valganciclovir and AIDS-Related-Opportunistic-Infections

Cytomegalovirus (CMV) is a common pathogen affecting the gastrointestinal tract in patients with AIDS. We report a case of CMV-induced pseudotumor of the duodenum in a patient with AIDS and review other reported cases of CMV-induced pseudotumors in the gastrointestinal tract. CMV-induced pseudotumor in patients with AIDS is an exceptionally rare clinical entity, and to our knowledge no reports have previously summarized this clinical entity.. All previous cases included in our literature review were found using a PubMed search (1980-November 2008) of the English-language medical literature applying the terms 'CMV infection', 'inflammatory mass', 'pseudotumor', and 'gastrointestinal tract'. The references cited in these articles were examined to identify additional reports.. Although CMV-induced duodenitis has been described in patients with HIV infection, to our knowledge CMV-induced pseudotumor of the duodenum has not been previously reported in the literature. We describe the first case of an AIDS patient with CMV pseudotumor responding to oral treatment with valganciclovir with complete resolution of the CMV mass. Among reports of non-duodenal pseudotumor reported in the English literature, we found only 14 cases of CMV-induced gastrointestinal pseudotumors in HIV-positive patients. The clinical manifestations, pathologic findings of the CMV pseudotumors, as well as the treatment and outcome of these HIV patients are reviewed.. CMV pseudotumor should be included in the differential diagnosis of gastrointestinal mass lesions in AIDS patients and in other immunocompromised patients. The tumor often responds to antiviral therapy, but resolution of a CMV mass as a result of oral antiviral therapy has not been previously described. Since pseudotumors secondary to CMV often respond to medical treatment, it is important that the physicians treating severely immunocompromised patients are aware of this entity.

Topics: AIDS-Related Opportunistic Infections; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Duodenal Diseases; Ganciclovir; HIV; HIV Infections; Humans; Male; Middle Aged; Valganciclovir

Herpes virus infections, particularly those caused by cytomegalovirus (CMV), lead to significant and, sometimes severe, clinical problems for the immunocompromised host. As effective agents have become available, several treatment and prevention strategies have evolved over the past decade, first in intra-venous form and more recently, as oral preparations. Valganciclovir, the valine ester of ganciclovir, is an orally administered, potent, antiviral agent active against all herpes viruses. When taken orally, valganciclovir has much-improved bioavailability compared with oral ganciclovir and achieves ganciclovir exposures similar to intravenous ganciclovir. Clinical trials evaluating the safety and efficacy of valganciclovir for the treatment of new AIDS-associated CMV retinitis showed equivalency to intravenous ganciclovir and prevented progression of quiescent disease. In solid organ recipients, once-daily valganciclovir has been proven equivalent to oral ganciclovir for the prevention of CMV infection. The high bioavailability and convenient dosing formulation make valganciclovir an attractive option for these indications.

Topics: AIDS-Related Opportunistic Infections; Antiviral Agents; Clinical Trials as Topic; Cytomegalovirus Infections; Cytomegalovirus Retinitis; Ganciclovir; Humans; Opportunistic Infections; Organ Transplantation; Valganciclovir

Valganciclovir (Valcyte, Roche), a prodrug of the deoxyguanosine analog ganciclovir (Cytovene, Roche), is indicated for induction and maintenance treatment of cytomegalovirus retinitis in patients with AIDS and for prevention of cytomegalovirus disease in selected high-risk solid organ transplant recipients. After oral administration, valganciclovir is rapidly absorbed and converted to ganciclovir by intestinal and hepatic esterases. Valganciclovir is a highly recognized substrate of the intestinal peptide transporter PEPT1, which underlies the tenfold higher bioavailability of ganciclovir after valganciclovir compared to oral ganciclovir administration. At oral dose of 900 mg, valganciclovir provides a systemic ganciclovir exposure that is comparable to intravenous ganciclovir, at the standard dose of 5 mg/kg of body weight. Subsequent phosphorylation of ganciclovir, which occurs preferentially within cytomegalovirus-infected cells, results in the active metabolite, ganciclovir triphosphate, which is responsible for suppressing viral DNA synthesis by competitively inhibiting the incorporation of the natural substrate deoxyguanosine into viral DNA and thereby, terminating cytomegalovirus replication.

