Improvement in insulin sensitivity after switching from an integrase inhibitor-based regimen to doravirine/tenofovir disoproxil fumarate/lamivudine in people with significant weight gain.

OBJECTIVES: We performed an observational, retrospective, cohort study to assess changes in insulin sensitivity after a switch from dolutegravir/lamivudine (DOL/3TC) or bictegravir/emtricitabine/tenofovir alafenamide (BIC/F/TAF) to doravirine/tenofovir disoproxil fumarate/3TC (DOR/TDF/3TC) in virologically suppressed people living with HIV with recent significant weight gain. METHODS: All non-diabetic patients with HIV treated with DOL/3TC or BIC/F/TAF for ≥12 months, with HIV RNA <20 copies/mL, and with a weight increase ≥3 kg in the last year, who underwent a switch to DOR/TDF/3TC were enrolled into the study. Serum levels of glucose, insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) index were evaluated every 6 months during a 12-month follow-up. RESULTS: Overall, 81 patients were enrolled: 41 were treated with DOL/3TC and 40 with BIC/F/TAF. At baseline, median HOMA-IR index was 3.18 and insulin resistance (HOMA-IR index >2.5) was present in 49 subjects (60%). At 12 months after the switch to DOR/TDF/3TC, change in mean serum glucose concentration was not significant, but the reduction in median concentration of insulin was significant (-3.54 mcrUI/L [interquartile range -4.22 to -2.87]; p = 0.012), associated with a significant reduction in mean HOMA-IR index (-0.54 [interquartile range -0.91 to -0.18]; p = 0.021). A significant reduction in total and low-density lipoprotein cholesterol was also reported, whereas decreases in mean body weight and mean body mass index were not significant. CONCLUSIONS: In our retrospective study in virologically suppressed people living with HIV treated with DOL/3TC or BIC/F/TAF and with recent weight gain, the switch to DOR/TDF/3TC led to a significant improvement in insulin sensitivity and plasma lipids, with a trend to decreased body weight.

Efficacy and Safety of Switching to Dolutegravir/Lamivudine in Virologically Suppressed People Living with HIV-1 Aged Over 65 Years.

Clinical trials of dual regimen dolutegravir/lamivudine (DOL/3TC) demonstrated potent efficacy and favorable safety in both antiretroviral therapy-naïve and -experienced patients, but data on older people are lacking. We aimed to evaluate virological efficacy and safety of DOL/3TC in suppressed older patients over a 12-month period. We performed a retrospective cohort study evaluating people living with HIV (PLWHIV) aged ≥65 years at our HIV Clinic who were switched to DOL/3TC. Eligible patients had baseline HIV-1 RNA <20 copies/mL, and no previous virological failures or known resistance mutations for lamivudine or dolutegravir. Inclusion criteria were met by 72 patients: 59 were men, median age was 69.2 years, and one or more comorbidities were present in 89% of patients. The most common reason for switch was simplification, followed by drug-drug interactions (DDIs) and toxicities. After 12 months, 64 (88.9%, by the intention-to-treat analysis) patients maintained HIV-1 RNA <20 copies/mL, and reasons for treatment failure were virological failure in three cases, adverse events in three, and missing data in two. Genotype resistance testing showed no resistance mutations for lamivudine or dolutegravir in subjects with virological failure. The number of potential DDIs decreased from 92 to 12 after switching to DOL/3TC, and a significant reduction in median total and low-density lipoprotein cholesterol was reported, while median change in body weight was not significant. In this real-life cohort, switching to DOL/3TC was associated with maintenance of virological control and good tolerability among persons aged >65 years, supporting use of this dual regimen in older PLWHIV.

Doravirine/lamivudine/tenofovir disoproxil fumarate in virologically suppressed people living with HIV: A real-life experience.

