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.

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.

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.

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.

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.

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.

Clinical management of dyslipidaemia associated with combination antiretroviral therapy in HIV-infected patients.

The introduction of potent combination antiretroviral therapy (cART) has had a remarkable impact on the natural history of HIV infection, leading to a dramatic decline in the mortality rate and a considerable increase in the life expectancy of HIV-positive people. However, cART use is frequently associated with several metabolic complications, mostly represented by lipid metabolism alterations, which are reported very frequently among persons treated with antiretroviral agents. In particular, hyperlipidaemia occurs in up to 70%-80% of HIV-positive subjects receiving cART and is mainly associated with specific antiretroviral drugs belonging to three classes of antiretroviral agents: NRTIs, NNRTIs and PIs. The potential long-term consequences of cART-associated dyslipidaemia are not completely understood, but an increased risk of premature coronary heart disease has been reported in HIV-infected patients on cART, so prompt correction of lipid metabolism abnormalities is mandatory in this population. Dietary changes, regular aerobic exercise and switching to a different antiretroviral regimen associated with a more favourable metabolic profile are the first steps in clinical management, but lipid-lowering therapy with fibrates or statins is often required. In this case, the choice of hypolipidaemic drugs should take into account the potential pharmacokinetic interactions with many antiretroviral agents.

Dual Raltegravir-Darunavir/Ritonavir Combination in Virologically Suppressed HIV-1-Infected Patients on Antiretroviral Therapy Including a Ritonavir-Boosted Protease Inhibitor Plus Two Nucleoside/Nucleotide Reverse Transcriptase Inhibitors.

BACKGROUND: Nucleoside reverse transcriptase inhibitor (NRTI)-sparing antiretroviral therapies may be useful in HIV-infected patients with resistance or intolerance to this class. METHODS: We performed an observational study of patients on suppressive antiretroviral therapy containing two NRTIs plus one ritonavir-boosted protease inhibitor who switched to a dual regimen containing raltegravir (400 mg twice daily) and darunavir/ritonavir (800/100 mg once daily) and were followed-up for 48 weeks. RESULTS: As a whole, 82 patients were enrolled. Mean duration of current regimen was 4.6 years and mean duration of plasma HIV RNA < 50 copies/mL before the switch was 46.2 months. Reason for simplification was toxicity in 76 patients and resistance to NRTIs in 13. After switching, the percentage of patients with HIV RNA < 50 copies/mL at week 48 was 92.7% in the intent-to-treat-exposed analysis and 97.6% in the per-protocol analysis. The switch led to a significant reduction in the mean triglyceride value (-85.2 mg/dL), in the prevalence of tubular proteinuria (-56%) and in the mean level of interleukin-6 (-0.94 pg/mL), with a significant increase in the mean phosphoremia (+0.58 mg/dL). Mean trough concentrations of both raltegravir and darunavir were within the therapeutic range. Two patients (2.4%) had virological failure due to suboptimal adherence and 4 subjects (4.9%) discontinued treatment due to adverse events, but no patients experienced Grade 3 or 4 adverse events. CONCLUSION: In our study, simplification to a dual therapy containing raltegravir plus darunavir/ritonavir after 48 weeks maintained viral suppression in more than 90% of patients and showed a good tolerability with a favourable effect on proteinuria, ipophosphoremia, and lipid metabolism.

HIV-1 early and late diagnosis in the Emilia Romagna Region (Italy): a three year study.

