Discontinuation of maintenance therapy for cytomegalovirus retinitis in HIV-infected patients receiving highly active antiretroviral therapy

OBJECTIVE: To study the safety of discontinuing cytomegalovirus (CMV) maintenance therapy among patients with cured CMV retinitis receiving highly active antiretroviral therapy (HAART). METHODS: Patients with a history of CMV retinitis who were receiving anti-CMV maintenance therapy and who had a CD4 cell count > 75 x 10(6) cells/l and a plasma HIV RNA level < 30000 copies/ml while on HAART were included in a multicentre prospective study. Maintenance therapy for CMV retinitis was discontinued at enrolment and all the patients were monitored for 48 weeks by ophthalmological examinations and by determination of CMV markers, CD4 cell counts and plasma HIV RNA levels. T helper-1 anti-CMV responses were assessed in a subgroup of patients. The primary study endpoint was recurrence of CMV disease. RESULTS: At entry, the 48 assessable patients had been taking HAART for a median of 18 months. The median CD4 cell count was 239 x 10(6) cells/l and the median HIV RNA load was 213 copies/ml. Over the 48 weeks, 2 of the 48 patients had a recurrence of CMV disease. The cumulative probability of CMV retinitis relapse was 2.2% at week 48 (95% confidence interval, 0.4-11.3) and that of all forms of CMV disease 4.2%. CMV blood markers remained negative throughout follow-up. The proportion of patients with CMV-specific CD4 T cell reactivity was 46% at baseline and 64% at week 48. CONCLUSIONS: CMV retinitis maintenance therapy may be safely discontinued in patients with CD4 cell counts above 75 x 10(6) cells/l who have been taking HAART for at least 18 months.     

Loss of cytomegalovirus (CMV) viraemia following highly active antiretroviral therapy in the absence of specific anti-CMV therapy.

OBJECTIVE: To determine the effect of highly active antiretroviral therapy (HAART) on cytomegalovirus (CMV) viraemia and retinitis in patients at high risk of disease. DESIGN: Sixteen patients with CMV viraemia, but no evidence of end organ disease at the time of first receipt of HAART including a protease inhibitor, were studied. No patient had ever received specific anti-CMV therapy. METHODS: CMV load in blood was measured using quantitative competitive PCR at baseline and for a median follow-up of 21 months. Regular ophthalmological screening for retinitis was conducted throughout the study period. RESULTS: All 16 patients became CMV negative by PCR following the commencement of HAART. CMV loads prior to treatment ranged from 2.0 x 10(3) to 4.1 x 10(6) copies/ml (median, 7.6 x 10(4) copies/ml). The median time to becoming PCR negative was 13.5 weeks (range, 5-40 weeks). Fourteen patients remained CMV negative throughout follow-up. CMV viraemia recurred in two patients; these individuals were indistinguishable with respect to either baseline parameters or response to antiretroviral therapy. None of the 16 patients developed CMV retinitis. CONCLUSIONS: HAART including a protease inhibitor can result in the complete suppression of CMV viraemia, an effect not previously observed in HIV-infected patients in the absence of specific anti-CMV therapy. This response correlated with protection against CMV retinitis in a group of patients at high risk of development of disease. These results help to explain why the natural history of CMV disease has altered since the introduction of such therapeutic regimens.     

Cessation of anti-CMV therapy in patients with CMV retinitis

Highly active antiretroviral therapy (HAART) has had a positive impact on the treatment of CMV retinitis, putting the disease in decline over the past few years. Some reports reveal lesions resembling well-controlled CMV retinitis in patients receiving HAART but who never received specific anti-CMV therapy. Further research is needed to learn more about this issue. Cessation of anti-CMV therapy seems most appropriate in patients with no detectable viral load and increased CD4 cell counts; however, questions remain whether the types of CD4 cells resulting from HAART provide adequate protection against CMV. The response in a patient with CMV retinitis who has never been treated with HAART is also unknown. Until guidelines are developed from results of controlled clinical trials, several recommendations are provided for physicians determining how to treat patients with CMV retinitis.     

