The Moderating Role of Caregiving on Fear of COVID-19 and Post-Traumatic Stress Symptoms.

Caregiving has been associated with increased levels of fear and post-traumatic stress symptoms (PTSS) during COVID-19 pandemic. However, there is a lack of studies that analyze when the relationship between fear and PTSS occur, using informal caregiving as a moderator variable. To explore this moderating role, we conducted a cross-sectional online study between November 2020 and January 2021. A total of 503 men and women from the Spanish general population completed the survey. Sociodemographic and Covid-19-related data, fear of COVID-19, PTSS symptoms, and current psychological history were assessed. Prevalence of informal caregiving in the sample was 16.5%. Increased levels of fear and PTSS were found in caregivers compared to non-caregivers. Female gender and high number of COVID-19 related risk factors was also associated with fear and PTSS severity. The moderation analyses showed an interaction effect between caregiving and fear of COVID-19 when predicting PTSS symptoms. Particularly, results showed that informal caregivers reported greater PTSS symptoms, when compared to non-caregivers with same levels of fear of COVID-19. This evidence suggests that being a caregiver could increase the fear's impact on PTSS severity in the context of pandemics. Further studies with larger samples are needed to confirm these findings.

Changes in Kidney Function and in the Rate of Tubular Dysfunction After Tenofovir Withdrawal or Continuation in HIV-Infected Patients.

INTRODUCTION: Longitudinal data on the changes in kidney function and tubular abnormalities in case of tenofovir disoproxil fumarate (TDF) withdrawal or continuation are scarce. METHODS: Prospective study of 228 patients receiving TDF, with 3 sequential determinations of serum creatinine, estimated glomerular filtration rate (eGFR), phosphatemia, and different urinary parameters (protein, albumin, phosphaturia, uricosuria, and glycosuria). Changes were analyzed in patients who interrupted TDF as compared to those who continued the same regimen. Proximal renal tubular dysfunction (PRTD) was defined as ≥2 tubular abnormalities. RESULTS: After a median follow-up of 59.5 months, 78 patients (34%) had PRTD, mainly proteinuria (40%) and phosphaturia (61%), and time on TDF explains the severity of tubular alterations and eGFR slopes. In 35 switching patients, there was a rapid and significant eGFR improvement (median +4.1 ml/min per 1.73 m; P = 0.02), leading to a 39%-83% reduction in the prevalence of tubular abnormalities and of PRTD in less than 1 year (66%-39%). In comparison, 193 patients continuing the same regimen for 21.2 months had a small but significant and progressive eGFR decrease (-2.9 mL·min·1.73 m; P < 0.01), and a progressive rise in the prevalence of phosphaturia, uricosuria, and glycosuria (+9%-56%). In linear mixed-effect model, subsequent eGFR impairment was associated with proteinuria and time on TDF, and eGFR improvement with TDF discontinuation. CONCLUSIONS: Our data support the role of use and time on TDF in eGFR decline and tubular dysfunction. In contrast, TDF withdrawal is followed by a rapid and significant, although partial, recovery of eGFR and tubular abnormalities.

Bone mineral density decline according to renal tubular dysfunction and phosphaturia in tenofovir-exposed HIV-infected patients.

