Patients Receiving Protease Inhibitors Research Articles

Protease inhibitor-based direct-acting antivirals are associated with increased risk of aminotransferase elevations but not hepatic dysfunction or decompensation

Cases of acute liver injury (ALI) have been reported among chronic HCV-infected patients receiving protease inhibitor (PI)-based direct-acting antiviral (DAA) regimens, but no analyses have compared the risk of ALI in patients receiving PI- vs. non-PI-based DAAs. Thus, we compared the risk of 3 ALI outcomes between patients (by baseline Fibrosis-4 [FIB-4] group) receiving PI-based or non-PI-based DAAs. We conducted a cohort study of 18,498 patients receiving PI-based DAA therapy (paritaprevir/ritonavir/ombitasvir±dasabuvir, elbasvir/grazoprevir, glecaprevir/pibrentasvir) matched 1:1 on propensity score to those receiving non-PI-based DAAs (sofosbuvir/ledipasvir, sofosbuvir/velpatasvir) in the 1945-1965 Veterans Birth Cohort (2014-2019). During exposure to DAA therapy, we determined development of: i) alanine aminotransferase (ALT) >200 U/L, ii) severe hepatic dysfunction (coagulopathy with hyperbilirubinemia), and iii) hepatic decompensation. We used Cox regression to determine hazard ratios (HRs) with 95% CIs for each ALI outcome within groups defined by baseline FIB-4 (≤3.25; >3.25). Among patients with baseline FIB-4 ≤3.25, those receiving PIs had a higher risk of ALT >200 U/L (HR 3.98; 95% CI 2.37-6.68), but not severe hepatic dysfunction (HR 0.67; 95% CI 0.19-2.39) or hepatic decompensation (HR 1.01; 95% CI 0.29-3.49), compared to those receiving non-PI-based regimens. For those with baseline FIB-4 >3.25, those receiving PIs had a higher risk of ALT >200 U/L (HR, 2.15; 95% CI 1.09-4.26), but not severe hepatic dysfunction (HR, 1.23 [0.64-2.38]) or hepatic decompensation (HR, 0.87; 95% CI 0.41-1.87), compared to those receiving non-PI-based regimens CONCLUSION: While risk of incident ALT elevations was increased in those receiving PI-based DAAs in both FIB-4 groups, the risk of severe hepatic dysfunction and hepatic decompensation did not differ between patients receiving PI- or non-PI-based DAAs in either FIB-4 group. Cases of liver injury have been reported among patients treated with protease inhibitor-based direct-acting antivirals for hepatitis C infection, but it is not clear if the risk of liver injury among people starting these drugs is increased compared to those starting non-protease inhibitor-based therapy. In this study, patients receiving protease inhibitor-based treatment had a higher risk of liver inflammation than those receiving a non-protease inhibitor-based treatment, regardless of the presence of pre-treatment advanced liver fibrosis/cirrhosis. However, the risk of severe liver dysfunction and decompensation were not higher for patients treated with protease inhibitor-based regimens.

Genomic instability in people living with HIV

The increased life expectancy of people living with HIV (PLWH) receiving antiretroviral treatment (ART) has transformed HIV infection into a chronic disease. However, patients may be at risk of accelerated aging and the accumulation of cellular damage, which may trigger the development of cancer. We evaluated genomic instability in HIV-positive individuals with different viral loads receiving antiretroviral treatment (ART) and in HIV ART-naïve individuals. We included 67 participants divided into four groups: group 1 (n = 24) HIV patients receiving reverse-transcriptase inhibitors (tenofovir/ emtricitabine/ efavirenz and abacavir/ lamivudine/ efavirenz), group 2 (n = 22) HIV patients receiving protease inhibitors combined with other antiretroviral drugs (tenofovir/ emtricitabine with ritonavir/ atazanavir or lopinavir/ ritonavir, and darunavir/ ritonavir/ raltegravir), group 3 (n = 13) HIV ART-naïve patients, and group 4 (n = 8) healthy individuals (controls). Nuclear abnormalities in buccal mucosal samples (micronuclei, binucleated cells, nuclear buds, karyorrhexis, karyolysis, and pyknosis) were quantified. Simultaneously, blood samples were taken to quantify CD4+, CD8+, and HIV viral load. There was a significant age difference between HIV ART-naïve patients and receiving ART groups. Infection time was longer in HIV patients with ART than in ART-naïve patients. There were no differences in sex, smoking, alcohol consumption, or number of micronucleated cells between the study groups. We found higher frequencies of binucleated cells and nuclear buds in HIV patients, HIV ART-naïve, and HIV ART patients compared to the control group. We found a positive correlation between nuclear buds and CD4/CD8 ratio in the HIV ART-naïve group. In conclusion, PLWH showed increased genomic instability. The CD4/CD8 ratio affects the numbers of nuclear buds and binucleated cells. These findings are pertinent to mechanisms of damage and possible strategies to mitigate carcinogenesis in PLWH.

