Use of Apixaban in Atrial Fibrillation With Ritonavir-Boosted Antiretroviral Therapy: A Case Report.

Purpose: Direct oral anticoagulants (DOACs) pose a challenge when given with potent CYP3A4 and P-gp inhibitors, such as the commonly prescribed pharmacokinetic booster ritonavir. As per the manufacturer, apixaban offers a dose reduction when administered concurrently with ritonavir; thus, we explore the clinical indication and safety of apixaban when given with ritonavir-boosted highly active antiretroviral therapy (HAART) in an HIV patient. Summary: We describe a 73-year-old male with extensive cardiac history, including a past medical history of resolved left ventricular thrombus, newly diagnosed non-valvular atrial fibrillation treated with warfarin, and HIV infection treated with ritonavir-boosted HAART. The patient presented to the emergency department with bleeding from multiple sites, necessitating the use of vitamin K. Consequently, his hospital course was complicated by episodes of minor bleeding and labile INR. Due to the complicated nature of his condition and the potential for drug-drug interactions (DDIs), he was transitioned from warfarin to apixaban. Since there is little readily available data to support the use of rivaroxaban and dabigatran with ritonavir, our patient was safely started on dose-reduced apixaban for stroke prophylaxis in atrial fibrillation due to the predictable nature of apixaban pharmacokinetics and proven superiority regarding adverse effects, as compared to other DOACs. Conclusion: Dose-reduced apixaban is a safe and viable choice in patients with atrial fibrillation warranting stroke prophylaxis while concurrently receiving ritonavir-boosted HAART.

Histomorphological study of the effects of aqueous extract of Curcuma longa on highly active antiretroviral therapy-induced testicular toxicity.

This study evaluates the effects of highly active antiretroviral therapy (HAART) and Curcuma longa on testicular histology, stereological parameters, body weight and relative organ weights, seminal fluid, testosterone, follicle-stimulating hormone, the antioxidant marker malondialdehyde (MDA), reduced glutathione (GSH) and superoxide dismutase (SOD) in adult male Wistar rat. Thirty-six adult male Wistar rats were grouped into A: distilled water (control); B: 100 mg/kg C. longa; C: 200 mg/kg C. longa; D: HAART only; E: HAART + 100 mg/kg C. longa; and F: HAART + 200 mg/kg C. longa. The rats were sacrificed after 8 weeks. Results showed a significant increase in abnormal morphology in group D when compared with group A. In group D, progressive sperm motility was significantly decreased compared with group F. The GSH level was significantly increased in group D compared with control group A, group E and group F. Histomorphological studies showed that HAART caused loss of germ cells and widening tubule lumen which were improved and partially restored by C. longa. This study suggests that C. longa improves testicular morphology and ameliorates HAART-induced toxicity. Further studies confirming putative mechanisms are required.

Política pública transcultural y factores no adherentes al TARGA del VIH-sida etnia Perú-Amazónica Kusu Pagata / Cross-cultural public policy and factors not adherent to HIV-aids HAART-Peru-Amazon ethnic group Kusu Pagata

Introducción: Uno de los problemas que afecta los pueblos indígenas latinoamericanos es la falta de datos epidemiológicos respecto a la prevalencia del VIH-sida, debido a que los sistemas de información y vigilancia no registran la variable etnicidad. Objetivo: Proponer una política pública transcultural para prevenir factores asociados a la no adherencia a la terapia antirretroviral de gran actividad del VIH-Sida de la etnia Amazónica Kusu Pagata. Métodos: Estudio descriptivo, transversal, con 18 pobladores diagnosticados de VIH-sida en la comunidad Kusu Pagata, Perú. 2018-2019. Se aplicó cuestionario validado por expertos y confiabilidad alfa de Cronbach (0,71). La variable investigada fue factores asociados a la no adherencia a terapia antirretroviral, la propuesta fue una política pública basada en la Teoría de Madeleine Leininger. Se utilizaron estadísticas descriptivas (promedio, desviación estándar) e inferencial (prueba de comparación de promedios para varianzas homogéneas Shapiro-Wilk y prueba F para comparación de varianzas de 1 cola). Resultados: La edad promedio del paciente no adherente al tratamiento fue 21 años, significativamente mayor que la de los adherentes (18,2) años. El 80 por ciento de los que acudieron al curandero fueron no adherentes al tratamiento, el 50 por ciento fueron adherentes y acudieron al establecimiento sanitario. El 64 por ciento consumió tratamientos con productos elaborados con plantas, los que se consideraron no adherentes al tratamiento farmacológico, el 71 por ciento tomó otros tratamientos alternos. Conclusión: Se propuso una política pública transcultural según Teoría de Madeleine Leininger para prevenir factores asociados a la no adherencia a la terapia antirretroviral del VIH-sida de la etnia Amazónica Kusu Pagata(AU)