Recovery of long-term natural protection against reactivation of CMV retinitis in AIDS patients responding to highly active antiretroviral therapy

OBJECTIVES: To see whether in severely immunosuppressed AIDS patients (with prior Cytomegalovirus retinal disease) who have significant increases in CD4+ lymphocytes following the initiation of highly active antiretroviral therapy (HAART) anti-Cytomegalovirus (CMV) maintenance therapy can be withdrawn with no subsequent progression of CMV retinitis. METHODS: Eight patients with AIDS and one or more previous episodes of CMV retinitis interrupted anti-CMV maintenance therapy following the successful beginning of HAART. CD4 cell counts and HIV-RNA were monitored monthly while measurement of CMV antigenemia and ophthalmoscopy were carried every 2 weeks thereafter. RESULTS: The HAART recipients in whom anti-CMV maintenance therapy had been interrupted had measureable increases of CD4+ T lymphocytes, substantial control of both HIV-RNA and CMV viraemia and did not show recurrence of retinitis during a mean follow-up of 98.4 weeks (range 78-120, SD 15.2). CONCLUSIONS: Anti-CMV maintenance therapy can be interrupted with no subsequent progression of retinal damage over a long time in patients with AIDS who successfully respond to HAART with a significant increase in CD4 cell count.     

Withdrawal of maintenance therapy for cytomegalovirus retinitis in AIDS patients exhibiting immunological response to HAART

BACKGROUND: Before the introduction of highly active antiretroviral therapy (HAART), CMV retinitis was a common complication in patients with advanced HIV disease and the therapy was well established; it consisted of an induction phase to control the infection with ganciclovir, followed by a lifelong maintenance phase to avoid or delay relapses. METHODS: To determine the safety of CMV maintenance therapy withdrawal in patients with immune recovery after HAART, 35 patients with treated CMV retinitis, on maintenance therapy, with CD4+ cell count greater than 100 cells/mm(3) for at least three months, but almost all patients presented these values for more than six months and viral load < 30000 copies/mL, were prospectively evaluated for the recurrence of CMV disease. Maintenance therapy was withdrawal at inclusion, and patients were monitored for at least 48 weeks by clinical and ophthalmologic evaluations, and by determination of CMV viremia markers (antigenemia-pp65), CD4+/CD8+ counts and plasma HIV RNA levels. Lymphoproliferative assays were performed on 26/35 patients. RESULTS: From 35 patients included, only one had confirmed reactivation of CMV retinitis, at day 120 of follow-up. No patient returned positive antigenemia tests. No correlation between lymphoproliferative assays and CD4+ counts was observed. CONCLUSION: CMV retinitis maintenance therapy discontinuation is safe for those patients with quantitative immune recovery after HAART.     

CMV retinitis recurs after stopping treatment in virological and immunological failures of potent antiretroviral therapy

OBJECTIVES: To determine predictors of clinical relapse of cytomegalovirus (CMV) end-organ disease in a cohort of 17 HIV-infected patients with healed and treated CMV retinitis (CMVR) who responded to HAART with an increase in CD4 cell counts to above 70 cells/mm3 and discontinued CMV maintenance therapy (MT). DESIGN: Seventeen patients were monitored for reactivation of retinitis. The CD4 cell counts, HIV RNA and peripheral blood mononuclear cell (PBMC) lymphoproliferative assays to CMV at 3 month intervals were compared between patients with and without reactivation of CMVR. Positive lymphoproliferative responses were defined as a stimulation index of 3 or greater. RESULTS: Five out of 17 (29%) patients experienced a recurrence of CMVR a mean of 14.5 months after stopping CMV MT and between 8 days and 10 months after CD4 cell counts fell below 50 cells/mm3. Median CD4 cell counts and plasma HIV RNA at reactivation were 37 cells/mm3 and 5.3 log10 copies/ml. Three patients recurred at a previously active site of the retina, one had contralateral CMVR, and one a recurrence of retinitis and pancreatitis simultaneously. Mean lymphoproliferative responses to CMV were 2.4 in patients with reactivation versus 21.0 stimulation index (SI) in patients without reactivation (P= 0.01). A model incorporating four variables (CD4 cell counts and HIV RNA at maintenance discontinuation, highest CD4 cell count, nadir HIV RNA and median lymphoproliferative responses) identified correctly 88% of patients with and without reactivation. CONCLUSION: CMV disease recurs after virological and immunological failure of HAART if CD4 cell counts drop below 50. In this situation, anti-CMV agents should be resumed before clinical reactivation ensues, because of the risk of contralateral retinal involvement and systemic disease.     

