Low rate of treatment failure with tenofovir, 3TC and AZT

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German investigators have found a low rate of treatment failure amongst patients receiving the nucleoside analogues (NRTIs) AZT and 3TC in combination with the nucleotide analogue, tenofovir. The study is published in the January 3rd edition of AIDS.

High rates of virological failure and resistance have previously been seen in patients receiving either triple NRTI therapy, or the nucleotide analogue tenofovir with the NRTIs 3TC and abacavir/or ddI. It is thought that this is because this regimen resulted in the developed of the K65R mutation. Other data, however, suggests that the inclusion of AZT may be protective against the development of the K65R mutation.

Investigators obtained retrospective data for 40 individuals treated with tenofovir (245mg once daily) and AZT and 3TC (150/300mg twice daily, coformulated as Combivir). All the patients had received previous HIV therapy prior to switching to tenofovir, AZT and 3TC, at which time 27 individuals had a viral load below 50 copies/ml and 13 patients had a detectable viral load (range 11,200 copies/ml – 398,000 copies/ml).

Glossary

detectable viral load

When viral load is detectable, this indicates that HIV is replicating in the body. If the person is taking HIV treatment but their viral load is detectable, the treatment is not working properly. There may still be a risk of HIV transmission to sexual partners.

nucleotide

A building block of DNA or RNA, chemical structures that store genetic information. 

exclusion criteria

Defines who cannot take part in a research study. Eligibility criteria may include disease type and stage, other medical conditions, previous treatment history, age, and gender. For example, many trials exclude women who are pregnant, to avoid any possible danger to a baby, or people who are taking a drug that might interact with the treatment being studied.

efficacy

How well something works (in a research study). See also ‘effectiveness’.

nucleoside

A precursor to a building block of DNA or RNA. Nucleosides must be chemically changed into nucleotides before they can be used to make DNA or RNA. 

Analysis was performed when patients had completed 24 weeks of treatment. At this point, 23 of the 27 patients who had started triple NRTI therapy with a viral load below 50 copies/ml still had a viral load below this level. In addition, eight of the 13 patients who had started treatment with tenofovir, AZT and 3TC with a detectable viral load now had a viral load below 50 copies/ml.

Median CD4 cell count increased both for patients with an undetectable viral load at baseline (415 cells/mm3 to 595 cells/mm3) and for patients with a detectable baseline viral load (354 cells/mm3 to 407 cells/mm3).

Investigators analysed the patients who experienced virological failure in more detail. Two patients said that they had had imperfect adherence and were excluded from further analysis. Genotypic analysis was performed on the remaining seven individuals who had a detectable viral load at both baseline and after 24 weeks of treatment. All had the M184V mutation, and six had the T215Y mutation, which is specific to AZT. Only one patient had the K65R mutation, associated with the failure of treatment with tenofovir, 3TC and abacavir/ddI.

The investigators note that some three patients with a detectable viral load at baseline had a sustained virological response to tenofovir, 3TC and abacavir, despite having baseline mutations conferring resistance to AZT.

“This observational cohort study…revealed an acceptable efficacy of a triple NRTI regimen combining tenofovir, 3TC and AZT”, write the investigators. The investigators add that no mutations conferring resistance to both AZT and tenofovir were seen in any patients, and theorise that common AZT mutations are “disadvantageous for HIV…when combined with the K65R mutation by rendering HIV susceptible to AZT again.”

The investigators conclude: “our preliminary data indicate that triple NRTI regimens including AZT and tenofovir may be more effective than other triple NRTI combinations.”

References

Mauss S et al. Low rate of treatment failure on antiretroviral therapy with tenofovir, lamivudine and zidovudine. AIDS 19: 101 – 103, 2005.