A case report: recurrent anemia related to long term acyclovir use in a pregnant HIV infected Ugandan.

This case report describes a pregnant patient with recent diagnosis of Human Immuno-Deficiency Virus (HIV) infection initiated on Anti-Retroviral Therapy (ART) in the second trimester, as well as high dose acyclovir high for large infected genital warts. She had no other HIV related opportunistic infections, and no prior anti tuberculosis treatment or preventive medication. Despite little response to acyclovir, patient was continuing on acyclovir for over 4 months. She subsequently developed recurrent anemia requiring frequent transfusion (14 units in total) over a 6-week period. On stopping acyclovir, the anemia subsided, a few weeks later she had a normal delivery, followed by surgical removal of the warts. At a follow-up 8 months later, she was well, with a healthy baby, and reported no other episodes of blood transfusion.

Acyclovir extravasation in a newborn: a case report.

OBJECTIVE: Extravasation of infused drugs is not a rare problem in medical practice. Acyclovir is a vesicant and an antiviral medication commonly used for young children. In the present study, we presented a neonate with soft tissue damage due to acyclovir extravasation. CASE REPORT: A female newborn (Iranian, Asian) with gestational age 37+2 weeks and breech presentation was born by Cesarean delivery from a mother with a recent history of Herpes simplex virus (HSV) infection (Yas Women's Hospital, Tehran, Iran). Intravenous administration of acyclovir was initiated through a peripheral catheter inserted on the dorsal side of the left hand. A few minutes after the second dose, the patient showed a diffused firm swelling, local discoloration, and induration in the dorsum of the hand. The peripheral catheter was removed immediately. Hyaluronidase was injected subcutaneously in five different regions around the catheterization site. Intermittent limb elevation and cold compression (for 10 minutes) were applied. Serial follow-ups and examinations were performed hourly to check limb inflammation, ischemia, and compartment syndrome. The limb swelling and discoloration significantly improved 4 hours after the second dose of hyaluronidase. CONCLUSION: Early diagnosis of acyclovir extravasation and immediate management could prevent severe complications in neonates. Further studies are needed to suggest a standard approach and treatment protocol for acyclovir extravasation.

Intralesional acyclovir versus intralesional Hepatitis-B vaccine in treatment of resistant plantar warts: a randomized controlled trial.

Treating plantar warts is still a challenging problem with a long list of diverse treatment options that none of them seems to be definitive. To evaluate the effectiveness of intralesional acyclovir versus intralesional Hepatitis-B vaccine (HBV) in treatment of multiple resistant plantar warts. Forty-eight patients with resistant plantar warts completed the study with no dropouts. They were randomized into 3 groups; group(A) receiving intralesional HBV, group (B) receiving intralesional acyclovir and group (C) receiving intralesional saline as a control group over 5 biweekly sessions or until wart clearance. Clinical outcome was assessed through sequential digital lesion photographing upon each visit. Treatment related adverse reactions were recorded. 43.8%, 37.5% & 18.7% of Groups A, B &C respectively showed a complete response. pain was obvious in 100% and 56.3% of cases receiving intralesional acyclovir and HBV respectively. Up to the 6 month follow up period, none of the complete responders in all groups returned with a recurrence. Both acyclovir and HBV showed comparable efficacy and seem to be promising options for treating plantar warts being safe, affordable, and theoretically safe in immunocompromised cases.

Antiviral medications for preventing cytomegalovirus disease in solid organ transplant recipients.