BACKGROUND: Doravirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) showing high efficacy and tolerability in both naïve and experienced people living with HIV (PLWHIV) in randomized trials, but scarce data are available to date from the real-life experience. METHODS: We performed an observational, retrospective study of PLWHIV on suppressive antiretroviral therapy who switched to a daily single-tablet regimen containing doravirine 100 mg, lamivudine 300 mg, and tenofovir disoproxil fumarate 300 mg. RESULTS: As a whole, 62 suppressed patients (51 men, median age, 51.7 years; median CD4 T+ lymphocyte count, 577 cells/mm3) were enrolled. After 12 months, 58 (93.5%) patients showed HIV RNA <20 copies/mL and reasons for treatment failure were virological failure in one case, missing data in one case, and adverse events in two cases. At month 12, a significant decrease in median serum level of triglycerides (median change -61.2 mg/dL; p = .009) and total cholesterol (median change -38.4 mg/dL; p = .021) was reported, while a not significant median weight increase was registered (+0.55 kg). CONCLUSIONS: In our study, simplification to a single-tablet regimen of doravirine/lamivudine/tenofovir disoproxil fumarate in virologically suppressed PLWHIV was effective and showed a good tolerability profile, in association with a significant improvement in serum lipid levels.

Rosuvastatin decreases serum inflammatory markers and slows atherosclerosis progression rate in treated HIV-infected patients with metabolic syndrome.

OBJECTIVES: Metabolic syndrome (MetS) is usually associated in general population with systemic inflammation and higher cardiovascular risk, but data about the effect of statins in patients with HIV infection and MetS are lacking to date. METHODS: Prospective cohort study of treated HIV-infected patients, aged from 40 to 60 years, with or without MetS, who started rosuvastatin (10 mg daily), and were followed-up for 12 months. The primary endpoint was change in serum levels of high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and tumour necrosis factor-α (TNF-α). The secondary endpoint was change in the carotid intima-media thickness (IMT). RESULTS: One hundred and twenty-five patients were enrolled: 61 with MetS (MetS group) and 64 without MetS (control group). After 12 months, rosuvastatin produced a significant decrease in mean serum levels of hsCRP (-0.28 mg/dL; p = .037), IL-6 (-2.1 pg/mL; p = .018) and TNF-α (-6.3 pg/mL; p = .004) in patients with MetS. On the contrary, in controls rosuvastatin did not lead to a significant change in mean levels of all biomarkers. After 12 months, the mean IMT increase at the carotid bifurcation was significantly lower in the MetS group than in the control group at the carotid bifurcation (0.017 vs. 0.031 mm; p = .037) and in all other anatomical sites. CONCLUSION: Our findings suggest that rosuvastatin is effective in reducing serum inflammation markers and slowing atherosclerosis progression rate in HIV-infected patients on cART and with MetS, while its effects on serum biomarkers and IMT increase seem to be negligible in those without MetS.

Short Communication: No Significant Increase in Body Fat Mass in Naive HIV-Infected Patients Starting Raltegravir Plus Tenofovir Disoproxil Fumarate/Emtricitabine.

A significant weight gain has been reported in HIV-infected patients starting combination antiretroviral therapy (cART) including integrase strand transfer inhibitors, but clinical data about changes in body fat mass are still lacking. An observational retrospective analysis was made to evaluate changes in body fat mass and weight in 39 cART-naive patients initiating a first antiretroviral treatment, including tenofovir disoproxil fumarate/emtricitabine plus raltegravir (RAL) or darunavir/ritonavir (DRV/r), and who had a follow-up of at least 12 months and a whole-body dual-energy X-ray absorptiometry performed at baseline and after 12 months. After 12 months, changes in weight and total fat mass were comparable and statistically not significant in both groups. The median increase [interquartile range (IQR)] in weight was +2.02 kg (+1.19, +2.95; p = .378) in RAL group, and +1.71 kg (+0.89, +2.54; p = .449) in DRV/r group. The median increase in body fat mass (IQR) was +1.27 kg (+1.09, +1.43; p = .278) in RAL group, and +1.04 kg (+0.89, +1.22; p = .781) in DRV/r group. In conclusion, in our study, an initial regimen including RAL plus tenofovir/emtricitabine after 12 months led to a small and nonsignificant increase in weight and body fat mass, and changes were comparable with a DRV/r-based initial regimen.