INTRODUCTION: The mechanisms underlying the effect of tenofovir disoproxil fumarate (TDF) on the decline of bone mineral density (BMD) have not been established, especially the effect of renal tubular dysfunction. METHODS: Longitudinal study of 90 patients with two successive dual X-ray absorptiometry scans after evaluation of serum and urinary parameters (proteinuria, albuminuria, phosphaturia, uricosuria, glycosuria, ß-2-microglobulin, and retinol-binding protein). RESULTS: After a median of 38 months on TDF, osteopenia at spine and hip was observed in 49 and 48%, and osteoporosis in 9 and 2%, respectively. There was a lineal correlation between BMD at femoral neck and time on TDF (Spearman's rho = -0.27; P = 0.01). One or more tubular abnormalities were observed in 80% of cases (hyperphosphaturia, 50%). A lower BMD correlated with phosphaturia (r = -0.25; P = 0.03), even with phosphataemia within normal limits. In fact, patients with previous improvement in phosphaturia had better BMD at inclusion (Spearman's rho = -0.33; P < 0.01). A second dual X-ray absorptiometry, after a median of 40.8 months (33.8-45.1; 627.7 patients-year on TDF), showed additional BMD reduction at hip in 50% of cases (36% with bone loss >3%), a decline associated with phosphaturia (ß, -0.31; P = 0.01) or number of tubular abnormalities (ß, -0.41; P = 0.01), but also with use of boosted protease inhibitors (ß, -0.47; P = 0.03) and BMD at inclusion (ß, -0.33; P = 0.03). CONCLUSION: Chronic abnormal phosphaturia explains, at least in part, progressive bone loss during TDF therapy. These data suggest that tubular dysfunction leads to an altered equilibrium between phosphataemia, phosphaturia, and bone as mechanism of progressive BMD decline.

Prevalence and significance of proximal renal tubular abnormalities in HIV-infected patients receiving tenofovir.

OBJECTIVES: Patients receiving tenofovir, disoproxil, fumarate (TDF) had an increased prevalence of proximal renal tubular dysfunction (PRTD), but contributing factors and its clinical significance remain controversial. DESIGN AND METHODS: Cross-sectional evaluation of different urinary parameters (proteinuria, albuminuria, phosphaturia, uricosuria, glycosuria) in 200 HIV-infected patients receiving TDF, 26 following TDF discontinuation, and 22 never treated with TDF, included in a prospective cohort study. PRTD was defined as two or more tubular abnormalities. RESULTS: After a median of 65 months (interquartile range, 42.7-84.7), at least one tubular alteration was found in 72% of patients, mostly proteinuria (42, 50, and 14% in current, previous and never TDF use; P=0.02) and phosphaturia (46, 42, and 14%; respectively, P < 0.01). PRTD was found in 63 patients (32%) receiving TDF, ranging from 14 to 46% according to concomitant hepatitis C virus coinfection, diabetes mellitus or hypertension arterial, in contrast with six (23%) following TDF discontinuation, and zero cases in no TDF-treated patients. The use of TDF [odds ratio (OR) 13.2; 95% confidence interval (CI) 1.4-22.7; P = 0.01], cumulative time on combination antiretroviral therapy (OR 1.011; 95% CI 1.07-1.019 per month; P = 0.01), and baseline estimated glomerular filtration rate (eGFR, OR 0.97; 95% CI 0.94-0.99 per ml/min per 1.73 m higher; P = 0.04) were associated with PRTD. The number of tubular abnormalities was linearly associated with eGFR decline since TDF initiation (ß-coefficient -0.15, P = 0.02), together with age (-0.18; P = 0.01), baseline eGFR (0.49, P = 0.01), diabetes mellitus (-0.19, P = 0.02), and time on TDF (-0.23; P = 0.01). CONCLUSION: The use of TDF leads to an increased rate of tubular dysfunction, and modulated by age, baseline eGFR, and classical factors, is associated with kidney function decline.

Dutrebis (lamivudine and raltegravir) for use in combination with other antiretroviral products for the treatment of HIV-1 infection.

Raltegravir and lamivudine have been part of highly active therapy regimens throughout the past years of antiretroviral therapy. A fixed-dose, single-tablet regimen comprising a non-poloxamer formulation of the integrase inhibitor raltegravir and the transcriptase inhibitor lamivudine (raltegravir/lamivudine; Dutrebis(®)) has been recently licensed for the treatment of HIV-1 infection. In several Phase I pharmacokinetic studies, one Dutrebis (150 mg lamivudine/300 mg raltegravir) fixed-dose combination tablet showed a higher bioavailability but comparable lamivudine and 400 mg raltegravir poloxamer exposures. Thus, the co-administration of raltegravir together with lamivudine created a potent, effective, well-tolerated antiretroviral combination, which could be more convenient for the patient. However, the disadvantage of twice a day administration, and the existence of other fixed-dose combinations limit its widespread clinical use. This article reviews pharmacokinetics data and appraises their potential use in current and future HIV therapy.