BACKGROUND: The risk of cytomegalovirus (CMV) infection in solid organ transplant recipients has resulted in the frequent use of prophylaxis to prevent the clinical syndrome associated with CMV infection. This is an update of a review first published in 2005 and updated in 2008 and 2013. OBJECTIVES: To determine the benefits and harms of antiviral medications to prevent CMV disease and all-cause death in solid organ transplant recipients. SEARCH METHODS: We contacted the information specialist and searched the Cochrane Kidney and Transplant Register of Studies up to 5 February 2024 using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs comparing antiviral medications with placebo or no treatment, comparing different antiviral medications or different regimens of the same antiviral medications for CMV prophylaxis in recipients of any solid organ transplant. Studies examining pre-emptive therapy for CMV infection are studied in a separate review and were excluded from this review. DATA COLLECTION AND ANALYSIS: Two authors independently assessed study eligibility, risk of bias and extracted data. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes and mean difference (MD) and 95% CI for continuous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: This 2024 update found four new studies, bringing the total number of included studies to 41 (5054 participants). The risk of bias was high or unclear across most studies, with a low risk of bias for sequence generation (12), allocation concealment (12), blinding (11) and selective outcome reporting (9) in fewer studies. There is high-certainty evidence that prophylaxis with aciclovir, ganciclovir or valaciclovir compared with placebo or no treatment is more effective in preventing CMV disease (19 studies: RR 0.42, 95% CI 0.34 to 0.52), all-cause death (17 studies: RR 0.63, 95% CI 0.43 to 0.92), and CMV infection (17 studies: RR 0.61, 95% CI 0.48 to 0.77). There is moderate-certainty evidence that prophylaxis probably reduces death from CMV disease (7 studies: RR 0.26, 95% CI 0.08 to 0.78). Prophylaxis reduces the risk of herpes simplex and herpes zoster disease, bacterial and protozoal infections but probably makes little to no difference to fungal infection, acute rejection or graft loss. No apparent differences in adverse events with aciclovir, ganciclovir or valaciclovir compared with placebo or no treatment were found. There is high certainty evidence that ganciclovir, when compared with aciclovir, is more effective in preventing CMV disease (7 studies: RR 0.37, 95% CI 0.23 to 0.60). There may be little to no difference in any outcome between valganciclovir and IV ganciclovir compared with oral ganciclovir (low certainty evidence). The efficacy and adverse effects of valganciclovir or ganciclovir were probably no different to valaciclovir in three studies (moderate certainty evidence). There is moderate certainty evidence that extended duration prophylaxis probably reduces the risk of CMV disease compared with three months of therapy (2 studies: RR 0.20, 95% CI 0.12 to 0.35), with probably little to no difference in rates of adverse events. Low certainty evidence suggests that 450 mg/day valganciclovir compared with 900 mg/day valganciclovir results in little to no difference in all-cause death, CMV infection, acute rejection, and graft loss (no information on adverse events). Maribavir may increase CMV infection compared with ganciclovir (1 study: RR 1.34, 95% CI: 1.10 to 1.65; moderate certainty evidence); however, little to no difference between the two treatments were found for CMV disease, all-cause death, acute rejection, and adverse events at six months (low certainty evidence). AUTHORS' CONCLUSIONS: Prophylaxis with antiviral medications reduces CMV disease and CMV-associated death, compared with placebo or no treatment, in solid organ transplant recipients. These data support the continued routine use of antiviral prophylaxis in CMV-positive recipients and CMV-negative recipients of CMV-positive organ transplants.

[Clinical features of acyclovir encephalopathy without acute kidney injury].

INTRODUCTION: Few reports have described acyclovir (ACV) encephalopathy without acute kidney injury (AKI). OBJECTIVE: This study clarified the clinical features of ACV encephalopathy without AKI compared to that with AKI. METHODS: Creatinine (Cre) levels were measured on admission. After admission, Cre was measured in a timely manner for the first seven hospital days. The minimum Cre level in these measurements was then determined. ACV encephalopathy was defined when two criteria were met: 1) neurological symptoms appeared after valacyclovir (VACV) administration, and 2) neurological symptoms improved after VACV discontinuation. AKI was defined when the Cre level on admission was >1.5 times higher than the minimum Cre level. The subjects were divided into AKI and non-AKI groups based on these findings. RESULTS: Eighteen patients had ACV encephalopathy (5 males, mean age 81.3±5.5 years old). All patients were prescribed VACV 3,000 mg/day. The minimum Cre was 1.93±1.76 mg/dL. AKI occurred in 10 (56.6%) patients. VACV was discontinued in all patients, and emergency hemodialysis treatment was administered in 10 (55.6%) patients. All patients recovered. Compared to the AKI group, the non-AKI group had a lower history of taking a Ca-blocker (33.3% vs 80.0%, p=0.092), a lower rate of emergency dialysis (16.9% vs 70.0%, p=0.059) and a longer time to clinical improvement (3.67±1.86 vs 2.20±0.63 days, p=0.073). CONCLUSION: ACV encephalopathy without AKI is characterized by a low rate of emergency dialysis, which may be linked to a prolonged duration of symptoms.

Valacyclovir or valganciclovir for cytomegalovirus prophylaxis: A randomized controlled trial in adult and pediatric kidney transplant recipients.

BACKGROUND: Valganciclovir (valG), a cytomegalovirus (CMV) prophylactic agent, has dose-limiting side effects. The tolerability and effectiveness of valacyclovir (valA) as CMV prophylaxis is unknown. METHODS: We conducted a randomized, open-label, single-center trial of valA versus valG for all posttransplant CMV prophylaxis in adult and pediatric kidney recipients. Participants were randomly assigned to receive valA or valG. Primary endpoints were the incidence of CMV viremia and side-effect related drug reduction with secondary assessment of incidence of EBV viremia. RESULTS: Of the 137 sequential kidney transplant recipients enrolled, 26 % were positive and negative for CMV antibody in donor and recipient respectively. The incidence of CMV viremia (4 of 71 [6 %]; 8 of 67 [12 %] P = 0.23), time to viremia (P = 0.16) and area under CMV viral load time curve (P = 0.19) were not significantly different. ValG participants were significantly more likely to require side-effect related dose reduction (15/71 [21 %] versus 1/66 [2 %] P = 0.0003). Leukopenia was the most common reason for valG dose reduction and granulocyte-colony stimulating factor was utilized for leukopenia recovery more frequently (25 % in valG vs 5 % in valA: P = 0.0007). Incidence of EBV viremia was not significantly different. CONCLUSIONS: ValA has significantly less dose-limiting side effects than valG. In our study population, a significant increase in CMV viremia was not observed, in adults and children after kidney transplant, compared to valG. TRIAL REGISTRATION NUMBER: NCT01329185.

