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HIV Medicine Jan 2005To evaluate the long-term safety and efficacy of the combination of hydroxychloroquine, hydroxyurea and didanosine. (Clinical Trial)
Clinical Trial
OBJECTIVES
To evaluate the long-term safety and efficacy of the combination of hydroxychloroquine, hydroxyurea and didanosine.
METHODS
We recruited antiretroviral-naive patients with viral loads less than 100 000 HIV-1 RNA copies/mL and CD4 counts greater than 150 cells/microL. All patients received hydroxychloroquine (200 mg), hydroxyurea (500 mg) and didanosine (125-200 mg) twice daily. Clinical and laboratory safety assessments and measurements of viral load and CD4 count were made at regular intervals, and genotypic resistance testing was performed on samples with detectable viral load at 48, 96 and 144 weeks.
RESULTS
Fourteen of the 17 patients who commenced therapy remained on treatment at 144 weeks. Treatment was well tolerated but caused neutropenia, usually mild and transient, in 12 patients (71%). Mean viral load was reduced by 1.6 log(10) copies/mL below baseline (P<0.001), eight patients (47%) had undetectable viral load (<400 copies/mL), and two patients (12%) had detectable viral load but no detectable resistance mutations at week 144. Four patients (24%) had detectable viral load together with major resistance mutations (three with both 74 V and 184 V, and one with both 62 V and 65R) at week 144, but still had viral load suppression below baseline. Mean CD4 count was increased by 106 cells/microL above baseline (P=0.07) at week 144.
CONCLUSIONS
This novel and well-tolerated combination controls viral replication during long-term follow up, with development of few resistance mutations. With careful monitoring it may be a useful strategy for delaying highly active antiretroviral therapy (HAART) and associated toxicity in selected patients with low initial viral loads.
Topics: Adult; Anti-HIV Agents; CD4 Lymphocyte Count; Didanosine; Drug Resistance, Viral; Drug Therapy, Combination; Female; HIV Infections; HIV-1; Humans; Hydroxychloroquine; Hydroxyurea; Male; Mutation; Treatment Outcome; Viral Load
PubMed: 15670247
DOI: 10.1111/j.1468-1293.2005.00259.x -
MedGenMed : Medscape General Medicine Oct 2007To study the effectiveness and tolerance of an antiretroviral therapy (ART) regimen composed of the antiretroviral agents (ARVs) stavudine (d4T) plus didanosine (ddI)... (Clinical Trial)
Clinical Trial
OBJECTIVE
To study the effectiveness and tolerance of an antiretroviral therapy (ART) regimen composed of the antiretroviral agents (ARVs) stavudine (d4T) plus didanosine (ddI) plus efavirenz (EFV) in patients with advanced HIV infection in Senegal.
DESIGN AND METHODS
This was an open-label, single-arm, 18-month trial in treatment-naive patients. The primary virologic end point was the percentage of patients with plasma HIV RNA < 500 copies/mL at months 6 (M6), 12 (M12) and 18 (M18). The primary analysis was done as intent-to-treat.
RESULTS
The staging of HIV disease, performed using the definitions of the US Centers for Disease Control and Prevention (CDC), was CDC stage B or C for all 40 recruited patients. At baseline, the mean CD4+ cell count was 133 +/- 92/mcL (+/- standard deviation [SD]; range 1-346), and 23% of patients had CD4+ cell counts below 50/mcL. The mean baseline plasma HIV RNA level was 5.5 +/- 0.4 log(10) copies/mL (+/- SD; range 4.6-5.9). The proportion of patients with plasma HIV-1 RNA below 500 copies/mL fell during the study from 73% (95% CI [56; 85]) at M6 to 56% (95% CI [41; 73]) at M12 and 43% (95% CI [27; 59]) at M18. Plasma HIV-RNA was below 50 copies/mL in 50% of study subjects (95% CI [31; 66]) at M6, 43% (95% CI [27; 59]) at M12, and 33% (95% CI [19; 49]) at M18. The mean increase in the CD4+ cell count was 105 +/- 125/mcL (n = 38) at M3 and 186 +/- 122/mcL (n = 21) at M18. Eight patients died, including 6 because of infectious complications. The last viral load (VL) value before death was < 500 copies/mL in all these patients except 1 nonadherent patient. Fifteen patients (37.5%) had peripheral neuropathy that was severe enough in 5 patients (12.5%) to require ddI and d4T discontinuation.
