Suppress HIV Replication

RANTES/CCL5, MIP-1a/CCL3, and MIP-1p/CCL4 Can Suppress HIV Replication 

It has been suspected for years that CD8 T cells produce soluble factors which suppress HIV-1 replication (9,10). Thus, it was of great interest when, in 1995, it was reported that at least some of these factors were the C-C chemokines RANTES/CCL5, MIP-la/CCL3, and MIP-ip/CCL4 (11). This was the first evidence that chemokines were connected to HIV biology. Whether RANTES, MIP- 

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Walker CM, Levy JA (1989) A diffusible lymphokine produced by CD8+ T lymphocytes suppresses HIV replication. Immunology 66 628-630 Walker RE, Bechtel CM, Natarajan V, Baseler M, Hege KM, Metcalf JA, Stevens R, Hazen A, Blaese RM, Chen CC, Lehman SF, Palensky J, Wittes J, Davey RT, Falloon J, Polls MA, Ko-vacs JA, Broad DF, Levine BL, Roberts MR, Masur H, Lane HC (2000) Long-term in vivo survival of receptor-modified syngeneic T cells in patients with human immunodeficiency virus infection. Blood 96 467 74... 

O The treatment goals for HIV infection are to maximally and durably suppress HIV replication, avoid the development of drug resistance, restore and preserve immune function, prevent opportunistic infections, and minimize adverse effects. 

O Currently, the goal of therapy is to maximally and durably suppress HIV replication in order to restore and preserve immune system function and minimize morbidity and mortality. Since HIV replication has been found in all areas of the body, it is important to use potent drug therapy that can achieve adequate concentrations in all tissues, including protected sites such as the brain and genital tract. 

The use of potent combination antiretroviral therapy to suppress HIV replication to below the levels of detection of sensitive plasma HIV RNA assays limits the potential for selection of antiretroviral-resistant HIV variants, the major factor limiting the ability of antiretroviral drugs to inhibit virus replication and delay disease progression. 

Answers to the above were not late coming in a remarkable follow-up paper, Inouye confirmed the activity of luzopeptin C against HIV-RT, and disclosed that, indeed, 4 suppresses HIV replication in infected MT-4 cells at non-cytopathic concentrations. Luzopeptin C must thus be selective for RT vis-d-vis human DNA polymerases ... 

Mackewicz CE, Barker E, Levy JA. Role of beta-chemokines in suppressing HIV replication. Science 1996 274 1393-1395. 

Kinter AL, Ostrowski M, Goletti D, et al. HIV replication in CD4+ T cells of HI V-infected individuals is regulated by a balance between the viral suppressive... 

The central goal of antiretroviral therapy is to decease morbidity and mortality through maximum suppression of HIV replication (HIV RNA level that is undetectable). Secondary goals include an increase in CD4 lymphocytes. 

The most effective means to accomplish durable suppression of HIV replication is the simultaneous initiation of combinations of effective anti-HIV drugs with which the patient has not been previously treated and that are not cross resistant with antiretroviral agents with which the patient has been treated previously. 

Finally, it is recognised that antiretroviral drugs, although they can temporarily suppress viral replication and improve symptoms, do not cure human immunodeficiency virus infection (HIV). Promotion of all possible measures to prevent new infections therefore remains essential and its need is not diminished by the availability of antiretroviral drugs. 

Only ART drug combinations containing at least 3 drugs from at least 2 ARV classes lead to durable suppression of HIV and translate into an improved immunologic state and quality of life. Individuals from RLS have been fortunate to benefit from earlier studies in developed countries and therefore early start of ART (CD4 count > 500/pl) or monotherapy/ dual therapy have been avoided in these settings. Several combination regimens with demonstrated effectiveness in achieving durable suppression of HIV replication are available. 

Mecfianism of Action A protease inhibitor that suppresses HIV protease, an enzyme necessary for splitting viral polyprotein precursors into mature and infectious viral particles. Therapeutic Effect Interrupts HIV replication, slowing the progression of HIV infection. 

Zidovudine is used to suppress the replication of the human immunodeficiency virus (HIV), which is responsible for aquired immune deficiency syndrome, AIDS (Figure 14.12). According to the World Health Organization, by the beginning of 2005 about 40 million people were infected with HIV and about 20 million people around the world had already lost their lives to AIDS. 

Walker CM, Moody DJ, Stites DP, Levy JA. CD8+ lymphocytes can control HIV infection in vitro by suppressing virus replication. Science 1986 234(4783) 1563-1566. 

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