Topics: AIDS-Related Opportunistic Infections; Antiviral Agents; Cytomegalovirus Infections; Ganciclovir; Humans; Immunocompromised Host; Injections, Intravenous; Organ Transplantation; Valganciclovir

Human cytomegalovirus (HCMV) infects about 60% of adults in developed world and more than 90% of developing countries population. In the immunocompetent host, initial infection and reactivation of latent infection are usually asymptomatic. However, in hosts with impaired cellular immune functions, such as transplant recipients, patients infected with human immunodeficiency virus (HIV) or undergoing anticancer chemo- and/or radiotherapy, the full pathogenic potential of the virus may be realized. HCMV is also among the most common causes of viral intrauterine infection affecting from 0.4 to 2.3% of live-born infants. Though in pregnant, immunocompetent women infections with HCMV are usually asymptomatic, severe infections may occur among congenitally infected fetuses and infants due to immaturity of their immune system. Approximately 40% of mothers with primary HCMV infections during gestation transmit virus to their infants. Although only 10% of infected infants are symptomatic at birth, 20 to 30% of these die. In addition, 5 to 15% of asymptomatic neonates are at risk of developing congenital anomalies later. In this outline we present anti-CMV drugs currently in clinical use and give examples of new molecules under laboratory and clinical development.

Topics: Acyclovir; AIDS-Related Opportunistic Infections; Antiviral Agents; Cidofovir; Cytomegalovirus Infections; Cytosine; Drugs, Investigational; Female; Foscarnet; Ganciclovir; Global Health; Humans; Infectious Disease Transmission, Vertical; Naphthalenesulfonates; Organophosphonates; Organophosphorus Compounds; Pregnancy; Pregnancy Complications, Infectious; Thionucleotides; Valacyclovir; Valganciclovir; Valine

The incidence of cytomegalovirus (CMV) disease, one of the most prevalent opportunistic infections in HIV-infected persons in the early 1990s, has decreased by more than 80% since the introduction of highly active antiretroviral therapy (HAART). The rare cases of CMV disease still observed in Western countries occur mainly in profoundly immunosuppressed patients who have failed to respond to HAART. A new finding is the occasional occurrence of inflammatory retinitis in some patients on HAART with a history of healed retinitis. New tools for CMV detection have become available recently, including use of polymerase chain reaction (PCR) to detect CMV DNA from plasma. It has been possible to redefine, in the HAART period, patients at risk for CMV disease as those who have a low CD4 cell count as well as a blood marker of CMV blood dissemination (plasma CMV DNAaemia or high pp65 antigenaemia). Besides the classical therapeutic approach using ganciclovir (GCV), foscarnet and cidofovir, development of valganciclovir (VGCV), an orally administered prodrug of GCV, appears promising. There is evidence to suggest that it is as effective as intravenous GCV for the treatment of CMV retinitis, and it is currently being studied as a pre-emptive therapy in patients at high risk for CMV disease. Finally, patients with inactive CMV retinitis receiving HAART and with stable immune reconstitution may be able to discontinue maintenance therapy provided a regular ophthalmological and virological surveillance is maintained.

Topics: AIDS-Related Opportunistic Infections; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Antiviral Agents; CD4 Lymphocyte Count; Cidofovir; Cytomegalovirus Infections; Cytosine; Drug Monitoring; Foscarnet; Ganciclovir; Humans; Organophosphonates; Organophosphorus Compounds; Polymerase Chain Reaction; Population Surveillance; Predictive Value of Tests; Prevalence; Risk Factors; Valganciclovir

To determine whether treatment with valganciclovir will improve visual acuity in eyes with immune recovery uveitis complicated by macular edema.. Prospective open label controlled Phase II drug study.. Five patients with chronic macular edema as a result of immune recovery uveitis were studied. Baseline fluorescein angiograms, best-corrected ETDRS visions, and cytomegalovirus (CMV) lymphoproliferative T-cell function assays were obtained and repeated after three months of valganciclovir therapy (900 mg daily) and again three months after withdrawal of therapy.. Vision improved by a mean of 11 letters in the treatment phase (P =.05). Graded angiograms showed three patients had treatment reduction of macular edema. One patient had rebound increase in macular edema after the withdrawal phase. The CMV lymphoproliferative response was not affected by the valganciclovir.. Results suggest valganciclovir treatment may benefit visual acuity in patients with macular edema from immune recovery uveitis.