Adipocytokine dysregulation, abnormal glucose metabolism, and lipodystrophy in HIV-infected adolescents receiving protease inhibitors

BackgroundLipodystrophy is common in HIV-infected patients receiving protease inhibitors (PIs), stavudine, and zidovudine. Adipocytokines may be altered in lipodystrophy. We evaluated risk factors, adipocytokine levels, insulin resistance, and lipid profiles in HIV-infected adolescents with different lipodystrophy types. MethodsA cross-sectional study was conducted in 80 perinatally HIV-infected adolescents receiving PI-based highly active antiretroviral therapy for ≥ 6 months. Patients underwent oral glucose tolerance tests and measurements of high-molecular-weight (HMW) adiponectin, leptin, resistin, insulin, and lipids. They were classified into 3 groups based on the clinical findings: no lipodystrophy, isolated lipoatrophy, and any lipohypertrophy (isolated lipohypertrophy or combined type). ResultsOf the 80 patients (median age, 16.7 years), 18 (22.5%) had isolated lipoatrophy, while 8 (10%) had any lipohypertrophy (four with isolated lipohypertrophy, and four with the combined type). In a multivariate analysis, longer exposure to stavudine (OR: 1.03; 95% CI, 1.01–1.06; p = 0.005) and indinavir (OR: 1.03; 95% CI, 1.01–1.06; p = 0.012) were associated with lipoatrophy, while longer exposure to didanosine (OR: 1.04; 95% CI, 1.01–1.08; p = 0.017) and indinavir (OR: 1.10; 95% CI, 1.00–1.21; p = 0.045) were associated with any lipohypertrophy. Leptin levels were highest in the any-lipohypertrophy group and lowest in the isolated-lipoatrophy group (p = 0.013). HMW adiponectin levels were significantly lowest in the any-lipohypertrophy group and highest in the no-lipodystrophy group (p = 0.001). There were no significant differences in the levels of resistin among the three groups (p = 0.234). The prevalence of insulin resistance (p = 0.002) and prediabetes/diabetes (p < 0.001) were significantly highest in the any-lipohypertrophy group. Patients with lipoatrophy and those without lipodystrophy had comparable degrees of insulin resistance (p = 0.292). In multiple linear regression analysis, adjusted for age, sex, and waist-height ratio, HMW adiponectin levels were associated with Matsuda index (β = 0.5; p = 0.003) and quantitative insulin sensitivity check index (QUICKI) (β = 40.1; p = 0.010) and almost significantly associated with homeostatic model assessment of insulin resistance (HOMA-IR) (p = 0.054). Leptin and resistin levels were not associated with HOMA-IR, Matsuda index, or QUICKI (all p > 0.05). ConclusionsAbnormal glucose metabolism and dysregulation of adipocytokines were common in the HIV-infected adolescents with lipohypertrophy and the combined type. Preventive screening for cardiovascular diseases caused by metabolic alterations should be routinely performed.