Introduction: One of the problems affecting Latin American indigenous peoples is the lack of epidemiological data regarding the prevalence of HIV-Aids, due to the fact that the information and surveillance systems do not register the ethnicity variable. Objective: To propose a cross-cultural public policy to prevent factors associated with non-adherence to highly active antiretroviral therapy for HIV-Aids of the Amazon Kusu Pagata ethnic group. Methods: Descriptive, cross-sectional study with 18 residents diagnosed with HIV-Aids in the Kusu Pagata community, Peru. 2018-2019. An expertly validated questionnaire and Cronbach's alpha reliability (0.71) were applied. The variable investigated was factors associated with non-adherence to antiretroviral therapy; the proposal was a public policy based on the Theory of Madeleine Leininger. Descriptive (mean, standard deviation) and inferential statistics (means comparison test for homogeneous Shapiro - Wilk variances and F-test for comparison of 1-tail variances) were used. Results: The average age of the patient not adherent to the treatment was 21 years, significantly higher than that of the adherents (18.2) years. 80.00 percent of those who went to the healer were non-adherent to the treatment, 50.00 percent were adherent and went to the health facility. 64.00 percent consumed treatments with products made with plants, those who were considered non-adherent to the pharmacological treatment, 71.00 percent took other alternative treatments. Conclusion: A cross-cultural public policy was proposed according to Madeleine Leininger's Theory to prevent factors associated with non-adherence to antiretroviral therapy for HIV-AIDS of the Amazon Kusu Pagata ethnic group(AU)

Momordica charantia mitigates hepatic injury following adjuvant treatment with antiretroviral drugs in diabetic animal models.

Momordica charantia (M. charantia) is a medicinal plant, used in traditional practice for treating diseases like hypertension and diabetes mellitus. This study investigated the possible hepato-protective effect of M. charantia following treatment with highly active antiretroviral therapy (HAART) in diabetic rats. 48 adult male Sprague Dawley rats were divided into seven groups (A-G) of 7 animals per group and treated according to protocols. Diabetes was induced with streptozotocin (STZ) by intraperitoneal injection (45 mg/kg body weight). The animals were euthanized on the 10th week with liver removed for examination and blood obtained via cardiac puncture and centrifuged to collect the sera. Blood glucose levels (BGL) were consistently and significantly raised (p < 0.05) in all groups not receiving the adjuvant M. charantia. Treatment with M. charantia reverses the increase in BGL to near normal. Markers of liver injury assayed showed significant increase (p < 0.05) in AST, ALP and ALT levels in groups not receiving M. charantia. Adjuvant HAART and M. charantia caused significant declines in the liver enzymes (p < 0.05). Serum GGT was not markedly altered. Treatment with M. charantia significantly restored liver enzymes elevations to near normal comparable to control. Histopathological observations ranged from severe hepatocellular distortions, necrosis and massive fibrosis following treatment of HAART in diabetic groups not receiving M. charantia. Treatment with M. charantia did not show any sign of hepatotoxicity as judged from the histological and biochemical observations.

Optimizing Treatment for Adults with HIV/AIDS in China: Successes over Two Decades and Remaining Challenges.

PURPOSE OF REVIEW: The introduction of the National Free Antiretroviral Therapy Program (NFATP) in 2003 by the China National Center for AIDS/STD Control and Prevention has led to dramatic increases in antiretroviral therapy (ART) coverage among HIV-infected Chinese patients. Despite limitations in the number of available free antiretroviral drugs, the overall mortality associated with HIV/AIDS has dropped from 39.3 per 100 person-years in 2002 to 3.1 in 2014. In this review, we summarize the challenges, responses, and achievements of antiretroviral therapy (ART) in China over the past 20 years. RECENT FINDINGS: Continuous optimization of the Chinese National Guidelines for HIV/AIDS Diagnosis and Treatment has been guided by data from serial domestic multi-center studies aimed at evaluating efficacy and toxicity of available ART regimens among Chinese patients with HIV, with the goal of maximizing adherence, access, and efficacy. In addition, increasing attention has been focused on the importance of continuity in the HIV care cascade to promote linkage to care, and address the multidisciplinary chronic care needs HIV/AIDS patients on lifelong ART. Great progress has been achieved in the past 20 years in terms of access to and optimization of antiretroviral treatment in China. As the number of patients receiving long-term ART continues to grow, the focus of HIV/AIDS treatment has gradually transitioned from urgent care to the management of non-AIDS-related chronic complications and control of chronic inflammation.

