More HIV patients with multidrug resistance

[Jim Allen]

Intressting read.

People resistant to older medication also have problems with newer drug, study finds

http://www.webmd.com/hiv-aids/news/20161201/doctors-seeing-more-hiv-patients-with-multidrug-resistance

By Robert Preidt

HealthDay Reporter

THURSDAY, Dec. 1, 2016 (HealthDay News) -- A significant number of people with HIV have strains of the AIDS-causing virus that are resistant to both older and newer drugs, researchers report.

The researchers looked at 712 HIV patients worldwide whose infection was not controlled by antiretroviral drugs. They found that 16 percent of patients whose infection was resistant to modern drugs had HIV mutations linked with resistance to older drugs called thymidine analogues.

Among patients whose HIV had this mutation, 80 percent were also resistant to tenofovir, the main drug in most modern HIV treatment and prevention programs, the researchers reported.

The findings were published in the Nov. 30 issue of The Lancet Infectious Diseases journal.

"We were very surprised to see that so many people were resistant to both drugs, as we didn't think this was possible," study lead author Ravi Gupta, of University College London, said in a school news release.

"Mutations for thymidine analogue resistance were previously thought to be incompatible with mutations for tenofovir resistance, but we now see that HIV can be resistant to both at once. This emphasizes the need to check the genetic profile of patient's virus before prescribing first-line treatments, as they may have already developed resistance to other treatments that they did not mention having taken," Gupta said.

Drug resistance typically occurs when patients fail to take their medications as directed by their doctor.

"To prevent these multi-resistant strains from developing, we need cheap, reliable systems to assess people before treatment," he said.

What's needed, Gupta said, are easy-to-use resistance-testing kits to help screen for drug resistance before giving treatment. This would also help doctors to "monitor HIV drug resistance globally more effectively," he said.

"However, until such kits are widely available, we could test the amount of virus in the bloodstream before and after giving treatment. Although not as precise as resistance testing, this could help us to detect treatment failure earlier and switch patients to second-line drugs," he added.

If a patient's HIV becomes resistant to first-line drugs, they're given second-line drugs that cause more side effects. But many rural patients don't have access to second-line drugs, so trying to preserve the effectiveness of first-line treatments is crucial, Gupta explained.

http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(16)30469-8/fulltext

HIV drug resistance explained.
https://www.poz.com/basics/hiv-basics/hiv-drug-resistance

[leatherman]

The researchers looked at 712 HIV patients worldwide whose infection was not controlled by antiretroviral drugs.

another piece of bad HIV reporting. These patients were not "worldwide" as all of the patients were from sub-Saharan Africa. If the same situation was happening in America, where many patients have TDF as part of their regimen, we would be seeing serious problems in the States. Also genotype testing is performed more regularly in the States to avoid prescribing meds in the first place that a patient would have a resistance to.

(while i can't say for sure, i would think if genotyping was finding "more HIV patients with multidrug resistance" (especially to TDF), it would be BIG news here in the States as the CDC is constantly ramping up the promotion of Truvada as PrEP)

We identified 712 patients who had viral failure with WHO-recommended, tenofovir-based first-line regimens in 20 studies across sub-Saharan Africa (table 1; appendix). Most (461 [65%]) patients were from southern Africa, with 159 (22%) patients from eastern Africa and 92 (13%) from west and central Africa. 481 (68%) of 712 infections were with HIV-1 subtype C (appendix).

http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(16)30469-8/fulltext

[Jim Allen]

  Most reporting is bad for the majority of health or study topics if i am honest.
On news of PrEP being made available (very limited) in the UK this week we again saw "Cure" found headlines .

Anyhow its seem to me the writer might be confused between the study results / pre study evidence that was from mutable regions. To be honest I feel 712 is not really statistically important as the sample size is too small but that is a frequent complaint I have with studies in general if I am honest.

I should have been more clear on the report and what i found interesting

My own interest was also more sparked by the subject of the evidence before the study not so much the result, however the first media report caught my eye that lead me to reading the study and I raised my eyebrow that it was not noticed before (The true %'s are irrelevant for me from the study as said I consider the sample size is too small) but noteworthy

Evidence before this study

We did a systematic review using PubMed and Embase, searching from Jan 1, 2000, up to Aug 15, 2016, without language limitations. Manuscripts of interest were also identified from the reference lists of selected papers, clinical trials registries, and abstracts from the Conference on Retroviruses and Opportunistic Infections (CROI) and International AIDS Society (IAS). We used the search terms “HIV” AND “Tenofovir” AND “thymidine analogue” OR “stavudine” OR “zidovudine” OR “AZT” OR “d4T”. We found no studies reporting the implications of previous thymidine analogue use on outcomes following tenofovir-based antiretroviral therapy (ART). One study investigated the implications of transition from thymidine analogue to tenofovir by use of a cross sectional survey in Myanmar before the introduction of tenofovir. The investigators tested viral loads in more than 4000 patients after 12 months of thymidine analogue-based ART to avoid substitutions in viraemic patients. They noted that a substantial proportion of patients were having treatment failure (13% had viral loads >250 copies per mL), in whom direct tenofovir substitution for the thymidine analogue would not be appropriate.

Added value of this study
Our results show that tenofovir-based first-line regimens are failing in a substantial proportion of patients who have evidence of previous exposure and drug resistance to older nucleoside (thymidine) analogues such as zidovudine and stavudine in sub-Saharan Africa. These individuals are likely to have developed drug resistance to the non-nucleoside reverse transcriptase inhibitor as well as the cytosine analogue, and therefore have high-level resistance to at least two of the three drugs present in tenofovir-based first line ART. Our data show that these individuals with thymidine analogue mutations have lower CD4 counts and therefore are at greater risk of clinical complications than are those without previous ART exposure.

Implications of all the available evidence
Cheap and effective viral load monitoring, resistance testing, or both could prevent the transition of patients with virological failure onto tenofovir-based first-line ART and also identify individuals with pre-existing drug resistance to first line agents arising from undisclosed prior ART. These individuals could then be treated with second-line regimens.

Jim