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There are currently three treatment options for liver hydatidosis: urgery, which remains the mainstay of radical treatment; ultrasound-guided aspiration (puncture/aspiration/injection/reaspiration--PAIR); and chemotherapy with benzimidazole compounds (albendazole and mebendazole). Chemotherapy is a noninvasive treatment and is less limited by the patient's status than surgery or PAIR but is not ideal when used alone. Albendazole, the drug most often used, appears to have the greatest efficacy of any agent used so far; nevertheless, apparent cure (shrinkage or disappearance of cysts) ranges only between 20% and 30% of cases. The possible contribution of perioperative chemotherapy offers the prospect of preventing recurrent disease, but it requires more clinical trials to establish that pre- or postoperative chemotherapy does prevent recurrence. The main adverse events are related to changes in liver enzyme levels and bone marrow suppression. About 10% to 20% of patients develop self-limited, reversible rises in transaminase levels; clinically severe pancytopenia or agranulocytosis is exceptional. Alopecia is observed during long-term treatment with albendazole. In all cases these events disappear once treatment is interrupted. According to the World Health Organization guidelines, chemotherapy is the preferred treatment when the disease is inoperable, when surgery or PAIR is not available, or when the cysts are too numerous. Another important indication for chemotherapy is the prevention of secondary echinococcosis. There is not yet formal consensus, as the efficacy and safety of some of the methods require further evaluation before we can establish comprehensive guidelines for the medical treatment of hydatidosis.

To assess prospectively the influence of the control of viral replication on the frequency of cytokine-producing T cells, and to correlate these changes with immune activation, we conducted a 15-month follow-up study of IFN-gamma- and IL-2-producing CD4+ and CD8+ T cells at a single-cell level in 12 previously untreated patients receiving highly active antiretroviral therapy (HAART). At baseline we observed a strikingly high proportion of IFN-gamma-producing CD8+ T cells. The treatment-induced decrease in the proportion of IFN-gamma-producing CD8+ T cells ran parallel to the decrease in HLA-DR+ and CD38+CD8+ T cell subsets and was associated with the reduction in HIV RNA level. IL-2-producing cells were mainly CD4+. As a consequence of CD4+ T cell loss, the number of IL-2-producing CD4+ T cells was lower in patients than in control subjects (52 vs. 171 cells/microl), but the proportion of these cells was unchanged (22.4 vs. 19.3). During therapy the proportion of CD4+ IL-2-producing cells was initially stable and then fell markedly at month 5, followed by a gradual return to previous values. The reduction in viral load was associated with the fall in the proportion of CD4+ activated subsets. Intracellular cytokine assays are a new approach to the assessment of T cell function in HIV infection. Our results suggest that the functional capacity of CD4+ T cells is probably less severely altered than previously thought on the basis of conventional assays. CD8+ T cells exhibit an increased capacity to produce IFN-gamma that is associated with an increase in activation marker expression. These alterations decrease partially and in parallel under treatment.

Objective: To characterize the immune changes after treatment of acute HIV-1 infection with triple nucleoside analogue therapy., Design: Immunological and virological parameters were monitored from day 0 to weeks 36-44 in eight patients [median CD4 cells = 451 cells/microl (range: 149-624), viral load = 4.8 log10 copies/ml (range: 6.5-3.3)] who started at time of primary HIV infection (PHI) a therapy including zidovudine (ZDV), didanosine (ddl), and lamivudine (3TC)., Methods: Lymphoid subsets were evaluated on peripheral blood lymphocytes by four-colour flow cytometry using a panel of mAbs directed against differentiation and activation markers., Results: We observed a median -2.1 (range: -1; -3.3) log10 copies/ml viral load decrease and a median +158 cells/microl (range: +7 to +316) CD4 cell count increase at week 4 reaching normal CD4 cell count values of 761 CD4 cells/microl (range: 389-1153) at weeks 36-44. Virus undetectability was obtained at week 24 for all subjects. A rapid CD4 T cell amplification involved both memory and naive CD4 T cells. This was associated with a very rapid and significant decrease in activation markers [human leukocyte antigen-DR (HLA-DR), CD38] on both CD4 and CD8 T cell subsets together with a CD8+CD28+ cell increase as early as week 4., Conclusions: These results show that early therapy with nucleoside analogues can correct the immunological abnormalities observed in CD4 and CD8 T cell subsets at the time of PHI. This early kinetics in T cell recovery appears to be faster than in established disease.