Topics: Adult; AIDS-Related Opportunistic Infections; Antiretroviral Therapy, Highly Active; Antiviral Agents; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes; Cytomegalovirus Retinitis; Female; Fluorescein Angiography; Ganciclovir; Humans; Immune System; Macular Edema; Male; Prospective Studies; Uveitis; Valganciclovir; Visual Acuity

Valganciclovir, an oral prodrug of the anti-cytomegalovirus (CMV) agent ganciclovir, was evaluated in a single-arm open-label safety study. AIDS patients (median CD4 lymphocyte count of 140 cells/microL) with treated CMV retinitis (N = 212) received 900-mg once-daily valganciclovir maintenance therapy with courses of 900-mg twice-daily valganciclovir induction therapy as needed to treat progression. After a median treatment duration of 372 days, the adverse event profile was similar to that reported for intravenous (IV) and oral ganciclovir. Adverse event rates of note were diarrhea (35%), nausea (23%), fever (18%), neutropenia (absolute neutrophil count <500 cells/microL) (10%), and anemia (hemoglobin <8.0 g/dL) (12%). Consistent with prior treatment studies of oral ganciclovir, IV catheter-related adverse events were uncommon (6%) and lower than previously reported for IV ganciclovir. The mortality rate was 0.072 deaths per patient-year. Progression of CMV retinitis occurred in 17% of patients during the study treatment period, usually in association with a low CD4 cell count. Other than a higher than expected frequency of oral candidiasis (17%), no clinical toxicities or laboratory abnormalities occurred during treatment with valganciclovir that have not been observed during treatment with ganciclovir.

Topics: Administration, Oral; Adult; AIDS-Related Opportunistic Infections; Antiretroviral Therapy, Highly Active; Antiviral Agents; Candidiasis, Oral; CD4 Lymphocyte Count; Cytomegalovirus Retinitis; Drug Tolerance; Female; Ganciclovir; HIV Infections; Humans; Male; Middle Aged; Prodrugs; Safety; Valganciclovir

Valganciclovir is the oral prodrug of ganciclovir. The pharmacokinetics of valganciclovir in patients with renal impairment is not known. Furthermore, it is not known whether there are any pharmacokinetic differences between patients who are positive for human immunodeficiency virus (HIV) and cytomegalovirus (CMV) and healthy subjects.. A total of 44 patients were included-18 with mild, medium, or severe renal impairment; 6 with end-stage renal disease who were on long-term hemodialysis; 8 HIV/CMV-positive patients with normal renal function; and 12 healthy subjects serving as controls. Valganciclovir and ganciclovir serum concentrations were measured after oral administration of 900 mg of valganciclovir. Pharmacokinetic parameters were estimated by means of noncompartmental and compartmental methods.. After oral administration of the prodrug valganciclovir, ganciclovir bioavailability was 60% and ganciclovir concentrations were higher (maximum concentration [C(max)], 8.5 microg/mL versus 5.8 microg/mL) and appeared later (time to maximum concentration [T(max)], 4.3 versus 2.0 hours) in patients with severe renal impairment compared with healthy subjects. The elimination half-life (t(1/2)) of ganciclovir was longer in patients with renal failure (t(1/2) of 68.1 hours in patients with end-stage renal disease compared with 3.5 hours in healthy subjects). Ganciclovir clearance was correlated with creatinine clearance (r = 0.975). Hemodialysis removed 50% of ganciclovir. We observed no differences in pharmacokinetics between HIV/CMV-positive patients and healthy subjects. A 2-compartment model with zero-order input and first-order elimination proved to be the most appropriate model for ganciclovir after oral administration of valganciclovir.. The dosage of valganciclovir has to be adjusted to the degree of renal impairment. Dosage adjustment is not necessary for HIV/CMV-positive patients.