It is crucial to establish the timing of infection and distinguish between early and long-lasting HIV-1 infections not only for partner notification and epidemiological surveillance, but also to offer early drug treatment and contain the spread of infection. This study analyzed serum and/or plasma samples with a first positive HIV antibody/antigen result coming from different Medical Centers in the Emilia Romagna Region, North East Italy, using the avidity assay, Western Blotting, RNA viral load, CD4 cell counts and genotyping assay. From May 2013 to May 2016, we certified 845 new HIV-1 infections, 18.7% of which were classified on the basis of avidity index as recent infections and 81.3% as long-lasting infections, with an estimated conversion time exceeding six months at the time of study. Western Blotting showed reactivity to only one or two HIV-1 proteins in recently infected patients (RIPs), while a complete pattern to gag, env and pol proteins was observed in most long-lasting infected patients (LLIPs). The median age, gender, nationality and risk transmission factors were comparable in RIPs and LLIPs. Phylogenetic analysis performed in available plasma disclosed B strains, non-B subtypes and circulating recombinant forms (CRFs) in both groups of patients, with a major presence of CRFs in non-Italian HIV subjects. The large number of patients unaware of their HIV status makes it crucial to discover hidden epidemics and implement appropriate targeted public health interventions.

Calcaneal quantitative ultrasound (QUS) and dual X-ray absorptiometry (DXA) bone analysis in adult HIV-positive patients.

Human immunodeficiency virus (HIV)-infected patients have an increased risk of developing osteopenia or osteoporosis compared with healthy individuals. Our aim was to compare dual X-ray absorptiometry (DXA), the gold standard for measuring bone mineral density (BMD), with bone quantitative ultrasound (QUS), an alternative technique for predicting fractures and screening low BMD, at least in postmenopausal populations. We analyzed DXA and QUS parameters to investigate their accuracy in the diagnosis and prediction of bone alterations in a cohort of 224 HIV-1-positive patients. The speed of sound (SOS), broadband ultrasound attenuation (BUA) and stiffness index (SI) parameters showed a moderate correlation with DXA, especially with total-body BMD (r coefficient of 0.38, 0.4 and 0.42 respectively), particularly in the female subgroup. In addition, multivariate analysis of HIV-positive patients assessed for vertebral fractures indicated that QUS was more effective than DXA at predicting the risk of fracture. QUS can be used as an additional tool for analyzing bone density in HIV-positive patients and its case of use and low cost make it especially suitable for resource-limited settings where DXA is not employed.

Tenofovir/emtricitabine/efavirenz plus rosuvastatin decrease serum levels of inflammatory markers more than antiretroviral drugs alone in antiretroviral therapy-naive HIV-infected patients.

OBJECTIVES: Statins are lipid-lowering drugs that exhibit anti-Inflammatory and immune-modulatory properties, leading to a reduction of serum levels of C-reactive protein (CRP) in the general population. DESIGN: To assess the anti-inflammatory effects of statins in HIV-infected patients, because very limited data are available today. METHODS: Longitudinal, observational study of HIV-infected adult patients naive to antiretroviral therapy who started tenofovir/emtricitabine/efavirenz and were followed-up for 48 weeks. Patients with baseline normal cholesterol level and taking only antiretroviral drugs (group A) were compared to those with baseline hypercholesterolemia who received rosuvastatin (10 mg daily) in association with antiretroviral treatment (group B). The primary observation was change in serum markers of inflammation (high-sensitivity C-reactive protein [hsCRP], interleukin-6 [IL-6], interleukin-8 [IL-8]) and tumor necrosis factor-α [TNF- α]) in both groups, whereas secondary observations include variations in CD4 lymphocyte count, HIV viral load, and occurrence of adverse events. RESULTS: Eighty-six patients were enrolled into the study: 46 in group A and 40 in group B. After 48 weeks, patients treated with antiretroviral therapy plus rosuvastatin had significantly greater decreases in serum concentrations of all Inflammatory markers than those taking antiretroviral therapy only. Changes in mean levels of hsCRP and TNF-α were -35.1% and -22.4% in group B and -8.2% and 5.4% in group A, respectively (P < .001, for both parameters). No significant differences in immunovirological parameters and safety profile were reported across the compared groups. CONCLUSIONS: Our findings suggest that tenofovir/emtricitabine/efavirenz plus rosuvastatin has a greater antiInflammatory effect than antiretroviral drugs only.

Prevalence of renal disease within an urban HIV-infected cohort in northern Italy.

