Combination Therapy With Hydroxyurea Versus Without Hydroxyurea As First Line Treatment Options for Antiretroviral-Naive Patients

Abstract

Purpose: This study analyzed whether combination therapy with hydroxyurea (HU) could be considered as first line treatment for antiretroviral-naive patients. Method: The prospective open-label study was carried out from March 1996 to May 2000. The antiretroviral treatments were treatment 1—didanosine 400 mg/day, stavudine 60/80 mg/day, and HU 500 mg/day; treatment 2—two nucleosides plus a protease inhibitor; treatment 3—didanosine, indinavir, and HU (500-1,000 mg/day). The viral load (VL) and CD4 determinations were performed at weeks 24, 48, 72, and 96. Results: The sample comprised 284 patients. The distribution of patients by levels of VL and CD4 were similar in the three treatment groups. At week 24, patients receiving T1 and T3 achieved higher percentages of undetectable VL (89% and 81%, respectively) with no significant differences (p = .127) between them. The T2 group showed a lower proportion (58%) of undetectable VL, which was significantly lower than T1 (p < .0001) and T3 (p < .0007). At week 48, the results were similar to week 24. At week 96, nearly all patients had undetectable viral load (UVL). The analysis of adverse effects showed that the T2 group at week 48 had a greater proportion of adverse effects that was significantly different from T1 (p = .0026); T3 had intermediate values with no significant difference from T2 (p = .45) and from T1 (p = .048). At week 48, T1 showed higher adherence level with significant difference from the other two treatments. Conclusion: Patients were followed for some 96 weeks and, with an intention-to-treat analysis, were found to do better virologically and Clinically in treatment groups containing HU. The combination of antiretroviral drugs with HU may be an excellent option as initial therapy because of its strong antiretroviral action, its lower rate of adverse effect, and the smaller cost as compared to other regimens.     

Hydroxyurea-induced genital ulcers and erosions: Two case reports

Hydroxyurea is a chemotherapeutic agent used for myeloproliferative disorders and sickle cell anemia that is well known to cause painful mucocutaneous ulcers, typically involving the legs or mouth. However, genital ulcerations due to hydroxyurea therapy are a rare, and likely underrecognized, adverse effect with only a few cases reported in the literature to date. Ulcers of the lower legs caused by hydroxyurea are associated with a diagnostic delay, and this is likely exacerbated in cases of genital ulceration due to a lack of awareness. Herein we present two cases of painful genital ulceration in patients on hydroxyurea therapy. In the first Case, an 87 year-old male with polycythemia vera developed an ulcer on the scrotum, which was assessed initially through virtual visits during the COVID-19 pandemic, and was refractory to topical and oral antibiotic treatments. The second case was a 79 year-old male with essential thrombocythemia and a history of persistent leg ulcers who developed erosions of the glans penis. Both patients experienced complete resolution within weeks of discontinuing hydroxyurea therapy. In conclusion, genital ulcers and erosions induced by hydroxyrea may be underrecognized in clinical practice, but if identified, withdrawal of hydroxyurea leads to quick resolution of these lesions and the associated pain.     

Severe excessive daytime sleepiness induced by hydroxyurea

Excessive daytime sleepiness (EDS) has been reported with many drugs, either as an extension of a hypnotic effect (e.g. central nervous system depressants) or as an idiosyncratic response of the patient. Here, we report unexpected and severe subjective and objective EDS induced by hydroxyurea therapy, with a favorable outcome after withdrawal. Clinical history, sleep log, polysomnography, and multiple sleep latency tests confirming the absence of other EDS causes are presented.     

Nitric oxide and cyclic GMP levels in sickle cell patients receiving hydroxyurea

Recent studies suggest that nitric oxide (NO) may partly be responsible for the beneficial effect of hydroxyurea (HU) in sickle cell disease (SCD) patients. NO stimulates cyclic guanosine monophosphate (cGMP) production, which mediates vasodilatation. We investigated the association between NO, cGMP and fetal haemoglobin (HbF) levels after HU administration. Our data showed that chronic HU significantly increased NO, cGMP, and HbF levels in SCD. Recently it was shown that HbF production was stimulated by cGMP-dependent protein kinase. Our results suggest that NO stimulates cGMP production, which then activates a protein kinase and increases the production of HbF.     

Chronic Leg Ulceration Associated with Polycythemia Vera Responding to Ruxolitinib (Jakafi®)

We present the case of a 63-year-old white male with bilateral chronic leg ulcers due to polycythemia vera and hydroxyurea therapy who demonstrated dramatic healing of his wounds in response to ruxolitinib (Jakafi^®, Novartis), a novel Janus kinase-1 and -2 inhibitor. This patient's wound had previously been refractory to multiple surgical interventions and immunosuppression. After the initiation of ruxolitinib, the patient underwent successful split-thickness skin grafting, with resultant healing of his wounds. He was stable without prednisone and other immunosuppressant therapy and had healed at 6 months. Ruxolitinib therapy could represent a novel option for patients who develop persistent inflammatory wounds in the setting of polycythemia vera and hydroxyurea therapy.     

The Effect and Side Effect of Hydroxyurea Therapy on Patients With β-Thalassemia: A Systematic Review to December 2012

Hydroxyurea (HU) is being used for patients with transfusion-dependent β-thalassemia major (β-TM) as well as non transfusion-dependent β-TM. As controversy exists regarding efficacy and safety of HU, we searched the published literature on efficacy, effectiveness and toxicity of HU in patients with β-TM. The research sources we used were: Medline, SID, PubMed, Scopus, Request, Web of Knowledge, Springer, Ovid, Cochrane searched up to October 2012. Using search terms sensitive to studies of clinical trials combined with searches on terms related to thalassemia and HU. We selected studies on randomized trials, quasi experimental trials (before and after design), case reports (with 1–5 cases), side effect studies in patients with β-TM, studies related to the mechanism of action and toxicity when used in patients with other hemoglobinopathies. We researched studies in English and Persian. Eligible articles were reviewed by two independent reviewers. Patient’s characteristics, duration of trial, outcome and side effects were extracted. The main outcomes were synthesized under a random-effects model. Heterogeneity was assessed using the Q statistic, Tau² and I². Subgroup analyses were performed and the statistics data (STATA) software used. More than 500 articles were reviewed. No randomized clinical trial was found. Seventeen trials with before and after designs were found, 16 case reports (1–5 cases), 19 articles for mechanism of action and 16 studies for side effects were published from 1969 to October 2012. Hemoglobin levels after treatment showed modest but significant increase in non transfusion-dependent β-TM (p?p?相似文献