COVID-19 in patients with HIV-1 infection: a single-centre experience in northern Italy.

BACKGROUND: Since the end of February 2020, the Coronavirus Disease 2019 (COVID-19) outbreak rapidly spread throughout Italy and other European countries, but limited information has been available about its characteristics in HIV-infected patients. METHODS: We have described a case series of patients with HIV infection and COVID-19 diagnosed at the S.Orsola Hospital (Bologna, Italy) during March and April, 2020. RESULTS: We reported a case series of 26 HIV-infected patients with COVID-19. Nineteen subjects were men, the median age was 54 years, 73% of patients had one or more comorbidities. Only 5 patients with interstitial pneumonia were hospitalized, but there were no admissions to intensive care unit and no deaths. CONCLUSIONS: In our experience, COVID-19 associated with HIV infection had a clinical presentation comparable to the general population and was frequently associated with chronic comorbidities.

Short Communication: No Significant Changes in Weight and Body Fat Mass in Suppressed HIV-Infected Patients Switched to Dual Combination Lamivudine Plus Dolutegravir or Raltegravir.

Weight gain associated with integrase inhibitor-based treatment has become a critical issue in the clinical management of HIV infection. We analyzed changes in weight and body fat mass in 54 virologically suppressed patients who switched to lamivudine plus raltegravir or dolutegravir. Overall, after 12 months we reported a not significant increase in weight (median, +1.74 kg; p = .223) and total fat mass (median, +1.13 kg; p = .188), and these changes were comparable between groups. The median change in lumbar spine bone mineral density (BMD) [interquartile range (IQR)] was +0.02 g/cm2 (-0.02, +0.05; p = .786), and the median change in femur neck BMD (IQR) was +0.04 g/cm2 (-0.03, +0.06; p = .598), and changes were comparable between groups. In conclusion, the switch to dolutegravir/lamivudine or raltegravir/lamivudine dual therapy in virologically suppressed patients did not produce significant increases in weight and body fat mass after a 12-month follow-up, in association with not significant changes in BMD.

Simplification to dual therapy containing lamivudine and raltegravir or dolutegravir in HIV-infected patients on virologically suppressive antiretroviral therapy.

BACKGROUND: Antiretroviral dual regimens including lamivudine and one boosted PI or dolutegravir are warranted in order to optimize combination ART (cART), prevent long-term toxicity and reduce the cost of treatments. OBJECTIVES: We hypothesized that a maintenance dual regimen of lamivudine plus raltegravir would be effective and as well tolerated as the dual maintenance combination of lamivudine plus dolutegravir. METHODS: We performed an observational, retrospective study of HIV-infected patients on suppressive ART who switched to a dual regimen containing lamivudine 300 mg once daily plus raltegravir 1200 mg once daily or dolutegravir 50 mg once daily. RESULTS: In total, 109 patients (79 men; mean age 46.4 years; mean CD4+ T lymphocyte count 605 cells/mm3) were enrolled. Overall, 50 subjects switched to lamivudine plus raltegravir (Group A) and 59 to lamivudine plus dolutegravir (Group B). After 12 months, 45 patients (90%) in Group A and 52 (88.1%) in Group B had HIV RNA <20 copies/mL. No patients had severe adverse effects in either group, and the percentages of patients with mild adverse effects were comparable, except for a higher incidence of headache and sleeping disturbances in Group B than in Group A (30.5% versus 14%, P < 0.001). A comparable and non-significant weight increase was reported in both groups (+1.91 kg in Group A and +2.28 kg in Group B). CONCLUSIONS: In our study, dual therapies containing lamivudine plus raltegravir or dolutegravir in virologically suppressed patients showed high and comparable efficacy, as well as good tolerability.

Weight gain in antiretroviral therapy-naive HIV-1-infected patients starting a regimen including an integrase strand transfer inhibitor or darunavir/ritonavir.

