3 Big Breakthroughs Were Made This Week in the Battle Against HIV
Over the past 15 or so years antiretrovirals have been the savior in the long battle against human immunodeficiency virus (HIV). Those with access to the drugs are generally able to keep the dangerous virus in check and live long, healthy lives. This, however, is not a cure, but a lifelong therapy that can be expensive and inaccessible to many in need. But this week three extremely promising pieces of research were released that could dramatically improve the way HIV is treated.
Early drug treatment in babies: Researchers in California have shown that the early treatment of a baby carrying HIV at birth with antiretroviral drugs has led to remission of the virus for the second time ever. Last year a first child was revealed to be "functionally cured" of HIV after using a similar treatment program. The treatment involves administering adult level doses of three antiretroviral drugs to the child as early as four hours after birth. For precautionary reasons, in previous treatment regimes HIV-positive babies have received lower doses of only two of these drugs several weeks after birth.
Different ways in which antiretrovirals stop HIV replication. Image Credit: Wikipedia
HIV-positive adults who take these drug cocktails daily see regression of the virus into "undetectable" levels (defined as less than 20 copies of the virus in a milliliter of blood). Unfortunately when treatment is stopped, the virus reawakens and continues replicating. But these findings suggest that the virus can in fact be stopped from replicating indefinitely.
The litmus test will be to look at further cases and monitor what happens after the children are taken off the treatment in the long term. Though in the newest case the baby is 9-months old and still on therapy, the first baby has been off treatment for two years and is still HIV-negative. Studies where the babies have started treatment after six weeks have seen the virus comes back after two years. This critical trial for early aggressive treatment is set to begin in three months, with 60 HIV-infected babies to be monitored.
Gene Therapy: Exciting avenues for treatment in adults have also advanced. Researchers at the University of Pennsylvania have described a potential new gene therapy for HIV patients in The New England Journal of Medicine. The study was inspired by the the first person to recover from HIV, Timothy Brown. Brown had his immune system wiped out during leukaemia treatment and was therefore transfused with donor bone-marrow stem cells. These cells carried a mutation in a gene called CCR5, which is found on T-cells and used by HIV as a gateway. People who have a mutation to this gene are resistant to HIV.
Image Credit: Science
The HIV gene therapy is based on the very same premise, but instead of conducting a risky bone marrow transplant, the patient's own cells are used. Cells are withdrawn and modified using a special "nuclease" enzyme to target and inactivate the CCR5 gene. The modified cells are then reintroduced into the body. The result: elevated levels of T-cells in all patients after several weeks and a much slower increase in HIV level. The gene-modified cells were HIV-resistant — the virus was unable to infect and destroy these T-cells.
"This is a first - gene editing has not to date been used in a human trial [for HIV]," Professor Bruce Levine of the University of Pennsylvania, told the BBC. "We've been able to use this technology in HIV and show it is safe and feasible, so it is an evolution in the treatment of HIV from daily antiretroviral therapy." The next stage of the trial is set to begin in April and will use higher amounts of cells for genetic modification.
A long-acting shot: There's also good news on the prevention front. In a study published in Science, researchers have shown that an experimental drug injected into the muscle of monkeys is able to confer temporary protection from HIV infection. The study was conducted by researchers at Aaron Diamond AIDS Research Center in New York and drug-maker GlaxoSmithKline. The injections use a drug called GSK744, which works by stopping a native enzyme HIV uses to insert its foreign DNA into the human genome. This prevents the virus from replicating, and eventually the viral DNA is destroyed.
Image Credit: NATAP
The trial showed that HIV-infected monkeys injected with GSK744 were protected between five and 10 weeks. But because humans metabolize the drug more slowly, researchers are hopeful that protection for human patients to last up to 3 months.
Will any of these become effective cures? These treatments currently have their limitations, but they all demonstrate encouraging promise.
It will probably take years before we can evaluate the true success of treating HIV-infected babies early with antiretrovirals. Researchers do not currently know how long treatment must continue in order to be effective or how long the virus stays away afterwards. While few babies are born in the U.S. with HIV thanks to drug treatment in mothers, in the developing world some 330,000 babies are born with HIV each year. With limited access to medical care and expensive daily antiretrovirals, early treatment of babies could be an effective strategy toward reducing HIV levels.
The gene therapy results are extremely exciting but still far away from replacing antiretrovirals. In the trials, the virus eventually returned in all but one of the patients. The goal is to develop a therapy where the majority of the immune system is genetically edited so that the cells are incapable of being infected with HIV. Newer enzymes that can successfully target DNA better than the current 20% rate may help achieve this goal in the future and eventually allow patients to control viral levels without need for the drugs.
Injection with GSK744 only lasts temporarily so won't be a replacement for a much coveted vaccine. But months of protection can be an effective prevention strategy in high-risk populations. This strategy has been previously implemented using antiretrovirals. Either way, GSK744 is an improvement because it's easier to give healthy people a shot every few months than drugs every day.
Estimated Number of Adults Needing Antiretroviral Therapy. Image Credit: KFF
While none of these treatments is yet a complete replacement for current antiretroviral drugs, it's exciting to find so many different promising strategies. Crucially, with lower costs and easier administration procedures (especially, no daily doses) these therapies have the potential to widen access to HIV treatment in much need areas.
Successful trials of new and different HIV treatments is outstanding news, even if it's still early days. In the fight against such a devastating virus, we need all the weapons we can get.