Treatment Review; Double Issue #26 & #27 November 1997
* One strong protease inhibitor + 2 NRTIs
Strong protease inhibitors (not listed in order of priority, the guidelines do not recommend any one of these protease inhibitors over another) are:
* nelfinavir (Viracept)
Recommended combinations of two NRTIs (not listed in order of priority, the guidelines do not recommend any one of these combinations over another) are:
* AZT (Retrovir) + ddI (Videx)
* d4T (Zerit) + 3TC (Epivir)
* AZT (Retrovir) + 3TC (Epivir)
* AZT (Retrovir) + ddC (HIVID)
Alternate Combinations
The guidelines list alternative combinations that may be less likely to reduce HIV viral load as effectively as the preferred combinations. However, the guidelines note that for the combination of two NRTIs with nevirapine (Viramune) further studies may show that it is as effective as the preferred combinations.
* nevirapine (Viramune) + 2 NRTIs (see list of combinations above)
* saquinavir (Invirase) + 2 NRTIs (see list of combinations above)
Not Generally Recommended
Not generally recommended because reductions in HIV viral load do not last as long as with the preferred three drug combinations.
Combinations of 2 NRTIs
Not Recommended
These treatments or combinations are not recommended due to evidence that they don't work or have side effects that are too similar.
* Any anti-HIV drug used alone(also known as monotherapy) and combinations of:
* d4T (Zerit) + AZT (Retrovir)
* ddC (HIVID) + ddI (Videx)
* ddC (HIVID) + d4T (Zerit)
* ddC (HIVID) + 3TC (Epivir)
NRTI: Nucleoside analog reverse transcriptase inhibitor. Approved NRTIs are AZT (Retrovir), ddI (Videx), ddC (HIVID), d4T (Zerit) and 3TC (Epivir).
NNRTI: Non-nucleoside analog reverse transcriptase inhibitor. Approved NNRTIs are nevirapine (Viramune) and delavirdine (Rescriptor).
Protease inhibitors (PIs): Approved protease inhibitors are indinavir (Crixivan), nelfinavir (Viracept), ritonavir (Norvir) and saquinavir (Invirase).
For more details on each drug, see the glossary.
Choosing NRTIs
The strongest NRTI combinations seem to be AZT + 3TC, d4T + 3TC or d4T + ddI. In an ongoing study, all three of these combinations had about the same anti-HIV effect when used in combination with a strong protease inhibitor (in this study they used Crixivan). The main differences were in side effects: AZT can cause nausea, headache and anemia (low red blood cells). Combinations using d4T and/or ddI can cause neuropathy which is pain in the hands and feet. 3TC can also sometimes cause neuropathy. Another concern is resistance. Combinations of NRTIs including AZT have sometimes been known to cause resistant HIV to develop that is not affected by any NRTI drug. This is called multi-drug resistance. It is not yet known whether NRTI combinations that don't include AZT can also cause multi-drug resistance.
Guidelines: Which Drugs To Change to Protease inhibitors and cross-resistance
Recent studies have shown that when HIV becomes resistant to one of the available protease inhibitors, the other protease inhibitor drugs will almost always be affected. In most studies done so far, the anti-HIV effect of a second protease inhibitor is lessened by resistance to the first, no matter which particular protease inhibitor drugs are used. This is called cross-resistance.
There isn't much information to help people work out what to do when an anti-HIV drug combination including a protease inhibitor stops working. The clearest recommendation is to try and change to a combination of entirely new anti-HIV drugs. Combinations of protease inhibitors with an NNRTI drug and two NRTIs have been tried in small studies with some successes reported. Combinations of two protease inhibitors with new NRTI and/or NNRTI drugs may also be a possibilty. Combinations of saquinavir (Invirase) with ritonavir (Norvir) and also saquinavir with nelfinavir (Viracept) have been studied. However, the largest of these protease inhibitor combination studies have been in people who hadn't taken protease inhibitors before. Early reports of double protease inhibitor combinations in people who have already tried protease inhibitors have been mixed. In some cases this may be because other anti-HIV drugs were not changed at the same time as the protease inhibitor combinations were started.
One problem has been the lack of clinical trials for people who have already used protease inhibitors and need new options. There are now some clinical trials that are enrolling people with protease inhibitor experience, call the Network for the latest information and referrals.
The guidelines admit that there is very little information on what to use when a three drug combination including a protease inhibitor stops working. The suggestions in each section are not listed in order of priority.
If the first combination was 2 NRTIs + nelfinavir (Viracept), the guidelines suggest:
* 2 new NRTIs + indinavir (Crixivan) + NNRTI* or
* 2 new NRTIs + ritonavir (Norvir) + NNRTI* or
* 2 new NRTIs + ritonavir (Norvir) + saquinavir (Invirase) or
* 2 new NRTIs + indinavir (Crixivan) or
* 2 new NRTIs + ritonavir (Norvir)
If the first combination was 2 NRTIs + ritonavir (Norvir), the guidelines suggest:
* 2 new NRTIs + nelfinavir (Viracept) + NNRTI* or
* 2 new NRTIs + ritonavir (Norvir) + saquinavir (Invirase)
If the first combination was 2 NRTIs + indinavir (Crixivan), the guidelines suggest:
* 2 new NRTIs + nelfinavir (Viracept) + NNRTI* or * 2 new NRTIs + ritonavir (Norvir) + saquinavir (Invirase)
If the first combination was 2 NRTIs + saquinavir (Invirase), the guidelines suggest:
* 2 new NRTIs + indinavir (Crixivan) + NNRTI* or
* 2 new NRTIs + ritonavir (Norvir) + saquinavir (Invirase)
* 2 new NRTIs + ritonavir (Norvir)
* 2 new NRTIs + nelfinavir (Viracept)
If the first combination was 2 NRTIs + nevirapine (Viramune), the guidelines suggest:
* 2 new NRTIs + a protease inhibitor
If the first combination was 2 NRTIs, the guidelines suggest:
* 2 new NRTIs + a protease inhibitor
If the first combination was 1 NRTI, the guidelines suggest:
* 2 new NRTIs + a protease inhibitor or
* 2 new NRTIs + nevirapine (Viramune)
* Of the available NNRTIs, currently nevirapine (Viramune) is thought to have a stronger anti-HIV effect. One doctor with a large HIV practice in New York City has also reported some success with delavirdine (Resciptor) in combination with indinavir (Crixivan) and two NRTIs in people who seemed to be getting resistant to indinavir. Further studies of NNRTIs in people who have already taken protease inhibitors are ongoing.
Knowledge, Action, Health: A Woman's Guide to HIV Treatments.
There is an excellent brochure available from Women Alive that talks about anti-HIV treatments as they relate to women living with HIV/AIDS. To get this brochure call (800) 554-4876, or send a request to Women Alive, 1566 Burnside Avenue, Los Angeles, CA 90019.
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