Topics: Administration, Oral; Adult; Aged; AIDS-Related Opportunistic Infections; Antiviral Agents; Biological Availability; Cytomegalovirus Infections; Drug Administration Schedule; Female; Ganciclovir; HIV Infections; Humans; Kidney Failure, Chronic; Male; Middle Aged; Prodrugs; Renal Dialysis; Valganciclovir

Valganciclovir is an orally administered prodrug that is rapidly hydrolyzed to ganciclovir. We compared the effects of oral valganciclovir with those of intravenous ganciclovir as induction therapy for newly diagnosed cytomegalovirus retinitis in 160 patients with the acquired immunodeficiency syndrome (AIDS).. The primary end point was photographically determined progression of cytomegalovirus retinitis within four weeks after the initiation of treatment. Secondary end points included the achievement of a prospectively defined satisfactory response to induction therapy and the time to progression of cytomegalovirus retinitis. After four weeks, all patients received valganciclovir as maintenance therapy.. Eighty patients were randomly assigned to each treatment group. Of the patients who could be evaluated, 7 of 70 assigned to intravenous ganciclovir (10.0 percent) and 7 of 71 assigned to oral valganciclovir (9.9 percent) had progression of cytomegalovirus retinitis during the first four weeks (difference in proportions, 0.1 percentage point; 95 percent confidence interval, -9.7 to 10.0). Forty-seven of 61 patients (77.0 percent) assigned to intravenous ganciclovir and 46 of 64 (71.9 percent) assigned to valganciclovir had a satisfactory response to induction therapy (difference in proportions, 5.2 percentage points; 95 percent confidence interval, -20.4 to 10.1). The median times to progression of retinitis were 125 days in the group assigned to intravenous ganciclovir and 160 days in the group assigned to oral valganciclovir. The mean values for the area under the curve for the ganciclovir dosage interval were similar at both induction doses and maintenance doses. The frequency and severity of adverse events were similar in the two treatment groups.. Orally administered valganciclovir appears to be as effective as intravenous ganciclovir for induction treatment and is convenient and effective for the long-term management of cytomegalovirus retinitis in patients with AIDS.

Topics: Acquired Immunodeficiency Syndrome; Administration, Oral; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Retinitis; Disease Progression; Female; Ganciclovir; HIV; Humans; Injections, Intravenous; Male; Prodrugs; Valganciclovir; Viral Load

We developed a mathematical simulation model to anticipate outcomes from an upcoming trial of targeted, preemptive cytomegalovirus (CMV) therapy in high-risk, human immunodeficiency virus (HIV)-infected patients identified by means of CMV polymerase chain reaction screening. We estimated the costs and consequences of CMV prophylaxis in patients with CD4(+) counts < or =100 cells/microL under various assumptions regarding disease progression, complication rates, drug effects, and costs. Without CMV preemptive therapy, lifetime costs average $44,600 with expected duration of survival of 19.16 quality-adjusted life-months and 213 CMV cases per 1000 patients. Targeted preemptive therapy with orally administered valganciclovir increases costs and duration of survival to $46,900 and 19.63 quality-adjusted life-months, respectively. CMV cases decrease to 174 per 1000 patients. The cost per quality-adjusted life-year gained is $59,000. This result compares favorably with other strategies in end-stage HIV disease but hinges on valganciclovir cost and efficacy assumptions and the absence of minimally effective salvage antiretroviral therapy for HIV. The upcoming trial should resolve the clinical uncertainty surrounding some of these assumptions.

Topics: AIDS-Related Opportunistic Infections; Antiviral Agents; Chemoprevention; Cost-Benefit Analysis; Cytomegalovirus; Cytomegalovirus Infections; Ganciclovir; HIV Infections; Humans; Models, Biological; Polymerase Chain Reaction; Predictive Value of Tests; Quality-Adjusted Life Years; Sensitivity and Specificity; Valganciclovir

The emergence of mutations conferring ganciclovir resistance was evaluated in an open-label randomized clinical trial that compared oral valganciclovir with intravenous ganciclovir as induction therapy, followed by maintenance with valganciclovir, for newly diagnosed cytomegalovirus (CMV) retinitis in 148 patients with acquired immunodeficiency syndrome. The presence of CMV mutations was directly assessed in patient leukocytes by polymerase chain reaction, followed by restriction fragment-length polymorphism (RFLP) for detection of the most common UL97 mutations associated with ganciclovir resistance and by sequencing of the viral UL97 gene. The cumulative percentages of patients with UL97-mutant viruses at 3, 6, 12, and 18 months (based on the number of patients on treatment at each time point) was 2.2%, 6.5%, 12.8%, and 15.3%, respectively. Of the 20 relevant UL97 mutations found by sequencing in 14 patients, 14 (70%) were detected by RFLP analysis. The rate of emergence of ganciclovir-resistant viruses with use of oral valganciclovir is no greater than that reported with use of intravenous ganciclovir.

