Short-term effects of treatment interruption

When a person stops taking antiretroviral therapy, HIV typically resumes replication almost immediately, which can lead to a rapid rise in viral levels. Viral load usually becomes detectable within about a week, and returns to pre-interruption levels within three months.

This burst of viral replication can trigger an acute retroviral syndrome similar to what some people experience when they first become infected with HIV. The syndrome is due to a systemic immune response, and is characterised by flu-like symptoms including fever, fatigue and swollen lymph nodes.

As HIV replication continues, the virus infects and kills more CD4 T-cells, leading to a falling CD4 cell count. Whilst CD4 cell decline may be delayed for some time after viral load starts to rise, and may then decrease slowly, in most people the CD4 count will eventually fall into the danger zone where opportunistic illnesses occur with greater frequency. Studies suggest that CD4 cell counts may drop faster and further in people who had low pre-treatment levels.

One treatment interruption study reported a CD4 cell decline of 128 cells/mm³ amongst people who stopped therapy for three months.¹ Another found that during a six-month treatment interruption, the CD4 cell decline showed a biphasic pattern, falling by 30 cells/mm³ per week during the first four weeks, then slowing to 3 cells/mm³ per week over the next five months.² Similarly, amongst people who interrupted treatment with a high current and lowest-ever CD4 cell count, the level fell by 20 cells/mm³ per week during the first eight weeks after stopping treatment, but then slowed to 2 cells/mm³ per week for the rest of the 96 week follow-up period.³

A person whose CD4 cell count is decreasing may first experience minor manifestations of immune impairment such as thrush, shingles, and more frequent herpes simplex outbreaks. Low platelet count (thrombocytopenia) may also occur. With further declines below 200, 100, and 50 cells/mm³, there is an increasing risk of AIDS-defining opportunistic infections such as Pneumocystis pneumonia (PCP), Mycobacterium avium intracellulare (MAI) and cytomegalovirus (CMV).