BACKGROUND: Renal disease is an increasingly recognized noninfectious comorbidity associated with human immunodeficiency virus (HIV) infection. METHODS: Our retrospective, cross-sectional study evaluated prevalence of nephropathy among HIV-infected patients followed up in our outpatient clinic during the year 2011. Renal dysfunction and chronic kidney disease (CKD) were defined as estimated glomerular filtration rate (eGFR) <90 ml/min per 1.73 m(2) and as renal damage or eGFR <60 ml/min per 1.73 m(2) over a 3-month or greater period, respectively. RESULTS: We enrolled 894 HIV-infected patients with a mean age of 44.2 years and a mean current CD4 lymphocyte count of 508 cells/mm(3). The prevalence of renal dysfunction and CKD was 27.4 and 21.3 %, respectively. Older age, male gender, hypertension, diabetes, proteinuria, hypertriglyceridemia, lower nadir CD4 cell count, current use of tenofovir or tenofovir plus a ritonavir-boosted protease inhibitor were independently associated with renal dysfunction. CONCLUSION: Renal dysfunction is a frequent comorbidity among HIV-infected persons and requires a careful clinical and laboratory monitoring of renal function.

Prevalence of sub-clinical vertebral fractures in HIV-infected patients.

Although the increased prevalence of low bone mineral density among HIV-infected patients has raised concern for increased fracture risk, few investigations have evaluated fracture rates. Increasing evidence indicates that HIV patients are at higher risk of osteoporotic fractures compared to the general population. This is a very important issue, because fragility fractures are complications with a significant prognostic value. Our study performed lateral spine X-ray to assess the prevalence of sub-clinical vertebral fractures in 202 HIV patients. Factors associated with vertebral fractures were also investigated. The prevalence of vertebral fractures was significantly high (23.3%): 14 subjects had SDI (spine deformity index)= 1, 22 SDI=2-3 and 11 SDI >4. Differences in the prevalence of vertebral fractures between naive and ART experienced patients was 18% vs. 24%, respectively. Furthermore, patients had a high prevalence of severe and multiple fractures; in 19 patients (40%) fractures involved multiple vertebrae. Patients with vertebral fractures were significantly older, with renal insufficiency and steroid use more frequently than subjects with no fractures. Our data suggest that the prevalence of vertebral fractures in HIV infection may be higher than expected, and lateral spine X-ray has a role in the screening of bone disease, at least in patients with a significant risk of fragility fractures.

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.

Incidence of renal toxicity in HIV-infected, antiretroviral-naïve patients starting tenofovir/emtricitabine associated with efavirenz, atazanavir/ritonavir, or lopinavir/ritonavir.

OBJECTIVES: We performed a retrospective cohort study of HIV-infected antiretroviral-naïve patients starting a first antiretroviral therapy with tenofovir/emtricitabine plus efavirenz (EFV), atazanavir/ritonavir (ATV/r), or lopinavir/ritonavir (LPV/r). METHODS: The incidence of renal impairment or proximal tubular dysfunction was evaluated during a 12-month follow-up. Renal impairment was diagnosed by a reduced estimated glomerular filtration rate (eGFR) calculated using the Modification of Diet in Renal Disease (MDRD) formula, and tubular dysfunction was diagnosed when ≥ 2 among proteinuria, glucosuria, hypouricaemia, hypophosphataemia, and hypokalaemia, were identified. RESULTS: A total of 235 patients were enrolled: 82 taking EFV, 78 ATV/r, and 75 LPV/r. The mean decline in eGFR after the 12-month follow-up was significantly greater in subjects treated with ATV/r (-10.4 ml/min/1.73 m(2)) than in those receiving EFV (- 5.1; p = 0.002) or LPV/r (-4.8; p = 0.003). Similarly, a significantly higher incidence of proximal tubulopathy was observed among ATV/r-treated patients (14.1%) compared with patients receiving EFV (4.9%) or LPV/r (5.3%). CONCLUSIONS: In our retrospective study, naïve patients receiving tenofovir/emtricitabine and ATV/r for 12 months showed a significantly higher decline in eGFR and a significantly higher incidence of proximal tubulopathy than those receiving tenofovir/emtricitabine plus EFV or LPV/r, even though clinically evident renal toxicity associated with tenofovir-based treatment is a very uncommon event.