Topics: AIDS-Related Opportunistic Infections; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Retinitis; DNA-Directed DNA Polymerase; Drug Resistance, Viral; Ganciclovir; Humans; Leukocytes; Mutation; Phosphotransferases (Alcohol Group Acceptor); Valganciclovir; Viral Proteins

We present the case of a 28-year-old man with recently-diagnosed human immunodeficiency virus and hepatitis C virus infection. He developed obstructive cholangiopathy secondary to cytomegalovirus and Kaposi sarcoma, both diagnosed by endoscopic retrograde cholangiopancreatography and biopsies. He received antiretroviral therapy, chemotherapy and valganciclovir with full recovery.

Topics: Abdominal Pain; Adult; AIDS-Related Opportunistic Infections; Antiretroviral Therapy, Highly Active; Bile Duct Diseases; Biopsy; Cholangiopancreatography, Endoscopic Retrograde; Cytomegalovirus; Diarrhea; Fever; Hepatitis C; HIV Infections; Humans; Male; Sarcoma, Kaposi; Valganciclovir; Weight Loss

Cytomegalovirus retinitis (CMVR) is an opportunistic infection in HIV-infected people. Intraocular or intravenous ganciclovir was gold standard for treatment; however, oral valganciclovir replaced this in high-income countries. Low- and middle-income countries (LMIC) frequently use intraocular injection of ganciclovir (IOG) alone because of cost.. Retrospective review of all HIV-positive patients with CMVR from February 2013 to April 2017 at a Médecins Sans Frontièrs HIV clinic in Myanmar. Treatment was classified as local (IOG) or systemic (valganciclovir, or valganciclovir and IOG). The primary outcome was change in visual acuity (VA) post-treatment. Mortality was a secondary outcome.. Fifty-three patients were included. Baseline VA was available for 103 (97%) patient eyes. Active CMVR was present in 72 (68%) eyes. Post-treatment, seven (13%) patients had improvement in VA, 30 (57%) had no change, and three (6%) deteriorated. Among patients receiving systemic therapy, four (12.5%) died, compared with five (24%) receiving local therapy (p = 0.19).. Our results from the first introduction of valganciclovir for CMVR in LMIC show encouraging effectiveness and safety in patients with advanced HIV. We urge HIV programmes to include valganciclovir as an essential medicine, and to include CMVR screening and treatment in the package of advanced HIV care.

Topics: Administration, Oral; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Retinitis; Female; Ganciclovir; HIV; Humans; Injections, Intraocular; Male; Middle Aged; Myanmar; Primary Health Care; Retrospective Studies; Treatment Outcome; Valganciclovir; Visual Acuity

Topics: Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Cytomegalovirus Infections; Cytomegalovirus Retinitis; Drug Packaging; Ganciclovir; Humans; Liver Transplantation; Opportunistic Infections; Valganciclovir

A number of studies have demonstrated that cytomegalovirus (CMV) viraemia is a strong predictor for CMV end-organ disease (EOD) and death in HIV-infected patients. We assess the efficacy and safety of pre-emptive anti-CMV therapy (PACT) for preventing these events. We performed a retrospective study of all HIV-infected patients seen in our institution who had detectable CMV viraemia in 2007. Seventy-one patients with advanced HIV disease (median CD4 cell count = 61 cells/mm(3)) were studied. Sixteen patients received PACT (mainly valganciclovir). Patients who received PACT had lower CD4 cell counts and higher blood CMV DNA levels. The cumulative incidence of CMV EOD and death at one year was 44% and 21% in patients with and without PACT, respectively (p = 0.013). Both PACT and high blood CMV DNA levels were significantly associated with CMV EOD and death in unadjusted analysis. In adjusted analyses, only blood CMV DNA levels remained significantly associated with the risk of CMV EOD and death, whereas PACT was associated with a non-significant trend towards reduced CMV EOD or death (hazard ratio: 0.25, p = 0.13). Five patients with PACT experienced severe drug-related adverse events. In conclusion, the use of PACT in HIV-infected patients with CMV viraemia could improve outcome but is associated with significant toxicity.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Antiviral Agents; CD4 Lymphocyte Count; Cytomegalovirus; Cytomegalovirus Infections; DNA, Viral; Female; Ganciclovir; HIV Infections; Humans; Immunocompromised Host; Incidence; Male; Middle Aged; Polymerase Chain Reaction; Retrospective Studies; Treatment Outcome; Valganciclovir; Viral Load; Viremia

