Initially, only nucleoside inhibitors of HIV reverse transcriptase were available for ther-apy of HIV infection and they were used singly. Currently, there are at least 16 approved therapeutic agents that inhibit either of two essential viral enzymes: reverse transcriptase or protease. Other antiviral agents under development include those that can block viral entry into the cell, and others that may inhibit viral integrase activity. It is clear that various combinations of these agents are preferable to produce effective virologic and clinical responses.
Because viral replication proceeds at the phenomenal rate of approximately 10,000 new viruses per day, it seems most rational to begin treatment as soon as infection is detected. However, considerations of toxicity, resistance development, quality of life, cost, and pa-tient wishes are extremely important additional determinants. Although these issues may cause debates regarding early intervention, there is a general consensus that combination therapy should be initiated when CD4+ count falls below 500/mm3 or the plasma HIV viral load is more than 5000 copies/mm3 of viral RNA.
RNA viruses tend to have frequent mutations, and the genome of HIV is highly variable. This results in part from the extremely high turnover rate of virions per day. As a result, resistance to an antiviral is a regular and often rapid development. Use of antiviral therapies that maximally suppress HIV viral load appear to diminish the appearance of resistant virus.
In addition to the primary treatment of HIV, patients with CD4+ counts of less than 200/mm3 should begin prophylactic regimens to prevent P. carinii pneumonia; when CD4+ counts are less than 75 to 100/mm3 they should receive prophylaxis for mycobacterial and fungal infection.
The spread of AIDS has been facilitated by changing sexual mores, injection drug use, and, in some parts of the world, disruption of family and tribal units as a consequence of industrialization and urbanization. These factors are obviously not subject to rapid change. Immediate prevention must be based on education about the means of transmis-sion and easy access to condoms and safe needles for those large numbers of people who continue to place themselves at risk. The epidemiologic and laboratory methods used to control foci of other major epidemic diseases pose particular problems in AIDS control at present. Quite apart from questions of potential discrimination against infected individu-als and the calamitous effects of false-positive serologic test results, the sheer magnitude and cost of case finding and contact tracing at present limit this approach. Detection and treatment of HIV-infected pregnant women has also been shown to be effective in reduc-ing perinatal infection.
Caesarian section, particularly elective rather than emergent, is also a preventive, as is the avoidance of breast feeding by HIV positive mothers. Much research is underway to develop vaccines against the virus, but the marked mutability of HIV greatly complicates this approach. Furthermore, passage of virus between fused cells and in syncytia protects it from antibody neutralization in established disease. The search continues for conserved epitopes of the surface glycopeptides that might provide possible antigenic targets. An-tiviral treatment utilizing combinations of agents may prevent infection of accidentally exposed individuals (eg, health care workers). This therapy must be initiated within hours of an accident if it is to have any chance of success.
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