PubMed · 9432382
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P I Fujiwara, L F Sherman. 1997. Multidrug-resistant tuberculosis: many paths, same truth.. https://pubmed.ncbi.nlm.nih.gov/9432382/
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Antigens derived from host cells are detectable in the envelope of human immunodeficiency virus type 1 (HIV-1) and result in a distinctive viral phenotype reflecting that of the host cell. An immunomagnetic capture assay targeting discriminatory host proteins was developed to differentiate between HIV-1 derived from macrophages and lymphocytes. HIV-1 propagated in macrophages or lymphocytes in vitro was selectively captured by monoclonal antibodies directed against the virally incorporated cell-type-specific host markers CD36 (macrophages) and CD26 (lymphocytes). Furthermore, by targeting these markers, virus of defined cellular origin was selectively captured from a mixed pool of in vitro-propagated viruses. This technique was further refined in order to determine the impact of opportunistic infection on HIV-1 expression from these cellular compartments in vivo. Analysis of cell-free virus purified from plasma of patients with HIV-1 infection suggested that in those with an opportunistic infection, viral replication occurred in activated lymphocytes. Interestingly, there was also significant replication in activated macrophages in those patients with untreated pulmonary tuberculosis. Thus, in addition to lymphocytes, the macrophage cellular pool may serve as an important source of cell-free HIV-1 in patients with opportunistic infections that lead to marked macrophage activation. This novel viral capture technique may allow researchers to address a wide range of important questions regarding virus-host dynamics.
BACKGROUND: In the era of highly active antiretroviral therapy (HAART), certain complications of HIV-disease as e.g. opportunistic infections and Kaposi s sarcoma (KS) have significantly diminished. New insights in pathological pathways revealed the role of co-viruses as HHV-8 and HCV so that in our days AIDS-associated KS and chronical hepatitis C (CHC) in HIV-infected persons can be considered as the result of opportunistic infections with HHV-8 or HCV respectively. - Though the overall incidence of AIDS-KS is declining, it remains as a reason of severe disease complication and fatal outcome. Actual therapeutic strategies have to be evaluated regarding safety and efficacy as a major option, while cost-effectiveness of treatment and quality of life aspects for the patient must also be included to assess a successful disease management within the up to now merely palliative setting. HIV-infection evidently triggers the natural course of CHC in terms of more progressive liver disease. Otherwise there seems to be no clinical benefit of HAART on CHC. Until recently IFN-alfa treatment was the only therapy available for patients with CHC. As initial therapy with a combination of IFN-alfa and ribavirin turned out to be more effective than IFN-monotherapy in HCV-infected persons, it has now to be considered to include anti-HCV-combination treatment into the therapeutic program of HIV-HCV-coinfected patients under HAART. - Within the 7th European Conference on Clinical Aspects and Treatment of HIV-Infection, which took place in Lisbon from October 23 to 27 1999, a satellite symposium was organized to evaluate actual treatment options in the management of special HIV-associated complications focussing on AIDS-KS and HCV-HIV-coinfection. METHODS: To evaluate the safety and efficacy of IFN-alfa-2b and ribavirin combination therapy in patients with CHC, a total of 1773 treatment-naive patients was recruited in two phase III clinical trials. They were randomized in 4 treatment schedules to receive IFN-alfa-2b plus ribavirin or placebo for 24 weeks or 48 weeks respectively. Cost-effectiveness data compared treatment with liposomal daunorubicin and pegylated liposomal doxorubicin in AIDS-KS-patients within two phase III studies. The assumptions were a comparable efficacy, gastrointestinal toxicity, and frequency of opportunistic infections (OI). A quality-of-life-study on KS-treatment with pegylated liposomal doxorubicin (PLD, Caelyx(R)) was based on a phase III study with an overall median survival of 160 days for the patients, who completed questionnaires with 30 items specific for HIV-related diseases. The health-related quality-of life (HRQL) assessment and analysis includes 11 domains, in which improvements were calculated within a multiple analysis to be significant if they are higher than 10 (at a 0-100 scale). RESULTS: In 1775 treatment-naive patients with CHC, response rates to a combination therapy of IFN-alfa-2b with ribavirin was significantly higher in all patient groups with more than 60% of sustained virological response in patients with genotype 2 and 3, while patients with genotype 1 (poorer prognosis) benefit from extended duration from 24 to 48 weeks (17% versus 29% of sustained virological response). - Pegylated liposomal doxorubicin (PLD, Caelyx(R)) in the treatment of AIDS-related KS is more effective and less toxic than BV or ABV. Cost-effectiveness analysis suggests that PLD is preferable over liposomal daunorubicin, BV and ABV. Regarding the HRQL-assessment, PLD came out to be superior in 9 of 11 domains tested, with the greatest improvement in general health and pain relief. CONCLUSIONS: As the combination therapy of IFN-alfa-2b with ribavirin is the first treatment in CHC, there is an urgent need to consider the therapeutical strategies in this field in HCH-HIV coinfected patients. (ABSTRACT TRUNCATED)
CONTEXT: Acquired immunodeficiency syndrome-related opportunistic illnesses (Ols) continue to occur after initiation of potent antiretroviral therapy in patients with human immunodeficiency virus (HIV) infection. Risk factors for clinical progression to Ols during potent therapy are not well defined. OBJECTIVE: To examine the incidence of and risk factors for Ols among patients treated with potent antiretroviral therapy in a population-based study. DESIGN: The Swiss HIV Cohort Study, a prospective cohort study of adult HIV-infected persons. SETTING: Seven study centers throughout Switzerland. PATIENTS: A total of 2410 cohort study participants with a potential follow-up of at least 15 months after starting potent therapy between September 1995 and December 1997. MAIN OUTCOME MEASURES: Disease-specific incidence of Ols during the 6 months preceding potent antiretroviral therapy and at 3 intervals after initiating therapy; risk factors for development of Ols during therapy. RESULTS: Of the 2410 participants, 143 developed 186 Ols after initiation of potent antiretroviral therapy. Incidence of any OI decreased from 15.1 per 100 person-years in the 6 months before therapy to 7.7 in the first 3 months after starting treatment, 2.6 in the following 6 months, and 2.2 per 100 person-years between 9 and 15 months. Reductions in incidence ranged from 38% per month for Kaposi sarcoma (P<.001) to 5% per month for non-Hodgkin lymphoma (P = .31). Baseline CD4 cell count continued to predict the risk of disease progression after initiating potent therapy. Compared with CD4 cell counts above 200 x 10(6)/L, the hazard ratio for developing Ols was 2.5 (95% confidence interval [CI], 1.4-4.5) for counts between 51 and 200 x 10(6)/L and 5.8 (95% CI, 3.2-10.5) for counts below 51 x 10(6)/L at baseline. Independent of baseline CD4 cell count, a rise in CD4 cell count by 50 x 10(6)/L or more and undetectable HIV-1 RNA in plasma (<400 copies/mL) by 6 months reduced risk of subsequent events, with hazard ratios of 0.32 (95% CI, 0.20-0.52) and 0.39 (0.24-0.65), respectively. CONCLUSIONS: Our data indicate that the risk of developing an OI for a person receiving potent antiretroviral therapy is highest during the initial months of therapy. Baseline CD4 cell count and immunologic and virologic response to treatment were strong predictors of disease progression in patients receiving potent therapy. Individuals with CD4 cell counts of 50 x 10(6)/L or below may need close clinical surveillance after initiation of potent therapy.