Higher CD4 cell counts in patients taking antiretroviral therapy are associated not only with a lower rate of HIV-related illnesses, but a lower rate of serious illnesses such as heart, kidney, and liver disease as well as some cancers, according to a US study published in the April 23rd edition of AIDS.
HIV treatment guidelines have recently been changed in the UK, Europe and US recommending that anti-HIV therapy should be started when a patient’s CD4 cell count is in the region of 350 cells/mm3, mainly because the SMART treatment interruption study showed that a higher CD4 cell count was associated with a lower risk of not only AIDS-defining illnesses, but also some serious diseases not traditionally associated with HIV.
The findings of the current study potentially add to our understanding of the importance of CD4 cell count in reducing the risk of serious illnesses not normally associated with HIV.
On the basis of their findings, the investigators comment, “if the potential reduction in non-AIDS risk as well as AIDS risk could be realized through earlier initiation of antiretroviral therapy (at CD4 cell counts greater than 350 cells/mm3), thereby maximizing CD4 cell recovery and minimizing time spent at lower CD4 levels, the public health benefit would be substantial.”
Potent antiretroviral therapy lowers HIV viral load, allowing the CD4 cell count to increase, thereby reducing the risk of HIV-related opportunistic infections and cancers. Thanks to the success of antiretroviral therapy, the main causes of illness and death in people with HIV are no longer HIV-related.
Investigators wished to see if they could find an association between CD4 cell count and the risk of serious non-HIV related illnesses in patients starting antiretroviral therapy. The study involved 1397 patients enrolled in the FIRST study, which recruited patients between 1999 and 2000. The median duration of follow-up was 60 months.
Median CD4 cell count 32 months after starting antiretroviral therapy was 444 cells/mm3. But the investigators noted that CD4 cell count at this time was related to patient’s CD4 cell count when anti-HIV treatment was initiated.
Individuals with a baseline CD4 cell count below 200 cells/mm3 had a median CD4 cell count of 335 cells/mm3 after 32 months of therapy, compared to a median CD4 cell count of 487 cells/mm3 for patients whose CD4 cell count was between 200 – 350 cells/mm3 when they started treatment and 666 cells/mm3 for those patients who started therapy with a CD4 cell count above 350 cells/mm3.
A total of 227 patients experienced an AIDS-defining event and there were 80 serious non-HIV-related illnesses during this period.
The investigators found that the rate of both HIV-related and non-HIV-related diseases declined as the patients’ CD4 cell counts increased. For patients with a CD4 cell count below 200 cells/mm3 the rate of HIV-related illness was 14% with 2% developing serious non-HIV-related illnesses.
Approximately 2% of patients with a CD4 cell count between 200 – 350 cells/mm3 developed an AIDS-defining illness, and nearly 2% experienced a serious non-HIV-related illness. Of the patients with a CD4 cell count above 350 cells/mm3, only 0.7% progressed to AIDS, with a similar proportion of patients developing another serious illness.
After adjusting for current HIV viral load and baseline characteristics, the investigators found that each 100 cell/mm3 increase reduced the risk of an AIDS-defining illness by 44% (p
The investigators also looked at the type of diseases patients developed. HIV-related illnesses at CD4 cell counts above 350 cells/mm3 were, on the whole, treatable and non-serious (although there were three lymphomas). Serious non-HIV-related illnesses at higher CD4 cell counts included eleven non-AIDS-related cancers, three cases of cirrhosis, and three heart-related events.
As expected, patients with a CD4 cell count below 200 cells/mm3 were vulnerable to potentially fatal HIV-related illnesses. Furthermore, there were also nine non-AIDS-defining cancers in this group of patients, six cases of stroke, and four cases of end-stage renal disease.
Analysis was also conducted to see if a relationship could be identified between types of non-HIV-related illnesses and particular patient characteristics. This showed that older age was associated with cardiovascular illness (each ten years, HR = 1.89, 95% CI: 1.28 – 2.80) as well as non-HIV-related cancers (HR = 2.29, 95% CI: 1.28 – 2.80). Unsurprisingly, infection with hepatitis B virus or hepatitis C virus was linked with a greater risk of liver-related illness ((HR = 13.04; 95% CI: 3.50 – 48.49). Black ethnicity was associated with a higher risk of kidney disease (HR = 11.60, 95% CI: 1.50 – 89.50).
The investigators comment that their findings show that “rates of non-AIDS diseases decrease with increasing CD4 counts”. They call for a randomised controlled trial “to determine the risk-benefit balance of starting antiretroviral therapy at higher CD4 counts.”
Reference
Baker JV et al. CD4+ count and risk of non-AIDS diseases following initial treatment for HIV infection. AIDS 22: 841 – 848, 2008.