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Both HIV load (amount of HIV RNA per unit of blood) and CD4 lymphocyte cell counts are important predictors of HIV disease progression and death. However, independent of these, opportunistic infections (infections that attack people with weakened immune systems) have a major impact on HIV-related deaths, according to a study supported by the Agency for Healthcare Research and Quality (HS07317). A second AHRQ-supported study (National Research Service Award training grant T32 HS00060) reveals that improving patients' CD4 counts is likely to improve their quality of life; lowering HIV load below detectable levels may improve physical functioning; and highly active antiretroviral therapy (HAART) negatively affects physical functioning. Both studies are summarized here.
Seage, GR., Losina, E., Goldie, S.J., and others (2002, August). "The relationship of preventable opportunistic infections, HIV-1 RNA, and CD4 cell counts to chronic mortality." Journal of Acquired Immune Deficiency Syndromes 30, pp. 421-428.
This study used data from the Multicenter AIDS Cohort Study (MACS), which contains interview and medical record data from 1984 through 1994, to determine the relationship between a history of preventable opportunistic infection (POI) and chronic mortality (death more than 30 days after acute infection). The researchers controlled for HIV-1 RNA, absolute CD4 cell counts, use of antiretroviral therapy, and age. The study sample consisted of 2,193 homosexual adult men from four U.S. cities who were HIV-infected but asymptomatic. They were followed for nearly 8 years. People with a history of POI (for example, Pneumocystis carinii pneumonia) were over 28 times more likely to die 30 days or more after the acute infection compared with those without such a history (mortality rate of 66.7 vs. 2.3 per 100 person-years).
After adjustment for CD4 count and maximum HIV viral load, people with a history of POI still had a risk of death that was seven times as high as those without such a history. CD4 count was also an independent risk factor for chronic mortality. In the absence of a history of POI, those with CD4 cell counts less than 50 had a risk of death that was nearly nine times as high as it was for those with CD4 counts higher than 200. Maximum HIV viral load had no independent effect on chronic mortality, but unlike CD4 counts, viral load was not measured every 6 months.
Older men had a 34 percent higher risk of death within 30 days, whereas the risk of death was 63 percent lower for those who used antiretroviral therapy. These results support the idea that HIV may cause mortality through a number of different pathways.
Gill, C.J., Griffith, JL, Jacobson, D., and others (2002, August). "Relationship of HIV viral loads, CD4 counts, and HAART use to health-related quality of life." Journal of Acquired Immune Deficiency Syndromes 30, pp. 485-492.
HIV viral load, CD4 count, and HAART have different effects on health-related quality of life (HRQL) among patients with HIV disease, finds this study. The investigators analyzed the independent effect of each of these three factors on HRQL for 513 HIV-infected people in four domains of HRQL: physical functioning (PF, ranging from rigorous activities like running to carrying groceries, and walking a block); role function (RF, whether health kept them from working at a job, going to school, or doing work around the house in the prior 4 weeks); energy level (EL, fatigue that kept them from doing things they wanted, for example); and health perceptions (HP) after adjustment for other factors affecting HRQL.
The mean age of study participants was 40 years, 26 percent were female, 38 percent were minority, 57 percent were gay or bisexual, 33 percent had used injectable drugs, and 44 percent were using HAART. Mean HRQL scores ranged from 55.5 for EL to 75.5 for RF out of 100 points. Compared with patients with CD4 counts over 500, patients with CD4 counts less than 200 had lower PF (-8.8 points), RF (-9.3 points), and HP (-7.8 points). Patients with detectable HIV loads had lower PF scores (-7.7 points) than those with undetectable viral load. A PF score difference of -7.7 and -8.8 is of slightly lower magnitude than the impact of having diarrhea and clinical depression simultaneously (-11.1 points) but of larger magnitude than either disease alone.
After adjusting for viral load and CD4 counts, HAART use was associated with lower PF scores (-5.4 points), probably due to disagreeable side effects, which is comparable in impact to having either diarrhea or clinical depression. Efforts to improve patients' CD4 counts are likely to also improve HRQL. Lowering viral loads may improve physical functioning but only if viral loads are suppressed to undetectable levels. Finally, the adverse effects of HAART on PF are likely to be outweighed by its positive effects on lowering viral load and increasing CD4 counts, conclude the researchers.
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