BACKGROUND: Weight gain after initiation of combination antiretroviral therapy (cART) is a possible side effect of all antiretroviral regimens, but it seems to be more evident in association with integrase strand transfer inhibitors (INSTIs). So, we aimed to evaluate weight change associated with an initial cART including one INSTI or darunavir-ritonavir (DRV/r). METHODS: A retrospective, observational, cohort study of antiretroviral therapy-naive adult HIV-positive patients starting an initial cART including raltegravir (RAL), dolutegravir (DTG), elvitegravir-cobicistat (EVG), or DRV/r. We compared changes in weight and body mass index (BMI) across the four groups during a 12-month follow-up. RESULTS: As a whole, 680 patients (470 males, mean age 42.1 years) were enrolled: 196 starting RAL, 174 DTG, 158 EVG/c, and 152 DRV/r. Baseline mean CD4 lymphocyte count was 455 cells/mm3 and 7.3% had an AIDS diagnosis. After 12 months, mean increase in body weight was 1.93 kg in the RAL group, 2.38 kg in the DTG group, 2.14 kg in the EVG group, and 1.85 in the DRV/r group. Mean increase in BMI was 0.71, 0.84, 0.77 and 0.63 kg/m2, respectively (p > 0.05 for each comparison). Therefore, no significant increases in weight and BMI were reported in each group, and no significant differences in weight and BMI changes were described across the four treatment groups. CONCLUSIONS: In our study, patients starting an initial cART including one INSTI or DRV/r after 12 months showed a small and comparable, but not significant, increase in body weight, whose long-term clinical consequences are unknown.

No progression of subclinical atherosclerosis in HIV-infected patients starting an initial regimen including tenofovir alafenamide/emtricitabine plus raltegravir, dolutegravir or elvitegravir/cobicistat during a two-year follow-up.

Objectives: Cardiovascular disease has become one of the most common comorbidities among HIV-infected patients, but available data about the correlation between antiretroviral drugs and progression rate of atherosclerotic disease are still limited. We evaluated the progression rate of carotid atherosclerosis in patients starting an initial antiretroviral regimen including one integrase strand transfer inhibitor (INSTI).Methods: Observational, prospective study involving HIV-1-infected, antiretroviral therapy-naive, adult patients who started an antiretroviral regimen including tenofovir alafenamide/emtricitabine (TAF/FTC) plus raltegravir (RAL group), elvitegravir/cobicistat (EVG/c group), or dolutegravir (DTG group). Patients with known cardiovascular disease or diabetes mellitus were excluded from the study. The progression rate of atherosclerosis has been assessed by carotid Doppler ultrasonography at baseline and after 24 months.Results: Overall, 102 patients were enrolled into the study: 73 males, with mean age of 48.7 years: 32, 36 and 34 patients were included in the RAL, EVG/c and DTG groups, respectively. The baseline features of the enrolled patients were comparable across the three groups. At 24 months, the mean intima-media thickness (IMT) increase at the carotid bifurcation was 0.026 mm in the RAL group, 0.029 mm in EVG/c group and 0.032 mm in DTG group. The mean IMT increases after 24 months were comparable across the three groups and statistically not significant in all the evaluated anatomical sites.Conclusions: The initial antiretroviral therapy with TAF/FTC plus RAL, EVG/c or DTG for 24 months led to a comparable and not significant effect on the progression rate of carotid atherosclerosis.

Factors associated with vitamin D deficiency in HIV-1 infected patients on combination antiretroviral therapy: a case-control study.

