During the early stages of infection, the reservoir is very susceptible to ART.
When people with HIV start antiretroviral treatment (ARV) a few weeks after infection, their viral reservoirs can be reduced by 99%, according to a new study. Although HIV begins to establish a viral reservoir shortly after infection, in the early stages the reservoir remains susceptible to ARVs.
As described in Science Translational Medicine, an international team of researchers from the University of Montreal's Hospital Research Center and other organizations analyzed blood and tissue samples collected by the U.S. Military Military Research Program's acute HIV infection cohort. Known as TV254 / SEARCH 010, the cohort was launched a decade ago in partnership with the Thailand Red Cross AIDS Research Center.
The cohort included people who contracted HIV not more than two weeks before, which means they were in what is known as the infection stage Fiebig I or II. These individuals underwent ARV treatment immediately.
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During Fiebig Stage 0, which lasts about 10 days after HIV infection, all signs of the virus are undetectable.
Stage I begins when a test can detect HIV RNA; lasts about seven days. Stage II begins when a test captures the p24 antigen, a viral protein, and lasts for about five days. Stage III begins when an ELISA test detects anti-HIV antibodies and lasts for about three days.
Stage IV begins when a Western lot test is positive or indeterminate and lasts for about six days. Stage V begins when a Western blot test is positive, but does not detect the integrase p31 antigen and lasts for about 70 days. And finally, stage VI, which lasts indefinitely and indicates chronic infection, begins when the Western blot test detects the p31 antigen.
The authors of the new study analyzed samples from 170 people in Thailand who had recently acquired HIV when they entered the TV254 study. The cohort members had a median age of 27 years. Ninety-six percent were men. They started ARVs at a median of two days after diagnosis.
The researchers found that people who started ARV treatment during stages I to III of Fiebig experienced a precipitous decline in the frequency of HIV infection in their cells, so that the reservoir was almost undetectable throughout the body. The rare infected cells that persisted were widely found in lymphoid tissues.
“The beginning of [ARV treatment, or ART] at this very early stage leads to a drastic decrease in the size of the viral reservoirs, clearing large wells of infected cells housed in lymphoid tissues and lymph nodes associated with the intestine, which are known to be preferred locations for HIV persistence during ART, ”said Nicolas Chomont, PhD, a professor at the University of Montreal, in a press release.
“Although the viral reservoirs of these people treated early are extremely small,” continued Chomont, “the virus is still there, and it can be said that there is no immediate clinical benefit at the moment.
However, since these early treated individuals have viral reservoirs 100 times smaller compared to our control group, we could reasonably think that it will be easier to eradicate these mini-reservoirs than the large ones in people who started ART later. "
Those who started ARVs during Fiebig stages IV or V experienced only a slight decline in the frequency of infection HIV in your cells.