Is HIV Superinfection Unhealthy?

August 13, 2014

Tim Lahey, M.D., M.M.Sc.

Tim Lahey, M.D., M.M.Sc., is an HIV doctor at Dartmouth-Hitchcock Medical Center where he is the chair of the clinical ethics committee. He is also associate professor at Dartmouth's Geisel School of Medicine, an HIV and tuberculosis researcher, and a contributor to The Atlantic, Scientific American and The New York Times.

People who contract HIV once can contract it again, often through the same risk behaviors that led to the initial infection. A long-standing question has been whether getting infected with a second strain of HIV leads to more rapid HIV disease progression than infection with a single strain.

To this point, a 24-year-old man who has sex with men recently asked me, "Doc, I already rang the bell, why do I care if I get HIV again?"

The first hints of an answer to this question arrived nearly 20 years ago. In 1997, researchers reported rapidly progressive immunodeficiency in a patient infected with two distinct strains of HIV. Since the patient mounted only weak immune responses to both viruses, the investigators could not determine if infection with two strains of HIV -- which they termed "dual infection" -- was the cause of the man's rapid disease progression or if other factors, such as his weak immune responses, were more to blame.

More evidence accrued in 2002 when investigators at the Massachusetts General Hospital showed that a patient with previously well-controlled HIV infection and robust T-cell responses against the virus later developed accelerated disease progression after infection with a new strain of HIV. They termed infection with a new strain of HIV "superinfection," and many in the HIV community worried that these findings cast doubt on the possibility of durable immune protection from diverse HIV viruses.

Neither report in individual patients could address whether dual infection or superinfection were associated with poorer clinical outcomes compared to infection with a single virus. In 2004, a study among five patients with dual infection -- including one with superinfection -- suggested that the average time to disease progression was under four years, i.e., faster than we expect routinely.

These data have helped guide clinical practice. Many clinicians urge patients with HIV to practice safer sex in part to avoid superinfection either because it could result in worsening HIV disease progression or because it may lead to the acquisition of a more resistant strain.


Now a new paper evaluates clinical outcomes in 21 female sex workers in Mombasa, Kenya, the largest cohort of people with proven HIV superinfection. To determine if HIV disease progression was impacted by superinfection, the investigators led by Julie Overbaugh in Seattle compared pre- and post-superinfection HIV viral loads and CD4 counts. They found a nearly significant increase in HIV viral load after superinfection (+0.21 log10, P = .09), but no difference in pre- and post-superinfection CD4 counts. In separate analyses, compared to women only infected with a single virus, women with superinfection showed slightly more rapid increases in HIV viral load over time (0.009 log10 HIV copies/mL/month faster viral load increase [P = .0008]) and a trend toward faster CD4-count decline. Despite these associations of superinfection with poorer virological control and potentially more rapid immunological deterioration, women with superinfection had the same disease progression-free survival as women infected with only one strain of HIV.

This is by far the largest study of people with HIV superinfection, and is thus an important contribution. Yet, it is still a small study that might not have been powered to detect subtle increases in the rate of HIV disease progression after superinfection. However, the authors' contention that HIV superinfection caused "no large difference in clinical outcome" is undeniably true.

When we counsel patients about HIV superinfection, we should not warn them that superinfection will quicken disease progression -- the best data available suggest this may not be true. However, patients do need to know that superinfection with a strain of HIV that is resistant to their current antiretroviral regimen could undermine treatment success. Most importantly, patients need to know that safer sex can help prevent other sexually transmitted infections, such as drug-resistant gonorrhea.

This is what I told my 24-year-old patient with HIV. He had indeed "rang the bell" already, but safer sex is still a good idea because there are many more bells out there that he does not want to ring.

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Reader Comments:

Comment by: Indydaddy (Wilton Manors, FL) Sat., Aug. 30, 2014 at 1:21 pm UTC
My partner of 17 years and I have never practiced safer sex together. We had both been poz for many years when we met. A study we enrolled in proved we had different strains of HIV. We have never had to switch medications due to drug resistance. Both have been undetectable since we met; with normal CD4 counts. I never believed the propaganda that poz partners need to practice safer sex.
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Comment by: rigo (Mexico) Sat., Aug. 30, 2014 at 6:55 am UTC
wouldnt it be better to call it doubleinfection instead of superinfection?
Every time I read about superinfection its a bit confusing about what are they talking about.
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Comment by: Brian Foley (Los Alamos, NM) Wed., Aug. 20, 2014 at 10:34 am UTC
Superinfection may only rarely be detrimental, but it is never good. Statistics really don't apply to individuals; nobody is 33% pregnant. Even if the odds are that superinfection will not hurt you, you don't want to be the unlucky one who is seriously harmed by it. As with all risks in life, it does not pay to be worrying and too cautious so you can't enjoy your life, but it is always wise to take all reasonable precautions.
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Comment by: Michael Buitron (Long Beach, CA) Sat., Aug. 16, 2014 at 2:17 pm UTC
It would have been nice if this post addressed the potential of superinfection and when it occurs. From my understanding of the current literature, those infected with multiple strains seems to occur either concurrently--or close enough to the time of the first infection--before an antibody response is mounted. Other cases of secondary infection with another strain seem to occur when the patient takes a drug "holiday" and a window briefly opens when the patient is vulnerable to a second strain.

One would think that if PrEP (the use of two ARVs) is effective at protecting an HIV-negative person from acquiring HIV in the first place, the use of HAART (three or more ARVs) would also render the possibility of acquiring a second strain moot.

From both an individual and public health perspective, all patients not on therapy should be counseled to start ARVs to not only protect their own health, but also to reduce the chances of passing HIV along to their partners. All patients regardless of their HIV status should be counseled of the risk of having unprotected sex with multiple partners.

From the perspective of 35 million people living with HIV, the handful of case studies of superinfection seem like a red herring, when the real issue is the possibility of the patient acquiring another STD or infecting someone else with HIV.
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Replies to this comment:
Comment by: Brian Foley (Los Alamos, NM) Wed., Aug. 20, 2014 at 10:41 am UTC
Michael makes some excellent points there. The term "superinfection" is for when it is known that the person had already made an immune response to the first strain of virus. For many dual infections it is not possible to know the timing of entry of the two strains. Factors such as drug treatment make the risks for each individual different, and the risks change over time. With people on good therapy, the worry is more about drug resistant strains, which can be rare in some parts of the world and more common in other parts of the world.
Comment by: Rick (Quincy, IL) Sat., Aug. 23, 2014 at 1:13 am UTC
"One would think that if PrEP (the use of two ARVs) is effective at protecting an HIV-negative person from acquiring HIV in the first place, the use of HAART (three or more ARVs) would also render the possibility of acquiring a second strain moot."

Ain't that the truth! More to the point, one has to wonder why we're still terrifying positive patients with scare stories about "superinfection", treatment failure, superbugs and HCV while we reassure PrEP users that they can bareback to their heart's content. It illustrates a sexual double standard, where the negative are encouraged to party like it's 1976 while the positive are told to shut up and drift away on some iceberg.

I can think of half a dozen reasons why we might be doing this. None of them are appropriate for a website that purports to be both for prevention and against stigma.

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