The Impact of 6-month Micronutrient Supplementation on Viral, Immunological, and Mental Health Profile of a Cohort of Highly Active Antiretroviral Therapy-Naive HIV-Positive Patients in Northern Nigeria.

BACKGROUND: HIV is a chronic disease with inflammatory reactions involving numerous elements of the immune system, resulting in an increased risk for other physical and psychiatric morbidities. Micronutrients, some of which possess anti-inflammatory properties, may help prevent the development of psychological disorders such as anxiety and depression in people living with HIV disease. OBJECTIVES: This study examined the profile of viral load, CD4 cell count, C-reactive protein, anxiety, and depression among highly active antiretroviral therapy (HAART)-naive HIV-positive patients receiving micronutrient supplementation over a 6-month period. MATERIALS AND METHODS: A total of ninety HAART-naïve HIV-infected patients completed the Hospital Anxiety Depression Scale. Their blood samples were taken for serum viral load, CD4 cell count, and C-reactive protein at baseline. They all received a micronutrient supplement for 6 months, and 68 participants who remained in treatment at 6 months were reassessed with the same parameters. RESULTS: After 6 months of micronutrient supplementation, the participants were found to have statistically significantly lower mean scores on the anxiety (t-test = 2.970, P = 0.003) and depression (t-test = 3.843, P = 0.001) subscales. They also had statistically significantly lower median CD4 cell count (P = 0.00) and C-reactive protein serum measures (P = 0.04). The median viral load decreased although the difference was not statistically significant. CONCLUSION: Micronutrient supplementation may reduce inflammatory reactions, anxiety, and depression in HAART-naive HIV-infected persons.

Oral candidal carriage correlates with CD4+ cell count but not with HIV and highly active antiretroviral therapy status.

AIM: The occurrence of oropharyngeal candidiasis (OPC) may be influenced by oral candidal carriage (OCC). Although OPC is strongly associated with low CD4+ cell count (400-700 cells/mm3 ) and a lack of highly active antiretroviral therapy (HAART), the effect of these two parameters on OCC is debatable. We investigated the oral candidal carriage, species diversity, antifungal susceptibility and the association of OCC with CD4+ cell count and HAART. METHODS: Oral candidal isolates from 120 HIV+ patients (60 receiving and 60 not receiving HAART) and 60 healthy controls were quantified, and their species determined using standard culture and biochemical methods, followed by antifungal susceptibility testing using the agar dilution method. RESULTS: The OCC was significantly higher in HIV+ patients; Candida albicans was the most frequently isolated species in both groups, followed by Candida tropicalis. Candidal density carriage correlated significantly with CD4+ cell count, but not with HIV and HAART status. Among the isolates from HIV+ patients, 35.4% showed reduced susceptibility to fluconazole. CONCLUSION: HIV status results in significantly elevated rates of OCC C albicans remains the predominant pathogen, although other species are emerging rapidly. Resistance to fluconazole is on the rise, and more efficient treatment strategies need to be implemented.

Virgin coconut oil extract mitigates testicular-induced toxicity of alcohol use in antiretroviral therapy.

The consumption of alcohol by people living with HIV/AIDS is associated with a graver prognosis. Long-term use of antiretrovirals may have certain health challenges that may be aggravated by concomitant alcohol use. This study investigated virgin coconut oil (VCO) as an adjuvant to the deleterious effects of highly active antiretroviral therapy (HAART) and alcohol on the cyto-architecture and functioning of the testis. Forty adult male Sprague-Dawley rats, weighing 165~176 g, were divided into eight groups and treated according to protocol. Testicular histology, stereological parameters, seminal fluid, testosterone, luteinizing hormone, follicle-stimulating hormone, the antioxidants marker malondialdehyde (MDA), and antioxidant glutathione (GSH) were examined. The use of ethanol alone and ethanol + HAART showed extensive degeneration in the seminiferous epithelium, decreased semen quality, disorganized basement membrane and widened, hypocellular interstitium. GSH was significantly decreased in the ethanol alone treated group with no significant effect on testosterone, LH, and MDA levels. Adjuvant treatment with VCO at low dose (2.5 mL/kg/bw) improved sperm motility with a partial restoration of the histopathological alterations. High doses of VCO (5.0 mL/kg/bw) showed greater improvement with respect to sperm counts, increased FSH hormonal and GSH antioxidant levels, and a well-preserved testicular cyto-architecture.

