Starting HIV treatment reduces the risk of serious non-AIDS-related diseases

Serious non-AIDS-defining illnesses are common in people recently diagnosed with HIV, Spanish investigators report in the online edition of AIDS. “Clinicians should be aware that during the initial follow-up after HIV diagnosis NAE [non-AIDS events] do occur,” comment the authors. “Older patients and those presenting with lower CD4 cell counts and higher viral load are at increased risk of their occurrence.”

However, the research also showed that HIV treatment reduced the risk of non-AIDS-related illnesses, especially kidney disease and psychiatric disorders including depression.

The introduction of effective antiretroviral treatment has lead to a significant change in the spectrum of illnesses seen in people with HIV. The AIDS-defining illnesses and cancers associated with immune suppression are becoming increasingly rare. In contrast, rates of non-AIDS-defining illnesses – such as cardiovascular disease, kidney disorders and liver disease – have increased. The exact reasons for this increase are unclear, but may include ageing of the HIV-infected population, co-infections, the side-effects of some antiretroviral drugs, the inflammatory effects of HIV and lifestyle factors such as smoking.

The Spanish researchers wanted to identify the overall spectrum of non-AIDS defining conditions that were causing illness in people recently diagnosed with HIV.

They therefore designed a study involving 5185 people. Most were diagnosed with HIV after 2004 and were enrolled in the CoRIS cohort. The participants were followed until 2010.

“This is the first large study addressing the occurrence of NAEs in recently diagnosed HIV-infected patients in the current era, when relatively non-toxic antiretroviral agents are available for treatment,” write the investigators.

Over three-quarters (79%) of the participants were men and the median age was 36 years.

During a median of 2.09 years of follow-up, a total of 423 non-AIDS-related events were diagnosed in 367 participants. The incidence of non-AIDS-related events was 29 cases per 1000 person-years. Some 318 AIDS-defining illnesses were also diagnosed, an incidence of 25 cases per 1000 person-years. The vast majority (88%) of AIDS-defining illnesses were diagnosed within three months of the initial HIV diagnosis. The investigators believe this was related to late diagnosis of HIV, which was a “prevalent and concerning issue” in their cohort.

HIV therapy was started by 68% of participants.

The most common non-AIDS-related illnesses were:

• Psychiatric (122 events).

• Liver disease (57 events).

• Cancers (54 events).

• Kidney disease (42 events).

• Cardiovascular disease (34 events).

Depression requiring drug therapy accounted for 70% of all psychiatric events. Lung cancer (20%), non-Hogkin's lymphoma (14%), cancer of the head or neck (12%), liver cancer (9%) and anal cancer (9%) were the most common malignancies. The investigators note that most of these cancers were related to viral co-infections or lifestyle factors. They therefore recommend that “additional strategies should be adopted during the initial care to contribute to reducing mortality in recently diagnosed HIV-infected patients, including a more exhaustive intervention on HCV [hepatitis C virus], papillomavirus and smoking habits among others”.

Incidence of non-AIDS-related illnesses fell from 35 cases per 1000 person-years in the period between 2004 and 2007 to 25 cases per 1000 person-years in the period 2007 to 2010 (p = 0.001).

This fall was accompanied by an increase in mean CD4 cell count at the time HIV therapy was started from 147 cells/mm³ to 278 cells/mm³ (p < 0.001).

After taking into account potential confounders, the investigators found that older age, a detectable viral load and a low CD4 cell count were associated with an increased risk of developing a non-AIDS-defining event. Antiretroviral therapy was associated with a lower risk of such events, especially psychiatric disorders and kidney disease. The authors believe this is “one of the most relevant findings” from their study. “To the best of our knowledge, no beneficial effect of cART [combination antiretroviral therapy] on different NAE categories had been demonstrated in cohort studies besides the SMART trial, in which structured interruptions of therapy were associated with a higher incidence of several NAEs compared to continuous therapy.”

A total of 173 participants (3%) died, and 29% of deaths were attributed to non-AIDS-related illnesses. The authors conclude: “NAEs are a frequent cause of morbidity and mortality during initial follow-up, with a predominance of psychiatric, hepatic and renal-related diseases. Our results suggest a beneficial effect of cART in the occurrence of NAEs, especially in psychiatric and renal-related NAEs.”

Masia M et al. Risk, predictors, and mortality associated with non-AIDS events in newly diagnosed HIV-infected patients: role of antiretroviral therapy. AIDS 26, online edition. DOI: 10.1097/QAD.0b013e32835a1156, 2012.