Correlation Between Duration Of Protease Inhibitor Therapy With Insulin Resistance In HIV Patients

Abstract Metabolic diseases related to Human Immunodeficiency Virus (HIV) caused an increase in the workload of health services. Prevalence of HIV infection in Indonesian provinces varied considerably, ranging from less than 0.1% to 4%. Several studies have analyzed the correlation between insulin resistance and the usage of antiretroviral drugs, especially protease inhibitors. The main mechanism that responsible for insulin resistance is related to glucose transporter inhibition (GLUT4). This study objective is to assess the correlation between prolonged administration of protease inhibitors and insulin resistance in patients with that have diagnosed with HIV. Method. This research is an observational research using a cross-sectional design. The study was carried at the POSYANSUS Polyclinic at H. Adam Malik General Hospital in August - December 2019. The study sample were 34 HIV-treated patients receiving protease inhibitor ARV therapy. The study was analysed using chi square. Results. The characteristics of the study subjects had the most frequent age range at the age of 34 - 49 years (54.3%), men (71.4%) and women (28.6%). The longest use of antiretroviral drugs is most in the 6-12 months group (60%). Insulin resistance number in this study was 13 people (37.1%). The average HOMA-IR value of the study subjects was 2 (0.8-16.5), fasting blood sugar levels were 86 (70-283) mg / dl, fasting insulin levels were 9.1 (4.1-79.4) (µU / ml)., urea levels of 20.88 ± 9.7 mg / dl and creatinine levels of 0.81 ± 0.15 mg / dl. There was a significant correlation between the duration of ARV treatment with insulin resistance (p = 0.018; OR 7.65) Conclusion. There is a significant correlation between the duration of ARV treatment with insulin resistance. The longer Protease Inhibitor was used, the bigger insulin resistance.

Adjustment of Immunosuppression for Liver Transplant Recipients Infected with HCV and Treated with Paritaprevir / Ritonavir - Ombitasvir/ Dasabuvir and Ribavirin

Introduction. Eradication rates of hepatitis C virus (HCV) infection is likely to rise after liver transplantation (LT). We aimed to evaluate the clinical role of a simple method for calcineurin inhibitors (CNI) adjustment in post-LT patients receiving paritaprevir / ritonavir / ombitasvir / dasabuvir and ribavirin (3D scheme). Material and Methods. We included post-LT adult patients between 2014 and 2017. All selected subjects had at least a 12-month follow-up receiving a stable dose of a CNI. All patients had HCV-1 infection, no liver cirrhosis and received the 3D scheme for 24 weeks. Serial blood concentration measurements of immunosuppressant drugs were obtained. CNI dose was adjusted since 3D scheme initiation and during follow-up until adequate levels were obtained. Results. A total of 10 LT patients (mean age 58.7 ± 11.26 years, 60 % women), out of LT 22, received the 3D regime. Tacrolimus was used in 9 patients: four patients received a dose of 0.5 mg every 10 days and 5 received doses of 0.25 mg every 5 days (mean levels, 9.07 ± 5.56 ng/mL). The trough concentration (Ctrough) was 2 ng / mL and the maximum concentration (Cmax) was 30 ng / mL. Only one patient was treated with cyclosporine (mean blood levels of 152.85 ± 54.55 ng / mL). All cases exhibited a sustained viral response. Discussion and Conclusions. It is possible to adjust CNI in LT patients under the 3D regime, with high response rates. Low CNI doses are required to avoid toxicity and side effects in HCV patients receiving protease inhibitors.

Impact of antiretroviral therapy on clinical outcomes in HIV + kidney transplant recipients: Review of 58 cases

Background: Antiretroviral therapy (ART) poses challenging drug-drug interactions with immunosuppressant agents in transplant recipients. We aimed to determine the impact of specific antiretroviral regimens in clinical outcomes of HIV + kidney transplant recipients. Methods: A single-center, retrospective cohort study was conducted at a large academic center. Subjects included 58 HIV - to HIV + adult, first-time kidney transplant patients. The main intervention was ART regimen used after transplantation. The main outcomes assessed at one- and three-years were: patient survival, death-censored graft survival, and biopsy-proven acute rejection; we also assessed serious infections within the first six months post-transplant. Results: Patient and graft survival at three years were both 90% for the entire cohort. Patients receiving protease inhibitor (PI)-containing regimens had lower patient survival at one and three years than patients receiving PI-sparing regimens: 85% vs. 100% ( p=0.06) and 82% vs. 100% ( p=0.03), respectively. Patients who received PI-containing regimens had twelve times higher odds of death at 3 years compared to patients who were not exposed to PIs (odds ratio, 12.05; 95% confidence interval, 1.31-1602; p=0.02). Three-year death-censored graft survival was lower in patients receiving PI vs. patients on PI-sparing regimens (82 vs 100%, p=0.03). Patients receiving integrase strand transfer inhibitors-containing regimens had higher 3-year graft survival. There were no differences in the incidence of acute rejection by ART regimen. Individuals receiving PIs had a higher incidence of serious infections compared to those on PI-sparing regimens (39 vs. 8%, p=0.01). Conclusions: PI-containing ART regimens are associated with adverse outcomes in HIV + kidney transplant recipients.