Fibrosis Regression Explains Differences in Outcome in HIV-/HCV-Coinfected Patients with Cirrhosis After Sustained Virological Response.

BACKGROUND AND AIMS: Fibrosis regression (FR) after sustained virological response (SVR) should produce a better outcome in hepatitis C (HCV)-/HIV-coinfected patients with liver cirrhosis, but there are no specific data in this issue. METHODS: We compared the incidence rate (IR) and the time to develop a liver complication and death in 133 cirrhotic patients according to SVR or/and FR. RESULTS: Of 42 patients with SVR, 23 (55%) had FR, in comparison with only 14 of the 91 (15%) without SVR. During a follow-up of 6.8 years (916.8 person-years), the IR of death, liver-related death, and liver-related complications were 2.45, 0.61, and 1.22 per 100 persons/year among SVR/FR, and 7.6, 5.9, and 6.81 among non-SVR without FR (p < 0.01), respectively. SVR patients without FR had also a lower rate of liver-related complications (1.78 vs 3.25; p = 0.02), but a worse IR of death (5.36) and liver-related death (2.68) than non-SVR patients with FR (1.3, and 0.65; p < 0.01). Moreover, FR was associated with less hospital admissions and decreasing alpha-fetoprotein levels. In Cox analysis, only FR was associated with a lower risk of death (adjusted hazard ratio, HR 0.36; 95% CI 0.15-0.86), and liver-related death (HR 0.15; 95% CI 0.03-0.65), whereas both FR (HR 0.09; 95% CI 0.03-0.3, p < 0.01) and SVR (HR 0.24; 95% CI 0.07-0.87) decreased the risk of liver-related complications. CONCLUSION: Fibrosis regression after SVR is associated with the highest reduction in death of any cause, liver-related mortality, and liver-related complications in HIV-/HCV-coinfected patients with cirrhosis.

Raltegravir plus two nucleoside analogues as combination antiretroviral therapy in HIV-infected patients who require cancer chemotherapy.

BACKGROUND: There are few data on the best combination antiretroviral therapy in patients with HIV infection who need cancer chemotherapy because of drug-drug interactions and increased risk of toxic effects. METHODS: We evaluated the safety, efficacy and interactions of a raltegravir (RAL)-based regimen in 30 HIV-infected patients who received antineoplastic agents. RESULTS: A total of 17 patients had a non-AIDS-defining malignancy (7 with Hodgkin disease) and 13 had an HIV-related cancer (9 non-Hodgkin lymphoma, 2 Kaposi sarcoma and 2 anal cancer). Overall, they received 49 cycles of chemotherapy with 19 different antineoplastic drugs, including antimetabolites in 4 patients (5-FU, gemcitabine), alkylating agents in 10 cases (cyclophosphamide, ifosfamide), vinca alkaloids in 17 patients (vincristine, vinblastine), anti-tumour antibiotics in 18 cases (doxorubicin), cisplatin or carboplatin in 6, and monoclonal antibodies in 13 patients (rituximab, trastuzumab, cetuximab). Six patients modified the doses of antineoplastic agents due to toxicity not related to raltegravir. During a median follow-up of 67.8 patient-years (median 170 days in concomitant therapy) there was only 1 case of virological failure and no patient discontinued RAL. Geometric mean trough levels of RAL were 143 ng/ml (79-455). There were no opportunistic infections, median CD4(+) T-cell count increased by 49 cells/ml and four (13%) patients died during the study (not related to AIDS progression). CONCLUSIONS: Our results show that a RAL-based regimen is safe and effective in patients requiring chemotherapy, irrespective of type and of duration of chemotherapy.

Efficacy and pharmacokinetics of the combination of etravirine plus raltegravir as novel dual antiretroviral maintenance regimen in HIV-infected patients.

