Page 54 - AIDSBK23C

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Response to antiretroviral therapy must be monitored by HIV-1 RNA and/or CD4
lymphocyte counts. The HIV-1 RNA level provides a better indicator of clinical benefit than
does the CD4 count. Before initiation of therapy, baseline values must be established by
obtaining at least two measurements of these parameters. Following institution of therapy,
response may be monitored aggressively with HIV-1 RNA and/or CD4 lymphocyte assays every
1 to 3 months. More conservative monitoring may occur at 6-month intervals. The goal of
aggressive therapy is a complete suppression to a measurable level <50 copies/mL of HIV-1
RNA in plasma.[256]
In general, within two weeks of the start of aggressive antiretroviral therapy, plasma
HIV-1 RNA will fall to about 1% of their initial value. A minimum 1.5 to 2.0-log decline should
occur by 4 weeks, and an early response by 4 to 8 weeks suggests continued HIV suppression.
Persons starting therapy with high plasma levels of HIV (>100,000 copies/mL) may take longer
to suppress, but failure to suppress viremia <50 copies/mL by 16 to 24 weeks of therapy suggests
poor adherence, inadequate drug absorption, or drug resistance.[256]
Suppression of viremia will reduce the level of HIV in genital secretions and reduce
transmissibility of HIV from infected persons.[132,294] In general suppression of viremia in
serum to a level below 1500 copies/mL is associated with a low rate of transmission of
HIV.[142] Despite suppression of viremia, even to undetectable levels, persons with HIV
infection must still be considered infectious and should continue to avoid behaviors that could
transmit infection to others. Even persons with undetectable levels of HIV-1 RNA in plasma
may still have virus detectable in genital secretions.[141]
Failure of treatment may not necessarily relate to the appearance of drug resistance. The
problems of patient adherence to the drug regimen and the drug potency contribute to treatment
failure. Patients who have a lower educational level have an increased risk for progression to
AIDS and death, even if ART is available.[295] Though dosing regimens for antiretroviral
therapy (ART) are complex, it is essential that patients adhere to the regimen for adequate and
continued suppression of viremia.[296] An adherence rate of 95% is required for optimal
suppression of viremia.[256] complications, as shown by a study in which ART was not
instituted until the CD4 count decreased below 250/µL and then discontinued when the count
exceeded 350/µL. There was a significantly increased risk of opportunistic disease or death from
any cause, as compared with continuous antiretroviral therapy.[297]
An important goal of aggressive antiretroviral therapy is suppression of HIV replication
to reduce the emergence of antiretroviral drug-resistance strains, which are the rate-limiting
th
factor to continued drug effectiveness and survival. At the end of the 20 century, ART therapy
was unable to suppress HIV-1 RNA to less than 400 copies/mL in 10 to 40% of patients starting
their first treatment regimen, and 20 to 60% of patients on a second or third antiretroviral
regimen demonstrated treatment failure.[298,299] 288, 289 Suppression of viremia is best
accomplished with simultaneous initiation of combination antiretroviral therapy, using drugs not
previously given and drugs not known to be subject to cross-resistance.[210] If suppression of
viremia is not adequate, then drug resistant HIV-1 variants arise that are capable of being
transmitted to others and may impact the spread of HIV-1 through inability to suppress HIV-1 in
infected persons.[300,301] 290, 291 In one study of newly infected persons, 16% had been
infected with HIV-1 variants with known resistance to antiretroviral agents.[302] 292
A change in the treatment regimen for HIV infection may be instituted for a variety of
reasons. Such a change may be prompted by increasing drug resistance, as indicated by
detectable HIV-1 RNA reappearing in plasma after complete suppression, or increasing HIV-1