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OI and Death Rates With Low CD4s and High vs Low Viral Load - Undetectable Viral Load Matters
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9th International Congress on Drug Therapy in HIV Infection, November 9-13, 2008, Glasgow
Mark Mascolini
Keeping viral loads low in people with a CD4 count under 200 has a profound impact on rates of opportunistic infections (OIs) and death, according to a large EuroSIDA analysis [1]. The study also found lower OI and death rates in treated people with measurable viremia and a sub-200 CD4 count than in people with low CD4s who stopped treatment altogether.
The study focused on three groups, all with CD4 counts below 200:
⋅ Group 1: 3164 people taking combination antiretrovirals with a viral load below 500
⋅ Group 2: 3537 people taking combination antiretrovirals with a viral load above 500
⋅ Group 3: 1601 people not taking antiretrovirals with a viral load above 500
Everyone had at least 1 month of prospective follow-up with a CD4 count below 200 after January 1997 and a viral load measured within 6 months of the sub-200 CD4 count. The EuroSIDA team defined combination antiretroviral therapy as at least a three-drug regimen including a protease inhibitor, a nonnucleoside, or abacavir. White men accounted for 70% of patient-years, gay men for 41%, injecting drug users for 25%, and heterosexually infected people for 25%.
New diagnoses of OIs and death were least frequent in group 1 at 5 events per 100 person-years, compared with 13 events per 100 person-years in group 2 and 53 events per 100 person-years in group 3. The five most common OIs were non-Hodgkin lymphoma (16 in group 1, 29 in group 2, 14 in group 3, total 59), tuberculosis (9, 29, 20, total 58), wasting (6, 32, 16, total 54), cytomegalovirus infection (2, 30, 8, total 40), and Pneumocystis pneumonia (8, 11, 20, total 39).
To determine incidence rate ratios for OIs and death, EuroSIDA statisticians ran a multivariate analysis adjusted for current CD4 count, viral load, calendar time of follow-up, age, antiretroviral naive versus experienced, ethnicity, risk group, hepatitis B or C status, and OI prophylaxis versus none. The death rate analysis also factored in prior AIDS diagnosis. The analysis determined that, compared with group 1, the OI rate in group 2 was almost twice higher (P < 0.001) and the OI rate in group 3 was 4 times higher (P < 0.001). The overall death rate was marginally lower in group 2 than in group 1, while group 3 had almost a 10 times higher death rate than group 1 (P < 0.001).
A multivariate analysis to figure incidence rate ratios for HIV deaths and non-HIV deaths factored in the same variables and determined that group 2 had about a twice higher HIV death rate than group 1, but that excess rate fell short of statistical significance (P = 0.115). The non-HIV death rate was significantly lower in group 2 than in group 1 (P = 0.004), and that accounted for the lower overall death rate in group 2. Group 3 had more than a 10 times higher HIV death rate than group 1 (P < 0.001), while the non-HIV death rate was almost 10 times higher in group 3 than in group 1 (P < 0.001). The analysis did not delve into specific causes of death to determine why the treated people with uncontrolled viremia had a lower non-HIV death rates than the treated people with controlled viremia. The EuroSIDA team said "further investigation into competing risk and specific causes of death is needed" to explain this surprise finding.
A sensitivity analysis excluding deaths that occurred within 3 months of stopping treatment in group 3 found that this group still had an 11.8 times higher HIV death rate and a 3.4 times higher non-HIV death rate than group 1. These results indicated that the inflated death rate in group 3 only partly reflects the practice of stopping antiretroviral therapy in terminally ill people. The investigators proposed that the lower death rate in group 2 than in group 3 suggests "a beneficial effect [of antiretroviral therapy] over and above what can be explained by suppression of viral load and increases in CD4 count."
Reference
1. Bannister WP, Mocroft A, Kirk O, et al. Opportunistic infections in immunocompromised but virologically suppressed HIV-infected patients. 9th International Congress on Drug Therapy in HIV Infection, November 9-13, 2008, Glasgow. Abstract O332.
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