[Moxibustion combined with highly active antiretroviral therapy for CD4+ and γ chain cytokines of HIV infected patients].

OBJECTIVE: To compare the effects of moxibustion combined with highly active antiretroviral therapy (HAART) and simple HAART for human immunodeficiency virus (HIV) infected patients. METHODS: A total of 100 patients with HIV receiving HAART were randomized into an observation group and a control group, 50 cases in each one. In the observation group, moxibustion was used at Zusanli (ST 36), Guanyuan (CV 4) and Sanyinjiao (SP 6), etc. combined with HAART of zidovudine, lamivudine, nevirapine and efavirenzone, etc. Simple HAART was used in the control group. The patients were observed for 18 months. The indexes were CD4+, CD4+/CD8+, interleukin 2 (IL-2), interleukin 7 (IL-7), the incidence of side effects and the score of quality of life. RESULTS: After treatment, CD4+, CD4+/CD8+, serum IL-2 and the scores of quality of life (physiological, psychological, social relation fields and comprehensive score) increased and serum IL-7 decreased compared with those before treatment in the two groups (P<0.01, P<0.05), with better results except CD4+ in the observation group (P<0.01, P<0.05). The incidences of gastrointestinal side effects and total side effects in the observation group were lower than those in the control group (14% (7/50) vs 32% (16/50), 58% (29/50) vs 80% (40/50), both P<0.05). CONCLUSION: Moxibustion combined with HAART for HIV infected patients could reduce the incidence of side effects, improve medication compliance, CD4+/CD8+, IL-2, IL-7 and the quality of life.

Moxibustion combined with highly active antiretroviral therapy for CDand γ chain cytokines of HIV infected patients / 中国针灸

<p><b>OBJECTIVE</b>To compare the effects of moxibustion combined with highly active antiretroviral therapy (HAART) and simple HAART for human immunodeficiency virus (HIV) infected patients.</p><p><b>METHODS</b>A total of 100 patients with HIV receiving HAART were randomized into an observation group and a control group, 50 cases in each one. In the observation group, moxibustion was used at Zusanli (ST 36), Guanyuan (CV 4) and Sanyinjiao (SP 6), etc. combined with HAART of zidovudine, lamivudine, nevirapine and efavirenzone, etc. Simple HAART was used in the control group. The patients were observed for 18 months. The indexes were CD, CD/CD, interleukin 2 (IL-2), interleukin 7 (IL-7), the incidence of side effects and the score of quality of life.</p><p><b>RESULTS</b>After treatment, CD, CD/CD, serum IL-2 and the scores of quality of life (physiological, psychological, social relation fields and comprehensive score) increased and serum IL-7 decreased compared with those before treatment in the two groups (<0.01,<0.05), with better results except CDin the observation group (<0.01,<0.05). The incidences of gastrointestinal side effects and total side effects in the observation group were lower than those in the control group (14% (7/50) vs 32% (16/50), 58% (29/50) vs 80% (40/50), both<0.05).</p><p><b>CONCLUSION</b>Moxibustion combined with HAART for HIV infected patients could reduce the incidence of side effects, improve medication compliance, CD/CD, IL-2, IL-7 and the quality of life.</p>

Dietary supplement interactions with antiretrovirals: a systematic review.

Many patients who take antiretroviral drugs also take alternative therapies including dietary supplements. Some drug-supplement combinations may result in clinically meaningful interactions. We aimed to investigate the evidence for dietary supplement interactions with antiretrovirals. A systematic review was conducted using multiple resources including PubMed, Natural Medicine Comprehensive Database, The Review of Natural Products, and Google Scholar. All human studies or case reports evaluating an interaction between a dietary supplement and an antiretroviral were selected for inclusion. Twenty-eight pharmacokinetic studies and case-series/case reports were selected for inclusion. Calcium carbonate, ferrous fumarate, some forms of ginkgo, some forms of garlic, some forms of milk thistle, St. John's wort, vitamin C, zinc sulfate, and multivitamins were all found to significantly decrease the levels of selected antiretrovirals and should be avoided in patients taking these antiretrovirals. Cat's claw and evening primrose oil were found to significantly increase the levels of antiretrovirals and patients should be monitored for adverse effects while taking these dietary supplements with antiretrovirals. This systematic review shows the importance of screening all human immunodeficiency virus patients for dietary supplement use to prevent treatment failure or adverse effects related to an interaction.

