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People 60 or Older Gain Fewer CD4s on ART Through 48 Months
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7th International Workshop on HIV and Aging, September 26-27, 2016, Washington, DC
Mark Mascolini
People starting antiretroviral therapy (ART) at age 60 or older gained substantially fewer CD4 cells through 48 months than 20-to-29-year-olds, according to analysis of almost 160,000 people in Africa [1]. The difference was especially marked in people who began ART with 200 to 350 CD4s.
Research in the United States determined that people who started ART with fewer CD4 cells initially gained CD4s at a pace similar to those who started at higher CD4 counts [2]. But 4 to 6 years after ART began, people who started with a lower CD4 count hit a CD4 plateau well below that of people who started at a higher count. University of Maryland researchers who conducted the new analysis noted that this finding is particularly relevant in sub-Saharan Africa, where many people still start ART with a low CD4 count. Research in the United States, Europe, and resource-limited countries found that older people gain fewer CD4 cells with ART than younger people, but it remains unclear whether the difference has a clinical impact.
To address these issues, University of Maryland investigators conducted a retrospective study of data from 157 PEPFAR-funded and AIDSRelief-supported facilities in Kenya, Nigeria, Tanzania, and Uganda. The analysis involved people at least 20 years old who started ART between August 2004 and September 2012. No one had ever taken an antiretroviral before, including single-dose nevirapine.
The study group included 38,854 people from 20 to 29 years old, 63,220 from 30 to 39 years, 36,959 from 40 to 49 years, 14,102 from 50 to 59 years, and 5025 who were 60 or older. Median pre-ART CD4 count was similar across groups; almost half of each age group began ART with a CD4 count of 200 or lower, while about one quarter started with 201 to 350 CD4s.
First the researchers looked at people who began ART with a CD4 count of 200 or lower and figured adjusted average differences in CD4 gain by age through 48 months of treatment. They adjusted CD4 gains for sex, WHO status, functional status, ART regimen, TB, and other opportunistic infections. All age groups rapidly gained CD4s in the first 6 months of ART, but after that the improvement curves diverged, with the 20-to-29 group clearly on top, the three middle age groups clustered in the middle, and the 60-or-older group at the bottom. The four younger groups all ended up with average CD4 counts around 450 at 48 months, while the 60-or-older group ended up with an averaged below 400 CD4s. Compared with the 20-to-29 group, the 60-or-older group gained an average 22 fewer CD4s at 12 months, 49 fewer CD4s at 24 months, and 63 fewer CD4s at 48 months. For the 50-to-59 group, respective CD4 gains at those points compared with the 20-to-29 group were 29 fewer, 37 fewer, and 35 fewer.
The same pattern applied to people who started ART with 201 to 350 CD4s: the 20-to-29-year group clearly on top through 48 months, the middle three age groups clumped in the middle, and the 60-or-older group clearly on the bottom. For the five age groups, average CD4s after 48 months of ART were all higher than 48-month averages in people who started ART with a CD4 count of 200 or lower. Compared with the 20-to-29 group, the 60-or-older group gained 77 fewer CD4s at 12 months, 92 fewer at 24 months, and 76 fewer at 48 months.
Among people who started ART with more than 350 CD4s, the 20-to-29 group gained more CD4s through 48 months than the other four age groups, winding up with an average CD4 count around 700, compared with a count around 600 in the four older groups. Compared with the 20-to-29 group, the 60-or-older group gained an average of 85 fewer CD4s after 12 months of ART, 154 fewer after 24 months, and 74 fewer after 48 months.
The University of Maryland team suggested that the CD4-gain difference between the youngest and oldest people may not be clinically relevant among those starting with CD4 counts below 200 or above 350. But they maintained that among people starting with 201 to 350 CD4s, differences in CD4 gain are clinically meaningful, and "delays in achieving the same level of immune reconstitution are more pronounced."
The investigators noted that their study is limited because CD4 data were collected for routine care, not for research, and because they lack data on duration of HIV infection, adherence, and viral load. But they reported that overall adherence and viral suppression were high in this cohort. And they argued that stratifying the analysis by pre-ART CD4 count helped assure that they were "comparing apples with apples."
How closely the findings apply to people in high-income countries remains unknown. The researchers stressed that Africans may differ from Westerners in their immunologic response to ART because of high levels of immune activation due to nutritional deficiencies and endemic infections.
References
1. Stafford KA, Magder LS, Hungerford LL, et al. The effect of age on immune system reconstitution among HIV infected patients on antiretroviral therapy in resource limited settings. 7th International Workshop on HIV and Aging, September 26-27, 2016, Washington, DC. Abstract 12.
2. Moore RD, Keruly JC. CD4+ cell count 6 years after commencement of highly active antiretroviral therapy in persons with sustained virologic suppression. Clin Infect Dis. 2007;44:441-446.
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