Purpose: To assess the tolerability and efficacy of intravitreal injections of foscarnet in cytomegalovirus (CMV) retinitis in acquired immunodeficiency syndrome (AIDS)., Methods: Patients with CMV retinitis resistant and/or intolerant to intravenous foscarnet and ganciclovir and resistant to intravitreal ganciclovir were included. The induction therapy consisted of intravitreal injections of 2,400 micrograms of foscarnet twice a week. The assessment was performed by clinical examination and photographies of the fundus., Results: Three patients (four eyes) have been included. Three eyes were administered seven and one eye eight intravitreal injections. The tolerability was good, but the efficacy was mere: the retinal lesions became less edematous, but they still extended., Conclusion: In these four eyes with CMV retinitis resistant to intravitreal ganciclovir, intravitreal injections of foscarnet were well tolerated but did not stop the progression of the retinitis.

Objective: To analyse the relationship between CD8+ lymphocyte phenotype alterations and plasma HIV RNA levels in HIV-infected patients treated with the zidovudine-didanosine combination., Methods: A total of 30 HIV-infected patients who had never received antiretroviral therapy and who were starting treatment with a combination of zidovudine and didanosine were prospectively studied. Multiparameter flow cytometric analysis of CD8+ lymphocytes and plasma HIV RNA determination were performed on day 0, day 15 and monthly from months 1 to 6., Results: Patients were divided into three categories according to the time-course of plasma HIV RNA levels. In 14 patients, an early and sustained fall in plasma HIV RNA to below the detection limit (500 copies/ml) was observed; in 10 patients, the fall was transient; in six patients, plasma HIV RNA was always detectable (non-responders). The mean CD4+ lymphocyte gain was 120 x 10(6)/l at month 6 in sustained and transient responders, and 55 x 10(6)/l in non-responders. A significant fall in the proportion of CD8+ lymphocytes with an activated phenotype was observed only in the two groups of responders, and was higher in the sustained responders (CD38+HLA-DR+, -56.8%; CD38+CD45RO+, -54.0%; HLA-DR+CD45RO+, -48.4%; CD38+CD28-, -47.3%)., Conclusion: A fall in the proportion of activated CD8+ lymphocytes is associated with the disappearance of HIV RNA from plasma during antiretroviral therapy. Undetectable plasma HIV RNA is not associated with a return to normal CD8+ lymphocyte activation status after 6 months of treatment, suggesting that viral replication persists in lymphoid tissues.

We reviewed the records of 15 Human Immunodeficiency Virus (HIV) infected patients with pulmonary cryptococcosis (PC). PC was the first AIDS-defining manifestation in nine patients. HIV infection was identified simultaneously with the onset of PC in 4 patients. The CD4+ lymphocyte count was low in all cases (median, 24/m3). Chest radiography showed interstitial infiltrates in 13 instances, associated with pleural effusion in 5 cases and hilar adenopathy in 2 cases. In one case, chest-X-ray showed isolated pleural effusion and was normal in one patient. For 11 of 12 patients, bronchoalveolar lavage fluid culture was positive for Cryptococcus neoformans. Seven of 15 patients had evidence of extrapulmonary cryptococcal disease with positive cerebrospinal fluid culture. Serum cryptococcal antigen was detected in all 15 patients. Concomitant lung infection with Pneumocystis carinii was diagnosed in 4 patients. First-line regimen was fluconazole in 10 patients and amphotericin B in 4 patients. Fluconazole has been prescribed in 7 patients as a permanent suppressive therapy and should be continued indefinitely.

Objective: To evaluate the efficacy and safety of liposomal encapsulated daunorubicin (DaunoXome) in the treatment of AIDS-associated mucocutaneous Kaposi's sarcoma., Design: A Phase II, multicentre, European, non-comparative, open study to assess the use of DaunoXome in patients with no prior anthracycline chemotherapy for Kaposi's sarcoma. The response rate, time to disease progression, and the incidence and severity of adverse events were documented., Setting: Hospital-based HIV units., Patients: Thirty HIV-seropositive patients with mucocutaneous Kaposi's sarcoma were enrolled and treated., Interventions: Treatment with DaunoXome at a dose of 40 mg/m2 intravenously once every 2 weeks. Treatment with antiretroviral agents and prophylaxis of opportunistic infections where indicated., Results: Of the 30 evaluable patients, 22 patients (73%) achieved a partial response. Median time to treatment response was 30 days (range, 15-202). For patients with a partial response, median time to treatment failure was 153 days (range, 15-558). Patients received a median of 10 cycles (range, 1-44). Adverse events were minimal. The most common side effect was granulocytopenia in 16 patients (53%)., Conclusion: DaunoXome is an effective and well-tolerated treatment for AIDS-associated mucocutaneous Kaposi's sarcoma and can be administered for prolonged periods. The myelosuppression can be managed by dose reductions and dose not preclude the concurrent use of antiretroviral therapies.