Treatment of CMV retinitis with intravitral ganciclovir in the HAART era

OBJECTIVE: To describe the course and outcome of cytomegalovirus (CMV) retinitis among AIDS patients treated with intravitreal ganciclovir and systemic highly active antiretroviral therapy (HAART). The secondary objective was to compare the course of CMV retinitis between patients receiving HAART and those not receiving this treatment. DESIGN: A retrospective cohort design consisting of 21 eyes from 16 patients with AIDS and CMV retinitis consecutively enrolled between January 1996 and August 1999. All patients received intravitreal ganciclovir therapy, and half of the patients began HAART as well. Duration of intravitreal therapy and ensuing disease quiescence, as well as CD4+ T cell counts at diagnosis and at cessation of ganciclovir, were calculated. Secondly, instantaneous hazards for outcomes such as CMV retinitis progression, ocular complications and mortality were compared. SETTING: Tertiary care centre in Ottawa, Ontario. RESULTS: Five of eight patients receiving HAART discontinued intravitreal ganciclovir after a mean treatment period of 428 days. During this period, their mean CD4+ count rose from 7.5 to 190microL. Subsequently, none of these patients experienced retinitis progression during follow-up periods lasting up to 820 days (mean of 617 days). Progression of CMV retinitis was 11.4 times more likely among those not receiving HAART (P=0.049). CONCLUSIONS: On initiating HAART, patients with CMV retinitis may enjoy significant recovery in CD4+ counts and sustained retinitis quiescence without specific anti-CMV therapy. Intravitreal ganciclovir injections seem well suited to offer effective CMV control during temporary periods of decreased CD4+ counts while awaiting HAART-mediated immune system reconstitution.     

Changes in the natural history of cytomegalovirus retinitis following the introduction of highly active antiretroviral therapy

OBJECTIVE: To determine the effect of highly active antiretroviral therapy (HAART) on the natural history of cytomegalovirus (CMV) retinitis. DESIGN AND PARTICIPANTS: Retrospective analysis of 103 consecutive patients diagnosed with CMV retinitis between 1990 and 1998. SETTING: Specialist HIV medicine department of a London hospital. MAIN OUTCOME MEASURES: Incidence of CMV retinitis, time to death following diagnosis, episodes of progression, incidence of inflammatory complications. The date of first use of HAART was January 1995. Data were censored on 30 June 1998. RESULTS: The incidence of CMV retinitis has declined dramatically following the introduction of HAART. Survival following CMV retinitis increased from a median of 0.65 years prior to 1995 to a median of 1.07 years after this date (P = 0.004). In multivariate analyses HAART was independently associated with improved survival (P = 0.02) and the association with year of diagnosis was no longer significant, suggesting that this effect is predominantly due to HAART. None of the patients receiving HAART experienced progression after 6 months of treatment. Complications of retinitis such as retinal detachment, uveitis and optic atrophy occurred in 39% of patients. The rare inflammatory complications of vitritis and cystoid macular oedema occurred only in recipients of HAART. CONCLUSIONS: The introduction of HAART has had a major impact on the natural history of CMV retinitis with improved survival time and decreased risk of progression following diagnosis. However, immune reconstitution may be associated with inflammatory complications which can result in significant visual loss in the absence of active CMV disease.     