Impact of antiretroviral therapy on clinical outcomes in HIV + kidney transplant recipients: Review of 58 cases.

Background: Antiretroviral therapy (ART) poses challenging drug-drug interactions with immunosuppressant agents in transplant recipients. We aimed to determine the impact of specific antiretroviral regimens in clinical outcomes of HIV + kidney transplant recipients. Methods: A single-center, retrospective cohort study was conducted at a large academic center. Subjects included 58 HIV - to HIV + adult, first-time kidney transplant patients. The main intervention was ART regimen used after transplantation. The main outcomes assessed at one- and three-years were: patient survival, death-censored graft survival, and biopsy-proven acute rejection; we also assessed serious infections within the first six months post-transplant. Results: Patient and graft survival at three years were both 90% for the entire cohort. Patients receiving protease inhibitor (PI)-containing regimens had lower patient survival at one and three years than patients receiving PI-sparing regimens: 85% vs. 100% ( p=0.06) and 82% vs. 100% ( p=0.03), respectively. Patients who received PI-containing regimens had twelve times higher odds of death at 3 years compared to patients who were not exposed to PIs (odds ratio, 12.05; 95% confidence interval, 1.31-1602; p=0.02). Three-year death-censored graft survival was lower in patients receiving PI vs. patients on PI-sparing regimens (82 vs 100%, p=0.03). Patients receiving integrase strand transfer inhibitors-containing regimens had higher 3-year graft survival. There were no differences in the incidence of acute rejection by ART regimen. Individuals receiving PIs had a higher incidence of serious infections compared to those on PI-sparing regimens (39 vs. 8%, p=0.01). Conclusions: PI-containing ART regimens are associated with adverse outcomes in HIV + kidney transplant recipients.

Lack of effects of statins on high-density lipoprotein subfractions in HIV-1-infected patients receiving protease inhibitors

BackgroundWe evaluated the effect of 45 days of rosuvastatin or pravastatin treatment on the distribution of HDL subfractions in HIV-1-infected individuals receiving boosted protease inhibitors (PIs) with cardiovascular risk. MethodsThe distribution of HDL subclasses by gradient gel electrophoresis was blindly assessed in 74 HIV-1-infected individuals receiving boosted PIs at baseline and at day 45 of statin treatment, and compared with the distribution obtained in 63 healthy normolipidemic individuals taken as controls. ResultsNo significant modification appeared in HDL distribution between the two arms of statins for the HIV-1-infected individuals. Nevertheless, when compared to controls, HDL subfractions showed a significantly lower HDL2b proportion and significantly higher proportions of HDL2a and HDL3b (P<0.001). ConclusionNo difference was observed in HDL distribution between pravastatin and rosuvastatin after 45 days treatment, in HIV-1-infected individuals under PIs. Nevertheless, when compared to healthy normolipidemic subjects, HDL distribution is clearly different, with a distribution in HIV-infected individuals under PIs associated with an increased cardiovascular risk.

Factors associated with virological rebound in HIV-infected patients receiving protease inhibitor monotherapy.

