HIV: Treatment, therapeutic schemes

Combinations of drugs are at present being used in the West (compare with tuberculosis and leukaemia chemotherapy). Various cocktails, that often have to be individually adapted, are used. As first-line treatment the WHO advises a scheme with 2 nucleoside analogues in combination with an NNRTI ("highly active antiretroviral therapy" or "HAART"). Alternatively, the combination of 2 nucleoside analogues and a protease-inhibitor can be used. Zidovudine, stavudine, lamivudine, abacavir, nevirapine and efavirenz penetrate into the cerebrospinal fluid and can thereby have a preventive effect on the occurrence of AIDS dementia. Any combination treatment should, therefore, contain one of these molecules. Videx® does not penetrate very well into the cerebrospinal fluid.

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The recommended therapy is a triple therapy consisting of:

• First line: 2 nucleoside analogues + 1 NNRTI

• Second line: 2 nucleoside analogues + 1 boosted protease inhibitor

Initial treatment regimens with minimal patient inconvenience:

• Combivir: 2 x 1 per day, in combination with Kaletra® 2 x 3 per day

  • Or

• Combivir: 2 x 1 per day, with Viramune 2 x 1 per day (for the first two weeks 1 per day)

  • Or

• Trizivir : 2 x 1 per day

  • Or

• Aztec: Once per day, in combination with Videx EC once per day and Sustiva once per day

Combinations of reverse transcriptase inhibitors to be avoided:

• DDC-D4T hence NOT: Hivid + (Zerit, Videx or Epivir), also not Retrovir + Zerit

• DDC-DDI

• DDC-3TC

• AZT-D4T

Combinations of reverse transcriptase inhibitors to be preferred:

• AZT-3TC: Combivir® is a fixed combination of 300 mg AZT with 150 mg 3TC.

• D4T-DDI

• D4T-3TC

• AZT-DDI

• AZT-DDC

Clinicians are aware that the development of resistance is a significant problem in achieving long-term success with highly active antiretroviral therapy (HAART). However, resistance is not an all or none phenomena, but instead comes in gradations. These gradations are defined by the increase in the inhibitory concentration of a particular drug to a level higher than that of wild-type viruses. In some cases viral resistance can be overcome by increasing plasma concentrations, something that is routinely done when ritonavir is used to slow down degradation of protease inhibitors ("boosted PI). The use of the C-trough/IC50 ratio (Inhibitory quotient or “IQ”) has been found to be a useful marker of antiretroviral efficacy.

Note: Compliance

Medication which has to be taken only once daily is easier to take than medication which requires multiple dosing. Once daily regimens improve compliance.

Can be given once daily : Viread®, Emtriva®, Videx EC®, Zerit XR®, Stocrin®, Reyataz®

Category: Medicine Notes