HIV viral load, co-infection with hepatitis C virus, and cirrhosis are all linked to thrombocytopenia in patients with HIV, US investigators report in the December 15th 2009 edition of the Journal of Acquired Immune Deficiency Syndromes.
The presence of thrombocytopenia was associated with a poorer prognosis, and the investigators comment, “our study demonstrates that thrombocytopenia remains a clinically significant problem in the current HIV treatment era.”
Before effective HIV treatment became available, thrombocytopenia – a low platelet count – was a common complication in patients with HIV, being seen in as many as 45% of patients with AIDS.
Thanks to antiretroviral therapy, patients with HIV can expect to live a long and healthy life and many HIV-related conditions are now rare.
However, the prevalence and risk factors for thrombocytopenia in the modern HIV treatment era are little understood. Gaining a better understanding of the condition is important as not only is it associated with major bleeding events, but it can also complicate treatment for both HIV and hepatitis C.
Investigators in New York therefore undertook a study that involved 73 HIV-infected patients with thrombocytopenia who were matched with HIV-positive patients of the same age and sex who did not have a low platelet count. The patients were all seen between 2004-05.
The patients with thrombocytopenia all had a platelet count below 100 x 106/l on at least three consecutive occasions.
Medical records were retrospectively examined to see if HIV-related factors such as duration of infection, viral load, CD4 cell count, and type and duration of antiretroviral treatment were related with thrombocytopenia. Information was also gathered on the patients’ hepatitis C infection status. The investigators also recorded if an individual had liver cirrhosis.
A total of 2298 HIV-infected patients were seen at the investigators’ clinics in 2004-05, and 3% were diagnosed with thrombocytopenia.
Of the 73 cases included in the study, 7% had extremely low platelet counts (below 10 x 106/l).
Thrombocytopenia persisted in approximately two-thirds of patients, a low platelet count still being present at the time of the final clinical evaluation.
Patients with thrombocytopenia were significantly more likely to have an HIV viral load above 400 copies/ml (odds ratio [OR], 5.3, 95% CI: 1.6 – 17.1; p = 0.006), have hepatitis C co-infection (OR = 24, 95% CI: 1.7 – 338.4, p = 0.019) and have liver cirrhosis (OR = 6.1, 95% CI: 1.6 – 22.6, p = 0.007).
The investigators found that 98% of individuals with persistently low platelet counts had at least one of these risk factors compared to just 53% of controls. Moreover, 15% of cases had all three risk factors compared to none of the controls.
In patients with neither hepatitis C nor cirrhosis, a detectable HIV viral load was strongly linked to thrombocytopenia (21 of 22 cases vs. 5 of 22 controls, p = 0.006). In contrast, amongst those with hepatitis C co-infection or cirrhosis, the prevalence of a detectable HIV viral load did not differ significantly between the cases and the controls.
Major bleeding events were significantly more common amongst the cases than the controls (13 vs. 5, p = 0.014). Amongst the patients with thrombocytopenia, major bleeding episodes were associated with liver cirrhosis (p = 0.003).
Furthermore, patients with thrombocytopenia were significantly more likely to die than the control patients (9 deaths vs. 0, p = 0.002). However, none of these deaths were a consequence of bleeding episodes.
“Uncontrolled HIV and hepatitis C virus replication were particularly associated with advanced liver disease, was strongly associated with thrombocytopenia in this study”, comment the investigators.
They emphasise that their study shows that HIV replication itself, rather than immune suppression or other HIV-associated disease was a significant factor for a persistently low platelet count. This finding adds to the accumulating evidence of the harm that uncontrolled HIV replication can cause.
The strong association between thrombocytopenia and co-infection with hepatitis C virus is likely to explain why platelet counts did not improve after HIV therapy was initiated. The investigators also note that advanced liver disease affects the ability of the liver to produce a key substance involved in platelet production.
“Thrombocytopenia still occurs frequently in HIV-infected patients and at levels that could predispose to bleeding and require treatment”, write the investigators.
The investigators believe their findings have clinical significance. They suggest that doctors should evaluate an HIV-infected patient for liver disease if they have thrombocytopenia.
They add that even “milder degrees of thrombocytopenia may predispose to bleeding and preclude the use of pegylated, which is of great relevance because a large burden of thrombocytopenia seems to be due to hepatitis C virus infection and related liver disease.”
“The better understanding of the risk factors for and etiology of thrombocytopenia initiated here will help guide whether antiviral, immune-based, or thrombopoietic therapies are appropriate initial treatment strategies for HIV-infected individuals with thrombocytopenia in future,” conclude the researchers.
Marks KM et al. Risk factors for thrombocytopenia in HIV-infected persons in the era of potent antiretroviral therapy. J Acquire Immune Defic Syndr 52: 595-99, 2009.