Novel combination antiretroviral regimens may be needed for selected HIV-infected patients with toxicity or resistance. We evaluated prospectively 25 virologically suppressed patients, largely pretreated (15.6 years on therapy) with antiretroviral drug toxicity (n=19) or interactions (n=9, mainly with chemotherapy against non-Hodgkin lymphoma or anti-HCV therapy), who switched to a dual therapy with etravirine (ETR) plus raltegravir (RAL). Patients were required not to have prior virological failure or resistance to both drugs. After a median follow up of 722 days (473-1088: 53.3 patients-year), there were no cases of transient virological replication or failure. Only 1 patient left therapy at day 10 due to a grade 2 rash, and therefore efficacy by intent-to-treat analysis was 96% at 48 weeks. There were no cases of liver toxicity grade 3-4, and total cholesterol (TC) and triglycerides (TG) levels decrease significantly after initiation (TC, -17 mg/dl; p=0.01; TG, -42 mg/dl; p=0.01), as well as the TC/High density lipoprotein-cholesterol ratio (from 4.35 to 4.28). Geometric mean plasma trough level of RAL was 166 ng/ml (IQR, 40-249), well above the inhibitory concentration 90 (IC(90)). In conclusion, a novel dual therapy with ETR plus RAL is effective and well tolerated, and it could be an option to maintain durable viral suppression in hard-to-treat HIV-infected patients.

Effect of a monthly dose of calcidiol in improving vitamin D deficiency and secondary hyperparathyroidism in HIV-infected patients.

There are no data about the optimal supplementation therapy in HIV-infected patients with vitamin D (25OHD) deficiency. The aim of this study was to assess the effect of an oral monthly dose of 16,000 IU calcidiol. We performed a longitudinal cohort study of 365 HIV-infected patients (24 % females) was with sequential determinations of 25OHD, serum parathyroid hormone (PTH), calcium, and alkaline phosphatase. The efficacy and safety of supplementation in 123 patients were compared against dietary and sun exposure advice. Overall, mean baseline 25OHD levels were 19.1 ng/ml (IQR 12-23.6), 63 % of patients had 25OHD deficiency and 27 % secondary hyperparathyroidism. After a median time of 9.3 months (95.61 patients-year on-treatment), 25OHD levels increased in comparison with non-supplemented patients (+16.4 vs. +3.2 ng/ml; p < 0.01), decreasing the rate of 25OHD deficiency (from 84 to 24 %), and decreasing serum PTH (-4.9 pg/ml) and the rate of secondary hyperparathyroidism (from 43 to 31 %; p < 0.001). This improvement was observed irrespective of HIV/HCV coinfection or the use of efavirenz. In a regression analysis, adjusting by seasonality, a lower baseline 25OHD was associated with persistence of deficiency (relative risk, RR 1.07; 95 % CI 1.03-1.1; p < 0.001), whereas calcidiol supplementation was the only factor associated with significant improvement (RR 0.38; 95 % CI 0.12-0.46; p < 0.001). This monthly dose showed no clinical toxicity, and no patient had 25OHD levels above 100 ng/ml, nor hypercalcemia. The use of monthly calcidiol is safe, easy to take, and largely effective to improve vitamin D deficiency and secondary hyperparathyroidism in HIV-infected patients.

Efficacy and safety of etravirine-containing regimens in a large cohort of HIV/HCV coinfected patients according to liver fibrosis.