Unlabelled: This study tries to demonstrate the importance of using follow-up trials and taking anxio-depressive status into account while interpreting cognitive impairment in HIV-infected subjects. Subjects included were: 18 HIV carriers, mostly homosexual, belonging to CDC groups II (4), III or IVC2 (7) and IV (7), selected within a cohort of 63, as having been assessed 3 times, with no focal or identified brain disease at entry. Our methods were: 1) psychiatric interview based on DSM III-R criteria, clinical scales (Spielberger's STAXI and the MADRS) and cognitive questionnaires; 2) neuropsychological evaluation including 16 subtests screening attention, memory, visuo-spatial function, motor dexterity, psychomotor speed, and language; 3) repeated assessment within a period ranging from 6 to 21 months., Results: At entry, cognitive status was impaired for 14 subjects (2 II, 5 III or IVC2, 7 IV). Disorders had disappeared for 7 subjects (2 II, 2 IVC2 and 3 IV) at following assessments allowing us to conclude on a psychogenic origin. For 7 subjects, cognitive status had either remained constant (3 III and 2 II) or had worsened within 7 to 17 months (2 IV), whereas psychiatric symptoms had decreased, implying HIV encephalopathy. Follow-up trials including 3 neuropsychological and psychiatric assessments and neuroimagery, if necessary, were required to ascertain the causes of cognitive impairment consequently attributed to anxio-depressive symptoms or HIV encephalopathy in 14 subjects.

We report the clinical and biological course of infection with human immunodeficiency virus (HIV) type 1 in 11 liver transplant recipients who acquired this infection between 1985 and 1987. Eight patients were infected by blood or blood products from graft-related transfusions and one by the graft itself; the remaining two patients were infected after transplantation and had independent risk factors. All patients received a triple-drug immunosuppressive regimen including cyclosporine. The mean duration of follow-up after liver transplantation was 52 months (standard error, +/- 32 months). Chronic graft rejection was documented in four cases. The cumulative incidences of HIV-related complications and HIV-related deaths were 82% and 27%, respectively. Three patients died rapidly of HIV disease. The survival rate 7 years after transplantation was 36% among the 11 HIV-infected patients, whereas it was approximately 70% among HIV-negative liver transplant recipients during the same period. The course of HIV infection in the four survivors did not appear to differ from that in other patients infected by blood transfusion.

Detection of Toxoplasma gondii in blood by means of the polymerase chain reaction (PCR) may facilitate the diagnosis and follow-up of cerebral toxoplasmosis in patients with AIDS. We evaluated this approach with seven patients with tissue culture-proven parasitemia, 14 patients with presumptive cerebral toxoplasmosis, and 17 healthy human immunodeficiency virus-positive controls. Each sample of blood was assayed on three different occasions by a PCR assay based on detection of the gene encoding the P30 surface protein. A positive PCR diagnosis required positivity in at least two of the three PCR tests. None of the controls had a positive PCR diagnosis, but six of the seven patients with parasitemia did. Cerebral toxoplasmosis was confirmed in 13 of the 14 patients with a presumptive diagnosis; diagnosis by PCR was positive before treatment for 9 of these 13 patients, whereas tissue culture was positive for only 1 patient. During treatment, blood samples were taken from 14 patients at regular intervals until day 12. PCR diagnosis became negative on ethidium-stained gels, but persistent signals were observed after hybridization, in some cases, for up to 12 days after initiation of therapy. PCR on venous blood could thus be a sensitive and noninvasive method for the diagnosis of cerebral and disseminated toxoplasmosis in AIDS patients and could be a potential tool for monitoring the effects of treatment.

