More Drug Resistance About

posted: 27/10/2010

There seems to be more transmitted drug-resistant HIV in the UK than we think, investigators say in HIV Medicine. The usual tests found 13% of undiagnosed HIV-positive gay men have drug-resistant virus. However, using more sensitive tests the researchers found 19% have become infected with drug resistant HIV.
 

Avoiding resistance

HIV treatment drug resistance is reduced by careful taking of HIV treatment, which is known as good adherence. Information and advice about better treatment taking and on adherence is in this booklet from NAM.

Rise and fall of resistance
The proportion of people who have become infected with drug-resistant HIV in the UK peaked at 12% in 2002. Better HIV treatment and care since then means this fell to 8% by 2006.

Resistance: test and treat

Everyone should be tested for drug resistance at the time of their HIV diagnosis. Drug resistance is measured at the time of HIV diagnosis because it becomes harder to find later. 

Even a little drug resistance reduces how well anti-HIV treatments will work. Knowing at the start what drugs someone’s HIV is already resistant to helps doctors and patients choose their personal best combination of HIV treatment drugs.

After treatment has begun if the treatment needs to be changed for any reason, there is a new online tool for deciding the best alternatives based on any drug resistance: HIV Treatment Response Prediction System (HIV-TRePS). 

Ordinary drug resistance tests not enough
The tests used normally to find resistance are only able to detect the main resistance types each person has. An international team of investigators wanted to see if a more sensitive test would find more resistance.

They tested 165 blood samples (anonymous) from undiagnosed gay men who used UK sexual health clinics between 2003 and 2006. None of the men knew they have HIV.

Sensitive tests find more

The samples were tested using both the normal method, and with a much more sensitive test that can find small amounts of the mutations resistant to first-line anti-HIV drugs.

Using the standard test, 21 samples (13%) were found with some drug resistance. This increased to 32 samples (19%) when the sensitive assay was used. This 45% increase in resistance levels was highly statistically significant.
 

Mutations found
They also looked for specific mutations.

• The standard test showed that 6% of patients had the K103N mutation (meaning resistance to efavirenz), and this rose to 7% with the more sensitive assay. This is not a significant difference.
• They did not find anyone with the Y181C mutation (resistant to efavirenz and nevirapine).
• One man had the M184V mutation (and resistance to 3TC or FTC). But this increased from 1 man (0.6%) to 13 men (8%) when both tests were used. This is highly statistically significant.

“The findings ... support the suggestion that M184V is as likely to be transmitted as other mutations”, write the study authors, adding, “this study contributes evidence to support the inclusion of minority assays for M184V surveillance.”

Rising drug resistance
Resistance rose by calendar year according to both methods. The standard test found 15% of samples in 2003 were drug resistant, and this rose to 19% using the sensitive test. In 2006 the standard test showed 10% of men have drug resistance, but this doubles when using both tests (highly statistically significant).
 

Is resistance still rising?
Resistance was found in 19% of undiagnosed gay men who were recently infected with HIV, and in 20% of those with long-standing infections. It appears drug resistance is still falling.

Source with reference

article abstract

Better treatment taking advice to avoid resistance

HIV Superinfection - Not Likely

posted: 27/01/2009

Researchers in America have found no evidence that unprotected sex between people with HIV who are regular partners leads to superinfection with another strain of the HIV virus. They used a long-term study involving 49 people with HIV. No evidence of superinfection was found.

Superinfection and reinfection mean much the same thing and some hyping up of reports happens. Superinfection is reinfection with another strain of HIV, that harms health. Most HIV reinfection causes no apparent harm. Studies show that about 1 in 20 people with HIV who are checked for reinfection for one year show signs of this, so reinfection itself is fairly common. One of these studies was of gay men, the other of women in Kenya. There have been claims in 30-40 case reports of actual superinfection around the globe.

Instead of damage by superinfection, this study found a clear relationship between long-term frequent exposure to their partner’s virus and a strong immune response to that virus, suggesting that repeated exposure eventually builds immunity against superinfection, which is good news.

What harm can superinfection cause?

There’s been a lot of debate about whether unprotected sex between people with HIV can lead to superinfection with the virus. People with HIV are frequently advised not to have unprotected sex even with other HIV-positive people because of a risk of superinfection. Superinfection is reinfection with different HIV, from someone else, that goes bad and damages health. The damage to health is that treatment can get more complicated because the other person's HIV may carry drug resistance, and people may get infected with a more aggressive strain of HIV.

HIV can transmit with it drug resistance even if the person passing it on has never taken any HIV treatment, because the person who had infected them gave them HIV which had some drug resistance.

Aggressive and drug-resistant HIV

Some of the reported cases of superinfection have involved infection with more aggressive or drug-resistant strains of HIV. But this hasn’t always been the case – other documented cases of superinfection don’t seem to have done any harm. So researchers in San Francisco wanted to get a better understanding of the long-term risks of superinfection. What they found makes much clearer the risks of people living with HIV having unprotected sex together. Is there enough evidence of superinfection now to reasonably advise positive people to use condoms when having sex with another person living with HIV?
 

The study looked at changes in the immune system and HIV of 49 people with HIV. All the participants were taking HIV treatment and had an undetectable viral load. All 49 people had HIV-positive partners with whom they were having unprotected sex. The researchers divided the people in the study into two groups, those with partners who had a detectable (20) viral load, and those with partners with an undetectable (29) viral load.