CONCLUSION
Virologic efficacy combination therapy with d4T, ddI, and EFV was measured by the percentage of patients with plasma HIV RNA values below 500 copies/mL and 50 copies/mL; for both parameters, virologic efficacy decreased during the study period. This is explained by the high mortality rate (20%) and treatment modifications due to adverse events (13%). These data strengthen the recently revised World Health Organization (WHO) guidelines advocating initiation of highly active antiretroviral therapy (HAART) before profound CD4 lymphocyte depletion occurs and avoiding HAART regimens containing d4T and ddI because of treatment-limiting side effects.
Topics: Administration, Oral; Adult; Alkynes; Antiretroviral Therapy, Highly Active; Benzoxazines; Cyclopropanes; Developing Countries; Didanosine; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; HIV Infections; Humans; Male; Maximum Tolerated Dose; Patient Compliance; RNA, Viral; Risk Assessment; Senegal; Severity of Illness Index; Stavudine; Survival Rate; Treatment Outcome; Viral Load
PubMed: 18311357
DOI: No ID Found -
Annals of Medicine and Surgery (2012) Dec 2023The risk of falls in people living with HIV (PLHIVs) on antiretroviral therapy (ART) has received little attention in the literature. The aim of the meta-analysis is to... (Review)
Review
OBJECTIVE
The risk of falls in people living with HIV (PLHIVs) on antiretroviral therapy (ART) has received little attention in the literature. The aim of the meta-analysis is to quantify the association between fall risk and various categories of drugs used in ART.
MATERIAL AND METHODS
PubMed, Google Scholar, Embase, and the Cochrane Central Register of Controlled Trials were systematically searched from inception to January 2023. Any observational study or controlled trial that reported on the relationship of at least one antiretroviral drug with falls in PLHIVs was included. Data on the frequency of single fallers, multiple fallers (≥2 falls), and non-fallers were extracted and studied for each drug and drug category. The pooled results were reported as an odds ratio (OR) with a 95% confidence interval (CI).
RESULTS
A total of five observational studies (51 675 participants) were included out of 414 articles obtained through a literature review. Stavudine use was found to be associated with an increased risk of single falls in PLHIVs (OR: 1.69, 95% CI: 1.08-2.66, =0.02). However, efavirenz (OR: 0.82, 95% CI=0.76-0.89, <0.001) and zidovudine (OR: 0.82, 95% CI=0.77-0.92, <0.001) were found protective against the single falls. Didanosine had no significant association with fall risk (OR: 1.23, 95% CI: 0.78-1.93, =0.37). Likewise, protease inhibitors, integrase inhibitors, nucleoside reverse transcriptase inhibitors, and non-nucleoside reverse transcriptase inhibitors were discovered to have no significant association with fall risk.
CONCLUSION
Most drug categories of ART have no significant association with the risk of falls in PLHIVs. However, certain drugs, such as didanosine and stavudine, which have the inherent effect of causing balance deficits and neuropathy, should be used cautiously.
PubMed: 38098550
DOI: 10.1097/MS9.0000000000001411 -
Journal of the International AIDS... Oct 2007To study the effectiveness and tolerance of an antiretroviral therapy (ART) regimen composed of the antiretroviral agents (ARVs) stavudine (d4T) plus didanosine (ddI)...
OBJECTIVE
To study the effectiveness and tolerance of an antiretroviral therapy (ART) regimen composed of the antiretroviral agents (ARVs) stavudine (d4T) plus didanosine (ddI) plus efavirenz (EFV) in patients with advanced HIV infection in Senegal.
DESIGN AND METHODS
This was an open-label, single-arm, 18-month trial in treatment-naive patients. The primary virologic end point was the percentage of patients with plasma HIV RNA < 500 copies/mL at months 6 (M6), 12 (M12) and 18 (M18). The primary analysis was done as intent-to-treat.