Topics: Administration, Oral; AIDS-Related Opportunistic Infections; Antiviral Agents; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes; Cytomegalovirus Retinitis; Female; Fluorescein Angiography; Foscarnet; Ganciclovir; Humans; Intravitreal Injections; Middle Aged; Retinal Vasculitis; Valganciclovir

Topics: AIDS-Related Opportunistic Infections; Anti-HIV Agents; Anus Diseases; Biopsy; Cytomegalovirus Infections; Ganciclovir; HIV Infections; Humans; Immunocompromised Host; Male; Middle Aged; Treatment Outcome; Ulcer; Valganciclovir

This study reports the surgical outcomes of acquired immunodeficiency syndrome (AIDS) patients with Cytomegalovirus retinitis (CMVR) -related retinal detachments(RD) in an Asian population.. Review of CMVR characteristics, surgical outcomes and complications in 19 eyes with CMVR-related RD that underwent surgery from January 2000 to June 2011.. CMVR was inactive in 73.7% of the eyes at time of surgery. Anatomical success was achieved in 14 eyes. Seven eyes (36.8%) had improvement of two or more lines in visual acuity (VA) and 8 eyes (42.1%) maintained VA. Thirteen eyes presented with worse than 6/120 vision, with 30.8% of them achieving ambulatory vision or better. Five eyes had re-detachments. Median durations from CMVR and immune recovery uveitis (IRU) diagnoses to RD were 2.7 and 1.0 months respectively.. Surgery for CMVR-related RD is associated with good anatomical outcomes with most eyes maintaining or having improved vision. CMVR lesion size of <50% retinal area is associated with better outcomes. Eyes with CMVR and IRU require close monitoring for RD.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Antiretroviral Therapy, Highly Active; Antiviral Agents; Asian People; CD4 Lymphocyte Count; Cytomegalovirus Retinitis; Endotamponade; Female; Ganciclovir; Humans; Laser Coagulation; Male; Middle Aged; Retinal Detachment; Scleral Buckling; Treatment Outcome; Valganciclovir; Visual Acuity; Vitrectomy

To describe the outcomes of different treatment approaches for cytomegalovirus (CMV) retinitis in the era of highly active antiretroviral therapy (HAART).. Prospective cohort study, the Longitudinal Study of the Ocular Complications of AIDS.. A total of 250 patients with CMV retinitis and a CD4+ T-cell count <100 cells/μl (n = 221) at enrollment or incident retinitis (n = 29) during cohort follow-up.. The effects of systemic therapy (vs. intraocular therapy only) on systemic outcomes and the effect of intraocular therapies (ganciclovir implants, intravitreal injections) on ocular outcomes were evaluated.. Mortality, CMV dissemination, retinitis progression, and treatment side effects.. Regimens containing systemic anti-CMV therapy were associated with a 50% reduction in mortality (adjusted hazard ratio [HR], 0.5; 95% confidence interval [CI], 0.3-0.7; P = 0.006), a 90% reduction in new visceral CMV disease (adjusted HR, 0.1; 95% CI, 0.04-0.4; P = 0.004), and among those with unilateral CMV retinitis at presentation, an 80% reduction in second eye disease (adjusted HR, 0.2; 95% CI, 0.1-0.5; P = 0.0005) when compared with those using only intraocular therapy (implants or injections). Compared with systemic treatment only, regimens containing intravitreal injections had greater rates of retinitis progression (adjusted HR, 3.4; P = 0.004) and greater visual field loss (for loss of one half of the normal field, adjusted HR, 5.5; P < 0.01). Intravitreal implants were not significantly better than systemic therapy (adjusted HR for progression, 0.5; P = 0.26; adjusted HR for loss of one half of the visual field, 0.5; P = 0.45), but the sample size was small. Hematologic and renal side effect rates were similar between those groups with and without systemic anti-CMV therapy. The rate of endophthalmitis was 0.017 per eye-year (EY) (95% CI, 0.006-0.05) among those treated with intravitreal injections and 0.01 per EY (95% CI, 0.002-0.04) among those treated with an implant.. In the HAART era, systemic anti-CMV therapy, while there is immune compromise, seems to provide benefits in terms of longer survival and decreased CMV dissemination.. Proprietary or commercial disclosure may be found after the references.

