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Tuesday 5th March 2013

Contents

Baby 'cured' of HIV with triple-drug therapy

Deborah Persaud from Johns Hopkins University School of Medicine at CROI 2013. © Liz Highleyman / hivandhepatitis.com.

The 20th Conference on Retroviruses and Opportunistic Infections (CROI 2013) opened with the exciting news of the 'functional cure' of an HIV-infected infant. This was achieved using triple-drug antiretroviral therapy which was initiated within hours of birth.

The child has now been off treatment for a year. HIV DNA has been detected at very low levels in the infant’s cells. However, there is no evidence that the virus is replicating – this is considered a functional cure.

The infant was born prematurely to a mother whose HIV infection was only diagnosed at the time of delivery. Her viral load was detectable at the time the baby was born.

Tests conducted 30 hours after delivery showed that the baby had detectable HIV DNA and RNA with a viral load of approximately 20,000 copies/ml.

A triple antiretroviral combination of AZT, (zidovudine, Retrovir), 3TC (lamivudine, Epivir) and nevirapine (Viramune) was immediately initiated. This combination is recommended for all infants born to a mother with a detectable viral load.

After seven days, nevirapine was replaced with Kaletra (lopinavir/ritonavir).  The infant’s viral load had fallen to undetectable levels (below 20 copies/ml) by day 29 of therapy. Treatment continued for 18 months.

At this point, the infant and caregiver were lost to follow-up. They returned six months later. Despite this interruption in treatment, the infant’s viral load was undetectable and remained so in subsequent testing.

Intensive testing found only very low levels of virus and no HIV replication in “resting” CD4 cells. Although DNA from the virus was detected in latent CD4 cells, there was no evidence of replication.

Doctors therefore believe this is a case of functional cure – no HIV replication after the discontinuation of therapy.

Only one other case of functional cure has so far been reported – the so-called 'Berlin patient'.

Studies are now being designed to see if a functional cure can be achieved in other infants with HIV.

Early treatment and the HIV reservoir

Dr Jintanat Ananworanich of SEARCH Thailand presenting at CROI 2013.

Other research presented to the conference may also have implications for the search for a cure.

Results of separate studies involving adults and adolescents who had started treatment very soon after their infection with HIV showed that very early treatment limited the size of the reservoir of latently infected CD4 memory cells.

The adult study was conducted in Thailand and involved 68 people diagnosed with very recent HIV infection. The immediate initiation of therapy was associated with a very small or undetectable reservoir of HIV DNA. This characteristic is also seen in so-called 'elite controllers' – people living with HIV who have a persistently low or undetectable viral load without the need for antiretroviral treatment.

In separate research, doctors looked at the viral characteristics of five adolescents who were infected with HIV at birth. They started antiretroviral treatment within two months of birth. It was impossible to detect HIV DNA capable of replication in any of these patients.

What of people who started treatment with chronic HIV infection? The news was less good. Researchers found very large reservoirs in people who had been taking suppressive antiretroviral therapy for as long as ten years. The participants in this study started treatment when their CD4 cell count was around 200 – this suggests they had had HIV for quite some time. Viral reservoirs declined with the duration of suppressive therapy, but still remained detectable. Older age and a higher baseline viral load were both associated with larger reservoirs.

HIV prevention: PrEP

Jeanne Marrazzo discusses results of the VOICE study at CROI 2013. © Liz Highleyman / hivandhepatitis.com.

Pre-exposure prophylaxis (PrEP) using the anti-HIV drug Truvada (FTC/tenofovir) was not effective at reducing HIV infections among heterosexual women in southern Africa.

Data from the large VOICE trial was presented to the conference.

The study involved over 5000 HIV-negative women in southern Africa and was designed to explore the efficacy of three uses of HIV treatment as prevention: PrEP with tenofovir only; PrEP with Truvada; and a vaginal microbicide.

The tenofovir PrEP and the microbicide had already been shown to be ineffective and these arms of the study were stopped in 2011.

Truvada PrEP has now also been shown to have no real impact on the risk of infection with HIV.

This is possibly because the women in the study were not taking the treatment. Reported levels of adherence were high. But drug-level monitoring showed that, at most, only 29% of women had detectable levels of the drug in their blood.

Younger age was a big risk factor for poor adherence, echoing the findings of other research.

The results show the difficulty of turning the promise of PrEP into reality.

However, results of an animal study suggest that injectable treatment dosed just four times a year could overcome these adherence problems.

Rhesus macaques were dosed with an injectable integrase inhibitor and then had rectal exposure to an HIV-like virus. None of the monkeys become infected. Concentrations of the drug remained above the levels needed to prevent infection with HIV for up to three months after dosing. 

Hepatitis C treatment

Edward Gane presenting at CROI 2013. © Liz Highleyman / hivandhepatitis.com.

A combination of three direct-acting anti-hepatitis C drugs has achieved a 100% response rate. The study involved people who had not taken treatment before (treatment-naive) and people who had hepatitis C which had previously failed to respond to therapy with pegylated interferon and ribavirin (null-responders).

The ELECTRON study involved 25 treatment-naive participants and nine null-responders. All had genotype 1 infection, the majority having the more difficult-to-treat 1a genotype.

They were treated with a combination of sofosbuvir, ledipasvir and ribavirin.

Therapy lasted for twelve weeks. At this point, all the participants had an undetectable hepatitis C viral load. This was also the case four and twelve weeks after the completion of therapy.

The treatment was safe and well-tolerated. Only 4% of participants discontinued their therapy because of side-effects. Anaemia, depression and headache were the most common side-effects.

Information resources for people living with HIV

Kay Francis, HIV Lead Midwife, Coleridge Unit, North Middlesex Hospital, with some NAM booklets.

We believe independent, clear and accurate information is vital in the fight against HIV.

We produce hundreds of information resources to support and empower individuals from the point of diagnosis through to making informed treatment decisions. We break down complex, and often frightening, information into something understandable and reassuring, to improve knowledge and confidence of life with HIV every step of the way.

All the titles in our popular booklet series and our innovative illustrated series The basics are available through our website, to read online or to download and share. Many of the titles have been translated into one of 17 languages, and all of the translated titles are available online too.

What might you learn or help someone else to understand today?

"I direct both patients and staff to this website for all their HIV needs. I live and breathe NAM. Thank you for the simplicity and clarity with which you present your information." Kay Francis, HIV Lead Midwife, Coleridge Unit, North Middlesex Hospital

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NAM is partnering with gTt (Barcelona), GAT (Lisbon) and LILA (Milan) to deliver the CROI 2013 bulletins, which have also been made possible thanks to support from Bristol-Myers Squibb. NAM’s wider conference news reporting services have been supported by Abbott, Boehringer Ingelheim, Janssen, Roche and ViiV Healthcare. The funders have no editorial control over the content of the materials.