INTRODUCTION: Etravirine has become an alternative in HIV/HCV coinfected patients because of safety and lack of interactions with anti-HCV drugs. The aim of this study was to establish the risk of liver toxicity in HIV/HCV coinfected patients receiving etravirine in the clinical setting, according to the degree of liver fibrosis and different accompanying drugs. MATERIAL AND METHODS: Cohort study of 211 patients initiating etravirine as part of their antiretroviral regimen. HCV coinfection was defined as a positive RNA-HCV, whereas baseline liver fibrosis was assessed by transient elastography at baseline. Hepatotoxicity was defined as an increased AST/ALT, 5-fold higher over upper, normal limits for patients with normal baseline values, or 3.5-fold if altered at baseline. RESULTS: HCV coinfection was observed in 145 patients (69%) with a longer time of HIV infection and time on HAART than mono-infected patients, and a lower nadir (182 vs 227 cells/mL; p=0.02) and baseline CD4+ count (446 vs 552 cells/mL; p=0.02). Etravirine was used with two nucleoside analogues in 62%, with boosted darunavir in 17%, with raltegravir in 10%, and with darunavir plus raltegravir or maraviroc in 10% of patients without differences according to HCV serostatus. Transient elastography in 117 patients performed at etravirine initiation (median, 33 days) showed fibrosis 1 and fibrosis 4 in 37% and 24% of cases, and median stiffness value was 8.25 kPa (3.5-69). During an accumulated follow-up of 449.3 patient-years (median, 611 days), only one coinfected patient with fibrosis 4 (stiffness value, 50.1 kPa), receiving a rescue regimen including darunavir/r plus maraviroc plus two nucleoside analogues, developed a grade 3-4 of liver toxicity (0.5%). There were no other episodes of liver toxicity, as defined, and only 6 (3%) and 9 patients (4%) had a grade 1 and 2 of toxicity, respectively, in most cases related to HCV coinfection (6 and 6 cases). Moreover, HCV coinfection or advanced fibrosis was not associated to a higher risk of etravirine discontinuation (26% vs 21%; p=0.27, log-rank test) or virologic failure (9% vs 11%, p=0.56). CD4+ cell count increase was lower in HCV patients (+23 vs +86 at 6 month; p=0.02). CONCLUSIONS: Etravirine is safe in HIV/HCV coinfected patients, even in presence of moderate and advanced liver fibrosis and as part of different antiretroviral regimens.

Efficacy, safety, and lack of interactions with the use of raltegravir in HIV-infected patients undergoing antineoplastic chemotherapy.

INTRODUCTION: Concomitant use of combination antiretroviral regimen (cART) and cancer chemotherapy is difficult due to complex interactions and increased toxicity. Raltegravir could be an adequate option through its favourable drug-drug interaction profile. METHODS: Prospective longitudinal study of HIV patients with cancer, AIDS related or not, undergoing chemotherapy. Patients without resistance or previous failure were switched or initiated raltegravir plus two nucleoside analogues. Plasma trough levels of raltegravir were measured. RESULTS: Overall, 28 patients receiving a raltegravir-based regimen (4 naive) with tenofovir-emtricitabine (18 cases) or abacavir-lamivudine (10 cases) were included. Mean age was 46.2 years (IQR, 39-52.7), and 79% were male. Median time of HIV was 201.7 months, CD4+ nadir was 268 cells/mm(3), and 75% had previous AIDS. At the diagnosis of neoplasia, 17 were on protease inhibitors and 4 with efavirenz. Ten patients had a non-HIV-related cancer (three breast, two pancreatic, one Ewing sarcoma, one myeloblastic leukemia, one melanoma, one parotid adenocarcinoma, one lung), and 18 had an HIV-related cancer (nine non-Hodgkin lymphoma, seven Hodgkin disease, two anal). Overall, 43% of patients received more than one line of chemotherapy, including antimetabolites in 12 patients (5-FU, capecitabine, methotrexate, gemcitabine), alkylating agents in 12 cases (ciclophosphamide, iphosphamide), vinca alkaloids in 20 patients (vincristine, vinblastine, vindesine), antitumor antibiotics in 16 cases (adriamycin), cisplatin o carboplatin in six and monoclonal antibodies in six patients (rituximab, trastuzumab, cetuximab). Six patients modified the doses of antineoplastic agents due to toxicity (four neutropenia), not related to raltegravir. During a median follow up of 12.7 patients-year in concomitant therapy, there was only 1 case of virological failure and no patient discontinued raltegravir. Plasma concentrations of raltegravir in eight patients showed a median concentration of 143 ng/mL (79-455). Four patients (14%) died during the study, not related to AIDS progression. Raltegravir was continued after chemotherapy in all the cases. CONCLUSIONS: A raltegravir-based therapy is safe and effective in HIV patients undergoing antineoplastic chemotherapy, regardless of the type of tumour, and type and duration of chemotherapy. Pharmacokinetic data show adequate raltegravir levels.

