Treatment interruptions: no addition to viral reservoir seen

Francois Houyez
Estimated reading time 2 minutes
This article is more than 23 years old.

One of the major concerns about structured treatment interruptions has been the potential for viral rebound to re-seed the lymph nodes, thus undermining future hopes of viral eradication or control by immune responses.

However, data presented at the recent Fifth International Workshop on HIV Drug Resistance and Treatment Strategies seems to contradict this view.

Cecile Tremblay, from the Massachusetts Hospital, Boston, reported on a cohort of 14 people who started treatment during acute HIV infection. The individuals decided to interrupt their antiretroviral treatment once their viral load had fallen below 50 copies HIV RNA per ml and remained suppressed for a unspecified period of time. These supervised treatment interruptions were mostly motivated by the patient’s request, in order to improve their quality of life. Doing so, it was decided to try to respond the following questions:

Glossary

acute infection

The very first few weeks of infection, until the body has created antibodies against the infection. During acute HIV infection, HIV is highly infectious because the virus is multiplying at a very rapid rate. The symptoms of acute HIV infection can include fever, rash, chills, headache, fatigue, nausea, diarrhoea, sore throat, night sweats, appetite loss, mouth ulcers, swollen lymph nodes, muscle and joint aches – all of them symptoms of an acute inflammation (immune reaction).

reservoir

The ‘HIV reservoir’ is a group of cells that are infected with HIV but have not produced new HIV (latent stage of infection) for many months or years. Latent HIV reservoirs are established during the earliest stage of HIV infection. Although antiretroviral therapy can reduce the level of HIV in the blood to an undetectable level, latent reservoirs of HIV continue to survive (a phenomenon called residual inflammation). Latently infected cells may be reawakened to begin actively reproducing HIV virions if antiretroviral therapy is stopped. 

plasma

The fluid portion of the blood.

treatment interruption

Taking a planned break from HIV treatment, sometimes known as a ‘drugs holiday’. As this has been shown to lead to worse outcomes, treatment interruptions are not recommended. 

ribonucleic acid (RNA)

The chemical structure that carries genetic instructions for protein synthesis. Although DNA is the primary genetic material of cells, RNA is the genetic material for some viruses like HIV.

 

  • Can STI contribute to the replenishment of viral reservoir?

  • Is there a chance that STI can increase the risk of resistance?

  • Does the virus evolve during sequential interruptions?

HIV was quantitatively cultured from serial dilutions of PBMCs when plasma HIV1 RNA was env and pol genes was performed from viruses recovered from these cultures, as well from plasma samples after viral load rose above 1000 copies/ml.

The results contradict the consensus view that an STI would undermine the potential benefits of treatment in primary infection: STI does not seem to replenish viral reservoirs since no statistically significant increase in IUPM was noticed before and after each treatment interruption. On the contrary, a >3 fold decrease in the virus reservoir was found in four of seven subjects following an STI.

There was also little sign of virus evolution: of four subjects with viable samples, none had major viral evolution.

But in one patient, the M184V mutation emerged during STI. It could be detected 21 days after treatment interruption. This may reflect the long intracellular half-life of 3TC triphosphate (active form), when the 3TC levels reached suboptimal concentrations that could select such a mutant.

Reference

Tremblay CL et al. HIV-1 evolution during repeated supervised treatment interruptions following early antiretroviral treatment of acute infection. Fifth International Workshop on HIV Drug Resistance and Treatment Strategies, abstract 19, 2001.

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