CMV retinitis and the controversies associated with highly active antiretroviral therapy and the immune recovery hypothesis

The aggressive multidrug regimen of highly active antiretroviral therapy (HAART) has offered some degree of promise of immune reconstitution in AIDS patients, a phenomenon that theoretically would impact positively on the incidence and severity of opportunistic infections. Some studies already have noted complete regression of cytomegalovirus (CMV) retinitis without specific use of anti-CMV agents in patients undergoing HAART. However, the role of HAART in CMV retinitis remains controversial among investigators. This review of the salient details regarding the controversies associated with CMV retinitis and the immune recovery hypothesis is meant to shed light on current and future therapeutic issues concerns. Early data seem to predict a decline in CMV retinitis. However, some investigators have noted that increased CD4 T-lymphocyte counts may not protect against CMV retinitis; therefore, the diagnosis cannot be excluded based on count alone. There is also the question of whether CMV retinitis progression in any way represents failure of HAART in those patients receiving this type of combination therapy. HAART is seen as an encouraging development in the treatment of AIDS and opportunistic infection, but its more specific therapeutic effect on CMV retinitis requires further research with controlled prospective clinical trials.     

Incidence and risk factors for developing cytomegalovirus retinitis in HIV-infected patients receiving protease inhibitor therapy. Spanish CMV-AIDS Study Group.

OBJECTIVE: To assess the incidence and risk factors for cytomegalovirus (CMV) retinitis in HIV-infected patients who initiated protease inhibitor-containing antiretroviral therapy. DESIGN AND SETTING: Prospective, multicentre study. PATIENTS: A cohort of 172 HIV-infected patients with a CD4 cell count below 100x10(6) cells/l at the time of protease inhibitor introduction. MAIN OUTCOME MEASURES: Confirmed CMV retinitis and mortality, according to CD4 cell count, HIV load, and CMV viraemia. RESULTS: The cumulative incidence of CMV retinitis was 5% at 1 year and 6% at 2 years. Only a positive CMV polymerase chain reaction (PCR) test at therapy initiation was significantly associated with the development of disease (relative hazard, 4.41; 95% confidence interval, 2.12-8.93; P<0.00001). The 12-month Kaplan-Meier CMV retinitis event rate was 38% in patients who were CMV PCR-positive compared with 2% in those who were CMV PCR-negative (P<0.001). Mean CMV load was significantly higher in those individuals who went on to develop CMV retinitis (3700 versus 384 copies/ml, P = 0.002). Only 2% of patients remained CMV PCR-positive after 3 months of protease inhibitor therapy, and CMV viraemia was not associated with a worse therapy response or shorter survival. Transient CMV positivity without a higher risk of disease was observed in 7% of patients at the first month on therapy. CONCLUSIONS: Protease inhibitor-containing antiretroviral therapy significantly reduces the incidence of CMV viraemia and disease. Although a positive CMV PCR test identifies those patients on therapy at highest risk of CMV retinitis, it is not associated with an increased risk of death or a worse response to protease inhibitor therapy.     

Plasma cytomegalovirus DNA, pp65 antigenaemia and a low CD4 cell count remain risk factors for cytomegalovirus disease in patients receiving highly active antiretroviral therapy