Lamivudine plus darunavir boosted with ritonavir as simplification dual regimen in HIV-infected patients.

INTRODUCTION: The combination of lamivudine plus a protease inhibitor boosted with ritonavir (PI/r) has become an alternative as simplification strategy in HIV-infected patients with toxicity/intolerance to other nucleoside analogues (NA). Lamivudine plus darunavir/r (DRV/r) could be an adequate once daily option. MATERIALS AND METHODS: Prospective cohort study of 48 HIV-infected patients on suppressive triple therapy-based HAART, HBV negative, who switched to lamivudine 300 mg plus DRV/r 800/100 mg once daily. RESULTS: Mean age was 50 yrs (35-74), and 65% were male. Thirty patients (63%) had HCV co-infection (fibrosis 4 in 7 cases, 23%). Median time of HIV infection was 19.1 years, and CD4+ count nadir was 220 cells/µL (2-604). They had received a mean of three regimens before (2-20), and 20 (42%) had a previous AIDS diagnosis. In eight cases, a previous resistance test showed two to seven secondary mutations in the protease gene, without resistance to DRV/r (one patient with the I84V mutation). At baseline, patients had viral suppression (<50 copies/mL) for a median time of 1263 days (341-1884), and they were receiving predominantly a PI based regimen (ATV in four, FPV in four, LPV in three, DRV in six) or an efavirenz-based regimen (seven). The main reason to switching to this dual therapy was toxicity (35 patients, 75%), mainly renal toxicity attributed to tenofovir (24 cases). During 104.3 patients-year of follow-up (median 912 days), only two patients (4%) failed at 27 and 505 days, due to non-adherence and lost to follow up, respectively. Total cholesterol and triglycerides increased significantly during the first six months after initiation (TC, from 185 to 269 mg/dL; p=0.01, TG from 118 to 185 mg/dL; p=0.03, TC/HDL ratio, from 4.09 to 4.66) and decreased after. Median estimated glomerular filtration rate (eGFR) improved during follow up (from 86 to 96.1 mL/min; p=0.13). In patients with renal toxicity as cause of switch there was a mild, no significant improvement during the first year (from 63.3 to 68.7 mL/min), although an improvement in protein-uria levels (protein/creatinine ratio, from 171 to 126 mg/g; p=0.04) was observed soon after initiation. CONCLUSIONS: Dual therapy with lamivudine plus darunavir boosted with ritonavir once daily is safe and effective as simplification strategy in HIV-infected patients.

A clinical and pharmacokinetic study of the combination of etravirine plus raltegravir in HIV patients with expanded intolerance or resistance.

INTRODUCTION: The combination of etravirine (ETR) plus raltegravir (RAL) could be an option for HIV patients with resistance, intolerance or important interactions with other drugs. However, there are few data on the efficacy, safety and pharmacokinetics of this dual therapy, taking into account the effect of HCV co-infection or the possible induction of ETR in the drug metabolism of RAL. MATERIAL AND METHODS: Cohort study of HIV patients initiating ETR plus RAL as dual therapy. Plasma trough levels of RAL were measured by LC/MS after at least one month on therapy. RESULTS: A total of 25 patients have been included in this combination since 2009. Mean age was 46 years, 72% were male, and 20 patients (80%) had HCV co-infection (seven patients with fibrosis 3-4). Median nadir CD4+ count was 109 (60-209), and 21 patients had an HIV RNA level below 50 copies/mL. Median time on previous therapy was 473 months (IQR, 395-570), and reasons for this dual therapy was toxicity/intolerance in 19, and interactions in nine (two chemotherapy, three DAAs, two methadone, two other). After a median follow up of 722 days (473-1088: 53.3 patients-year), there were no cases of blips or virological failure. Six patients (24%) discontinued therapy after more than 1.5 year on therapy, in four cases due to lost follow up and in two due to simplification after finishing the reason for interaction. There were no cases of liver toxicity, and only two patients increased slightly transaminases values (grade 1 and 2). Total cholesterol and triglycerides levels decrease significantly after initiation (TC, from 182 to 165 at one year; p=0.01; TG from 185 to 143 mg/dL; p=0.01). CT/HDL ratio decreases from 4.35 to 4.28 after six months. Geometric mean plasma trough level of RAL was 166 ng/mL (IQR, 40-249) and only one patient (6%) was below the in vitro IC50 of the wild type. CONCLUSIONS: The combination of ETR plus RAL as dual therapy is effective and safe in patients with expanded intolerance or interactions. There are no significant pharmacokinetic interactions between both drugs.

