Cytomegalovirus infection: the point in 2001

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.     

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.     

Failure of a prospective trial to detect cytomegalovirus retinitis after initiation of highly active antiretroviral therapy

Thirty-one patients with AIDS with CD4+ T-cell counts of less than 75/mm3 were enrolled in a prospective study to determine the incidence of cytomegalovirus (CMV) retinitis and changes in CD4+ T-cell counts and viral loads following initiation of highly active anti-retroviral therapy (HAART). Patients were assessed using an Amsler grid, a visual field test, a questionnaire, and direct and indirect funduscopy. Only one patient developed an opportunistic infection, and the majority of patients had a threefold decrease in their viral loads and an increase in CD4+ T-cell counts within 2 months of initiating HAART. These findings support the belief that recent therapies modify the natural history of HIV infection and that new clinical approaches will be needed to address the changing profile of HIV/AIDS patients. None of our patients developed CMV retinitis. The findings add to those of other researchers, and suggest that if CMV retinitis does develop after HAART, it is an unusual finding that may be due to preexisting, subclinical retinitis rather than failure of HAART to reconstitute full immune cell recovery.     

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.     

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.     

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.     

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.     

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.     

Monitoring cytomegalovirus retinitis prevalence in an HIV-seropositive cohort: the assessment of improvements observed following the introduction of highly active antiretroviral triple therapy

This paper concerns the ophthalmic assessment of patients with acquired immunodeficiency syndrome (AIDS) for a number of eye conditions and in particular cytomegalovirus (CMV) retinitis. CMV has been the most common opportunistic infection associated with AIDS and the leading cause of blindness among AIDS patients. There have been early indications of a widespread fall in CMV prevalence internationally following the introduction of a new highly active antiretroviral triple (HAART) therapy. Our study sought to assess the position for Ireland. Our cohort was the entire population of stage IV AIDS patients attending the country's leading referral centre. The total number of patients examined was 167 and the period of examination was 1 May 1995 to 30 April 1997. HAART was introduced in March 1996, so the data permitted a 'before and after' comparison of various clinical findings. The incidence of new CMV cases was found to be 4 among the 102 patients examined in the first 12-month period and one among 107 patients examined in the second 12-month period. There were accompanying declines in HIV-related noninfectious retinal vasculopathy (HIVR), keratitis and other conditions. The findings are promising, but we argue that caution is needed in assessing long-term trends. In the paper we discuss a number of methodological issues in the collection and analysis of the clinical data and in the interpretation of results.     

Sustained cytomegalovirus-specific CD4+ T cell response associated with prevention of recurrence of cytomegalovirus retinitis without secondary prophylaxis after highly active antiretroviral therapy in patients with AIDS.

It has been demonstrated that the cytomegalovirus (CMV)-specific CD4(+) T cell response could be restored after ganciclovir and highly active antiretroviral therapy (HAART) in AIDS patients. In this study, we first confirmed the above observation cross-sectionally. We then performed a prospective longitudinal study over a period of 48 weeks. The second study included nine patients. All patients had received HAART. Five patients had a history of retinitis that was, however, under control after discontinuation of anti-CMV therapy more than 1 year before this study (group A). The other four had active CMV retinitis at the start of this study and anti-CMV therapy was required to control retinitis (group B). Median periods between commencement of HAART and the start of this study in group A and in group B were 27 and 4.5 months, respectively. Within both groups, the number of CD4(+) T cells that produced tumor necrosis factor alpha in response to CMV antigen did not vary throughout the observation period (Friedman test; p > 0.05). However, the median number of responsive CD4(+) T cells in group A patients was significantly higher than in group B (p < 0.05). Our results demonstrate that the number of CMV-responsive CD4(+) T cells increased when HIV was well controlled with HAART and was then maintained, and suggest that these cells may play an important role in the control of retinitis in patients with AIDS.     

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.     

AIDS并发巨细胞病毒性视网膜炎

目的探讨艾滋病(AIDS)并发巨细胞病毒(CMV)性视网膜炎的临床特点和治疗转归.方法观察分析北京协和医院确诊为AIDS并发CMV视网膜炎的5例患者的临床和实验室资料、治疗转归.结果 5例CMV视网膜炎患者的9只眼均经眼底散瞳检查确诊.全部患者均为AIDS晚期患者,CD+4T淋巴细胞计数3～36/mm3,在确诊CMV视网膜炎时均已合并其它机会性感染.平均年龄29.2±5.1岁.临床症状有视物模糊、视力下降等.眼底检查有典型的视网膜血管炎,表现为沿血管分布的黄白色病损、黄白色颗粒及视网膜出血,但玻璃体透明或轻微混浊.4例接受更昔洛韦(GCV)治疗的患者病情均得到控制,眼底病变消退,但其中1例视力丧失(失明)无法恢复;1例患者未特殊治疗死于多种机会感染.结论中国CMV视网膜炎的表现和国外文献报道的类似,多发生于晚期AIDS患者,不及时治疗将导致视力丧失,早期诊治非常重要.建议对于CD+4 T细胞计数<50/mm3以及存在眼外CMV感染的AIDS患者,应常规作眼底检查;反之,对于拟诊CMV视网膜炎的所有患者,均应常规筛查血清HIV抗体.     