OBJECTIVE: To study the natural history and the current risk factors for cytomegalovirus (CMV) disease in the context of highly active antiretroviral therapy (HAART). SETTING: Prospective multicentre cohort in 15 university hospitals in France. METHODS: A group of 198 patients with CD4 cell count < 100 x 10(6) cells/l (or < 200 x 10(6) cells/l under HAART for at least 2 months), no previous CMV disease and CMV-positive serology were followed every 4 months clinically and for virological testing including HIV RNA and CMV blood markers (culture, pp65 antigenaemia, plasma CMV DNA and CMV late mRNA by the polymerase chain reaction). RESULTS: At inclusion, median CD4 was 77 x 10(6) cells/l (0-308) and 85% of the patients received protease inhibitors. The percentage of patients receiving HAART reached 99% at 12 months. After a follow-up of 23.6 months, the incidence of CMV disease was 3.2/100 patient-years [95% confidence interval (CI) 1.3-5.0]. In univariate Cox models, all the CMV markers, a CD4 cell count remaining < 75 x 10(6) cells/l and an HIV viral load > 100,000 copies/ml were predictive for CMV disease. The hazard ratios for CMV disease were 11 for blood culture; 14 and 70 for pp65 antigenaemia of > or = 1 and > or = 100 nuclei/200,000 cells, respectively; 35 for plasma CMV DNA; 6 for CMV mRNA; 29 for CD4 < 75 x 10(6) cells/l; and 12 for HIV RNA > 100,000 copies/ml. In a stepwise multivariate analysis, only three covariates were independently associated with the occurrence of a disease: plasma CMV DNA, pp65 antigenaemia > or = 100 nuclei/200,000 cells and a CD4 count < 75 x 10(6) cells/l. CONCLUSION: CMV blood markers and CD4 count < 75 x 10(6) cells/l remain risk factors for CMV disease in patients receiving HAART. Analysis of plasma CMV DNA by the polymerase chain reaction is a reproducible and standardized tool that could be used as a decision marker for initiating CMV pre-emptive therapy.     

Cytomegalovirus antigenemia and outcomes of patients undergoing allogeneic peripheral blood stem cell transplantation: effects of long-term high-dose acyclovir prophylaxis and preemptive ganciclovir treatment

Cytomegalovirus (CMV) disease is a frequent cause of morbidity and mortality following allogeneic hematopoietic stem cell transplantation. In order to investigate the relationships between antigenemia, high-dose acyclovir (HDACV) prophylaxis, preemptive ganciclovir (GCV) therapy, and outcomes, we analyzed the records of 105 patients, including both pediatric and adult populations, who underwent allogeneic peripheral blood stem cell transplantation (PBSCT) and who were at risk for CMV reactivation and disease (both recipient and donor seropositive). All received HDACV until neutrophil engraftment, but prophylaxis was continued till post-transplant day 180 only in pediatric patients in conjunction with weekly CMV pp65 antigenemia monitoring. Antigenemia-guided preemptive strategy with GCV was used for all patients. CMV antigenemia developed in 45 patients (42.9%) and CMV disease in 13 (12.4%). The frequencies for antigenemia were 31.3 and 63.2% in pediatric and adult groups (P = 0.002). All CMV diseases were in the adult group (P<0.001). Age at transplantation, underlying disease, long-term HDACV prophylaxis and acute graft versus host disease (aGVHD) were all found to be a significant risk factors for antigenemia. All of these factors other than aGVHD and conditioning regimen were also the significant risk factors for CMV disease. However, when we analyzed the pediatric and adult patients separately, dropping "long-term HDACV prophylaxis," none of these parameters were significant risk factors for CMV disease. In conclusion, we hypothesize that long-term HDACV prophylaxis in the GCV era results in a low incidence of CMV reactivation and disease in patients undergoing PBSCT.     

Clinical features of late cytomegalovirus infection after hematopoietic stem cell transplantation

Late cytomegalovirus (CMV) disease beyond day 100 after hematopoietic stem cell transplantation (HSCT) has become an increasing problem after the introduction of preemptive ganciclovir (GCV) administration. To clarify the risk factors and outcome for late CMV reactivation and disease, we retrospectively analyzed the records of 101 Japanese adult patients who underwent allogeneic HSCT between 1998 and 2005 at our hospital. Fifty-one developed late positive CMV antigenemia, with a cumulative incidence of 53%. Recipient CMV seropositivity, the use of alemtuzumab, chronic GVHD, and high-dose steroids were significantly associated with late positive antigenemia. Eight patients developed late CMV disease, with a cumulative incidence of 8%, including retinitis and gastrointestinal disease. None progressed to a fatal disease. The use of alemtuzumab was identified as an independent significant risk factor for late CMV disease, although it was not associated with increased non-relapse mortality. Among the 51 patients with late positive antigenemia, 28 had consistently less than three positive cells, 25 of whom showed negative conversion without antiviral agents. In conclusion, late CMV antigenemia appeared to develop frequently, especially in patients with profound immune suppression; however, a fatal outcome could be prevented by optimal preemptive therapy. Low-level antigenemia may not require antiviral treatments.     