Topics: Adult; AIDS-Related Opportunistic Infections; Antiretroviral Therapy, Highly Active; Antiviral Agents; CD4 Lymphocyte Count; Cytomegalovirus Retinitis; Drug Implants; Female; Follow-Up Studies; Ganciclovir; Humans; Intravitreal Injections; Male; Middle Aged; Prospective Studies; T-Lymphocytes; Valganciclovir; Visual Acuity; Visual Fields

Immune reconstitution syndrome (IRS) is a complication caused by reactivation of the immune system that can occur after starting highly active antiretroviral therapy (HAART) in patients with acquired immunodeficiency syndrome (AIDS). Severe IRS associated with cytomegalovirus (CMV) in both eyes who had lost his left vision is reported.. A 37-year-old man with AIDS who had started HAART discontinued his medication. Two weeks after the re-induction of HAART, he suffered CMV retinitis OU. Vitreous opacity OU appeared 3 days later, and optic neuritis OS appeared 6 days after the onset; and visual acuity OS decreased to 0.06. As the number of CD 4 positive T lymphocytes (CD 4) increased from 39 to 118/microl in both the pre- and- post HAART, we diagnosed IRS and started anti- CMV and systemic steroid therapy and discontinued the HAART. The focus of CMV retinitis was improved; however, visual acuity OS did not improve.. Severe IRS with visual loss induced by CMV retinitis after HAART needs to be considered in low CD 4 level patients during the induction phase.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Antiretroviral Therapy, Highly Active; Antiviral Agents; CD4 Lymphocyte Count; Cytomegalovirus Retinitis; Ganciclovir; Humans; Immune Reconstitution Inflammatory Syndrome; Male; Severity of Illness Index; Treatment Outcome; Valganciclovir; Visual Acuity

Topics: Acyclovir; Aged; AIDS-Related Opportunistic Infections; Drug Resistance, Viral; Drug Therapy, Combination; Eye Infections, Viral; Ganciclovir; Humans; Immunocompromised Host; Male; Prednisone; Retinal Necrosis Syndrome, Acute; Valganciclovir

Topics: Acquired Immunodeficiency Syndrome; Africa South of the Sahara; AIDS-Related Opportunistic Infections; Anti-Retroviral Agents; Antiviral Agents; Asia, Southeastern; Blindness; CD4 Lymphocyte Count; Cytomegalovirus Retinitis; Developing Countries; Disease Outbreaks; Drug Costs; Ganciclovir; Health Services Accessibility; Humans; Mass Screening; Ophthalmoscopy; Program Development; Treatment Outcome; Valganciclovir

