More evidence for starting HIV treatment earlier?

HIV treatment guidelines are now recommending that anti-HIV therapy should be started when a person’s CD4 cell count is around 350 cells/mm³.

But is there a case for starting treatment at even higher CD4 cell counts?

Evidence presented to CROI suggests that there might. Investigators looked at rates of HIV disease progression and death from 23 cohorts. They found that HIV-positive individuals had a higher risk of death than the general population, even when CD4 cell counts were above 350 cells/mm³.

Over 46,000 patients were included in the researchers’ anaylsis. Gay men had only a slightly increased risk of death compared to the general population, but for heterosexual men and women the risk of death was three times greater and some ten times greater for injecting drug users.

Although the researchers do acknowledge that factors other than HIV may underlay the increased risk of death for some patients, particularly injecting drug users, they did find that HIV itself was causing death, even amongst patients with higher CD4 cell counts.

Results from this study seem likely to contribute to the debate about the best time to start anti-HIV treatment. Some doctors now think that there are benefits to commencing antiretroviral therapy at a CD4 cell count of 500 cells/mm³.

Benefits to starting immediate treatment when a patient has an opportunistic infection

Patients who are ill because of HIV-related opportunistic infections are generally recommended to start anti-HIV therapy as soon as possible.

Introducing anti-HIV therapy whilst a patient is still receiving treatment for their opportunistic infection reduces the risk of risk of death or further disease progression, compared to waiting until treatment for the opportunistic infection is completed, and doesn’t increase the risk of side-effects, a study presented to CROI shows.

US researchers compared two groups of patients who were ill because of HIV and who were not taking antiretroviral therapy. One group of patients started anti-HIV therapy and treatment for their opportunistic infection at the same time. The other group of patients waited to start anti-HIV treatment until they’d completed therapy for their infection.

The study didn’t include patients with tuberculosis.

Overall, just under half the patients taking immediate or deferred anti-HIV treatment experienced no further HIV disease progression and managed to get their HIV viral load to undetectable levels.

But further analysis of the results showed that patients who deferred anti-HIV treatment were about 50% more likely to develop another AIDS-defining illness or die than those taking immediate treatment. And CD4 cell counts increased at a slower rate in those waiting to start treatment.

Starting treatment immediately didn’t have any additional risks. There were no difference in rates of adherence between the two groups of patients. Nor was there any difference in the risk of developing an immune reconstitution inflammatory syndrome once treatment was started.

Biomarkers may explain risk of treatment interruptions

Patients who take treatment interruptions have indicators of increased inflammation as well as dysfunction in the lining of the blood vessels. This could explain the increased risk of illness and death due to diseases not usually associated with HIV, such as heart, kidney and liver disease, seen in the SMART study.

Researchers looked at the results of the SMART and STACCATO treatment interruption studies. They told CROI that HIV replication during structured treatment breaks affected key biomakers that indicate inflammation, increased blood clotting and endothelial dysfunction – reduced flexibility in the lining of blood vessels, an early sign of heart disease.

Darunavir works well in treatment-experienced children

Anti-HIV treatment can work well in children. But there are fewer antiretroviral drugs available for the treatment of HIV in children than adults, and this can be a real problem as many children have drug-resistant HIV.

Darunavir (Prezisata) is a ritonavir-boosted protease inhibitor and is an important treatment option for adults with drug-resistant virus.

Results from a study presented to CROI show that darunavir/ritonavir is a safe and effective treatment in children and adolescents who’ve taken a lot of anti-HIV treatment.

A total of 80 children aged between six and 17 years were included in the study. They received the most effective anti-HIV drugs chosen by resistance tests, and darunavir/ritonavir dosed by weight. The children had a lot of resistance to anti-HIV drugs.

But after six months of treatment with the darunavir/ritonavir-based combination, 50% had a viral load below 50 copies/ml and almost two-thirds had a viral load below 400 copies/ml.

Only one patient stopped taking treatment because of side-effects, although most of the children did report a mild side-effect, such as tummy problems, or fever.

Research points to the prospect of a once-monthly anti-HIV drug

Once-daily anti-HIV treatment was considered a breakthrough, but researchers are now developing an anti-HIV drug that might need to be taken just once a month.

An experimental NNRTI called rilpivirine has been formulated with nanoparticles. Results in animals suggest that once-monthly injections could be enough to treat HIV.

Researchers are trying to find other drugs that could be formulated in a similar way. This could mean that potent, multi-drug anti-HIV treatment could be developed that is injected monthly.

This technology could also be used for HIV prevention to provide long-lasting pre-exposure prophylaxis or a as a microbicide.