Background: Pneumocystis carinii pneumonia and toxoplasmic encephalitis are frequent life-threatening opportunistic infections in patients with human immunodeficiency virus (HIV) infection. Primary prophylaxis against P. carinii pneumonia is now common, but there are few data on regimens for primary prophylaxis against toxoplasmosis., Methods: We conducted a randomized trial that compared two prophylactic regimens: dapsone (50 mg per day) plus pyrimethamine (50 mg per week) was compared with aerosolized pentamidine (300 mg per month). The patients had symptomatic HIV infection, no history of P. carinii pneumonia or symptomatic toxoplasmosis, and CD4+ counts below 200 per cubic millimeter (0.2 x 10(9) per liter)., Results: In an intention-to-treat analysis, after a median follow-up of 539 days P. carinii pneumonia developed in 10 patients in each group, whereas toxoplasmosis developed in 32 of 176 patients in the pentamidine group and 19 of 173 patients in the dapsone-pyrimethamine group. Those assigned to pentamidine had a risk of P. carinii pneumonia that was similar to the risk in those assigned to dapsone-pyrimethamine (adjusted relative risk, 1.13; 95 percent confidence interval, 0.44 to 2.92; P = 0.79), but a higher risk of toxoplasmosis (adjusted relative risk, 1.81; 95 percent confidence interval, 1.12 to 2.94; P = 0.02). Among the 262 patients with serologic evidence of past exposure to Toxoplasma gondii, the relative risk of symptomatic toxoplasmosis was 2.37 times higher in those assigned to pentamidine (95 percent confidence interval, 1.3 to 4.4; P = 0.006). More patients discontinued dapsone-pyrimethamine than pentamidine because of toxicity (42 vs. 3; P < 0.001). Survival was similar in the two groups., Conclusions: For primary prevention of P. carinii pneumonia, dapsone-pyrimethamine is as effective, though not as well tolerated, as aerosolized pentamidine. Dapsone-pyrimethamine also prevents first episodes of toxoplasmosis.

Between 1989 and 1990, 10 HIV-infected patients with renal involvement (proteinuria and/or renal failure) were followed. The 5 men and 5 women black (4 Haitians, 3 Zairians, 2 Congolese and 1 Angolan). Their mean age was 31.7 +/- 4 years. No known risk factor was identified and transmission was probably heterosexual. When renal disease was diagnosed, 4 patients had AIDS, 5 had ARC and 1 was asymptomatic. Kidney biopsies were performed in 7 patients: 4 HIV-associated nephropathies (HIV AN) with segmental and focal hyalinizations, 1 thrombotic angiopathy, and 2 interstitial nephropathies, 1 with proliferative glomerulonephritis. The clinical, biological and radiographic patterns of 2 of the remaining 3 patients were suggestive of HIV AN. Four of the 6 patients with HIV AN developed end-stage renal disease within 5 +/- 2.5 months; renal function in the other 2 remained stable for 25 and 41 months, respectively, while they were receiving zidovudine, but deteriorated rapidly within weeks of withdrawing this drug. Zidovudine may have delayed the evolution of the nephropathies in these patients.

Objective: To study the degree of immunogenicity of each HIV-1 protein., Design: In most viral systems, antiviral cytotoxic T-lymphocytes (CTL) from a given donor preferentially recognize only one or a small number of viral proteins., Methods: Anti-HIV CTL were generated by in vitro stimulation of peripheral blood mononuclear cells from seropositive donors and tested against multiple HIV-1 proteins or groups of proteins encoded by seven genes (env, gag, pol, nef, rev, tat and vif). Using autologous target cells infected with recombinant vaccinia viruses expressing one of the HIV-1LAI proteins, we compared the cytolytic activities obtained from bulk culture with those found in limiting dilution analysis (LDA)., Results: Our results were noteworthy for the following reasons. (1) Each responding donor reacted simultaneously to multiple proteins; this is very unusual in other viral systems. Anti-Gag CTL were detected in most, and anti-Pol in approximately three-quarters, of the patients, together with very high amounts of the corresponding CTL precursors in LDA. CTL against Env and Nef were found in two-thirds of the patients, while Vif- and Rev-specific CTL were less frequent. Finally, Tat was seldom recognized by CTL, but its antigenicity was revealed in LDA. (2) All responding cells revealed in bulk cultures as well as in LDA were CD8+ T-cells, and their in vitro differentiation did not require the help of CD4+ T-cells. (3) Proteins from the HIV-1LAI isolate were recognized with high frequency by CTL from seropositive donors, most certainly being infected by other isolates, which suggests that relatively conserved epitopes are predominant targets of CTL., Conclusion: Taken together, these results are encouraging for vaccine purposes, since anti-HIV-1 CTL stimulation is thought to be a requirement for such a vaccine.

To assess the response to and tolerance of recombinant interferon-alpha administration in patients with chronic hepatitis C and human immunodeficiency virus (HIV) infection, 12 patients with chronic hepatitis C and HIV infection were given interferon-alpha, 1, 3, or 5 million units thrice weekly, for 4 or 6 months. Four patients had a complete response (normal serum alanine aminotransferase activity [ALT]), 3 had a near-complete response (serum ALT less than one-and-one-half times the upper limit of normal), and 5 had no response at the end of administration. Histologic examination of liver showed an improvement in 1 patient with complete response and no improvement in another patient with no response. In patients with chronic hepatitis C with HIV infection, the response to and tolerance of recombinant interferon-alpha were not different from those usually observed in patients with chronic hepatitis C infection without HIV infection.