Cytomegalovirus (CMV) retinitis was a much-feared visual complication of late-stage acquired immunodeficiency syndrome (AIDS) in the past. Its incidence has waned significantly owing to the benefits of potent antiretroviral combination therapy, which for many individuals has provided some degree of immune reconstitution and avoidance of opportunistic infections, particularly this blinding disease.. A 45-year-old white man with long-standing, multidrug-resistant human immunodeficiency virus (HIV) infection and severe immunodeficiency despite multiple antiretroviral drug regimens, presented to the eye clinic reporting decreased vision and spider web patterns in his left eye for the past week. Best-corrected visual acuity was 20/20 in the right (O.D.) and 20/25 in the left eye (O.S.). Dilated funduscopic examination of the left eye found vasculitis of the midperipheral inferonasal arcade in the midperiphery, with surrounding intraretinal hemorrhage and granular retinal necrosis. Diagnosis of cytomegalovirus retinitis was made, and the patient began induction therapy with oral valganciclovir 900 mg twice a day for 3 weeks. Maintenance therapy after retinitis stabilization was 900 mg every day until any observed recurrence of infection. Three months after complete resolution of the active retinitis, the patient returned to the clinic reporting new floaters of recent onset. A reactivation of the CMV retinitis warranted a reinduction with valganciclovir 900 mg orally twice a day for 3 weeks.. This case is illustrative of the efficacy and relative ease of administration of valganciclovir, the newest medication approved for treatment and maintenance of CMV retinitis. Despite his severe immunodeficiency, our patient tolerated the induction and maintenance therapy of oral valganciclovir well, and the CMV retinitis was stabilized and resolved with full recovery of visual acuity.

Topics: Administration, Oral; AIDS-Related Opportunistic Infections; Anti-Retroviral Agents; Cytomegalovirus Retinitis; Follow-Up Studies; Ganciclovir; HIV; Humans; Male; Middle Aged; Valganciclovir

Topics: AIDS-Related Opportunistic Infections; Antiretroviral Therapy, Highly Active; Antiviral Agents; CD4-Positive T-Lymphocytes; Cytomegalovirus Retinitis; Ganciclovir; Humans; Macular Edema; Uveitis; Valganciclovir

We report a pharmacokinetic study in a 6-year-old girl with congenital human immunodeficiency virus type 1 and cytomegalovirus coinfection maintained on iv ganciclovir for 6 years. Increasing infection and thrombosis caused by her iv device necessitated alternative therapy. Single dose pharmacokinetics of ganciclovir 4.4 mg/kg iv and valganciclovir 13.2 and 26.3 mg/kg po were studied with high performance liquid chromatography/tandem mass spectrometry. The two oral dosages yielded areas under the concentration curve of 14.3 and 28.7 microg x h/ml, equivalent to 43% bioavailability of ganciclovir from valganciclovir, which exceeded the area under the concentration curve of 11.1 microg x h/ml yielded by ganciclovir 4.4 mg/kg iv. Oral valganciclovir achieved therapeutic and dosage-proportional plasma concentrations in the child we studied.

Topics: Administration, Oral; AIDS-Related Opportunistic Infections; Antiviral Agents; Area Under Curve; Biological Availability; Child; Chromatography, High Pressure Liquid; Cytomegalovirus Infections; Female; Ganciclovir; Humans; Mass Spectrometry; Valganciclovir

Topics: AIDS-Related Opportunistic Infections; Antiviral Agents; Cytomegalovirus Retinitis; Ganciclovir; Humans; Male; Middle Aged; Retinal Hemorrhage; Thrombocytopenia; Valganciclovir

Topics: Administration, Oral; AIDS-Related Opportunistic Infections; Antiviral Agents; Cytomegalovirus Infections; Ganciclovir; Humans; Immunohistochemistry; Male; Middle Aged; Skin Ulcer; Valganciclovir; Wound Healing

Topics: Aged; AIDS-Related Opportunistic Infections; Antiviral Agents; Blindness; Fatal Outcome; Ganciclovir; Herpes Zoster Ophthalmicus; Humans; Male; Retinal Necrosis Syndrome, Acute; Valganciclovir; Viral Load; Visual Acuity

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Cystitis; Cytomegalovirus Infections; Fatal Outcome; Ganciclovir; Hemorrhage; Humans; Lymphoma, AIDS-Related; Male; Valganciclovir

Topics: AIDS-Related Opportunistic Infections; Antiviral Agents; Clinical Trials as Topic; Cytomegalovirus Retinitis; Ganciclovir; Humans; Prodrugs; Valganciclovir

Topics: AIDS-Related Opportunistic Infections; Antiviral Agents; Aristolochic Acids; Arrhythmias, Cardiac; Cytomegalovirus Retinitis; Dietary Supplements; Drug Labeling; Ganciclovir; Humans; Kidney Diseases; Methadyl Acetate; Narcotics; Opioid-Related Disorders; Phenanthrenes; Phytotherapy; Prodrugs; United States; United States Food and Drug Administration; Valganciclovir