The importance of timely initiation of combination
antiretroviral therapy (cART) to prevent major AIDS-defining
cancers
Looking specifically at Kaposi Sarcoma (KS)
and non-Hodgkin lymphoma (NHL), the authors used data on 689 cases
and 4,588 controls and found that an initially low and decreasing
CD4 cell count during the year prior to diagnosis was predictive of
both malignancies. The association between a weak and weakening
immune system and cancer risk was significant even when the
analysis was restricted to the period after 2000, when cART was
widely available.
However, the study also showed that the
incidence of both cancers increased in patients who had initiated
cART in the previous 3 months (odds ratio 2.31; 95% confidence
interval 1.33, 4.00) after adjusting for immune deficiency. The
authors highlight that “most of this increased cancer risk is
explained by the immunodeficiency characteristic of the period
before cART initiation.”
They add “there may be some additional risk
resulting from immune reconstitution during the first few months
after cART initiation.”
Immune reconstitution inflammatory syndrome
(IRIS) is typically characterised by clinical deterioration shortly
after the start of treatment and is often classified as either
paradoxical worsening of existing untreated disease or the
‘unmasking’ of previously subclinical disease. IRIS most often
presents with an opportunistic infection, especially TB.
The equivalent forms of IRIS in patients with
KS would include an increasing number or size of lesions that were
present before cART (‘flare’) or the diagnosis of KS soon after
beginning cART.
The authors conclude, “On the basis of our
findings, however, the main risk factor for the appearance of these
malignancies is immunodeficiency; and, therefore, the timely
initiation of cART remains the best strategy to avoid the
development of these malignancies.”
Jaffe H, De Stavola B, Carpenter
L, Porter K and Cox D. Immune reconstitution and risk of
Kaposi sarcoma and non-Hodgkin lymphoma in HIV-infected adults.
AIDS 2011. 25:1395-1403.
[Pubmed]
Read more about the study on the
EATG,
aidsmap, and IAS
websites.
Read more about the CASCADE
Collaboration.