Primary prophylaxis against opportunistic infections is a capital advance in the management of HIV-infected patients. In cases with pneumocystosis prophylaxis is recommended when the number of T4 cells reaches 200/mm3 or 15 to 20% and constitutes a major incitation to apply for detection of seropositivity. It can be predicted that other prophylaxis of this type will be available for other main opportunistic infections whose proportion is increasing due to extension of the patient's life expectation (e.g. toxoplasmosis). Research in this field relies on new drugs, on the use of older drugs, and above all on experimental models providing a good preclinical evaluation. The development of combined prophylactic treatments against several opportunistic infections is a priority target. Maintenance treatments are systematically given after a first opportunistic infection.

In order to identify the target epitopes recognized by specific CTL in the NEF protein of HIV-1, 33 peptides derived from the HIV-BRU sequence were tested with NEF-specific CTL generated from HIV-seropositive donors. Six different epitopes were identified and several points were remarkable: 1) They were all located in two regions of the central part of the NEF protein corresponding to residues 73 to 94 and 113 to 147, respectively. 2) The CTL issued from a single donor could recognize several peptides of the NEF protein. 3) Some of these peptides could be recognized in association with at least two or three different HLA class I molecules. 4) Two different overlapping epitopes were present in a relatively short sequence of 15 amino acids. These results suggest that multiple epitopes corresponding to different HLA restrictions could coexist in a relatively small region of the NEF protein. The implications of these results in vaccine strategies using synthetic peptides bearing CTL epitopes are discussed.

The diagnosis of Pneumocystis carinii pneumonia (PCP) rests on the isolation of this micro-organism in patients whose latest blood count, less than 2 months old, shows less than 250 CD4 lymphocytes per cubic mm and who present with signs of impaired lung function. Bronchoalveolar lavage (BAL) is the reference diagnostic method, but induced expectoration may be the initial examination, in which case BAL is performed only when the latter fails or gives negative results. Prognostic factors are those of any interstitial pneumonia plus those specific to PCP and those associated with HIV infection. It is only when no initial severity factor is present that cure can be contemplated, provided the effectiveness of treatment is evaluated daily. Cotrimoxazole is the reference drug for comparisons with all new treatments; the indications of corticosteroid therapy and the necessity of intensive care techniques are now better determined. The frequency of PCP and its mortality rate should be reduced, and one may look forward to a time when this disease will be rare and atypical, thereby raising other diagnostic and therapeutic problems.

To investigate the possibility of human immunodeficiency virus-(HIV) 1 infection of liver cells, liver samples from 17 patients with either acquired immunodeficiency syndrome (AIDS, 13), AIDS-related complex (ARC, 3), or lymphadenopathy syndrome (LAS, 1) were studied. A monoclonal antibody directed against the p24 gag HIV-1 protein was used in an immunoperoxidase assay and yielded positive results in seven out of 17 samples. Staining by anti-p24 antibody was of three types: diffuse in Kupffer cells of most samples, inside granuloma in cells that were probably histiocytes, and in some sinusoidal cells whose origin was difficult to ascertain. Attempts to locate the CD4 membrane antigen showed that it was mainly present on endothelial sinusoidal cells. These results indicate that liver cells, including Kupffer cells, might be infected by HIV-1, and that these cells might be involved in certain liver lesions observed during HIV-1 infection, particularly sinusoidal abnormalities.

In order to determine the extent of liver abnormalities occurring during acquired immunodeficiency syndrome, the available histological analyses of liver samples (32 biopsies, 52 autopsies) from 71 AIDS patients, for the period 1982-1986, were studied retrospectively. Hepatomegaly was the most common clinical symptom (23 patients, 32.4%), while jaundice was rare, being seen in only 5 cases (7%). Progressive anicteric cholestasis was the most frequently observed biological anomaly (29/52, 55.7%). Ten patients had liver infections: 2 Mycobacterium tuberculosis, 8 Mycobacterium avium intracellulare. Cytomegalovirus was present in 3 patients and 1 individual was infected with Cryptococcus neoformans. Granulomatous hepatitis was associated with these infectious agents in 11 patients, but remained unexplained in 11 others. Three patients had cholangitis (2 with CMV inclusions, 1 unexplained). Among the 32 biopsies, 5 elucidated the origin of unexplained fever. Kaposi's sarcoma of the liver was found in 10/52 autopsy samples (19%) and hepatic lymphoma in 2 cases. Non-specific histological lesions were common: inflammation of the portal spaces (48 cases, 67.6%), steatosis (32 patients, 45%), peliosis hepatis (9 cases, 12.6%) and sinusoidal dilations (39 cases, 54.9%).