Acyclovir dosing in herpes encephalitis: A scoping review.

BACKGROUND: Herpes encephalitis, a rare yet potentially fatal viral infection, is treated exclusively with acyclovir, the sole antiviral medication used for this condition. Acyclovir recommended dose is 10 mg/kg/dose intravenous every 8 hours; however, it is unclear what body weight should be utilized in obese patients. Using the ideal body weight may result in subtherapeutic ineffective concentrations, while utilizing the actual body weight might result in acyclovir induced adverse effects, either nephrotoxicity or neurotoxicity or both. OBJECTIVE: The objective of this scoping review is to explore existing evidence regarding acyclovir dosing for obese patients afflicted with herpes encephalitis. METHODS: MEDLINE, EMBASE, Scopus, Web of Science, and CINAHL databases were searched on 26 May 2023, with no language restrictions. Two independent reviewers utilized the Covidence software to carry out the screening and selection of the articles. A total of 22 articles were included in the current review. RESULTS: The prevalence of acyclovir-associated nephrotoxicity ranged from 13% to 21%, while the prevalence of neurotoxicity was not clearly defined. However, there is lack of evidence regarding what may arise from subtherapeutic concentrations. An approach has been suggested to help clinicians to give the most appropriate acyclovir dose to herpes encephalitis patients. Patients with normal kidney function could receive the normal doses based on actual weight if normal weight and based on adjusted body weight if obese. On the other hand, if the patients are experiencing augmented renal clearance, they could receive up to the maximum recommended doses. CONCLUSION: Overall, there is a lack of consistency on which body weight to use to calculate acyclovir dose in obese patients. So it is recommended that further studies compare the concentration of intravenous acyclovir between obese and nonobese patients and relating the resultant concentration with patient outcomes.

Acyclovir-Induced Nephrotoxicity in Adults with Viral Encephalitis.

OBJECTIVE: To determine the frequency of parenteral Acyclovir-induced Acute Kidney Injury (AKI) in patients with viral encephalitis. STUDY DESIGN: Descriptive study. Place and Duration of the Study: Department of Neurology, Liaquat National Hospital, Karachi, from January to December 2021. METHODOLOGY: A total of 89 suspected and proven cases of encephalitis receiving IV Acyclovir were collated. All had extensive medical histories and underwent CSF studies with +/- brain imaging. CSF routine and viral PCR were done. Acyclovir-induced AKI was defined as a rise in serum creatinine of >0.3 mg/dl in 48 h or by ≥1.5 times the baseline value, and its severity was staged into 1 (risk), 2 (injury), and 3 (failure) according to the KDIGO guidelines (Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group, 2012). Patients' variables, including age, gender, presenting features, comorbid conditions, and CSF findings, were divided into two groups, i.e. with and without AKI. RESULTS: This research included 89 patients with a mean age of 48 years. AKI occurred in 34 patients (38.2%). The frequency of AKI with Stage 1 was 24%, Stage 2 was 44%, and Stage 3 was 32%; approximately two-thirds of cases were in Stage 2 and 3 (p >0.05). Five patients (5.6%) from Stage 3, required dialysis. CONCLUSION: AKI is an important adverse effect of parenteral acyclovir, which necessitates its early identification and timely management. Renal function monitoring is essential for patients on Acyclovir treatment as they are at risk for AKI. KEY WORDS: Acyclovir, Acute kidney injury, Viral encephalitis, Creatinine, Kidney Disease Improving Global Outcomes.

