Summary Background Combination antiretroviral therapy (cART) has been shown to reduce mortality and morbidity in patients with HIV. As viral replication falls, the CD4 count increases, but whether ...the CD4 count returns to the level seen in HIV-negative people is unknown. We aimed to assess whether the CD4 count for patients with maximum virological suppression (viral load <50 copies per mL) continues to increase with long-term cART to reach levels seen in HIV-negative populations. Methods We compared increases in CD4 counts in 1835 antiretroviral-naive patients who started cART from EuroSIDA, a pan-European observational cohort study. Rate of increase in CD4 count (per year) occurring between pairs of consecutive viral loads below 50 copies per mL was estimated using generalised linear models, accounting for multiple measurements for individual patients. Findings The median CD4 count at starting cART was 204 cells per μL (IQR 85–330). The greatest mean yearly increase in CD4 count of 100 cells per μL was seen in the year after starting cART. Significant, but lower, yearly increases in CD4 count, around 50 cells per μL, were seen even at 5 years after starting cART in patients whose current CD4 count was less than 500 cells per μL. The only groups without significant increases in CD4 count were those where cART had been taken for more than 5 years with a current CD4 count of more than 500 cells per μL, (current mean CD4 count 774 cells per μL; 95% CI 764–783). Patients starting cART with low CD4 counts (<200 cells per μL) had significant rises in CD4 counts even after 5 years of cART. Interpretation Normalisation of CD4 counts in HIV-infected patients for all infected individuals might be achievable if viral suppression with cART can be maintained for a sufficiently long period of time.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Single‐tablet regimens (STRs) of highly safe and effective combination antiretroviral therapy (cART) have had a significant beneficial impact on the clinical outcomes and lives of people living with ...HIV (PLHIV). As a consequence, healthcare professionals caring for PLHIV in high‐income countries have increasingly focused on issues beyond those related to HIV itself, i.e. HIV‐related neurological disease, or associated opportunistic infections, which include co‐infections, and primarily age‐ and lifestyle‐related comorbidities such as cardiovascular disease, diabetes mellitus, renal impairment, osteoporosis and frailty. This review considers drug side effects and comorbidities seen in PLHIV and evaluates the role of a recently licensed STR – bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) – in mitigating some of those challenges. Factors that need to be evaluated for initial cART regimens include: pretreatment CD4 cell count; plasma HIV RNA; HIV drug resistance; hepatitis B co‐infection; HLA‐B*5701 status; drug‐drug interactions; pregnancy and pregnancy potential; psychiatric and physical comorbidities such as renal or bone disease, as well as simplicity and adherence‐friendliness, all of which need to be considered in all lines of therapy. BIC/FTC/TAF constitutes a new STR that includes an unboosted integrase strand transfer inhibitor with a high barrier against resistance with TAF and FTC. Its virological efficacy was non‐inferior to dolutegravir‐based regimens previously recommended by most guidelines for treatment initiation in large double‐blind, randomised clinical trials in treatment‐naïve or switch patients over 96 weeks. Tolerability and pharmacological properties of the regimen make it a useful tool to address several of the clinical management issues raised above.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Darunavir/ritonavir (DRV/r) is a second-generation protease inhibitor used in treatment-naïve and -experienced HIV-positive adult patients. To evaluate efficacy and safety in these patient settings, ...we performed a meta-analysis of randomized controlled trials. We considered eight studies involving 4240 antiretroviral treatment (ART)-naïve patients and 14 studies involving 2684 ART-experienced patients. Regarding efficacy in the ART-naive patients, the virological response rate was not significantly different between DRV/r and the comparator. For the ART-experienced failing patients, the virological response rate was significantly higher with DRV/r than with the comparator (RR 1.45, 95% CI: 1.01-2.08); conversely, no significant differences were found between the treatment-experienced and virologically controlled DRV/r and comparator groups. Regarding safety, the discontinuation rates due to adverse events (AEs) and DRV/r-related serious adverse events (SAEs) did not significantly differ from the rates in the comparator group (RR 0.84, 95% CI: 0.59-1.19 and RR 0.78, 95% CI: 0.57-1.05, respectively). Our meta-analysis indicated that DRV/r-based regimens were effective and tolerable for both types of patients, which was consistent with published data.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The aim of this study was to evaluate the impact of early treatment with corticosteroids on SARS-CoV-2 clearance in hospitalized COVID-19 patients. Retrospective analysis on patients admitted to the ...San Raffaele Hospital (Milan, Italy) with moderate/severe COVID-19 and availability of at least two nasopharyngeal swabs. The primary outcome was the time to nasopharyngeal swab negativization. A multivariable Cox model was fitted to determine factors associated with nasopharyngeal swab negativization. Of 280 patients included, 59 (21.1%) patients were treated with steroids. Differences observed between steroid users and non-users included the proportion of patients with a baseline PaO
/FiO
≤ 200 mmHg (45.8% vs 34.4% in steroids and non-steroids users, respectively; p = 0.023) or ≤ 100 mmHg (16.9% vs 12.7%; p = 0.027), and length of hospitalization (20 vs 14 days; p < 0.001). Time to negativization of nasopharyngeal swabs was similar in steroid and non-steroid users (p = 0.985). According to multivariate analysis, SARS-CoV-2 clearance was associated with age ≤ 70 years, a shorter duration of symptoms at admission, a baseline PaO
/FiO
> 200 mmHg, and a lymphocyte count at admission > 1.0 × 10
/L. SARS-CoV-2 clearance was not associated with corticosteroid use. Our study shows that delayed SARS-CoV-2 clearance in moderate/severe COVID-19 is associated with older age and a more severe disease, but not with an early use of corticosteroids.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Objective
To compare the incidence of hypertension in people living with HIV receiving integrase strand transfer inhibitor (INSTI)‐based antiretroviral therapy (ART) versus non‐nucleoside reverse ...transcriptase inhibitors (NNRTIs) or boosted protease inhibitors (PIs) in the RESPOND consortium of HIV cohorts.