The Protease Inhibitor Monotherapy Versus Ongoing Triple Therapy (PIVOT) trial found that protease inhibitor monotherapy as a simplification strategy is well tolerated in terms of drug resistance but less effective than combination therapy in suppressing HIV viral load. We sought to identify factors associated with the risk of viral load rebound in this trial. PIVOT was a randomized controlled trial in HIV-positive adults with suppressed viral load for at least 24 weeks on combination therapy comparing a strategy of physician-selected ritonavir-boosted protease inhibitor monotherapy versus ongoing triple therapy. In participants receiving monotherapy, we analysed time to confirmed viral load rebound and its predictors using flexible parametric survival models. Of 290 participants initiating protease inhibitor monotherapy (80% darunavir, 14% lopinavir, and 6% other), 93 developed viral load rebound on monotherapy. The risk of viral load rebound peaked at 9 months after starting monotherapy and then declined to approximately 5 per 100 person-years from 18 months onwards. Independent predictors of viral load rebound were duration of viral load suppression before starting monotherapy (hazard ratio 0.81 per additional year <50 copies/ml; P < 0.001), CD4 cell count (hazard ratio 0.73 per additional 100 cells/μl for CD4 nadir; P = 0.008); ethnicity (hazard ratio 1.87 for nonwhite versus white, P = 0.025) but not the protease inhibitor agent used (P = 0.27). Patients whose viral load was analysed with the Roche TaqMan-2 assay had a 1.87-fold risk for viral load rebound compared with Abbott RealTime assay (P = 0.012). A number of factors can identify patients at low risk of rebound with protease inhibitor monotherapy, and this may help to better target those who may benefit from this management strategy.

Treatment Outcome and Regimens of Lipid-Lowering Drugs among HIV-Infected Patients Receiving Protease Inhibitors

Objective: To determine treatment outcome and regimens among human immunodeficiency virus (HIV)-infected patients receiving protease inhibitors treated with lipid-lowering drugs. Material and Method: This retrospective, descriptive study was conducted in HIV-infected outpatients who were receiving protease inhibitors treated with lipid-lowering drugs at Bamrasnaradura Infectious Disease Institute during January 1st, 2014 to December 31st, 2014. Results: Of 121 patients identified, the mean age was 46.7±8.9 years. Sixty-two point eight percent received statins alone of which the most commonly prescribed regimens were atorvastatin 20 mg/day (20.7%) and atorvastatinfenofibrate combination (16.5%). One year after treatment, the patients’ mean CD4+ count was 621.6 cell/mm3 and about 98.3% of patients had HIV-1 viral load ≤ 20 copies/mL. However, the eighty-six of patients (71.1%) still had dyslipidemia; the mean values for total cholesterol, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and triglycerides were 230.5, 150.0, 52.6 and 283.3 mg/dL, respectively. There were no reported adverse drug events. Conclusion: HIV-infected patients receiving protease inhibitors treated with lipid-lowering drugs had virologically suppressed outcomes for at least 1 year but these regimens could not improve lipid values to achieve the therapeutic targets in the treatment of dyslipidemia.

Safety profile of boceprevir and telaprevir in chronic hepatitis C: Real world experience from HCV-TARGET

The safety profiles of boceprevir and telaprevir in the treatment of chronic hepatitis C, administered in academic and community centres across the United States, were evaluated. In 90 medical centres, patients with chronic HCV received pegylated interferon, ribavirin, and either telaprevir or boceprevir per local standard of care. Demographic, adverse event, clinical, and virological data were collected during treatment and follow-up. A total of 2084 patients (97% HCV genotype 1) received at least one dose of a protease inhibitor. At baseline, 38% of patients had cirrhosis, and 57% had received at least one prior treatment for hepatitis C. Serious adverse events occurred in 12% of patients receiving protease inhibitor therapy. Overall, 66% of patients experienced anaemia, leading to frequent ribavirin dose reductions (42%) and erythropoietin use (37%); 11% received blood transfusion. More than 90% of patients had adverse events that led to a prescription, treatment, or dosage change, and 39% of patients discontinued treatment early, most commonly because of adverse events (18%) or lack of efficacy (16%). Hepatic decompensation events occurred in 3% of all patients. Age, female gender, cirrhosis, HCV genotype 1 subtype, creatinine clearance, platelet levels, albumin levels and haemoglobin levels were independent predictors of anaemia. Five deaths occurred. Overall, 52% of all patients achieved a sustained virologic response. In academic and community centres, where chronic hepatitis C patients commonly have advanced liver disease, triple therapy was associated with a high rate of adverse events and involved frequent treatment modifications and adverse event management.

Effects of rosuvastatin and pravastatin on high-density lipoprotein subfractions in HIV-1-infected patients receiving protease inhibitors

Effects of rosuvastatin and pravastatin on high-density lipoprotein subfractions in HIV-1-infected patients receiving protease inhibitors

Inflammatory, procoagulant markers and HIV residual viremia in patients receiving protease inhibitor monotherapy or triple drug therapy: a cross-sectional study.

