PRIMATE LENTIVIRUS GROUP : they all use CD4 as receptor (hence infect CD4+ Th lymphocytes) and have a conic core which undergoes maturation after budding.

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  • In 2004 there are 6 million people living with HIV/AIDS in developing countries that urgently need access to antiretroviral treatment (ART), but only 400,000 have this access. A year's supply of a brand-name cocktail therapy for HIV/AIDS costs 562 US$, while the generic version costs 140 US$. The average annual salary in Botswana, where 38.8% of adult population is infected, is 3,440 US$. HIV sanctuaries are CD4+ resting T-lymphocytes (t1/2= 8.5 days; activable by administering IL-2), macrophages (t1/2 = 14 days), microglial cells and Langerhans cells. Therapy endpoint is to obtain [vRNA] < 5,000 / mL. Antigenic drift may create up to 15 different quasi-species in the same individual. The theory that structured treatment interruptions (STI) / ‘pulsing’ HAART, in chronically infected HIV-positive patients, apart from giving the patients a break from the side effects of drugs, allows the virus to mutate back to a form that is more susceptible to therapy has been discredited by the Swiss-Spanish Intermittent Treatment Trial (SSITT). The "drug holiday" could actually be detrimental, causing more frequen progression of disease and speeding up the attack on the immune system. However this study only included patients in whom HIV was detectable in the blood and the virus had already become resistant to drugs, and did not apply to individuals who are being successfully treated with HAART. Monitoring blood for cell counts or viral levels is essential to check that patients are taking their medicines, or to ensure that the virus has not become resistant to the drugs given, but patients in Africa, for example, often miss out on essential blood-cell monitoring because it requires fresh, refrigerated blood and expensive FACS machines. A new cheaper approach uses ELISA of dried whole blood spots to measure CD4+ lymphocyte counts in HIV-1-infected patientsref. Through week 48, the combination of tenofovir DF and emtricitabine plus efavirenz fulfilled the criteria for noninferiority to a fixed dose of zidovudine and lamivudine plus efavirenz and proved superior in terms of virologic suppression, CD4+ lymphocyte response, and adverse events resulting in discontinuation of the study drugsref. In a RCT in Abidjan, Côte d'Ivoire, patients on CD4-guided HAART (CD4GT) with interruption and reintroduction thresholds at 350 and 250 cells/ml, respectively had severe morbidity rates 2.5-fold higher than those on CT. This difference was mainly due to high rates of common diseases in patients with CD4 count 200–500/mlref. HIV-infected patients fail to fully recover cell-mediated immunity despite HAART. To identify regulatory factors, the phenotype and function of in vitro CMV-stimulated T cells from HAART recipients were studied. CFSE-measured proliferation showed CD4+ and CD8+ cells dividing in CMV-stimulated cultures. Compared with healthy controls, CMV-stimulated lymphocytes from HAART recipients had lower 3H-thymidine incorporation; lower IFN-g and TNF-a production; higher CD4+CD27-CD28- and CD8+CD27-CD28- frequencies; lower CD4+CD25hi; and higher FoxP3 expression in CD8+CD25hi cells. CMV-specific proliferation correlated with higher IFN-g, TNF-a and IL10 levels and higher CD4+perforin+ and CD8+perforin+ frequencies. Decreased proliferation correlated with higher CD4+CD27-CD28- frequencies and TGF-b1 production, which also correlated with each other. Anti-TGF-b1 neutralizing antibodies restored CMV-specific proliferation in a dose-dependent fashion. In HIV-infected subjects, decreased proliferation correlated with higher CMV-stimulated CD8+CD25hi frequencies and their FoxP3 expression. FoxP3- and TGF-b1-expressing regulatory T cells contribute to decreased immunity in HAART recipientsref. T-cell recovery after HAART in HIV-reconstituting-adults could be the consequence of antigen-independent peripheral T-cell expansion while in HIV-reconstituting-children thymic output could play a predominant role in immune reconstitutionref. Immunological follow-up was performed in 45 early chronical HIV-1-infected patients during short STI cycles during the first 12 weeks after the definitive interruption of HAART (DTI) and, thereafter, until VL reached a plateau. During STI cycles, CD8+, CD8+, CD28+, activation markers and naive CD4+ T cells increased significantly (p < 0.0001), while both naive CD8+ and memory CD4+ T cells decreased. During DTI, CD8+ CD28+ T cells fell and CD4+ naive T cells stabilized and the rest of the T cell subsets presented changes similar to those during STI cycles. Despite a transient increase in LPR to recall antigens and HIV proteins during STI cycles, LPR to polyclonal stimuli and pathogens decreased over the study. Differences in T cell subset dynamics and LPR observed throughout the study suggest that multiple exposures to low levels of antigen could improve the immune system, mainly by driving T cell maturation. Conversely, higher and longer viral replication after cessation of HAART overwhelms the immune system. These data may help to guide future immune-based therapiesref. Initial treatment with either NRTI+NNRTI or NRTI+PI regimens, but not NRTI+NNRTI+PI because of toxic effects, is a good strategy for long-term antiretroviral management in treatment-naive patients with HIVref.
    Mice infected with the LP-BM5 mixture of murine leukemia viruses (MuLV) develop a syndrome termed murine AIDS (MAIDS), characterized by a rapid and persistent proliferation of B and CD4+ >T cells, hypergammaglobulinemia, phenotypic abnormalities of lymphocyte subsets and increasingly severe defects of cellular and humoral immunity. Later in the course of disease, malignant transformation of both T and B cells may occur. Induction of MAIDS requires expression of the MA and p12 portions of the gag gene of replication-defective viruses designated BM5def or Du5H. MAIDS can be induced by helper-free defective virus, but in disease induced by the LP-BM5 virus mixture, nonpathogenic, replication-competent ecotropic, and mink cell focus-forming (MCF) viruses serve as helpers for cell-to-cell transmission of the defective genome and are known to accelerate development of the disease. Infection of B cells is required for efficient infection of T cells and macrophages.

    The world's largest donor for fighting AIDS is the USA, which spent $2.4 billion in 2004. But it is being pressured by conservative religious groups toward abstinence-only programs and away from vulnerable groups like prostitutes, homosexuals and drug addicts. Included in the U.S. contribution is some $450 million, or 1/3 of the budget of the Global Fund to Fight AIDS, Tuberculosis and Malaria -- a powerful independent organization of governments, business and private groups, first proposed by Annan 4 years ago. The new head of the group's policy and strategy committee is Randall Tobias, who runs the Bush administration's AIDS program. Some officials are worried that the fund will adopt U.S. positions, but others say such fears are groundless. Worldwide some $8 billion will be available in 2005 to implement programs in 135 low- and middle-income countries, a dramatic 23% increase over the previous year. Of this amount, rich countries have contributed some $6.7 billion, 6 times greater than the world spent in 2001

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