RESULTS
The staging of HIV disease, performed using the definitions of the US Centers for Disease Control and Prevention (CDC), was CDC stage B or C for all 40 recruited patients. At baseline, the mean CD4+ cell count was 133 +/- 92/mcL (+/- standard deviation [SD]; range 1-346), and 23% of patients had CD4+ cell counts below 50/mcL. The mean baseline plasma HIV RNA level was 5.5 +/- 0.4 log10 copies/mL (+/- SD; range 4.6-5.9). The proportion of patients with plasma HIV-1 RNA below 500 copies/mL fell during the study from 73% (95% CI [56; 85]) at M6 to 56% (95% CI [41; 73]) at M12 and 43% (95% CI [27; 59]) at M18. Plasma HIV-RNA was below 50 copies/mL in 50% of study subjects (95% CI [31; 66]) at M6, 43% (95% CI [27; 59]) at M12, and 33% (95% CI [19; 49]) at M18.The mean increase in the CD4+ cell count was 105 +/- 125/mcL (n = 38) at M3 and 186 +/- 122/mcL (n = 21) at M18. Eight patients died, including 6 because of infectious complications. The last viral load (VL) value before death was < 500 copies/mL in all these patients except 1 nonadherent patient. Fifteen patients (37.5%) had peripheral neuropathy that was severe enough in 5 patients (12.5%) to require ddI and d4T discontinuation.
CONCLUSION
Virologic efficacy combination therapy with d4T, ddI, and EFV was measured by the percentage of patients with plasma HIV RNA values below 500 copies/mL and 50 copies/mL; for both parameters, virologic efficacy decreased during the study period. This is explained by the high mortality rate (20%) and treatment modifications due to adverse events (13%). These data strengthen the recently revised World Health Organization (WHO) guidelines advocating initiation of highly active antiretroviral therapy (HAART) before profound CD4 lymphocyte depletion occurs and avoiding HAART regimens containing d4T and ddI because of treatment-limiting side effects.
PubMed: 19825141
DOI: 10.1186/1758-2652-9-4-7 -
Journal of Vitreoretinal Diseases 2022This article describes a case of didanosine (DDI)-associated retinal toxicity in a patient with a heterozygous pathogenic variant in the CRB1 gene.
PURPOSE
This article describes a case of didanosine (DDI)-associated retinal toxicity in a patient with a heterozygous pathogenic variant in the CRB1 gene.
METHODS
Case report.
RESULTS
A middle-aged patient with HIV controlled on HAART therapy, and a remote 10-year year history of treatment with DDI and tenofivir, presented with external ophthalmoplegia and well-circumscribed, midperipheral patterns of bilateral pigmentary retinopathy and chorioretinal atrophy in both eyes. Genetic testing revealed a heterozygous pathogenic variant in the gene that encodes a protein (Crumbs homolog 1) involved in regulation of cell polarity and junctions and is localized adjacent to mitochondria in the ellipsoid and myoid area.
CONCLUSIONS
This case highlights a potential role for genetic susceptibility to retinal toxicity in DDI-associated retinal toxicity. Large, prospective pharmacogenomics studies may be informative to further elucidate the role of genetic risk factors in drug-induced retinal toxicity.
PubMed: 37007923
DOI: 10.1177/24741264211044599 -
European Review For Medical and... Feb 2020The current study was designed to investigate the effects of some nucleoside reverse transcriptase inhibitors (NRTIs) on HSV-1 infection.
OBJECTIVE
The current study was designed to investigate the effects of some nucleoside reverse transcriptase inhibitors (NRTIs) on HSV-1 infection.
MATERIALS AND METHODS
Initially, the SwissTargetPrediction server was used to predict the interactions between HSV-1 thymidine kinase and acyclovir, stavudine, zidovudine, didanosine, and entecavir. The effect of each component on Vero cell viability was assessed by the MTT assay. After treatment, the cell supernatants were collected, and HSV-1 replication was analyzed by quantitative real-time PCR.
RESULTS
The qPCR results revealed that viral titers were reduced 41, 40, 19, 44, and 31-fold in the presence of acyclovir, zidovudine, stavudine, didanosine, and entecavir, respectively.
CONCLUSIONS
Our findings indicate that NRTIs significantly reduce HSV-1 replication in cell culture.