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.     

Discontinuation of maintenance CMV therapy in HAART responders

The effectiveness of highly active antiretroviral therapy (HAART) in suppressing HIV and restoring some immune system function has enabled some patients to discontinue additional maintenance therapy for cytomegalovirus (CMV) retinitis. Research from the ICAAC conference in 1997 and the Ocular Immunology Service at the Johns Hopkins Hospital suggest that anti-CMV therapy can be successfully stopped in certain patients. There are no guidelines for discontinuing CMV therapy, and researchers have to rely on the results of clinical trials. ACTG 379 and ACTG 350 are studies attempting to measure time to reactivation after termination of CMV therapy, and CMV viral load after cessation of therapy, respectively. These studies will be useful in determining therapy option, and length of treatment. It is suggested that clinicians resume anti-CMV therapy in patients whose CD4 counts dip below 50 cells/mm3, and monitor all patients monthly for changes and for signs of immune recovery vitritis.     

Association between cytomegalovirus-specific reactivity of T cell subsets and development of cytomegalovirus retinitis in patients with acquired immunodeficiency syndrome.

The association between cytomegalovirus (CMV)-specific reactivity of T cell subsets and development of CMV retinitis (CMV-R) was prospectively studied in 50 CMV-seropositive AIDS patients. The frequency of CMV-specific CD69 expression on CD8 T cells was similar in patients with and patients without CMV-R (median, 1.0% vs. 1.2%; P=.14). However, the frequency of CMV-specific CD69 expression on CD4 T cells was significantly lower in patients with CMV-R than in those without CMV-R (median, 0.4% vs. 2.25%; P<.001). CMV-specific CD4 T cell reactivity in patients who developed CMV-R shortly after starting highly active antiretroviral therapy (HAART) remained low, although the CD4 cell counts increased markedly. Therefore, development of CMV-R is associated with a poor CMV-specific reactivity of CD4 T cells but not with poor reactivity of CD8 T cells. Development of CMV-R after initiation of HAART is associated with a poor reconstitution of CMV-specific immune response, rather than with immune rebound.     

Neurologic cytomegalovirus complications in patients with AIDS: retrospective review of 13 cases and review of the literature

Neurological disorders caused by Cytomegalovirus (CMV) in patients with Acquired Immunodeficiency Syndrome (AIDS) are rarely reported in the Highly Active Antiretroviral Therapy (HAART) period. The objective of this study was to describe the main clinical and laboratory features of patients with CMV-related neurological complications in HIV-infected patients admitted to a referral center in S?o Paulo, Brazil. CMV disease requires the identification of the virus in the cerebrospinal fluid (CSF) using Polymerase Chain Reaction (PCR). Thirteen cases were identified between January, 2004 and December, 2008. The median age of patients was 38 years and nine (69%) were men. At admission all patients were aware of their HIV status and only four (31%) patients were on HAART. Patients who were not on antiretroviral therapy before admission received HAART while inpatients. CMV disease was the first AIDS-defining illness in eight (62%) patients. The neurologic syndromes identified were diffuse encephalitis (n = 7; 62%), polyradiculopathy (n = 7; 54%), focal encephalitis (rhombencephalitis) (n = 1; 8%), and ventriculo-encephalitis (n = 1; 8%). Seven (54%) patients presented extra-neural CMV disease and four (31%) had retinitis. The median of CD4+ T-cell count was 13 cells/μL (range: 1-124 cells/μL). Overall in-hospital mortality was 38%. Eight patients used ganciclovir or foscarnet (in-hospital mortality: 50%) and five patients used ganciclovir and foscarnet (in-hospital mortality: 20%). None of the patients fulfilled the diagnosis criteria of immune reconstitution inflammatory syndrome. Four patients were lost to follow-up, and three patients presented immune recovery and discontinued secondary prophylaxis. Although infrequent, distinct neurological syndromes caused by CMV continue to cause high mortality among AIDS patients. Survival depends upon the use of effective antiviral therapy against CMV and the early introduction of HAART.     