Terapia nutricional em pacientes portadores do HIV em uso de TARV frente ao desenvolvimento de distúrbios metabólicos induzidos pela medicação / Nutrition therapy in HIV-infected patients against antiretroviral therapy-induced metabolic disorders

Embora a incidência de casos de pacientes portadores do vírus HIV ainda esteja aumentando, através da terapia antirretroviral (TARV) é possível melhorar a qualidade de vida e diminuir os agravos provocados pela patologia. No entanto, com a TARV observam-se efeitos colaterais importantes relativos ao metabolismo: resistência à insulina/intolerância à glicose, hipertensão arterial, lipodistrofia e dislipidemia. O objetivo do presente estudo foi revisar a literatura em busca de um maior entendimento acerca do efeito da terapia nutricional associada ou não às alterações nos hábitos de vida em pacientes portadores do HIV que fazem uso de TARV frente ao desenvolvimento de distúrbios metabólicos induzidos pela medicação. Foram revisados 11 estudos que preenchiam os critérios de inclusão, sendo que sete estudos demonstraram que a terapia nutricional apresenta impacto em alterações metabólicas, portanto uma adequada orientação nutricional deve ser parte integrante do tratamento de pacientes HIV positivos em terapia antirretroviral.

Although the incidence of cases of patients with HIV has increased, it is possible to improve the quality of life and reduce the complications caused by the disease through highly active antiretroviral therapy (HAART). However, HAART presents important side effects related to metabolic alterations: insulin resistance/glucose intolerance, hypertension, dyslipidemia, and lipodystrophy. The aim of the present study was to review the literature, searching for a better understanding of the effect of nutrition therapy associated or not with the alterations in lifestyle in HIV patients who use HAART, given the development of metabolic disorders induced by medication. We reviewed 11 studies that met the inclusion criteria, and seven studies showed that the nutrition therapy has impact on metabolic alterations; therefore a proper nutritional guidance should be an integral part of the treatment of HIV-positive patients on antiretroviral therapy.

A two-week regimen of high-dose integrase inhibitors does not cause nephrotoxicity in mice.

BACKGROUND: The integrase inhibitors, raltegravir and dolutegravir, are nucleoside reverse transcriptase inhibitor-sparing agents which may be used as part of first-line antiretroviral therapy for HIV. These drugs inhibit creatinine secretion through organic cation transporters, thus elevating serum creatinine without affecting glomerular filtration. We sought to determine whether subtle signs of nephrotoxicity could be observed in mice administered a two-week regimen of high-dose integrase inhibitors. METHODS: C57BL/6 mice were fed standard water (CTRL, n = 6), raltegravir-containing water (40 mg/kg/day, n = 6), or dolutegravir-containing water (2.7 mg/kg/day, n = 6) for two weeks and sacrificed. Endpoints were assessed including urine microalbumin, kidney injury molecule-1 renal tissue gene expression, renal histopathology, serum creatinine, and blood urea nitrogen. RESULTS: The results are NOT consistent with a direct nephrotoxic effect of the integrase inhibitors in mice. Serum creatinine was significantly elevated in raltegravir and dolutegravir mice (p < 0.05) compared to control (raltegravir = 0.25 mg/dl, dolutegravir = 0.30 mg/dl versus CTRL = 0.17 mg/dl). Blood urea nitrogen, cystatin C, and urine microalbumin were unchanged. Kidney injury molecule-1 tissue expression in raltegravir and dolutegravir groups was nonsignificantly elevated compared to control (1.2-fold compared to control). Renal histopathology by periodic acid-Schiff staining failed to reveal glomerular or tubular renal injury in any group. CONCLUSION: These studies are consistent with integrase inhibitors competitively inhibiting creatinine secretion. While no evidence of direct nephrotoxicity was observed after two weeks of high-dose drug administration, additional studies may be performed to understand whether these drugs lead to chronic nephropathy.

Plasma Micronutrient Concentrations Are Altered by Antiretroviral Therapy and Lipid-Based Nutrient Supplements in Lactating HIV-Infected Malawian Women.