Topics: Animals; Antiviral Agents; Chlorocebus aethiops; Dose-Response Relationship, Drug; Herpesvirus 1, Human; Reverse Transcriptase Inhibitors; Vero Cells; Virus Replication
PubMed: 32096195
DOI: 10.26355/eurrev_202002_20204 -
European Journal of Medical Research 2009Chronic HCV co-infection is present in up to one third of HIV-positive patients in Europe. In recent years, apart from the traditional transmission route of intravenous... (Review)
Review
Chronic HCV co-infection is present in up to one third of HIV-positive patients in Europe. In recent years, apart from the traditional transmission route of intravenous drug abuse, outbreaks of sexually transmitted acute HCV infections, mainly among HIV-positive men who have sex with men, have contributed to the overall disease burden. - Because the natural course of HCV infection is substantially accelerated in HIV-co-infection, end-stage liver disease has become the most frequent cause of non-AIDS related death in this population. Therefore every HIV/HCV co-infected patient should be evaluated for possible anti-HCV therapy with the goal of reaching a sustained virological response and thus cure of hepatitis C infection. The standard of care for the treatment of chronic HCV infection in HIV-infected remains a pegylated interferon in combination with weight-adapted ribavirin. - HAART should not be withheld from HCV co-infected patients due to concerns of drug related hepatotoxicity and in patients with reduced CD4-cell counts HAART should be started first. Under pegylated interferon and ribavirin combination therapy drug to drug interactions and cumulated toxicity between nucleoside analogues and anti-HCV therapy may be observed and concomitant didanosine use is contraindicated and zidovudine and stavudine should be avoided if possible. - The development of new drugs for the treatment of chronic hepatitis C represents a promising perspective also for HIV positive patients. However, these substances will probably reach clinical routine for HIV patients later than HCV monoinfected patients. Therefore at present waiting for new drugs is not an alternative to a modern pegylated interferon/ribavirin therapy.
Topics: Antiretroviral Therapy, Highly Active; Coinfection; Europe; HIV Infections; Hepatitis C, Chronic; Humans; Interferons; Ribavirin
PubMed: 20149983
DOI: 10.1186/2047-783x-14-12-507 -
Endocrinology, Diabetes & Metabolism... 2017An 11-year-old male with perinatally acquired human immune deficiency virus (HIV) infection on antiretroviral regimen, which included abacavir plus lamivudine (Epzicom),...
UNLABELLED
An 11-year-old male with perinatally acquired human immune deficiency virus (HIV) infection on antiretroviral regimen, which included abacavir plus lamivudine (Epzicom), didanosine, ritonavir and atazanavir presented with bilateral axillary striae, increased appetite, fatigue, facial swelling and acute weight gain. Two months prior to presentation, the patient had received a diagnostic and therapeutic intra-articular triamcinolone injection in the knee for pain relief and subsequently became progressively swollen in the face, developed striae bilaterally at the axillae, experienced increased appetite, fatigue and an 8 pound weight gain. During the endocrine workup, suspicion for adrenal insufficiency prompted 24-h urine collection for free cortisol, which was found to be undetectable (below LLQ of 1.0 µg/L). This prompted further evaluation of the hypothalamic-pituitary axis (HPA) by standard dose adrenocorticotropic hormone (ACTH) stimulation test. A 250 µg cosyntropin stimulation test was performed and confirmed HPA axis suppression. Baseline cortisol level was <1 µg/dL and stimulated cortisol level at 30 min was 3.8 µg/dL. The patient was diagnosed with iatrogenic Cushing syndrome and suppression of HPA axis secondary to the drug interaction between ritonavir (RTV) and intra-articular triamcinolone injection. Following endocrine evaluation and workup, the patient was admitted for planned orthopaedic procedure including elective left hamstring lengthening, distal femoral osteotomy and patellar tendon advancement. Taking into consideration the diagnosis of iatrogenic Cushing syndrome, at the start of the surgical procedure, 100 mg IV stress dose of hydrocortisone followed by 50 mg hydrocortisone every 8 h for 24 h was administered. Stress dosing was discontinued 24 h after the procedure. Throughout the hospitalization and upon discharge, the patient continued his ART. From initial presentation, patient has remained clinically stable throughout surgery and postoperative period.
LEARNING POINTS
Drug-drug interaction between ritonavir and triamcinolone can cause Cushing syndrome.Although triamcinolone has a half-life of 3 h, an intra-articular injection may be systematically absorbed for 3 weeks after injection, and adrenal suppression may last as long as 30 days.Co-administration of ritonavir and corticosteroids may result in an increase of plasma levels of corticosteroids levels, as they are both eliminated by CYP3A metabolism, and this interaction has the potential to prolong the half-life of triamcinolone several fold.No specific guidelines are available for the management of iatrogenic Cushing syndrome secondary to ritonavir and corticosteroids.One treatment option includes replacing ritonavir with a non-protease inhibitor-based regimen.Initiating hydrocortisone replacement therapy to prevent an adrenal crisis is also an alternate option.
PubMed: 29118985
DOI: 10.1530/EDM-17-0076 -
Applied Health Economics and Health... 2009Highly active antiretroviral therapy (HAART) provides dramatic health benefits for HIV-infected individuals in Africa, and widespread implementation of HAART is... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Highly active antiretroviral therapy (HAART) provides dramatic health benefits for HIV-infected individuals in Africa, and widespread implementation of HAART is proceeding rapidly. Little is known about the cost and cost effectiveness of HAART programmes.
