inhibition of reverse transcriptase, to prevent the virus from transforming RNA into DNA and integrating into the genome of the host cell;inhibition of the integration of proviral DNA into cellular DNA to avoid the production of new viral proteins;inhibition of the subsequent steps (assembly and release of complete viral particles) to prevent the formation of new viruses.
It has now been demonstrated that combined therapy, with synergistic drugs, is preferable to monotherapy in order to achieve three main objectives: the effective suppression of viral replication, which is essential for improving the immune response; inhibition or slowing of the onset of resistance; specific intervention on different cell or tissue reservoirs of the virus.
Currently, the decision as to when to initiate antiretroviral therapy must be assessed by considering the number of CD4 + lymphocytes and the extent of plasma viraemia. Drug change occurs when viral replication resumes, especially when followed by CD4 reduction or clinical worsening.
The recognition of subjects who have a greater risk of developing into a full-blown disease is of particular relevance today due to the ever-increasing availability of drugs. Some indicators have proved to be particularly useful and are defined as “markers or indicators of progression”; they can be divided into virological, immunological and clinical.
Among the virological indicators, the one usually used is plasma viraemia (the degree of viral replication). Plasma concentrations of HIV RNA reflect the rate of replication of the active virus and consequently the destruction of CD4 T cells.
Immunological indicators take into account the state of immune deficiency: during the chronic phase of the infection, the number of CD4 + T lymphocytes decreases, and the reduction is closely associated with the development of opportunistic infections and tumors.
It is therefore natural to consider the reduction of CD4 + lymphocytes an important indicator of progression of the infection: rapid decreases in the absolute number and percentages of CD4 (greater than 10% per year = “rapid decline”) are an unfavorable sign.
The usual clinical markers are oral candidiasis, oral villous leukoplakia, herpes zoster, seborrheic dermatitis, persistent lymphadenomegaly, significant weight loss and constant low-grade fever.The prognosis marker currently considered the most reliable for clinical evolution and for monitoring the efficacy of therapy is represented by the CD4 lymphocyte count.
For the purpose of a correct clinical control of all asymptomatic seropositive subjects, it is considered sufficient to prescribe a determination of plasma viraemia after about 6-9 months from acute infection (“setpoint”), every 3-4 months in never treated patients, at the start of therapy, 4 weeks after initiation and every 3-4 months during therapy and at the onset of a clinical event.
As a rule, antiretroviral therapy is indicated in the presence of AIDS-related clinical events, when the viral load exceeds 30,000 copies of the virus per milliliter of blood, or when CD4 lymphocytes are less than 350 per microliter.