Nearly all patients in southern Africa who have received treatment with the NNRTIs efavirenz or nevirapine would benefit from therapy with etravirine, a study published in the December 15th edition of the Journal of Acquired Immune Deficiency Syndromes suggests.
“Over 90% of patients previously exposed to efavirenz or nevirapine in the southern African treatment programmes will remain susceptible to etravirine despite prolonged exposure to first-line NNRTI-based regimens”, comment the investigators.
A number of new potent antiretroviral drugs have recently become available, meaning that many patients with extensive experience of antiretroviral therapy have a good chance of achieving and maintaining an undetectable viral load.
One of these drugs is the non-nucleoside reverse transcriptase inhibitor (NNRTI) etravirine (Intelence), manufactured by Tibotec. Research in the UK suggests that nearly all patients with resistance to the older NNRTIs efavirenz (Sustiva, also in the combination pill Atripla) or nevirapine (Viramune) would benefit from therapy with the drug.
Little, however, is known about the drug’s potential effectiveness in southern Africa. First-line antiretroviral therapy in this region is based upon regimens that include older nucleoside analogues such as d4T and AZT, and access to viral load testing to monitor the effectiveness of treatment is limited.
As a result patients may go for longer before switching to second-line treatment, and as a result accumulate a much wider range of drug resistance mutations, including a larger number of NNRTI-related mutations.
Resistance profiles from 296 patients in Johannesburg who had experienced the virological failure of their treatment provided investigators with an opportunity to assess the likely benefit of etravirine.
Most (266) of these patients had taken treatment that included efavirenz (201) or nevirapine (25).
Eleven individual resistance mutations have been associated with reduced susceptibility to etravirine, and the more of these that a patient has, the less likely they are to benefit from therapy.
Moreover, certain mutations (Y181I and Y181V followed by L1001, K101P, Y181C and M230L) are especially associated with a poor response to etravirine. An algorithm has been developed that scores such mutations allowing investigators to more accurately assess a patient’s suitability for treatment with the drug.
Only one patient had the Y181I mutation and none had Y181V.
The investigators calculated that only 9% of patients had a resistance pattern that could impact on their response to etravirine. When using a different weighting system, this was reduced to 5%.
Although the researchers are encouraged by these results, they note that future use of etravirine in resource-limited settings “is likely to depend on cost and availability.”
The recent decision by UNITAID, the international drug purchase fund for HIV, TB and malaria, to launch a patent pool to license patents for antiretroviral drugs to generic producers, could bring down the price of drugs for second-line treatment.
Stevens WS et al. Will etravirine work in patients failing nonnucleoside reverse transcriptase inhibitor-based treatment in southern Africa? J Acquir Immune Defic Syndr 52: 655-56.