Initiating Therapy in the Patient with Asymptomatic HIV Infection
Tables V and VI summarize the recommendations regarding when to initiate therapy and what regimens to use. In general, any patient with less than 500 CD4 + T cells/mm3 or greater than 10,000 (bDNA) or 20,000 (RT-PCR) copies of HIV RNA/ml of plasma should be offered therapy.
Table 5. Indications for the initiation of antiretroviral therapy in the chronically HIV-infected patient
CD4+ T Cell Count and HIV RNA
|Symptomatic (AIDS, thrush, unexplained fever)
||CD4+ T Cells <500/mm3or
HIV RNA >10,000 (bDNA) or >20,000 (RT-PCR)
|Treatment should be offered. Strength of recommendation is based on prognosis for disease-free survival as shown in Table IV and willingness of the patient to accept therapy.*
||CD4+ T Cells >500/mm3and
HIV RNA <10,000 (bDNA) or <20,000 (RT-PCR)
|Many experts would delay therapy and observe; however, some experts would treat
* Some experts would observe patients with CD4+ T cell counts between 350-500/mm3 and HIV RNA levels <10,000 (bDNA) or <20,000 (RT-PCR).
Table 6. Recommended for treatment of established HIV infection
||Strong evidence of clinical benefit and/or sustained suppression of plasma viral load (2,42,43) One choice each from column A and column B. Drugs are listed in random, not priority, order:
||ZDV + ddI (AI)
||d4T + ddI (AII)
||ZDV + ddC (AI)
||ZDV + 3TC# (AI)
Saquinavir SGC or HGC (BII)
|d4T + 3TC# (AII)
||Less likely to provide sustained virus suppression or data inadequate (44,45).
Nevirapine or delavirdine + 2 NRTIs (Column B, above)***(BII)
|Not generally recommended:
||Strong evidence of clinical benefit but initial virus suppression is not sustained in most patients (46-49).
2 NRTIs (Column B, above)(CI) Saquinavir-HGC + 2 NRTIS (Column B, above)II(CI)
||Evidence against use, virologically undesirable, or overlapping toxicities
All monotherapies ##(DI)
d4T + ZDV (DI)
ddC +ddI ### (DII)
ddC +d4T ### (DII)
ddC + 3TC (DII)
* Virologic data and clinical experience with saquinavir-SGC (Fortovase) are limited in comparison with other protease inhibitors.
** Use of ritonavir 400 mg b.i.d. with saquinavir-SGC (Fortovase) 400 mg b.i.d. results in similar drug exposure and activity as when using 400 mg b.i.d. of saquinavir-HGC (Invirase) in combination with ritonavir. However, this combination with Fortovase has not been extensively studied, and gastrointestinal toxicity may be greater when using Fortovase.
*** The combination of any of the 3 available NNRTIs + 2 NRTIs can suppress viremia to undetectable levels in the majority of patients remaining on treatment for > 28 weeks. An efavirenz- containing regimen has been shown to compare favorably to a PI-containing regimen with regard to suppression of viremia through 36 weeks; such head-to-head comparative trials have not been performed with nevirapine or delavirdine. Of note, use of efavirenz, nevirapine or delavirdine may result in resistance that precludes efficacy of any other member of this drug class.
# High-level resistance to 3TC develops within 2- 4 weeks in partially suppressive regimens; optional use is in 3-drug antiretroviral combinations that reduce viral load to undetectable levels. P Use of saquinavir-HGC (Invirase) is generally not recommended, except in combination with ritonavir.
## Zidovudine monotherapy may be considered for prophylactic use in pregnant women with low viral load and high CD4 + T cell counts to prevent perinatal transmission, as discussed under
### This combination of NRTIs is not recommended based on lack of clinical data using the combination and/or overlapping toxicities.
Comparison of the results obtained from the RT-PCR and bDNA assays using the manufacturer’s controls consistently indicate that the HIV-1 RNA values obtained by RT-PCR are approximately two times higher than those obtained by the bDNA assay (12). Thus, the MACS values must be multiplied by approximately 2 to be consistent with current RT-PCR values. A third test for HIV RNA, the Nucleic-Acid Sequence Based Amplification (NASBA), is currently used in some clinical settings.
When initiating therapy in the patient naïve to antiretroviral therapy, one should begin with a regimen that is expected to reduce viral replication to undetectable levels. Based on the weight of experience, the preferred regimen to accomplish this is 2 nucleoside analogues (NRTIs) and one potent protease inhibitor (Pl); however, recent data with the use of efavirenz (an NNRTI) in place of the PI may support such a substitution (Table VI). Alternative regimens have been employed; these include ritonavir and saquinavir (with one or two nucleoside analogues) or nevirapine as a substitute for the protease inhibitor. Ritonavir and saquinavir (hard gel capsule) dual PI therapy (without an NRTI) appears to be potent in suppressing viremia below detectable levels, and has convenient BID dosing. At least one additional NRTI be used when the physician elects to use 2 PIs as initial therapy. Using 2 NRTIs alone does not achieve the goal of suppressing viremia to below detectable levels as consistently as does combination treatment with 2 NRTIs and a PI and should be used only if more potent treatment is not possible. Online Canadian Pharmacy