir-rilpivirine group and 364 (71%) of 511 participants in the CAR group reported adverse events. The most common adverse events were nasopharyngitis (49 [10%] for dolutegravir-rilpivirine vs 50 [10%] for CAR) and headache (41 [8%] vs 23 [5%]). More participants taking dolutegravir-rilpivirine (17 [3%]) reported adverse events leading to withdrawal than did participants taking CAR (three [<1%]). INTERPRETATION: Dolutegravir-rilpivirine was non-inferior to CAR over 48 weeks in participants with HIV suppression and showed a safety profile consistent with its components. Results support the use of this two-drug regimen to maintain HIV suppression. FUNDING: ViiV Healthcare and Janssen Pharmaceutica NV.

Overdose of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide in an HIV-1-infected subject with attempted suicide.

INTRODUCTION: Data are lacking regarding overdose of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF). MATERIAL AND METHODS: We present the first report of suicidal attempt with E/C/F/TAF in a Human Immunodeficiency Virus-infected subject. RESULTS: A reversible acute renal failure with no proximal tubulopathy and neuropsychiatric issues are discussed. E/C/F/TAF withdrawal resulted in favourable renal and neuropsychiatric outcomes. The suicide attempt seemed unrelated to the integrase strand transfer inhibitor, being evenly explained within the context of stressful personal conflicts. CONCLUSION: A suicidal attempt with an E/C/F/TAF overdose in an HIV-infected patient, resulted in a favourable outcome from a renal and neuropsychiatric standpoint.