Recent advances in rilpivirine: new data and promising treatment option.

The usefulness of every antiretroviral drug in the clinical setting should be continuously evaluated, since registration studies may not adequately reflect real-world patient populations. Rilpivirine was developed in an effort to generate patient-tailored drugs with high convenience and minimal side effects. By now, rilpivirine is currently licensed for use with other antiretroviral agents, and as a single agent or a single-tablet regimen with tenofovir and emtricitabine , in antiretroviral-naive, HIV-1-infected adults with < 100,000 HIV-1 RNA copies/ml because of a higher rate of virological failure above this level. However, after its introduction several questions remained to be elucidated, such as the efficacy of rilpivirine with abacavir/lamivudine, or its use in switching strategies, a useful alternative for patients with toxicity or intolerance. Cumulative data suggest the efficacy and safety of the combination of abacavir/lamivudine plus rilpivirine in the clinical setting, and an increasing number of patients received rilpivirine after protease inhibitor, efavirenz, or nevirapine-based therapy without compromising rilpivirine exposure after the change. Moreover, rilpivirine is a substrate and weak inducer of the CYP3A4, but there are no significant pharmacokinetic interactions with new anti-hepatitis C compounds such as telaprevir, simeprevir, daclatasvir, ledipasvir, and sofosbuvir, an important issue for a drug with low risk of hepatoxicity. As a new and promising strategy, rilpivirine has been evaluated with darunavir and dolutegravir in dual therapies, without need of dose adjustment and with adequate preliminary data. Therefore, to date, new data on rilpivirine confirm the good results observed in the clinical trials.

Prevalence of insulin resistance and risk of diabetes mellitus in HIV-infected patients receiving current antiretroviral drugs.

OBJECTIVE: HIV-infected patients had a higher prevalence of insulin resistance (IR) and risk of diabetes mellitus (DM) than that observed in healthy controls, but there are no data about the current prevalence considering the changes in HIV presentation and the use of newer antiretroviral drugs. DESIGN: Longitudinal study which involved 265 HIV patients without DM, receiving first (n=71) and advanced lines of antiretroviral therapy (n=194). METHODS: Prevalence of IR according to clinical and anthropometric variables, including dual X-ray absorptiometry (DXA) scan evaluation. IR was defined as homeostasis model assessment of IR≥3.8. Incident DM was assessed during the follow-up. RESULTS: First-line patients had a short time of HIV infection, less hepatitis C virus coinfection, and received mainly an efavirenz-based regimen. Overall, the prevalence of IR was 21% (55 patients, 6% in first-line, 27% in pretreated). In a logistic regression analysis, significant associations were found between the waist/hip circumference ratio (RR 10; 95% CI 1.66-16; P<0.01, per unit), and central fat in percentage (RR 1.08; 95% CI 1.01-1.17; P=0.04, per unit) as evaluated by DXA, and IR. During 770.8 patient-years, DM was diagnosed in 8% (22 patients), mostly in pretreated patients (10 vs 4%; P=0.1). Thus, the overall rate of incident DM was 2.85 per 100 person-years, mostly in previous IR (10.39 vs 0.82/100 person-years; P=0.01). CONCLUSIONS: A lower prevalence of IR is observed in the current HIV-infected patients with fewer risk factors and receiving newer antiretroviral drugs. IR continues to identify patients at high risk for developing DM in the short term.