Initiation of Therapy
Leading Regimens to consider
• 2 Nucleoside RTI's + Protease Inhibitor
- NNRTI sparing
• 2 Nucleoside RTI's + Non-Nucleoside RTI
- PI sparing
• 3 Nucleoside RTI's (including abacavir)
- PI and NNRTI sparing
Advantages and disadvantages of class sparing regimens
Regimen |
Possible Advantages |
Possible Disadvantages |
Drug Interaction Complications |
Impact on future Options |
PI based HAART regimen (NNRTI-sparing) |
clinical, virologic, and mmunologic efficacy well-documented.
Continued benefits sometimes seen despite viral breakthrough.
Resistance requires multiple mutations
Targets HIV at two steps of viral replication (RT and PI) |
May be difficult to use and adhere to Long-term side effects may include lipodystrophy,* hyperlipidemia, and insulin resistance |
Mild to severe inhibition of cytochrome P450 pathway; Ritonavir is most potent inhibitor, but this effect can exploited to boost levels of other Pis |
Preserves NNRTI for use in treatment failure
Resistance primes for cross-resistance with other Pis |
NNRTIs-based HAART regimen (PI-sparing) |
Sparing of PI-related side effects
Generally easier to use and adhere to compared with Pis |
Comparability to PI-containing regimens with regard to clinical endpoints unknown
Resistance Conferred by single or few mutations |
Fewer drug-drug interactions Pis |
Preserves Pis for later use
Resistance usually leads to cross resistance across entire NNRTI class |
Triple NRTI Regimen (NNRTI -and PI-sparing) |
Generally easier to Use and adhere to compared with PIs
Sparing of PI and NNRTI side effects
Resistance to 1 NRTI does not confer cross-resistance to entire class |
Compatibility to PI-containing regimens with regard to clinical endpoints unknown
Long-term virologic efficacy with high baseline plasma vital load (i.e.,> 100 000 copies/ml may be suboptimal |
Generally manageable drug interaction problems |
Preserves both PI and NNRTI classes for later use
Limited cross-resistance within the NRTI class |
• Some side effects being attributed to protease inhibitor therapy, such as lipodystrophy, have not been proven to be strictly associated with use of protease inhibitor-containing regimens. Lipodystrophy has also been discerened uncommonly in patients on NRTIs alone and patients on other antiretroviral therapy.
|
Possible first line Regimen for Adults (with substitutions)
• Zidovudine/Lamivudine/Nelfinavir (or LPV or Indinavir)
- Stavudine for Zidovudine (in case of toxicity)
• Zidovudine/Lamivudine/Efavirenz (or Nevirapine)
- Stavudine for Zidovudine (in case of toxicity)
• Zidovudine/Lamivudine/Abacavir
- Stavudine for Zidovudine (in case of toxicity)
• Stavudine, Didanosine, Efavirenz
• Stavudine, Lamivudine, Nelfinavir
• Stavudine, Didanosine, Nevirapine
|
The choice of regimen should take consideration of patient's affordability, drug potency and other factors detailed in this book.
There is an interim WHO ARV Treatment Working Group drafting guidelines for Resource Poor Settings. Kenya is a member of the steering team and the recommended 1st line drugs will be indicated in the 2nd Edition of this booklet.
The following table of recommendations is based on IAS and DHHS guidelines for antiretroviral therapy.
Antiretroviral drug regimens are comprised of one choice each from column A and B. Drugs are listed in alphabetical and not in priority order.
Strongly recommended |
Column A |
Column B |
| |
Efavirenz |
Stavudine + Didanosine |
| |
Indinavir |
Stavudine + Lamivudine |
| |
Nelfinavir |
Zidovudine + Didanosine |
| |
Ritonavir + Indinavir |
|
| |
Ritonavir + Lopinavir |
|
| |
Ritonavir + Saquinavir |
|
Recommended as alternatives |
Column A |
Column B |
| |
Abacavir |
Didanosine + Lamivudine |
| |
Amprenavir |
Zidovudine + Zalcitabine |
| |
Delarvidine |
|
| |
Nelfinavir + Saquinavir |
|
| |
Ritonavir |
|
| |
Saquinavir |
|
No recommendation/ insufficient data |
Hyroxyurea in combination with antiretroviral drugs |
|
| |
Ritonavir + Amprenavir. |
|
| |
Ritonavir + Nelfinavir |
|
Not recommended/should not be offered |
All monotherapies whether from column A or B including Hydroxyurea |
|
| |
Column A |
Column B |
| |
Saquinavir (Invirase) except with Ritonavir |
Stavudine + Zidovudine |
| |
|
Zalcitabine + Didanosine |
| |
|
Zalcitabine + Lamivudine |
| |
|
Zalcitabine + Stavudine |