BackgroundProtease inhibitor monotherapy is associated with more frequent episodes of viral rebounds above 50 copies/mL than triple therapy. Objective: To evaluate if, compared to triple-drug therapy, protease inhibitor monotherapy is associated with increased levels of inflammatory/procoagulant markers and more frequent plasma residual viremia detection.MethodsIn this cross-sectional study, we included patients treated for ≥ 1 year with darunavir/ritonavir or lopinavir/ritonavir as monotherapy (n = 72) or with two nucleos(t)ides (n = 74). All samples were tested for CRP, IL-6, fibrinogen and D-dimer. Residual viremia was determined using an ultrasensitive qualitative nested-PCR of the HIV pol gene with a limit of detection of 1 copy of HIV-RNA.ResultsWe found no differences in levels of inflammatory/procoagulant markers or in the proportion of patients with plasma residual viremia detection by treatment group.ConclusionThe long-term treatment with protease inhibitor monotherapy in the setting of routine clinical practice is not associated with a higher prevalence of plasma residual viremia or more elevated inflammatory/procoagulant markers levels than triple drug therapy.

Plasma metabolomics identifies lipid abnormalities linked to markers of inflammation, microbial translocation, and hepatic function in HIV patients receiving protease inhibitors

BackgroundMetabolic abnormalities are common in HIV-infected individuals on antiretroviral therapy (ART), but the biochemical details and underlying mechanisms of these disorders have not been defined.MethodsUntargeted metabolomic profiling of plasma was performed for 32 HIV patients with low nadir CD4 counts (<300 cells/ul) on protease inhibitor (PI)-based ART and 20 healthy controls using liquid or gas chromatography and mass spectrometry. Effects of Hepatitis C (HCV) co-infection and relationships between altered lipid metabolites and markers of inflammation, microbial translocation, and hepatic function were examined. Unsupervised hierarchical clustering, principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), Random forest, pathway mapping, and metabolite set enrichment analysis (MSEA) were performed using dChip, Metaboanalyst, and MSEA software.ResultsA 35-metabolite signature mapping to lipid, amino acid, and nucleotide metabolism distinguished HIV patients with advanced disease on PI-based ART from controls regardless of HCV serostatus (p<0.05, false discovery rate (FDR)<0.1). Many altered lipids, including bile acids, sulfated steroids, polyunsaturated fatty acids, and eicosanoids, were ligands of nuclear receptors that regulate metabolism and inflammation. Distinct clusters of altered lipids correlated with markers of inflammation (interferon-α and interleukin-6), microbial translocation (lipopolysaccharide (LPS) and LPS-binding protein), and hepatic function (bilirubin) (p<0.05). Lipid alterations showed substantial overlap with those reported in non-alcoholic fatty liver disease (NALFD). Increased bile acids were associated with noninvasive markers of hepatic fibrosis (FIB-4, APRI, and YKL-40) and correlated with acylcarnitines, a marker of mitochondrial dysfunction.ConclusionsLipid alterations in HIV patients receiving PI-based ART are linked to markers of inflammation, microbial translocation, and hepatic function, suggesting that therapeutic strategies attenuating dysregulated innate immune activation and hepatic dysfunction may be beneficial for prevention and treatment of metabolic disorders in HIV patients.

Prevalence of Vitamin D Deficiency and Its Related Risk Factor in a Spanish Cohort of Adult HIV-Infected Patients: Effects of Antiretroviral Therapy