BACKGROUND: Little is known about the influence of antiretroviral therapy with or without micronutrient supplementation on the micronutrient concentrations of HIV-infected lactating women in resource-constrained settings. OBJECTIVE: We examined associations of highly active antiretroviral therapy (HAART) and lipid-based nutrient supplements (LNS) with concentrations of selected micronutrients in HIV-infected Malawian women at 24 wk postpartum. METHODS: Plasma micronutrient concentrations were measured in a subsample (n = 690) of Breastfeeding, Antiretrovirals, and Nutrition (BAN) study participants who were randomly assigned at delivery to receive HAART, LNS, HAART+LNS, or no HAART/no LNS (control). HAART consisted of protease inhibitor-based triple therapy. LNS (140 g/d) met energy and micronutrient requirements of lactation. Multivariable linear regression tested the association of HAART and LNS, plus their interaction, with micronutrient concentrations, controlling for season, baseline viral load, and baseline CD4 count. RESULTS: We found significant HAART by LNS interactions for folate (P = 0.051), vitamin B-12 (P < 0.001), and transferrin receptors (TfRs) (P = 0.085). HAART was associated with lower folate (with LNS: -27%, P < 0.001; without LNS: -12%, P = 0.040) and higher TfR concentrations (with LNS: +14%, P = 0.004; without LNS: +28%, P < 0.001), indicating iron deficiency. LNS increased folate (with HAART: +17%, P = 0.037; without HAART: +39%, P < 0.001) and decreased TfR concentrations (with HAART only: -12%, P = 0.023). HAART was associated with lower vitamin B-12 concentrations only when LNS was present (-18%, P = 0.001), whereas LNS increased vitamin B-12 only when no HAART was present (+27%, P < 0.001). HAART, but not LNS, was associated with higher retinol-binding protein (RBP; +10%, P = 0.007). We detected no association of HAART or LNS with selenium, ferritin, or hemoglobin. CONCLUSION: The association of HAART with lower folate, iron deficiency, and higher RBP plus the attenuation of LNS effects on folate and vitamin B-12 when combined with HAART has implications for the health of lactating HIV-infected women taking HAART in prevention of mother-to-child transmission programs. This trial was registered at clinicaltrials.gov as NCT00164736.

Assessment of quality of life in a cohort of newly diagnosed patients on HAART regimen, in resource restricted tribal region of chhattisgarh, India: a prospective study.

BACKGROUND: Highly active antiretroviral therapy regimens have resulted in the systemic/clinical healing for human immune deficiency virus-infected patients but the consequence of antiretroviral therapy on the whole quality of life has become a major concern. The current study correlates the relationship of quality of life with successful highly active antiretroviral therapy. AIM: To determine the health-related quality of life in human immune deficiency virus-infected patients on highly active anti-retroviral therapy regimen in tribal region of Chhattisgarh. DESIGN: An open label prospective study. MATERIALS AND METHODS: Health-related quality of life was assessed using a standardized questionnaire, the Medical Outcomes Survey Short Form 36. Physical health summary scores and mental health summary scores were compared of pre-Highly Active Anti-Retroviral Therapy (at baseline) and post 12 months of therapy. RESULTS: The increase in CD4 cell counts was extremely significant (P < 0.0001). The Physical Composite Summary (P value = 0.0003) improved significantly, whereas the Mental Composite Summary (with a baseline value of 40.7), post 12 months, was calculated as 42.8 (P value = 0.2371) and was statistically not significant. CONCLUSION: Efficacy measurement is the key ingredient of highly active anti-retroviral therapy, which must also include assessment of health-related quality of life to maximize the holistic approach towards disease.

Higher vitamin D levels in HIV-infected out-patients on treatment with boosted protease inhibitor monotherapy.

