Alarming surge in drug-resistant HIV uncovered

While it isn’t related to the primary focus of the parent article, it gives some useful context.

>> At the end of this first stage, the viral load stabilizes at a level that can, puzzlingly, last for many years. Doctors refer to this level as the set point. A patient who is untreated may survive for a decade with no HIV-related symptoms and no lab findings other than a persistent viral load and a low and slowly declining T cell count.

>> Eventually, however, the asymptomatic stage ends and AIDS sets in, marked by a further decrease in the T cell count and a sharp rise in the viral load. Once an untreated patient has full-blown AIDS, opportunistic infections, cancers and other complications usually cause the patient's death within two to three years.

>> The key to the mystery was in the decade-long asymptomatic stage. What was going on then? Was HIV lying dormant in the body? Other viruses were known to hibernate like that. The genital herpesvirus, for example, hunkers down in nerve ganglia to evade the immune system. The chicken pox virus also does this, hiding out in nerve cells for years and sometimes awakening to cause shingles. For HIV, the reason for the latency was unknown.

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>> When the researchers reran the experiment, fit the data to the model's predictions and estimated its parameters again, they obtained results even more staggering than before: 10 billion virus particles were being produced and then cleared from the bloodstream each day. Moreover, they found that infected T cells lived only about two days. The surprisingly short life span added another piece to the puzzle, given that T cell depletion is the hallmark of HIV infection and AIDS.

>> The discovery that HIV replication was so astonishingly rapid changed the way that doctors treated their HIV-positive patients. Previously physicians waited until HIV emerged from its supposed hibernation before they prescribed antiviral drugs. The idea was to conserve forces until the patient's immune system really needed help because the virus would often become resistant to the drugs. So it was generally thought wiser to wait until patients were far along in their illness.

>> Ho and Perelson turned this picture upside down. There was no hibernation. HIV and the body were locked in a pitched struggle every second of every day, and the immune system needed all the help it could get and as soon as possible after the critical early period of infection. And now it was obvious why no single medication worked for very long. The virus replicated so rapidly and mutated so quickly, it could find a way to escape almost any therapeutic drug.

>> Perelson's mathematics gave a quantitative estimate of how many drugs had to be used in combination to beat HIV down and keep it down. By taking into account the measured mutation rate of HIV, the size of its genome and the newly estimated number of virus particles that were produced daily, he demonstrated mathematically that HIV was generating every possible mutation at every base in its genome many times a day. Because even a single mutation could confer drug resistance, there was little hope of success with single-drug therapy. Two drugs given at the same time would stand a better chance of working, but Perelson's calculations showed that a sizable fraction of all possible double mutations also occurred each day. Three drugs in combination, however, would be hard for the HIV virus to overcome. The math suggested that the odds were something like 10 million to one against HIV being able to undergo the necessary three simultaneous mutations to escape triple-combination therapy.

>> When Ho and his colleagues tested a three-drug cocktail on HIV-infected patients in clinical studies in 1996, the results were remarkable. The level of virus in the blood dropped about 100-fold in two weeks. Over the next month it became undetectable.

[0] https://scientificamerican.express.pugpig.com/2019/03/13/how...