Douglas Dieterich, Mt Sinai School of Medicine, New York. © Liz Highleyman / hivandhepatitis.com

Several studies presented at the conference show that newer protease inhibitors for hepatitis C treatment perform well in people with HIV/HCV co-infection, and have fewer serious side-effects than currently available HCV protease inhibitors.

Adding the investigational hepatitis C protease inhibitor simeprevir to pegylated interferon/ribavirin achieves a 75% response rate in people with hepatitis C and HIV co-infection.

The study involved 106 people with co-infection, most of whom were taking antiretroviral therapy.

The majority (80%) had the difficult-to-treat genotype 1a hepatitis C infection, 12% had advanced fibrosis and 9% had cirrhosis.

All received a triple combination of anti-hepatitis C drugs, comprising simeprevir with pegylated interferon and weight-based ribavirin.

Response rates twelve weeks after completing treatment were as high as 75% for people who had not taken treatment for hepatitis C before and 80% for people who had previously had a partial response to hepatitis C treatment.

Overall, 75% of participants who completed therapy had a sustained virological response to treatment (their hepatitis C was considered to be cured).

Only 4% of participants stopped treatment because of side-effects.

Improved responses in people with co-infection were also seen when the investigational protease inhibitor faldaprevir was added to standard hepatitis C therapy.

The study involved 308 people, a fifth of whom had relapsed after a previous course of hepatitis C therapy.

At week 4, 60% of people who had not taken treatment before and three-quarters of people who had experienced a relapse had an undetectable hepatitis C viral load. The proportions had increased to 82 and 91% at week 12.

The most common side-effects were nausea, tiredness, diarrhoea, headache and weakness.

Anaemia was observed in 18% with a similar proportion developing rash and 16% neutropenia.

The researchers think this shows that faldaprevir is less toxic than existing hepatitis C protease inhibitors.

Doctors speaking at CROI think these second-generation protease inhibitors represent a real improvement on currently available in drugs in this class. Both drugs could be available for use with pegylated interferon and ribavirin within 18 months in the United States and some European countries.

Karen Tashima, Brown University, presenting at CROI 2013. © Liz Highleyman / hivandhepatitis.com

Research involving treatment-experienced patients has shown that it is possible to construct effective antiretroviral regimens that do not include drugs from the nucleoside reverse transcriptase inhibitor (NRTI) class.

Improvements in treatment mean that an undetectable viral load is a realistic goal for nearly everyone, including people who have changed treatment several times (sometimes referred to as having extensive experience of HIV treatment) and who have drug-resistant virus.

Combinations for heavily treatment-experienced patients are selected after testing for drug resistance. They often include drugs the patient has taken previously (‘recycled’ drugs), including NRTI agents that are often only partly effective.

But this strategy increases the number of pills a person has to take (the ‘pill burden’) and can also lead to more side-effects.

Doctors in the US wanted to see if it was possible to construct an effective HIV treatment regimen that didn’t include NRTIs.

They therefore designed a study involving 360 people who needed to change their HIV treatment because it was failing. All were taking HIV therapy based on a protease inhibitor and had a viral load above 1000 copies/ml.

About half had CCR5-tropic virus and were therefore candidates for therapy with maraviroc (Celsentri, Selzentry).

The most widely used new combination comprised the integrase inhibitor raltegravir (Isentress), the ritonavir-boosted protease inhibitor darunavir (Prezista) and the NNRTI etravirine (Intelence).

Doctors and study participants then selected the NRTIs they’d most like to use.

The participants were then randomised to take or omit these NRTIs from their drug regimen.

After one year, treatment outcomes were broadly similar between the people who took NRTIs and those who omitted this class of drug. Similar proportions had a detectable viral load (26 vs 30%) and CD4 cell gains were similar.

Omitting NRTIs didn’t seem to have any benefits in terms of side-effects.

One of the study investigators concluded, “You don’t need to include NRTIs when new active agents are on board.” 

Research conducted in a resource-limited setting also showed the effectiveness of second-line HIV therapy that omitted NRTIs.

The study was conducted in Africa, Asia, Latin America and Australia.

Patients received therapy with lopinavir/ritonavir (Kaletra, Aluvia) and raltegravir (Isentress).

It was designed to see if this combination offered a viable alternative to the second-line regimen for resource-limited settings advocated by the World Health Organization (WHO): ritonavir-boosted lopinavir or atazanavir (Reyataz) with two NRTIs, which could be recycled from the first-line regimen.

The study involved 558 adults whose HIV treatment had failed to suppress viral load.

A year after switching to second-line therapy, 66% of the participants taking raltegravir and 66% of those taking NRTIs had an undetectable viral load.

CD4 cell gains were higher with the NRTI-sparing regimen.

The researchers believe the raltegravir-based regimen is effective, simple and tolerable.

The new integrase inhibitor dolutegravir appears to outperform raltegravir (Isentress) in treatment-experienced patients with resistance to two or more anti-HIV drugs.

Dolutegravir has performed well in clinical trials and is currently awaiting regulatory approval in Europe, Canada and the US.

The present study involved 715 people with detectable viral load despite taking HIV therapy.

All had resistance to two or more anti-HIV drugs. However, none had previously received therapy with an integrase inhibitor.

They were randomised to take either dolutegravir or raltegravir as part of their HIV treatment combination.

Six months later, 79% of the study participants who were taking dolutegravir had an undetectable viral load compared to 70% of those taking raltegravir.

Outcomes were especially favourable for dolutegravir among people who had a high viral load at the start of the study.

Treatment was stopped by 2% of participants in the dolutegravir group compared to 4% of people taking raltegravir.

An advantage of dolutegravir is that it is taken once daily whereas raltegravir is a twice-daily drug.

Dr Frederick Sawe of the Kenya Medical Research Institute presenting at CROI 2013.

Routine viral load monitoring reduces the risk of virological failure by almost half, a study conducted in Kenya has shown.

Monitoring of viral load is the exception rather than the rule in resource-limited settings. WHO recommends that patients should have a confirmatory viral load test if treatment failure is suspected, and six-monthly monitoring if this is feasible.

Researchers wanted to gain a better understanding of the benefits of six-monthly monitoring.

They designed a study involving 820 people starting HIV treatment for the first time. Half were randomised to have their viral load monitored twice a year.

The risk of virological failure was reduced by 46% among the people who received routine viral load monitoring.

Just 1% of people in the viral load monitoring group needed to start second-line therapy because of virologic failure; this compared to 7% of people who received standard care.

Delegates to CROI were also told about strategies to overcome barriers to viral load testing.

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Dr Chelsea Polis of USAID presenting at CROI 2013.

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