Multivariate guard-bands and total risk assessment on multiparameter evaluations with correlated and uncorrelated measured values

Abstract The quality, efficacy, and safety of medicines are usually verified by analytical results. Measurement uncertainty is a critical aspect for the reliability of these analytical results. The pharmacopeial compendia usually adopt a simple acceptance rule that does not consider information from measurement uncertainty. In this work, we compared decision-making using simple acceptance and decision rules with the use of guard-band for multiparameter evaluation of ofloxacin ophthalmic solution and acyclovir topical cream. Ciprofloxacin ophthalmic solution and acyclovir topical cream samples were subject to pharmacopeial tests and assays. Multivariate guard-band widths were calculated by multiplying the standard uncertainty (u) by an appropriate multivariate coverage factor (k'). The multivariate coverage factor (k') was obtained by the Monte Carlo method. According to the simple acceptance rule, all the results obtained for ciprofloxacin ophthalmic solution and acyclovir topical cream are within the specification limits. However, the risk of false conformity decisions increases for ciprofloxacin tests. Decisions made using the simple acceptance rule and decision rules with the use of guard-band may differ. The simple acceptance rule may increase the risk of false conformity decisions when the measured value is close to the regulatory specification limits and/or when the measurement uncertainty value is inappropriately high. Nevertheless, the guard-band decision rule will always reduce the risk of false conformity decisions. Therefore, using information on measurement uncertainty in conformity assessment is highly recommended to ensure the proper efficacy, safety, and quality of medicines.

Encefalitis por virus varicela zoster: a propósito de un caso / Encephalitis by varicella zoster virus: a propos of a case

Se trata de una paciente blanca, femenina, de 79 años, que en el curso de un herpes zoster oftálmico comienza con manifestaciones clínicas neurológicas, que se interpretaron inicialmente como reacciones adversas al tratamiento oral con aciclovir; siendo el sistema nervioso central la localización extracutánea más frecuente de este herpes virus; y la forma más común de afectación neurológica en esta infección es una encefalitis, se pensó en esta entidad a pesar de su atipicidad no reportada en la bibliografía consultada, lo que motivó a realizar una revisión exhaustiva de este tema. La paciente evolucionó satisfactoriamente con desaparición de los síntomas y signos clínicos.

It deals with a 79-years-old, white, female patient, beginning with neurological clinical manifestations in the course of ophthalmologic zoster herpes. Initially they were interpreted as adverse reactions of the acyclovir treatment. Being the central nervous centre the most frequent extra-cutaneous location of this herpes virus, and encephalitis the most common neurologic affection in this infection, we thought about this entity despite of its atypicity, which was not found in the consulted bibliography. It motivated us to make an exhaustive review of this theme. The evolution of the patient was positive, disappearing the clinic signs and symptoms.

Insuficiência renal aguda associada ao uso de aciclovir endovenoso / Acute renal failure related to intravenous acyclovir

OBJETIVO: Avaliar a incidência e evolução da IRA em pacientes que utilizaram aciclovir por via intravenosa. MÉTODOS: Foram revisados, durante um período de sete meses consecutivos, os prontuários médicos de pacientes acima de 13 anos de idade que usaram aciclovir endovenoso (EV) por cinco dias ou mais. A IRA foi considerada quando a creatinina sérica, previamente normal, aumentava acima de 2 mg/dl. Foi analisado o tipo de tratamento instituído nos casos de IRA e sua evolução. RESULTADOS: Oitenta e cinco pacientes receberam aciclovir por via endovenosa durante o período estudado. Foram incluídos no estudo 41 pacientes. A IRA desenvolveu-se em 8 dos 41 pacientes estudados (19,5 por cento). O tempo médio para o início do aumento dos níveis séricos da creatinina, após o início do uso da droga, foi de 4,2 dias, com o pico dos níveis da creatinina sérica aparecendo entre 3 a 14 dias (média 7,1 dias). A recuperação da função renal, avaliada pela queda dos níveis da creatinina, variou de 1 a 7 dias ( média de 3,6 dias). A resolução da IRA ocorreu após medidas gerais de hidratação, aumento do tempo de infusão e ajuste da dose do aciclovir. CONCLUSÃO: O aciclovir provocou IRA em 19,5 por cento dos pacientes, que evoluíram bem em todos os casos observados, com retorno da função renal pré-tratamento após medidas de hidratação, reajuste da dose e aumento do tempo de infusão. Não houve necessidade de hemodiálise em nenhum paciente. A droga apresenta segurança de uso, desde que cuidados sejam implementados durante sua administração.

Herpes simplex cutáneo-mucoso y virus de inmunodeficiencia humana (HIV) / Herpes simplex cutaneous-mucous and human immunodeficiency virus (HIV)

El virus herpes simplex (HSV) constituye una de las enfermedades que más comunmente afectan a los humanos y el déficit inmunológico producido por el virus de inmunodeficiencia humana (HIV), predispone claramente a su reactivación. A medida que cae el recuento de CD4 pueden desarrollarse lesiones herpéticas mucocutáneas severas y notarse hallazgos de características inusuales. El HSV es la infección viral que produce lesiones cutáneas en pacientes HIV(+) con mayor frecuencia. Además, el HSV puede ser un cofactor en la adquisición de la infección por HIV. El aciclovir es el agente antiviral de elección para el tratamiento del HSV en pacientes inmunodeprimidos. El foscarnet es muy efectivo cuando la infección es resistente al aciclovir