New CMV drug won't replace other therapies

Injectable fomivirsen (Vitravene) showed promise in premarketing clinical trials of AIDS patients with advanced cytomegalovirus (CMV) retinitis. Isis Pharmaceuticals says the drug works by interrupting the production process of proteins involved in human disease. The drug inhibits viral proteins critical to the CMV virus life cycle, delaying disease progression. The best candidates for taking fomivirsen are those who have recently started highly active antiretroviral therapy (HAART). Side effects include pressure in the eye after injection, a decrease in bone marrow, and inflammation.     

Therapy and Prevention of Cytomegalovirus Retinitis

Highly active antiretroviral therapy (HAART) has redefined the natural history of cytomegalovirus (CMV) retinitis. Once a major cause of blindness in AIDS patients, its incidence has plummeted and its clinical course has been altered. The potential of HAART for immunologic restoration should guide treatment decisions, and may ultimately lead to the possibility of withdrawal from maintenance anti-CMV therapy. However, new cases of CMV retinitis have begun to emerge in virologic and immunologic failures to HAART. The impact of HAART continues to evolve with the discovery of sight-threatening immune recovery uveitis. Specific anti-CMV treatment strategies have expanded and improved to include therapeutic options not requiring the parenteral route of administration such as valganciclovir, which has enhanced oral bioavailability.     

A fatal case of cytomegalovirus ventriculoencephalitis in a mycosis fungoides patient who received multiple umbilical cord blood cell transplantations

Cytomegalovirus (CMV) infection is latent in the majority of adult humans. The reactivation of CMV causes pneumonia and gastrointestinal disease in severely immunosuppressed patients, who consequently suffer very high mortality due to CMV central nervous system disease. We report here a case involving a 28-year-old female patient with mycosis fungoides who underwent umbilical cord blood transplantation three times and developed CMV ventriculoencephalitis. The patient's CMV viremia was successfully preempted with ganciclovir (GCV) as indicated by undetectable CMV antigenemia; despite this successful treatment, the patient developed CMV ventriculoencephalitis. Foscarnet (FCV) therapy led to a temporary recovery, after which CMV ventriculoencephalitis recurred, and the patient died after receiving combination GCV and FCV therapy. Autopsy samples revealed CMV ventriculoencephalitis, as indicated by numerous inclusion-bearing cells (Owl's eye). It is likely that this patient harbored a GCV-resistant CMV strain; however, it was not possible to obtain nucleic acids suitable for use in assessing this possibility.     

HIV and cytomegalovirus viral load and clinical outcomes in AIDS and cytomegalovirus retinitis patients: Monoclonal Antibody Cytomegalovirus Retinitis Trial

OBJECTIVE: To determine the association of cytomegalovirus (CMV) viremia with mortality and CMV retinitis progression in newly diagnosed and relapsed CMV retinitis. DESIGN: Ancillary study of a randomized, placebo-controlled, phase III clinical trial. PATIENTS: A total of 83 patients with AIDS and CMV retinitis, enrolled during the first phase of the Monoclonal Antibody Cytomegalovirus Retinitis Trial, were administered MSL-109 or placebo as adjuvant therapy for CMV retinitis. MAIN OUTCOME MEASURE(S): Mortality and CMV retinitis progression. RESULTS: Treatment with MSL-109 did not predict either progression of CMV retinitis or mortality. Detection in plasma CMV DNA at baseline predicted mortality, but CMV antigenemia did not. CMV DNA was a better predictor of mortality than a high HIV viral load. Neither CMV DNA nor antigenemia predicted the progression of CMV retinitis. Among newly diagnosed patients, there was a decline in the proportion with detectable CMV viral load and CMV antigenemia in response to anti-CMV therapy. However, there was a rebound in CMV viral load to 25% and CMV antigenemia to 54.6% at 6 months. In relapsed patients, anti-CMV therapy was not associated with a change in the percentage with detectable CMV-DNA or CMV antigenemia over time. CONCLUSION: In patients with AIDS and CMV retinitis, the detection of plasma CMV DNA was associated with a higher risk of mortality than was a high HIV viral load. Anti-CMV therapy provided a transient reduction in CMV viremia in newly diagnosed but not relapsed patients with CMV retinitis. Adjuvant therapy with MSL-109 was ineffective in clearing CMV-DNA and CMV antigen from the plasma.     