OBJECTIVE
To determine the incremental cost effectiveness of a home-based HAART programme in rural Uganda.
METHODS
A computer-based, deterministic cost-effectiveness model was used to assess a broad range of economic inputs and health outcomes. From the societal perspective, the cost effectiveness of HAART and cotrimoxazole prophylaxis was compared with cotrimoxazole alone, and with the period before either intervention. Data for 24 months were derived from a trial of home-based HAART in 1045 patients in the Tororo District in eastern Uganda. Costs and outcomes were projected out to 15 years. All costs are in year 2004 values. The main outcome measures were HAART programme costs, health benefits accruing to HAART recipients, averted HIV infections in adults and children and the resulting effects on medical care costs. The first-line HAART regimen consisted of standard doses of stavudine, lamivudine, and either nevirapine or, for patients with active tuberculosis, efavirenz. Second-line therapy consisted of tenofovir, didanosine and lopinavir/ritonavir. For children, first-line HAART consisted of zidovudine, lamivudine and nevirapine syrup; second-line therapy was stavudine, didanosine and lopinavir/ritonavir.
RESULTS
The HAART programme, standardized for 1000 patients, cost an incremental $US1.39 million in its first 2 years. Compared with cotrimoxazole prophylaxis alone, the programme reduced mortality by 87%, and averted 6861 incremental disability-adjusted life-years (DALYs). Benefits were accrued from reduced mortality in HIV-infected adults (67.5% of all benefits), prevention of death in HIV-negative children (20.7%), averted HIV infections in adults (9.1%) and children (1.0%), and improved health status (1.7%). The net programme cost, including the medical cost implications of these health benefits, was $US4.10 million. The net cost per DALY averted was $US597 compared with cotrimoxazole alone. Many HIV interventions have a cost-effectiveness ratio in the range of $US1-150 per DALY averted.
CONCLUSIONS
This study suggests that a home-based HAART programme in rural Africa may be more cost effective than most previous estimates for facility-based HAART programmes, but remains less cost effective than many HIV prevention and care interventions, including cotrimoxazole prophylaxis.
Topics: Adult; Antiretroviral Therapy, Highly Active; Cost-Benefit Analysis; Female; HIV Infections; Home Care Services; Humans; Male; Quality-Adjusted Life Years; Uganda
PubMed: 19905037
DOI: 10.2165/11318740-000000000-00000 -
The American Journal of Medicine Apr 1991Although 3'-azido-3'-deoxythymidine (zidovudine, AZT) has demonstrated efficacy in the treatment of human immunodeficiency virus (HIV) infection, there are limitations... (Clinical Trial)
Clinical Trial Review
Although 3'-azido-3'-deoxythymidine (zidovudine, AZT) has demonstrated efficacy in the treatment of human immunodeficiency virus (HIV) infection, there are limitations associated with its use. Consequently, other agents, such as 2',3'-dideoxycytidine (ddC) and 2',3'-dideoxyinosine (ddI), are being assessed for the treatment of patients with HIV infection. However, the most effective therapy for HIV infection may be combination therapy with zidovudine and any of a number of other therapies. To obtain maximum efficacy, combination regimens should include agents that do not share cross-resistance, have different mechanisms of action, and have different dose-limiting toxicities; the relative merits of a concurrent dosage schedule (limits drug failure) and a consecutive dosage schedule (limits toxicity) must also be considered. In addition, the shift between administering a starting regimen and a rescue regimen should be based on time on therapy, disease breakthrough, or drug complication. Eventually, the shift may be precipitated by the in vitro resistance patterns of individual viruses, as is now the case with antibiotics for infection. Several trials are currently in progress to assess combination therapy with zidovudine and ddC; initial results indicate that the combination may allow for improved efficacy and decreased side effects, compared with treatment with either drug alone. Trials of combination therapy with ddI, interferon alfa, and acyclovir are also in progress. It is hoped that these initial studies will pave the way for rational drug sequencing in the treatment of patients with acquired immunodeficiency syndrome.
Topics: Acquired Immunodeficiency Syndrome; Clinical Trials as Topic; Didanosine; Drug Therapy, Combination; Humans; Interferon Type I; Recombinant Proteins; Zalcitabine; Zidovudine
PubMed: 1850192
DOI: 10.1016/0002-9343(91)90405-m