OBJECTIVES: We investigated the vitamin D status of patients receiving frequently used types of combination antiretroviral therapy (cART), including boosted protease inhibitor (PI) monotherapy. METHODS: For this cross-sectional study, out of 450 HIV-infected patients followed in the Hospital Severo Ochoa (Madrid, Spain), we selected 352 patients for whom vitamin D levels had been measured (January 2009 to December 2010). We collected the following data: demographics, cART duration, main cART regimen, viral load (VL), CD4 cell count, and concentrations of 25(OH)-vitamin D [25(OH)-D], parathyroid hormone (PTH), albumin and calcium. Vitamin D status cut-off points were: (1) deficiency (vitDd): 25(OH)-D < 20 ng/mL; (2) insufficiency (vitDi): 25(OH)-D from 20 to 29.99 ng/mL; and (3) optimal (vitDo): 25(OH)-D ≥ 30 ng/mL. RESULTS: The percentages of patients with vitDd, vitDi and vitDo were 44, 27.6 and 28.5%, respectively. Twenty-nine out of 30 (96.7%) Black patients had vitDd or vitDi, vs. 71.6% in the global sample (P < 0.001). Former injecting drug users (IDUs) had a higher prevalence of vitDo (P < 0.001) than patients in other transmission categories. Among patients with vitDd, vitDi and vitDo, the proportions of patients with a VL ≤ 50 HIV-1 RNA copies/mL were 77.4, 68 and 91%, respectively (P < 0.0001). Of the cART regimens, only boosted PI monotherapy was associated with significant differences in vitamin D levels (P = 0.039). Multivariate logistic regression analysis showed an increased risk of vitDi or vitDd associated with the following variables: Black vs. Caucasian ethnicity [odds ratio (OR) 10.6; 95% confidence interval (CI) 1.2-94; P = 0.033]; heterosexual (OR 2.37; 95% CI 1.13-4.93; P = 0.022) or men who have sex with men (MSM) (OR 3.25; 95% CI 1.25-8.50; P = 0.016) transmission category vs. former IDU; and VL > 50 copies/mL (OR 2.56; 95% CI 1.10-7.25; P = 0.040). A lower risk of vitamin D insufficiency or deficiency was found in patients on boosted PI monotherapy vs. no treatment (OR 0.08; 95% CI 0.01-0.6; P = 0.018). CONCLUSIONS: Our data show an increased risk of vitamin D deficiency or insufficiency in patients with detectable VL and a Black ethnic background. Among cART regimens, boosted PI monotherapy was associated with a lower risk of vitamin D deficiency or insufficiency. The more favourable vitamin D status in former IDUs was probably attributable to a higher frequency of outdoor jobs in this group of patients.

Nutritional assessment and lipid profile in HIV-infected children and adolescents treated with highly active antiretroviral therapy / Avaliação nutricional e do perfil lipídico em crianças e adolescentes infectadas pelo HIV tratadas com terapia antirretroviral de alta potência

INTRODUCTION: HIV-infected children and adolescents treated with highly active antiretroviral therapy (HAART) regimens that include a protease inhibitor (PI) can show significant improvements in clinical outcomes, nutritional status and quality of life. The study aimed to report nutritional and metabolic alterations for pediatric patients continuously exposed to HAART and for healthy controls for up to 1 year. METHODS: Clinical, anthropometric, lipid profile and food intake data were collected prospectively over approximately 12-months for each patient. RESULTS: Fifty-one individuals were studied, of these, 16 were healthy. After 12 months follow-up, HIV-positive individuals remained below the healthy control group parameters. No change was observed concerning food intake. Triglyceride serum levels were higher in patients using protease inhibitor at the onset of the study [PI groups: 114 (43 - 336), and 136 (63 - 271) versus control group: 54.5 (20 - 162); p = 0.003], but after twelve months follow-up, only the group using protease inhibitor for up to two months presented higher values [140 (73 - 273) versus 67.5 (33 - 117); p = 0.004]. HDL-cholesterol was lower in HIV-positive individuals [HIV-positive groups: 36 (27 - 58) and 36 (23 - 43); control 49.5 (34 - 69); p = 0.004]. CONCLUSIONS: HIV-infected children and adolescents treated with highly active antiretroviral therapy showed compromised nutritional parameters compared to a paired healthy control group. Individuals using protease inhibitor presented worse triglyceride serum levels compared to their healthy counterparts.

INTRODUÇÃO: Crianças e adolescentes infectadas pelo HIV e tratadas com terapia antirretroviral de alta potência (TAAP), que inclui inibidor de protease (IP) podem apresentar significante melhora clínica no estado nutricional e na qualidade de vida. O objetivo é relatar as alterações nutricionais e metabólicas em pacientes pediátricos expostos a TAAP e controles saudáveis durante 1 ano. MÉTODOS: O perfil clínico, antropométrico e lipídico, bem como dados da ingestão alimentar foram coletados prospectivamente durante aproximadamente 12 meses. RESULTADOS: Cinquenta e um indivíduos foram estudados. Dezesseis eram saudáveis. Após 12 meses de acompanhamento, indivíduos HIV-positivo permaneceram abaixo dos parâmetros do grupo controle saudável. Nenhuma mudança foi observada em relação à ingestão alimentar. Níveis séricos de triglicerídeos foram maiores em pacientes usando inibidor de protease no começo do estudo [IP grupo: 114 (43 - 336), e 136 (63 - 271) versus grupo controle: 54.5 (20 - 162); p = 0.003], porém após doze meses de acompanhamento, apenas o grupo que recebeu inibidor de protease por não mais do que dois meses apresentou maiores valores [140 (73 - 273) versus 67.5 (33 - 117); p = 0.004]. HDL-colesterol foi menor nos indivíduos HIV-positivos [grupo HIV-positivo: 36 (27 - 58) e 36 (23 - 43); controle 49.5 (34 - 69); p=0.004]. CONCLUSÕES: Crianças e adolescentes infectadas pelo HIV e tratadas com terapia antirretroviral de alta potência tiveram seus parâmetros nutricionais comprometidos quando comparados com o pareado grupo controle. Indivíduos usando inibidor de protease apresentaram piores níveis séricos de triglicerídeos quando comparados com os saudáveis.

