J HIV particle

(mature virion)


Nucleoside AT inhibitors, non-nucleoslde HT inhibitors

FIGURE 50-1 Replicative cycle of HIV-1 showing the sites of action of available antiretroviralagents. Available anti-retroviral agents are shown in blue. Key: RT, reverse transcriptase; cDNA, complementary DNA; mRNA, messenger RNA; RNase H, ribonuclease H; gp120 + gp41, extracellular and intracellular domains, respectively, of envelope glycoprotein.

a result of new host immune responses and target cell depletion, the number of infectious virions— as reflected by the plasma HIV RNA concentration (also known as viral load)—declines to quasi-steady state. This set point of viral activity reflects the interplay between host immunity and the pathogenicity of the infecting virus. In the average infected individual, several billion infectious virus particles are produced every few days.

Eventually, the CD4 lymphocyte count begins a steady decline, accompanied by a rise in the plasma HIV RNA concentration. Once the peripheral CD4 count falls to <200 cell per mm3, there is an increasing risk of opportunistic infection. Sexual acquisition of CCR5-tropic HIV-1 is associated with a median time to clinical disease—usually an opportunistic infection such as Pneumocystis carinii pneumonia—of 8-10 years. Occasional patients can harbor HIV for more than two decades without significant decline in CD4 count or clinical immunosuppression; this may reflect a combination of favorable host immunogenetics and immune responses.

An important question is whether HIV disease is a consequence purely of CD4 lymphocyte depletion or also involves other factors. Most natural history data support the former. Regardless, successful therapy is based on inhibition of HIV replication; treatments designed to boost the host immune system without exerting a direct antiviral effect have had no reliable clinical benefit.

Principles of HIV Chemotherapy

Current treatment assumes that all aspects of the disease derive from direct toxic effects of HIV on host cells, mainly CD4 T lymphocytes. The goal of therapy therefore is to suppress viral replication as much as possible for as long as possible.

Deciding when to initiate therapy has been the subject of some debate. The advent of more effective drugs capable of increasing CD4 cell counts to normal or near normal levels led some to advocate a strategy of early use of combination drug therapy regardless of disease stage or symptoms. It now appears that true eradication of HIV is not possible, at least with current drugs, as there is a reservoir of long-lived, quiescent T cells harboring infectious HIV DNA incorporated into the host chromosome. Natural history studies also point to a low risk of short-term disease progression when the CD4 cell count is >350 cells per mm3 or plasma HIV RNA concentrations were <50,000 copies per mL. The toxic risks of long-term combination chemotherapy, the need for nearly perfect adherence to prescribed regimens, the inconvenience of some regimens, and the high cost of lifelong treatment point to a risk-benefit ratio that favors treating only patients with low CD4 counts and/or very high viral load (Table 50-1).

Drug resistance is also an extensive and serious problem. Because of the high mutation rate of HIV and the tremendous number of infectious virions, there is a high likelihood that any infected individual will harbor viruses with single-amino-acid mutations conferring some degree of resistance

U.S. Department of Health and Human Services Guidelines for Initiating Therapy in Treatment-Naive HIV-infected Patients, 2004

A. Patient Characteristics

Clinical Category

CD4 Count

Plasma HIV RNA


AIDS-defining illness*

Any value

Any value


or severe symptoms

Was this article helpful?

0 0
Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

Get My Free Ebook

Post a comment