26 Mar

Antiretroviral Therapy – Changing Therapy – part4

Criteria for Changing Therapy

  • Less than a 0.5–0.75 log reduction in plasma HIV RNA by 4 weeks following initiation of therapy, or less than a 1 log reduction by 8 weeks;
  • Failure to suppress plasma HIV RNA to undetectable levels within 4–6 months of initiating therapy.
  • Repeated detection of virus in plasma after initial suppression to undetectable levels, suggesting the development of resistance.
  • Any reproducible significant increase, defined as 3-fold or greater, from the nadir of plasma HIV RNA not attributable to intercurrent infection, vaccination, or test methodology except as noted above;
  • Persistently declining CD4 + T cell numbers, as measured on at least two separate occasions;
  • Clinical deterioration (Dlll). In this regard, a new AIDS-defining diagnosis that was acquired after the time treatment was initiated suggests clinical deterioration but may or may not suggest failure of antiretroviral therapy.

Therapeutic Options When Changing Antiretroviral Therapy

Table XIV summarizes some of the most important guidelines to follow when changing a patient’s antiretroviral therapy. Table XV outlines some of the treatment options available when a decision has been made to change the antiretroviral regimen. A change in regimen because of treatment failure should ideally involve complete replacement of the regimen with to which the patient is naïve and to which cross-resistance is not anticipated. This typically would include the use of 2 new NRTIs and one new PI or NNRTI, two PIs with one or two new NRTIs, or a PI combined with an NNRTI. Dose modifications may be required to account for  interactions when using combinations of PIs or a PI and NNRTI (Table XII).

Table 15. Possible Regimens For Patients Who Have Failed Antiretroviral Therapy

 

Prior Regimen New Regimen (Not listed in priority order)
2 NRTIs + 2 new NRTIs +

Nelfinavir (NFV)

RTV; or IDV; or SQV + RTV; or NNRTI## +
RTV; or NNRTI + IDV**

Ritonavir (RTV)

SQV + RTV**; NFV + NNRTI; or NFV + SQV

Indinavir (IDV)

SQV + RTV; NFV + NNRTI; or NFV + SQV

Saquinavir (SQV)

RTV + SQV; or NNRTI + IDV
2 NRTIs + NNRTI 2 new NRTIs + a protease inhibitor
2 NRTIs 2 new NRTIs + a protease inhibitor
2 new NRTIs + RTV + SQV
1 new NRTI
+ 1 NNRTI + a protease inhibitor
2 protease inhibitors + NNRTI
1 NRTI 2 new NRTIs + a protease inhibitor
2 new NRTIs + NNRTI
1 new NRTI + 1
NNRTI + a protease inhibitor

 

* These alternative regimens have not been proven to be clinically effective and were arrived at through discussion by the panel of theoretically possible alternative treatments and the elimination of those alternatives with evidence of being ineffective. Clinical trials in this area are urgently needed.

# RTV=ritonavir, IDV=indinavir, SQV=saquinavir, NVP=nevirapine, NFV=nelfinavir, DLV=delavirdine

** There are some clinical trials with viral burden data to support this recommendation

## Nevirapine induces and delavirdine inhibits CYP450 enzymes, and this must be considered in combining these with other agents. Efavirenz is a mixed inducer/inhibitor of CYP450 enzymes; concentration of concomitantly administered can be increased or decreased depending upon the specific enzyme pathway involved.

Treatment Regimen for Primary HIV Infection

The therapeutic regimen for acute HIV infection should include a combination of two nucleoside reverse transcriptase inhibitors and one potent protease inhibitor. Although most experience to date with protease inhibitors in the setting of acute HIV infection has been with ritonavir, indinavir or nelfinavir. Potential combinations of agents available are much the same as those used in established infection, listed in Table VI.

Duration of Therapy for Primary HIV Infection

Once therapy is initiated many experts would continue to treat the patient with agents indefinitely because viremia has been documented to reappear or increase after discontinuation of therapy (CII). The optimal duration and composition of therapy are unknown and ongoing clinical trials are expected to provide data relevant to these issues. The difficulties inherent in determining the optimal duration and composition of therapy initiated for acute infection should be considered when first counseling the patient regarding therapy. Buy antiviral drugs.

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