Methods
Eligible people with HIV were aged ≥18 years who initiated a new three‐drug ART regimen for the first time (baseline), did not have hypertension, and had at least two follow‐up blood pressure (BP) measurements. Hypertension was defined as two consecutive systolic BP measurements ≥140 mmHg and/or diastolic BP ≥90 mmHg or initiation of antihypertensives. Multivariable Poisson regression was used to determine adjusted incidence rate ratios (aIRRs) of hypertension, overall and in those who were ART naïve or experienced at baseline.
Results
Overall, 4606 people living with HIV were eligible (INSTIs 3164, NNRTIs 807, PIs 635). The median baseline systolic BP, diastolic BP, and age were 120 (interquartile range IQR 113–130) mmHg, 78 (70–82) mmHg, and 43 (34–50) years, respectively. Over 8380.4 person‐years (median follow‐up 1.5 IQR 1.0–2.7 years), 1058 (23.0%) participants developed hypertension (incidence rate 126.2/1000 person‐years, 95% confidence interval CI 118.9–134.1). Participants receiving INSTIs had a higher incidence of hypertension than those receiving NNRTIs (aIRR 1.76; 95% CI 1.47–2.11), whereas the incidence was no different in those receiving PIs (aIRR 1.07; 95% CI 0.89–1.29). The results were similar when the analysis was stratified by ART status at baseline.
Conclusion
Although unmeasured confounding and channelling bias cannot be excluded, INSTIs were associated with a higher incidence of hypertension than were NNRTIs, but rates were similar to those of PIs overall, in ART‐naïve and ART‐experienced participants within RESPOND.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
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.
Abstract
Objectives
To investigate the long-term safety and efficacy of a treatment switch to dual ART with atazanavir/ritonavir + lamivudine versus continuing a standard regimen with ...atazanavir/ritonavir + 2NRTI in virologically suppressed patients.
Methods
ATLAS-M is a 96 week open-label, randomized, non-inferiority (margin −12%) trial enrolling HIV-infected adults on atazanavir/ritonavir + 2NRTI, with stable HIV-RNA <50 copies/mL and CD4 counts >200 cells/mm3. At baseline, patients were randomized 1:1 to switch to atazanavir/ritonavir + lamivudine or to continue the previous regimen. Here, we report the 96 week efficacy and safety data. The study was registered with ClinicalTrials.gov, number NCT01599364.
Results
Overall, 266 subjects were enrolled (133 in each arm). At 96 weeks, in the ITT population, patients free of treatment failure totalled 103 (77.4%) with atazanavir/ritonavir + lamivudine and 87 (65.4%) with triple therapy (difference +12.0%, 95% CI +1.2/+22.8, P = 0.030), demonstrating the superiority of dual therapy. Two (1.5%) and 9 (6.8%) virological failures occurred in the dual-therapy arm and the triple-therapy arm, respectively, without development of resistance to any study drug. Clinical adverse events occurred at similar rates in both arms. A higher frequency of grade 3–4 hyperbilirubinemia (66.9% versus 50.4%, P = 0.006) and hypertriglyceridaemia (6.8% versus 1.5%, P = 0.031) occurred with dual therapy, although this never led to treatment discontinuation. A significant improvement in renal function and lumbar spine bone mineral density occurred in the dual-therapy arm. The evolution of CD4, HIV-DNA levels and neurocognitive performance was similar in both arms.
Conclusions
In this randomized study, a treatment switch to atazanavir/ritonavir + lamivudine was superior over the continuation of atazanavir/ritonavir + 2NRTI in virologically suppressed patients, with a sustained benefit in terms of improved renal function and bone mineral density.
Background. Atazanavir is a once-daily protease inhibitor (PI) for the treatment of human immunodeficiency virus (HIV) infection that has previously been studied in cohorts of treatment-naive and ...treatment-experienced patients. Limited data are available on the usefulness of switching from a PI-based regimen to a regimen based on a different PI, such as atazanavir, in HIV-infected patients experiencing virologic suppression but seeking regimen simplification. Methods. The Switch to Another Protease Inhibitor (SWAN) study was a 48-week, open-label trial involving HIV-positive patients with virologic suppression who were receiving stable PI-based regimens (with or without ritonavir). Patients were randomized 2 : 1 to switch to atazanavir (400 mg per day)—or, if they were receiving tenofovir, to atazanavir-ritonavir (300/100 mg per day)—or to continue to receive their existing PI. The proportion of patients who experienced virologic rebound (defined as an HIV RNA load ≥50 copies/mL) was compared through study week 48. Results. Patients either received an atazanavir-containing regimen (278 patients) or continued to receive a comparator PI-containing regimen (141 patients). The proportion of patients who experienced virologic rebound was significantly lower among those who switched to an atazanavir-containing regimen (19 7% of 278) than it was among those who continued to receive a comparator PI regimen (22 16% of 141; P = .004). Patients who switched to atazanavir therapy experienced significantly fewer total cholesterol, fasting triglyceride, and non—high density lipoprotein cholesterol elevations than did patients in the comparator PI group (P < .001); patients receiving atazanavir had comparable rates of adverse event—related discontinuation and serious adverse events. Conclusions. In patients with virologic suppression who were receiving other PIs, switching to a once-per-day regimen containing atazanavir provided better maintenance of virologic suppression (as demonstrated by significantly lower rates of virologic rebound and treatment failure than those observed with continued unmodified therapy), a comparable safety profile, and improved lipid parameters, compared with those for patients who continued their prior PI-based regimen through 48 weeks.
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