Thrombocytopenia associated with treatment interruptions: HIV replication a cause

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A quarter of patients interrupting antiretroviral therapy developed thrombocytopenia, French investigators report in the December 15th edition of the Journal of Acquired Immune Deficiency Syndromes.

“Even a short treatment interruption of a few weeks could lead to severe thrombocytopenia”, comment the investigators.

The development of thrombocytopenia during treatment interruptions was correlated with a fall in CD4 cell count and an increase in viral load. A separate US study in the same issue of the journal and reported here on also found that a detectable viral load was a risk factor the development of thrombocytopenia.



A reduction in platelets (blood cells responsible for blood clotting). This results in spontaneous bruising and prolonged bleeding.



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. 

detectable viral load

When viral load is detectable, this indicates that HIV is replicating in the body. If the person is taking HIV treatment but their viral load is detectable, the treatment is not working properly. There may still be a risk of HIV transmission to sexual partners.


Confounding exists if the true association between one factor (Factor A) and an outcome is obscured because there is a second factor (Factor B) which is associated with both Factor A and the outcome. Confounding is often a problem in observational studies when the characteristics of people in one group differ from the characteristics of people in another group. When confounding factors are known they can be measured and controlled for (see ‘multivariable analysis’), but some confounding factors are likely to be unknown or unmeasured. This can lead to biased results. Confounding is not usually a problem in randomised controlled trials. 

odds ratio (OR)

Comparing one group with another, expresses differences in the odds of something happening. An odds ratio above 1 means something is more likely to happen in the group of interest; an odds ratio below 1 means it is less likely to happen. Similar to ‘relative risk’. 

Interrupting HIV therapy is not recommended as a treatment strategy. The results of the SMART study showed that individuals who interrupted their treatment had a significantly higher risk of developing both HIV- and non-HIV-related illnesses than those who took continuous antiretroviral treatment.

Thrombocytopenia – a shortage of platelets – can be a symptom of HIV infection. It was common before effective antiretroviral therapy became available, with some research suggesting that the condition was present in as many as 45% of patients with AIDS. Although incidence of thrombocytopenia fell after the introduction of combination HIV therapy, the latest US research suggests that approximately 3% of patients a year still develop the condition.

The risk of thrombocytopenia during treatment interruptions has not previously been described. Therefore investigators from the French ANRS 106-Window Trial analysed the incidence and risk factors for this condition comparing patients who took intermittent HIV therapy and those who took continuous HIV treatment. The study lasted 96 weeks, with the monitoring of patients at intervals of eight weeks.

A total of 391 patients were recruited to the study, and 197 took intermittent treatment, the rest taking antiretroviral therapy without a break. There were no significant differences between the two arms of the study at baseline. All were taking stable antiretroviral therapy, had an undetectable viral load, and the median CD4 cell count on entry to the study was 741 cells/mm3.

Thrombocytopenia was diagnosed if a patient has a platelet count below 150 x 103/mm3, and severe thrombocytopenia is their count was below 50 x 103/mm3.

Overall, 50 individuals (25%) of the patients interrupting their antiretroviral treatment developed thrombocytopenia compared to 19 (10%) of those taking continuous HIV treatment. This difference was highly significant (p

Thrombocytopenia developed within a median of only nine weeks amongst patients interrupting their treatment, compared to a median of 40 weeks in those taking continuous treatment.

Severe thrombocytopenia was diagnosed in 5% of those in the treatment interruption arm and just 1% of the continuous treatment arm (p = 0.03).

Statistical analysis that controlled for potentially confounding factors showed that the development of thrombocytopenia was significantly associated with interruptions in HIV treatment (odds ratio [OR], 4.10; 95% CI: 2.14-7.85), a low platelet count on entry to the study (OR, 3.41; 95% CI: 2.30-5.06), and a history of HIV-related thrombocytopenia (OR, 11.87; 95% CI: 2.43-57.93).

Platelet counts fell rapidly in those taking treatment interruptions, and were already significantly lower in this group after the first interruption (p

Moreover, the investigators found that falls in platelet counts were significantly associated with CD4 cell count (p

“We were able to show that the risk of thrombocytopenia is high among patients interrupting their antiretroviral therapy, with a 96-week incidence of near 25%”, comment the investigators.

Noting that platelet counts dropped soon after treatment was interrupted, the investigators write, “it is important…to remind patients and physicians that even a short treatment interruption cycle of a few weeks could lead to severe thrombocytopenia and that platelet counts should be carefully monitored if antiretroviral therapy has to be discontinued.”

The investigators suggest “the decrease in platelet count observed during each treatment interruption is…likely to be a direct consequence of HIV replication.”

Treatment interruptions should be “strictly forbidden” for patients with low platelet counts and a history of thrombocytopenia, recommend the investigators. They conclude, “thrombocytopenia…is another limitation of intermittent treatment, which should be avoided as much as possible.”


Bouldouyre M-A et al. Incidence and risk factors of thrombocytopenia in patients receiving intermittent antiretroviral therapy: a substudy of the ANRS 106-Window trial. J Acquire Immune Defic Syndr 52: 531-37, 2009.