Summary of the 5th Conference on Retroviruses and Opportunistic Infections

Research highlights from the Fifth Conference on Retroviruses and Opportunistic Infections are presented in the following five areas: 1) major messages concerning AIDS treatment and outcomes; 2) research findings on new antiretroviral agents; 3) prevention and treatment of opportunistic infections; 4) research on HIV transmission routes and rapid test strategies for HIV; and 5) the cost of AIDS health care and resource allocation. Important information delivered at the conference includes research on CD4 cell response during acute retroviral syndrome and long-term prognosis, viral burden nadir predicting long-term antiviral success, opportunistic infections and viral burden under 5,000, impaired phosphorylation after prolonged AZT therapy, and successful salvage in patients failing indinavir. The most important observations of antiretroviral agents are discussed for the following drugs: amprenavir, efavirenz, abacavir, and adefovir. Additional research is summarized on the reduction in the frequency of opportunistic infections in the age of highly active antiretroviral therapy (HAART), including the frequency of resistance during treatment of CMV retinitis and the treatment of tuberculosis and viral burden. Tables include results from selected clinical trials of antiretroviral therapy and results from research on salvage regimens. Finally, evidence is highlighted revealing that the cost of hospitalization has been substantially reduced but is offset by pharmaceutical costs.     

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-specific CD4+ T cell responses in human immunodeficiency virus type 1-infected patients with high CD4+ T cell counts and recurrent retinitis

Clinical histories are reported for 2 patients treated with highly active antiretroviral therapy (HAART) who experienced multiple relapses of cytomegalovirus (CMV) retinitis, despite suppression of human immunodeficiency virus type 1 (HIV-1) viremia and improvement in CD4+ T cell counts (to >400 cells/microL). CMV-specific CD4+ T cell immune reconstitution was measured directly, using cytokine flow cytometry, which revealed persistent deficits in CMV-specific CD4+ T cell responses in both patients. CMV-specific T cells constituted 0.14% and 0.05% of the total CD4+ T cell count in these patients, which is significantly lower than the percentages for 34 control subjects (0.6%-46%; CD4+ T cell count range, 7-1039 cells/microL; P=.019). Deficits in pathogen-specific immune responses may persist in some individuals, despite suppression of HIV-1 replication and substantial increases in circulating CD4+ T cells after HAART, and such deficits may be associated with significant morbidity from opportunistic infections.     

Pulmonary complications in patients with AIDS

HIV infection was first reported in 1981 in USA. It has been 20 years since then. Owing to understandings of pathogenesis of this disease and development of new drugs such as the HIV-specific protease inhibitor (PI), prognosis of disease has been tremendously improved. Especially after 1997 in Japan, the strategy of anti-HIV treatment shifted from two drugs combination to three drugs combination, which is called highly active antiretoviral therapy (HAART). HAART was so effective that prevalence of HIV associated opportunistic infections were decreased dramatically. Mortality among hospitalized HIV-infected patients was decreased from 6.7% in 1996 to 2.6% since then in ACC. However, 80% of patients receiving HAART suffered from side effects and 15% of them had to be changed their treatment due to side effects. Furthermore, an unexpected side effect, namely lipodystrophy syndrome (LDS), was emerged among patients who were receiving HAART more than one year. LDS was first reported as re-distribution of lipid such as central obesity with or without lipo-atrophy from extremities and/or face. Now only cosmetic change, but also it is associated with elevation of lipid and glucose level. Therefore, those patients who have LDS are in face of the risk for the ischemic heart diseases. Our survey indicated that the rate of LDS in Japanese patients were almost same as that of Caucasian patients reported elsewhere. Opportunistic infections associated with HIV infection Treatment for HIV infection consists of two major arms; one is use of anti-HIV drugs to prevent development of AIDS described above and the other is diagnosis, treatment, and prophylaxis of opportunistic infections. There are five very important opportunistic infections; Pneumocystis carinii pneumonia (PCP), cryptococcus meningitis, toxoplasma encephalitis, cytomegalovirus (CMV) infection, and Mycobacterium avium complex (MAC) bacteremia. Because if these five were able to diagnose, a patient can survive under appropriate treatment. On the other hand, if these were not diagnosed, patient must be AIDS death. After introducing HAART, number of CMV retinitis, MAC bacteremia, and AIDS dementia complex were decreasing. However, number of PCP sustained high because PCP is the first indicator disease of AIDS if the patient did not know his HIV status. The first choice of drug is sulfamethoxazole/trimethoprim (ST) for PCP treatment. If the patient were in severe respiratory failure, corticosteroid is used concomitantly. Treatment is usually continued for 3 weeks. We have successfully treated 45 out of 47 cases of PCP for 4 years. However, those patients treated with ST for 3 weeks were limited only 35% because of very high rate of side effects of ST. If the patient was intolerant to ST, treatment was switched to pentamidine. After finishing the treatment, the patient is to be treated with a 5-day course of oral desensitization to ST. More than 80% of patients who were previously intolerant to ST became successfully getting tolerance by this method.