HIV virus suppresses virus in humanized mice

A team of Yale researchers tested a new chemical compound that suppresses HIV, protects immune cells, and remains effective for weeks with a single dose. In animal experiments, the compound proved to be a promising new candidate to enhance current HIV treatment regimens-without increasing toxic side effects.

The finding builds on the work of senior co-authors Karen S. Anderson and William L. Jorgensen, who used computational and structure-based design methods to develop a class of compounds that target a viral protein essential for HIV to replicate.

The researchers refined this class of compounds to boost potency, lower toxicity, and improve drug-like properties in order to identify a promising preclinical drug candidate. In collaboration with Priti Kumar's lab at Yale, the drug candidate was tested in mice with transplanted human blood cells and infected with HIV.

In the humanized mice, the compound achieved key goals of HIV treatment: It suppressed the virus to undetectable levels in the blood; it protected the immune cells that the virus infects; and it worked synergistically with approved HIV medications, the researchers said.

Additionally, working with Yale drug delivery expert Mark Saltzman and his laboratory, the researchers found that the effects of a single dose of the compound, delivered in a long-acting nanoparticle form lasted for a month. The compound has potential for improving treatment for HIV.
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Juluca for treating virologically suppressed HIV-1 Infection

FDA Approves Juluca (dolutegravir and rilpivirine) for the maintenance and treatment of virologically suppressed HIV-1 Infection. This is the first complete treatment regimen containing only two drugs to treat certain adults with human immunodeficiency virus type 1 (HIV-1) instead of three or more drugs included in standard HIV treatment.

Juluca is a fixed-dose tablet containing two previously approved drugs (dolutegravir and rilpivirine) to treat adults with HIV-1 infections whose virus is currently suppressed on a stable regimen for at least six months, with no history of treatment failure and no known substitutions associated with resistance to the individual components of Juluca.

Limiting the number of drugs in any HIV treatment regimen can reduce toxicity for patients, HIV weakens a person’s immune system by destroying important cells that fight disease and infection. Juluca’s safety and efficacy in adults were evaluated in two clinical trials of 1,024 participants whose virus was suppressed on their current anti-HIV drugs.

 Participants were randomly assigned to continue their current anti-HIV drugs or to switch to Juluca. Results showed Juluca was effective in keeping the virus suppressed and comparable to those who continued their current anti-HIV drugs. The most common side effects in patients taking Juluca were diarrhea and headache.

Serious side effects include skin rash and allergic reactions, liver problems and depression or mood changes. Juluca should not be given with other anti-HIV drugs and may have drug interactions with other commonly used medications.
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HIV treatment prevents cognitive decline

HIV-positive patients have the same risk of dementia as any other person if they take viral-suppressing medication and live a healthy lifestyle. One of the most debilitating effects of HIV is the neurocognitive decline, which can range from memory and language issues to dementia. Until now, research suggested that even those who take anti-retroviral therapy, the viral suppressing drug, had a higher risk of brain disorders than the general population.

Those who successfully suppress their viral load and live healthily have the same lifetime risk of dementia and other brain disorders as any other person. Older patients' brains may already have been ravaged by the disease, and medication couldn't reverse the damage, which would typically trigger symptoms within three or four years.

Researchers examined adults with HIV treated with cART with good viral suppression as well as those who did not have HIV for comparison. Both groups were about half women, with an average age of around 48 for the HIV-positive adults and 51 for the HIV-negative adults. Over the course of two years, the researchers assessed their brain changes using MRI scans.

They focused on the cortical thickness and subcortical volumes. They also assessed their cognitive performance using neuropsychological assessments. Those with HIV had poorer cognition and reduced brain thickness and volume than adults without HIV. However, by the end of the study, there were barely any differences between the two groups.
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