Frequent Genetic Defects in the HIV-1 5' LTR/gag Gene in Hemophiliacs Treated with Korean Red Ginseng: Decreased Detection of Genetic Defects by Highly Active Antiretroviral Therapy.

We investigated whether Korean red ginseng (KRG) and highly active antiretroviral therapy (HAART) affect the frequency of gross deletion in 5'LTR/gag in 20 hemophiliacs. This study is a prospective study in 20 hemophiliacs who were infected with Korean subclade B of HIV-1 from two cash-paid plasma donors in 1990. Over a 13-year period, we obtained 436 amplicons of 5'LTR/gag genes by nested polymerase chain reaction using 147 peripheral blood mononuclear cells. Of the 436 amplicons, 92 (21.1%) showed gross deletion in 5'LTR/gag. Despite of a 2.3-fold higher monthly dose of KRG intake, the frequency of gross deletion in 5'LTR/gag (16.4%) was significantly decreased during HAART compared with 28.1% prior to HAART (p<0.01). Gross deletion in 5'LTR/gag was 10% more detected on KRG-therapy than prior to KRG-therapy (p<0.05). In addition, we also obtained 28 amplicons containing premature stop codon or isoleucine at initiation codon of 254 amplicons sequenced on KRG intake (7.5%) or HAART (13.6%) compared with 0% before KRG intake. These findings indicate that high frequency of gross deletion in 5'LTR/gag and genetic defects prior to HAART are significantly associated with KRG intake and the detection of gross deletion in 5'LTR/gag is decreased by HAART.

New options in the treatment of lipid disorders in HIV-infected patients.

Since the introduction of HAART, there was a remarkably change in the natural history of HIV disease, leading to a notable extension of life expectancy, although prolonged metabolic imbalances could significantly act on the longterm prognosis and outcome of HIV-infected persons, and there is an increasing concern about the cardiovascular risk in this population. Current recommendations suggest that HIV-infected perons undergo evaluation and treatment on the basis of the Third National Cholesterol Education Program Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (NCEP ATP III) guidelines for dyslipidemia, with particular attention to potential drug interactions with antiretroviral agents and maintenance of virologic control of HIV infection. While a hypolipidemic diet and physical activity may certainly improve dyslipidemia, pharmacological treatment becomes indispensable when serum lipid are excessively high for a long time or the patient has a high cardiovascular risk, since the suspension or change of an effective antiretroviral therapy is not recommended. Moreover, the choice of a hypolipidemic drug is often a reason of concern, since expected drug-drug interactions (especially with antiretroviral agents), toxicity, intolerance, effects on concurrent HIV-related disease and decrease patient adherence to multiple pharmacological regimens must be carefully evaluated. Often the lipid goals of patients in this group are not achieved by the therapy recommended in the current lipid guidelines and in this article we describe other possibilities to treat lipid disorders in HIV-infected persons, like rosuvastatin, ezetimibe and fish oil.

A Case of Atypical Progressive Outer Retinal Necrosis after Highly Active Antiretroviral Therapy

This is a report of an atypical case of progressive outer retinal necrosis (PORN) and the effect of highly active antiretroviral therapy (HAART) on the clinical course of viral retinitis in an acquired immunodeficiency syndrome (AIDS) patient. A 22-year-old male patient infected with human immunodeficiency virus (HIV) presented with unilaterally reduced visual acuity and a dense cataract. After cataract extraction, retinal lesions involving the peripheral and macular areas were found with perivascular sparing and the mud-cracked, characteristic appearance of PORN. He was diagnosed as having PORN based on clinical features and was given combined antiviral treatment. With concurrent HAART, the retinal lesions regressed, with the regression being accelerated by further treatment with intravenous acyclovir and ganciclovir. This case suggests that HAART may change the clinical course of PORN in AIDS patients by improving host immunity. PORN should be included in the differential diagnosis of acute unilateral cataract in AIDS patients.