We analyzed serum 25(OH) cholecalciferol [25(OH)D] levels and factors related to deficiency (<20 ng/ml) or insufficiency (<30 ng/ml) in a cohort of Spanish HIV-infected patients and compared them with an age- and latitude-matched population from another study. We prospectively assessed 25(OH)D deficiency/insufficiency in a cohort of 352 HIV patients during 2009-2010. Predisposing factors were recorded and their relationship to low levels was assessed by logistic regression; a nutritional survey examined intake, nutritional status, and sunlight exposure in a subgroup of 92 patients. We studied the correlation of 25(OH)D with parathyroid hormone (PTH) and alkaline phosphatase. Age-, sex-, and race/ethnicity-adjusted vitamin D deficiency (<20 ng/ml) was 44.0% (95% CI, 38.8-49.4%) and insufficiency (<30 ng/ml) was 71.6% (95% CI, 66.9-76.3). Deficiency was 16.4% more prevalent in our sample than in non-HIV-infected Spaniards. Lower sunlight exposure was the only factor related to lower levels in the lifestyle and nutritional survey (p=0.045). In multiple logistic regression, higher body mass index (BMI), black race/ethnicity, lower seasonal sunlight exposure, men who have sex with men (MSM), and heterosexual transmission categories, efavirenz exposure and lack of HIV viral suppression were independently associated with deficiency/insufficiency. These variables predicted 79% of cases [AUC=0.872 (95% CI, 0.83-0.91)]. Patients receiving protease inhibitors (PIs) [OR 4.0 (95% CI, 1.3-12.3); p=0.014] or NNRTI [OR 3.6 (95% CI, 1.7-11.2); p=0.025] had higher odds of increased PTH levels; this was significant only in 25(OH)D-deficient patients (p=0.004). As in less insolated areas, the prevalence of vitamin D deficiency/insufficiency was high in HIV-infected patients in Spain; among treated patients, levels were higher with PIs than with efavirenz.

Dyslipidaemia in HIV-1-infected patients receiving protease inhibitors after initial treatment with first-line-based non-nucleoside reverse transcriptase inhibitors: a cross-sectional study

ObjectivesLipid abnormalities associated with antiretroviral therapy in people with HIV infection are more frequent with protease inhibitors (PI)-based regimens. Whether effects extend to patients receiving a PI subsequent to failure...

Antiretroviral treatment-induced dyslipidemia in HIV-infected patients is influenced by the APOC3-related rs10892151 polymorphism

BackgroundThe recently observed association between the APOC3-related rs10892151 polymorphism and serum triglyceride levels has prompted us the possibility to explore whether this genetic variant may play a major role in human immunodeficiency virus (HIV)/antiretroviral therapy-induced dyslipidemia.MethodsWe determined the rs10892151 genotype distribution and serum apolipoprotein (apo) C-III concentration in a group of HIV-infected patients (n = 208) and in a group of age and sex-matched healthy volunteers (n = 200). Circulating lipid and lipoprotein levels were followed for 12 months after antiretroviral treatment initiation in the HIV-infected group.ResultsThere were no significant variations in the frequency of the A allele between the healthy and HIV-infected groups (7.5 vs. 8.6%, respectively; p = 0.7); additionally, the A allele was not related to serum apo C-III concentration. However, among patients receiving protease inhibitor (PI) treatment, carriers of the A allele had significantly increased serum triglyceride (5.76 ± 2.54 mmol/L) and total cholesterol (6.63 ± 2.85 mmol/L) concentrations together with depressed levels of HDL-cholesterol (0.75 ± 0.3 mmol/L) when compared with patients not carrying the allele (2.43 ± 1.32, 5.2 ± 2.17 and 1.24 ± 0.4 mmol/L, respectively) at the end of the study. This effect was only evident for HDL-cholesterol concentration when patients were treated with non-nucleoside reverse transcriptase inhibitors (1.05 ± 0.4 vs. 1.28 ± 0.4 mmol/L).ConclusionsThe A allelic variant of the rs10892151 polymorphism is not associated with serum apo C-III concentration, but predisposes HIV-infected patients to less favorable lipid profile, particularly in those patients treated with PIs.

The success of endosseous implants in human immunodeficiency virus–positive patients receiving antiretroviral therapy: A pilot study