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.

Statin therapy decreases serum levels of high-sensitivity C-reactive protein and tumor necrosis factor-α in HIV-infected patients treated with ritonavir-boosted protease inhibitors.

BACKGROUND: Statins are lipid-lowering drugs that exhibit anti-inflammatory and immune-modulatory properties, leading to a reduction of serum levels of C-reactive protein (CRP) in the general population. OBJECTIVE: Because very limited data are available today, our objective was to assess the lipid-lowering effects of statins and their capacity to decrease selected soluble markers of inflammation in HIV-infected patients. METHODS: Retrospective cohort study of HIV-infected adult patients with hypercholesterolemia who were receiving a stable antiretroviral regimen including a ritonavir-boosted protease inhibitor and who started a lipid-lowering therapy with rosuvastatin (10 mg daily), atorvastatin (10 mg daily), or pravastatin (40 mg daily) and were followed-up for at least 12 months. One hundred and fifty-one patients were enrolled in the study: 51 in the rosuvastatin group, 47 in the atorvastatin group, and 53 in the pravastatin group. The primary observation was change in plasma lipid levels and serum markers of inflammation (high-sensitivity C-reactive protein [hsCRP], interleukin-6 [IL-6], and tumor necrosis factor-α [TNF- α]), while secondary observations include immunovirological parameters and safety profile of statins. RESULTS: One year after starting the statin therapy, patients treated with rosuvastatin had significantly greater decreases in total cholesterol and LDL cholesterol than subjects on atorvastatin or pravastatin. All statins led to a similar, significant reduction in serum levels of hsCRP and TNF-α, without correlation between biomarkers and lipid values, and toxicity rates were similar for all 3 statins. CONCLUSION: Our findings suggest that rosuvastatin has a significantly greater lipid-lowering effect than atorvastatin or pravastatin, but all 3 statins exert a similar effect in lowering markers of inflammation as hsCRP and TNF-α.

Lopinavir/ritonavir trough concentrations with the tablet formulation in HIV-1-infected women during the third trimester of pregnancy.

OBJECTIVES: An observational, open-label study was performed to assess changes of lopinavir/ritonavir plasma concentrations during pregnancy. METHODS: Adult HIV-1-infected women during the third trimester of pregnancy and on stable antiretroviral treatment including zidovudine/lamivudine plus lopinavir/ritonavir tablets (400/100 mg twice daily) were asked to participate. This group was compared with a group of non-pregnant HIV-1-infected women receiving the same antiretroviral regimen. The trough plasma concentration (C(trough)) of lopinavir and ritonavir was assessed at steady-state by a validated high-performance liquid chromatography (HPLC)-tandem mass spectrometry method. RESULTS: A total of 41 HIV-positive female patients were enrolled in the study, with a median age of 28 y (range 20-37 y). These patients were stratified into 2 groups: 21 women in the third trimester of pregnancy (group A) and 20 non-pregnant women (group B). The geometric mean (95% confidence interval (CI)) plasma C(trough) of lopinavir was 4205 (2418-6896) ng/ml in group A and 5098 (3187-8084) ng/ml in group B. The reduction in lopinavir plasma levels observed in group A was not significant (geometric mean ratio 0.87, 95% CI 0.62-1.32; p = 0.411). No correlation was found between lopinavir plasma levels and adverse events (such as diarrhoea and hyperlipidaemia) or immunological parameters of HIV disease, and no changes in plasma HIV viral load were reported. CONCLUSION: In this study, a slight but not significant decrease in the plasma lopinavir C(trough) was found during the third trimester of pregnancy, suggesting that standard dosing of the tablet formulation is also appropriate during the later stages of pregnancy.