The aim of our study was to assess risk factors associated with vitamin D deficiency among HIV-1-infected patients on combination antiretroviral therapy (cART). A retrospective, case-control study was conducted to assess risk factors associated with vitamin D deficiency among HIV-1-infected adults on stable cART. Vitamin D deficiency was defined as 25-OH vitamin D concentration <30 ng/mL. A total of 195 patients (77% males, mean age 49.2 years) were enrolled into the study: 98 subjects with vitamin D deficiency (cases) and 97 with normal vitamin D serum concentration (controls). The mean serum concentration + standard deviation (SD) of vitamin D was 18.2+6.7 ng/mL among cases and 39.6+13.4 ng/ mL among controls. Current cART including tenofovir disoproxil fumarate (TDF) (OR 1.65; 95% CI, 1.31 to 1.94), osteoporosis (OR 1.78; 95% CI, 1.25 to 2.09), males who have sex with males (MSM) risk category (OR 1.59; 95% CI, 1.19 to 2.21), chronic hepatitis C (OR 1.44; 95% CI, 1.17 to 1.86), previous or current cancer (OR 1.47; 95% CI, 1.13 to 1.79), metabolic syndrome (OR 2.57; 95% CI, 1.96 to 2.98), and hepatic steatosis (OR 1.59; 95% CI, 1.17 to 2.05) were significant associated with an increased risk of vitamin D deficiency. On the other hand, current CD4+ lymphocyte count >600 cells/mm3 and current HIV RNA <20 copies/mL were significantly associated with a lower risk of vitamin D deficiency. In our case-control study, vitamin D deficiency is associated with TDF exposure, osteoporosis, and metabolic disturbances.

Prevalence of chronic kidney disease among HIV-1-infected patients receiving a combination antiretroviral therapy.

BACKGROUND: Chronic kidney disease (CKD) has become one of the most frequent non-infectious comorbidities in the aging HIV-infected population on long-standing combination antiretroviral therapy (cART). METHODS: We conducted a retrospective, cross-sectional study including HIV-infected adult patients attending our HIV outpatient clinic during the years 2017 and 2018 to assess prevalence and associated risk factors of CKD. Estimated glomerular filtration rate (eGFR) was measured by Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation. CKD was diagnosed and classified according to the National Kidney Foundation guidelines. Logistic regression was employed to identify factors associated with CKD. RESULTS: We enrolled 2339 HIV-infected patients (91% were Caucasian) with a mean age of 45.3 years and a mean current CD4 lymphocyte count of 531 cells/mm3. CKD was diagnosed in 311 subjects (13.3%). Overall, 294 (12.6%) patients had albuminuria, 108 (4.6%) had eGFR < 60 mL/min/1.73 m2, and 78 (3.3%) had albuminuria plus eGFR < 60 mL/min/1.73 m2. Stages 4-5 of CKD were documented in 23 (1%) cases. Age greater than 50 years, male gender, hypertension, diabetes mellitus, high triglycerides, nadir CD4 cell count < 200 cells/mm3, current use of tenofovir disoproxyl fumarate (TDF) and of TDF plus a ritonavir-boosted protease inhibitors were independently associated with CKD, while current use of abacavir plus one integrase inhibitor was associated with a reduced risk of CKD. CONCLUSION: There is a significant prevalence of CKD among HIV-infected persons in association with both traditional and HIV-specific risk factors, requiring a careful periodic monitoring of renal function in these patients.

Improvement in liver steatosis after the switch from a ritonavir-boosted protease inhibitor to raltegravir in HIV-infected patients with non-alcoholic fatty liver disease.

Background: The ritonavir-boosted protease inhibitor (PI/r) use has been associated with several metabolic abnormalities, and the non-alcoholic fatty liver disease (NAFLD) is becoming a very frequent comorbidity among HIV-infected patients. Methods: We performed an observational, prospective study of HIV-infected patients with NAFLD, receiving one PI/r plus two nucleoside analogues, who switched from the PI/r to raltegravir or were treated only with lifestyle modification, maintaining antiretroviral therapy unchanged. Changes in liver steatosis after 12 months were evaluated by transient elastography and measurement of controlled attenuation parameter (CAP). Results: As a whole, 61 patients (46 males; median age, 55.4 years) were enrolled, and 32 of them have been switched from PI/r to raltegravir. At baseline, median CAP was 259 dB/m, 28 (45.9%) subjects had a moderate-to-severe hepatic steatosis (CAP ≥260 dB/m), and 19 patients (31.1%) had elevated aminotransferases. Type-2 diabetes mellitus was present in 5 persons, and chronic HCV coinfection in 4. At month 12, the median decrease in CAP values was -27 dB/m in patients switched to raltegravir and -11 dB/m in those with unchanged cART (p = .021). The number of patients with CAP ≥260 dB/m decreased from 16 to 6 (-62.5%) in patients switched to raltegravir and from 12 to 8 (-33.3%) in the other group (p = .037). Conclusion: After 12 months, HIV-infected patients with NAFLD switching from a PI/r to raltegravir showed a significantly greater decrease in the hepatic steatosis degreee in comparison with those with unchanged cART and treated only with lifestyle modification.