In a pilot study, the authors aimed to determine the success rate of dental implants placed in patients who were positive for human immunodeficiency virus (HIV) and were receiving different regimens of highly active anti-retroviral therapy (HAART). They considered patients' levels of cluster of differentiation (CD) 4(+) cells and viral load, and they attempted to verify whether patients with baseline biochemical signs of bone mineral density loss could experience osseointegration impairment.One of the authors, a dentist, placed dental implants in the posterior mandibles of 40 volunteers, divided into three groups: one composed of HIV-positive patients receiving protease inhibitor (PI)-based HAART; a second composed of HIV-positive patients receiving nonnucleoside reverse transcriptase inhibitor-based HAART (without PI); and a control group composed of HIV-negative participants. The authors assessed peri-implant health six and 12 months after implant loading. They analyzed the success of the implants in relation to CD4(+) cell counts, viral load and baseline pyridinoline and deoxypyridinoline values.The authors followed 59 implants for 12 months after loading. Higher baseline levels of pyridinoline and deoxypyridinoline found in HIV-positive participants did not interfere with osseointegration after 12 months of follow-up. Average peri-implant bone loss after 12 months was 0.49 millimeters in group 1, 0.47 mm in group 2 and 0.55 mm in the control group.The placement of dental implants in HIV-positive patients is a reasonable treatment option, regardless of CD4(+) cell count, viral load levels and type of antiretroviral therapy. Longer follow-up periods are necessary to ascertain the predictability of the long-term success of dental implants in these patients.Limited published scientific evidence is available to guide clinicians in regard to possible increased risks associated with dental implant placement in HIV-positive patients.

Assessment of factors influencing health-related quality of life in HIV-infected patients

Health-related quality of life (HRQL) is used in the assessment of chronic illness. Regarding HIV infection, HRQL assessment is an objective for physicians and institutions since antiretroviral treatment delays HIV clinical progression. The aim of this study was to determine the factors with the most influence on HRQL in HIV-infected people and to create a predictive model. We conducted a cross-sectional study in 150 patients in a tertiary hospital. HRQL data were collected using the Medical Outcomes Study HIV Health Survey (MOS-HIV) questionnaire. The research team created a specific template with which to gather clinical and sociodemographic data. Adherence was assessed using the Simplified Medication Adherence Questionnaire (SMAQ) and depression data were obtained using the Beck Depression Inventory, Second Edition (BDI-II) inventory. Logistic regression models were used to identify determinants of HRQL. HIV-related symptoms and presence of depression were found to be negatively associated with all the MOS-HIV domains, the Physical Health summary score and the Mental Health summary score. Patients receiving protease inhibitor (PI)-based treatment had lower scores in four of the 11 domains of the MOS-HIV questionnaire. Gender, hospitalization in the year before enrolment, depression and parenthood were independently related to the Physical Health Score; depression and hepatitis C virus coinfection were related to the Mental Health Score. Optimization of HRQL is particularly important now that HIV infection can be considered a chronic disease with the prospect of long-term survival. Quality of life should be monitored in follow-up of HIV-infected patients. The assessment of HRQL in this population can help us to detect problems that may influence the progression of the disease. This investigation highlights the importance of a multidisciplinary approach to HIV infection.

Long-term follow-up of 11 protease inhibitor (PI)-naïve and PI-treated HIV-infected patients harbouring virus with insertions in the HIV-1 protease gene

Amino acid insertions in the protease gene have been reported rarely, and mainly in patients receiving protease inhibitors (PIs). The aim of the study was to assess the long-term viro-immunological follow-up of HIV-infected patients harbouring virus with protease insertions. Cases of virus exhibiting protease insertions were identified in routine resistance genotyping tests. Therapeutic, immunological and virological data were retrospectively collected. Eleven patients harbouring virus with a protease gene insertion were detected (prevalence 0.24%), including three PI-naïve patients. The insertions were mainly located between codons 33 and 39 and associated with surrounding mutations (M36I/L and R41K). The three PI-naïve patients were infected with an HIV-1 non-B subtype. Follow-up of these PI-naïve patients showed that the insert-containing virus persisted for several years, was archived in HIV DNA, and displayed a reduced viral replicative capacity with no impact on resistance level. Of the eight PI-experienced patients, 63% were infected with HIV-1 subtype B; one had been antiretroviral-free for 5 years and seven were heavily PI-experienced (median duration of follow-up 24 months; range 10-62 months). The protease insertion was selected under lopinavir in four patients and under darunavir in one, in the context of major PI-resistance mutations, and following long-term exposure to PIs. The insert-containing virus persisted for a median of 32 months (range 12-62 months) and displayed no specific impact on phenotypic resistance level or viral replicative capacity. Our data, obtained during long-term follow-up, show that insertions in the protease gene do not seem to have an impact on resistance level. This finding supports the recommendation of PI-based regimens, although further work is required to confirm it.