Correlates of change in cytomegalovirus viremia in patients with advanced human immunodeficiency virus infection who require transfusion

The Viral Activation Transfusion Study compared leukocyte-reduced to unfiltered red blood cell transfusions in human immunodeficiency virus (HIV)- and cytomegalovirus (CMV)-coinfected patients. Relationships between serially measured plasma CMV load and clinical and laboratory outcomes over a median of 12 months were examined in 511 subjects. At baseline, subjects had a median of 15 CD4(+) cells/mm(3), 25% had CMV disease, and 21.5% were viremic. No relationship was found between changes in CMV viremia and changes in HIV RNA. Increased CMV viremia was associated with a concomitant fall in Karnofsky score. Highly active antiretroviral therapy (HAART) led to a decrease in CMV viremia after a 90-day delay. After adjustment for HIV load and CD4(+) cell count, CMV viremia remained associated with an increased risk of CMV disease (relative hazard, 5.78). In late-stage HIV-infected patients, CMV viremia was associated with lower functional status and increased risk of CMV disease. HAART suppressed CMV viremia only after a delay of several months.     

Spontaneous remission of cytomegalovirus retinitis in a patient infected with the human immunodeficiency virus

BACKGROUND: We report a case of CMV retinitis cured in an AIDS patient after two months of regular HAART therapy without CMV medications. CASE REPORT: A 37-year-old patient (baseline CD4 count 47/ml) receiving HAART (2 NRTI and 1 IP) showed poor compliance and had increased his CD4 count for two months reaching 263/ml although HIV viral load remained high (71,840 copies/ml). His fundus was normal. He was evaluated 8 months after a period of loss to follow-up: his CD4 count was 65/ml, HIV viral load was 123,000 copies/ml, CMV serology for IgV and viruria were positive, viremia was negative, his fundus revealed a healed CMV retinitis. Six months later and without any CMV therapy, no relapse has been observed while regularly taking HAART medications. CONCLUSION: Few cases have been reported in which HAART therapy with good immune response and reduced HIV viral load lead to complete regression of CMV retinitis without specific CMV medication. This case suggests that, even with an uncontrolled HIV viral load, HAART via transient immune restoration may contribute to resolving CMV retinitis.     

Cytomegalovirus (CMV)-specific CD4+ T lymphocyte immune function in long-term survivors of AIDS-related CMV end-organ disease who are receiving potent antiretroviral therapy

To better understand the relation of cytomegalovirus (CMV)-specific CD4+ T lymphocyte immunity and clinical outcome in AIDS-related CMV end-organ disease, 2 patient groups were prospectively studied: patients recently diagnosed with active CMV end-organ disease and survivors of CMV retinitis who had responded to highly active antiretroviral therapy and had quiescent retinitis when anti-CMV therapy was discontinued. Most patients with active CMV disease had negative CMV-specific CD4+ T lymphocyte responses at diagnosis, as measured by lymphoproliferation (7/7) or cytokine flow cytometry (3/5) assays. In contrast, all 10 subjects with quiescent retinitis and >150 absolute CD4+ T lymphocytes/microL whose anti-CMV therapy was discontinued during 6 months of follow-up had positive CMV-specific immune responses at least once by each assay. However, 6 of these 10 subjects also had negative CMV-specific immune responses > or =1 time. Such patients may be at risk for future CMV disease progression and should be closely monitored.