Improvement in insulin sensitivity and serum leptin concentration after the switch from a ritonavir-boosted PI to raltegravir or dolutegravir in non-diabetic HIV-infected patients.

OBJECTIVES: An observational, prospective, cohort study was performed to assess changes in insulin sensitivity and serum leptin level after a switch from a ritonavir-boosted PI (PI/r) to raltegravir or dolutegravir in HIV-infected adults on stable combination ART (cART). METHODS: Non-diabetic HIV-infected patients receiving suppressive cART including tenofovir disoproxil fumarate/emtricitabine plus one PI/r, who underwent a switch from the PI/r to raltegravir (group A) or dolutegravir (group B), were enrolled in the study. Serum levels of insulin, leptin and the homeostasis model assessment of insulin resistance (HOMA) index were evaluated during a 12 month follow-up. RESULTS: Overall, 86 patients were enrolled: 45 patients were included in group A and 41 were included in group B. The mean age was 45.7 years and 74 (86%) patients were male. After 12 months of follow-up, a significant reduction in the mean concentration of leptin and insulin was reported both in group A [-0.61 ng/mL (P < 0.001) and -2.5 mIU/L (P = 0.008), respectively] and in group B [-0.54 ng/mL (P = 0.005) and -2.1 mIU/L (P = 0.017), respectively], without a significant difference between the groups. A significant and comparable reduction in the mean HOMA index was reported both in group A [-0.55 (P = 0.004)] and in group B [-0.49 (P < 0.001)], as well as a significant decrease in lipid levels. CONCLUSIONS: In HIV-positive subjects on suppressive cART, the switch from a PI/r to raltegravir or dolutegravir led to a significant and comparable reduction in both HOMA index and serum leptin level, reflecting a similar and significant improvement in insulin sensitivity.

Rosuvastatin and atorvastatin preserve renal function in HIV-1-infected patients with chronic kidney disease and hyperlipidaemia.

BACKGROUND: Hyperlipidaemia is a risk factor for the progression of chronic kidney disease (CKD), which is a frequent comorbidity in patients with HIV-1 infection, but the renal effects of statins remain unclear. METHODS: We performed an observational, prospective study of HIV-infected patients on suppressive antiretroviral therapy, with CKD and hyperlipidaemia, and starting a lipid-lowering treatment with rosuvastatin, atorvastatin or omega-3 fatty acids. CKD was defined as an estimated glomerular filtration rate (eGFR) ≤ 60 mL/min/1.73 m2 for >3 months. RESULTS: As a whole, 69 patients (53 men, 58 Caucasian, median age 56.2 years) were enrolled. Overall, 25 patients started rosuvastatin (10 mg daily, group A), 23 patients atorvastatin (20 mg daily, group B), and 21 started omega-3 fatty acids (3 g daily, group C). At baseline, median eGFR was 54.4 mL/min/1.73 m2, and the eGFR ranged between 50 and 60 mL/min/1.73 m2 in 87% of patients. After 12 months, the median eGFR decline was significantly lower in group A (-0.84 mL/min/1.73 m2) and in group B (-0.91 mL/min/1.73 m2) in comparison with the group C (-1.53 mL/min/1.73 m2; p < 0.001 for both comparisons). The median decrease in prevalence of proteinuria and high-sensitivity C-reactive protein was also significantly greater in groups A and B than in group C, while the incidence of treatment discontinuations was comparable across the three groups. CONCLUSION: In our study, rosuvastatin and atorvastatin showed a significant protective effect on the renal function compared to omega-3 fatty acids in HIV-1-infected patients with CKD and dyslipidaemia.