Gay men studied

All 49 are gay men, a fact that is buried deep in the report. George House Trust suspects this is only due to the funding-threat Bush has cast over much HIV research and care for groups of people who are targets of US Christian conservatives' abhorence. Research into protective gels for anal sex has long been held back for the same reason. The early indications are that the new president is moving swiftly to end discrimination around HIV funding. 

Partners show strong immune response

The study found no evidence that any of the 49 men had been infected with another strain of HIV. Instead, they found that men who were exposed to their partner’s HIV developed a strong immune response to it. The men's immune systems were working well and seem to be preventing health damage from the partner's HIV.

Risks now much clearer

This study is important because it makes the risks of superinfection much clearer for the many people with HIV who choose to have unprotected sex with HIV-positive partners, which is known as sero-sorting.

The findings suggest that even where an individual has drug-resistant virus and a detectable viral load, the risks of superinfecting an HIV-positive partner with that drug-resistant virus are low, even for sexually receptive partners (receptive partners are at more risk than insertive ones).

What about people with more partners?

The findings provide no information about what happens if an individual with HIV has sex with many different partners with HIV (because the study only looked at HIV positive gay men and their regular positive partner), but the study’s lead author Chris Willberg, now of the Biomedical Research Centre at the University of Oxford, told aidsmap: “We would speculate that it is regular exposure to the same epitopes that is required to stimulate the responses. What we did not explore is the ability for new [epitope] responses to be developed through exposure.”

George House Trust takes that as a meaningful 'perhaps not, but we didn't study that' because there's evidence (from a study of Nairobi sex workers referred to in the aidsmap article) that superinfection is more likely if the sex is with many positive partners rather than just one.

And because the risks for transmission of HIV are always highest being receptive in anal sex, and then run in this order: being insertive in anal sex, being a woman in heterosexual vaginal sex, being a man in heterosexual vaginal sex, this means gay men who have multiple positive partners take rather more risk of superinfection than the Nairobi women sex workers.

And as the number of positive partners rises, the greater the risk.

It needs another study to answer the 'is there a risk of superinfection with multiple partners' question, and a scientific study seems very difficult to arrange. This is because casual partners cannot be identified in advance; some will have undetectable viral loads but others won't, and this means the numbers needed for such a study would have to be huge; obtaining agreement to take part from many casual partners doesn't seem possible; and some partners would be uncontactable, or refuse to take part. We can't realistically expect to see any scientific answer soon for people who want information now on the risks with multiple partners.

Low risk with more partners seems likely

It's inevitable that some people will speculate and want an informed view, following this reassuring superinfection study. Considering the evidence in the studies, how the body responds, and especially how few cases (just 30-40) have been reported from around the globe, one reasonable view is the risks are low of having much poorer health through superinfection resulting from unprotected sex with multiple partners, even if the partners have detectable viral loads.

This is because sero-sorting with multiple partners among gay men living with HIV is fairly common and has been happening for some years, and if superinfection damage was common, we would be having far more case reports from around the world. Superinfection is big news, so case reports are likely whenever serious problems occur.

However each person needs to make their own decisions on which risks to take when science can't give us an answer. People living with HIV interested in this should discuss with the doctor their advice and interpretation of the evidence. Then make their own decision.

More risk

If the person's health is not so good, exposing the immune system to even more stress from different people's HIV is rather more risky and the health damage could be more significant.   

The far more serious risk from unprotected sex with multiple partners for most positive gay men (whether or not the partners have HIV) is of other STIs. LGV, syphilis, and hepatitis C are particularly likely and harzardous to health when men with more partners already have HIV. Our advisers are always willing to discuss levels of risk and how men can keep these within limits that are comfortable while having a satisfying sex-life, without judging what men do or any associated drug use.

Women too

Aidsmap also asked the study's leading author a really important question many positive women and their partners need answering - do positive women have the same low risk of superinfection from a positive partner as men?

His reply means 'as long as things work in the same way for women, and this looks very likely,' which women and their partners will welcome, but he unhelpfully cloaks this in a long scientific answer: “The most logical explanation for the maintained responses that we observed is that they were driven by receptive exposure to HIV antigen derived from the viremic partner,” Chris Willberg commented. “Therefore, we would expect to see the same results in women also receptively exposed to viremic partners. If the mechanisms responsible for driving the responses in this study are the same as those that drive responses in exposed uninfected individuals, then there is plenty of evidence to suggest women would respond in a similar manner.”

We think 2/10 would be a fair mark for 'ability to communicate' with HIV positive women (and partners), who deserve a clear answer to this plain question. The scientific explanation is exact and complex, yet the actual answer disguised by all these words is clear - but only after repeated reading. Researchers need to make much better efforts to communicate plainly in everyday language the important lessons of their research and expertise, because the public ultimately fund most of the work carried out for our benefit. 17 words give the same answer, but plainly, as over 80.

Other risks - including STIs and pregnancy - remain

For both women and men, unprotected sex can have other health consequences. In the UK, LGV and syphilis are seen much more often in HIV-positive gay men, clearly due to unprotected sex. What’s more, unprotected sex between HIV-positive gay men is also linked to sexual transmission of hepatitis C virus.

Women may also expose themselves to the range of sexually transmitted infections and may become pregnant as a result of unprotected sex. A positive woman wanting to have a baby should talk first with her HIV doctor about when and how best to become pregnant and the ways of minimising the risk of having a positive child. With the right care and treatment this risk is now very low, about 1 in 100.

Further information and reference from aidsmap

The free online journal article