Older Age When Starting Antiretrovirals Lowers Chance of Good CD4 Gain

Starting antiretroviral therapy at an older age lowered chances of gaining at least 100 CD4 cells in the first 2 years of treatment, according to results of a large US-Canadian study.¹ The impact of age on CD4 gains held true regardless of whether people started a Norvir (ritonavir)-boosted protease inhibitor (PI) (such as Kaletra, Prezista, or Reyataz) or a nonnucleoside (such as Intelence, Sustiva, or Viramune). Age did not affect viral load response to first-line therapy in this NAACCORD analysis.

Triple antiretroviral therapy dramatically raised life expectancy in people with HIV. Now researchers project that half of all US adults with HIV will be 50 or older by 2015.²˒³ Some previous studies found lower CD4 count gains and better viral load responses to triple antiretroviral therapy in older people than younger people, but these findings were not consistent from study to study. Current antiretroviral treatment guidelines do not suggest that older HIV-positive people should start therapy at a CD4 count different from younger adults.

To look more closely at how age might affect CD4 and viral load responses to a first antiretroviral combination, NA-ACCORD researchers planned this study. This is the first study to assess the impact of age and type of first combination on CD4 and viral load responses to first-line treatment.

• How the study worked. The North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) is an ongoing study of people in HIV-positive study groups (cohorts) throughout the United States and Canada. This particular study examined findings on more than 12,000 people from 19 cohorts.

  To be included in this study, cohort members had to be at least 18 years old and had to start their first antiretroviral combination with a Norvir-boosted PI or a nonnucleoside between January 1, 1998 and December 31, 2008. The researchers did not include people who stopped or changed their antiretroviral combination within 1 month of starting. The NA-ACCORD team divided people into five age groups:

  • 18 to 29

  • 30 to 39

  • 40 to 49

  • 50 to 59

  • 60 or older

  Then the researchers determined how many people (1) gained at least 100 CD4 cells in the first 2 years of treatment and (2) reached a viral load below 500 copies in the first 2 years of treatment. Finally, the investigators used the latest statistical techniques to figure out how age, race, gender, and other factors affected chances of meeting each of those goals.

• What the study found. The study involved 12,196 adults starting their first antiretroviral combination: 71% started with a nonnucleoside and 29% started with a Norvir-boosted PI. Their age averaged 42 years and ranged from 18 to 83 when they began treatment. Most study participants (76% to 92% across the five age groups) were men, 29% to 41.5% were white, 31.5% to 38% were black, and 7% to 13% were Hispanic. The year when treatment began averaged 2003 in all age groups. Average starting CD4 counts ranged from 205 to 250 in the five age groups, and average starting viral loads ranged from about 45,000 to 55,000 copies.

  Half of the study participants did not stay on their first antiretroviral combination for 24 months: 25% changed to a different combination and 25% stopped treatment for at least 1 month. A higher proportion of people who started a PI changed or stopped treatment in the first 2 years (57% versus 48% who started a nonnucleoside).

  CD4-cell gains in the first 2 years of treatment were lower in older people than in younger people. This finding held true regardless of whether people started a Norvir-boosted PI or a nonnucleoside. Starting treatment with a PI versus a nonnucleoside lowered chances of reaching a viral load below 500 copies in the first year of treatment. But age did not have a significant impact on viral load response.

Statistical analysis that weighed factors influencing CD4 and viral load response to treatment in the first 2 years of therapy identified several factors that affected response rates independently of all other factors (Figures 1 and 2). Chances of gaining at least 100 CD4 cells in the first 2 years of therapy were lower in (1) older people than in younger people, (2) men than in women, (3) people with a lower viral load when treatment began, (4) people who started treatment in the late 1990s and early-to-mid 2000s than in those who started in more recent years (not shown in figure), and (5) people who got infected through sex between men and women or from injecting drugs than in people who got infected through sex between men (Figure 1).

Chances of reaching a viral load below 500 copies in the first 2 years of treatment were lower in (1) blacks than in whites, (2) people who got infected through sex between men and women or from injecting drugs than in people who got infected through sex between men, (3) people who started treatment in late the late 1990s and early 2000s than in those who started in more recent years (not shown in figure), and (4) people with a higher viral load when treatment began (Figure 2). Older age did not raise or lower chances of reaching a viral load below 500 copies.

• What the results mean for you. This large, well-planned study produced several important findings. Because the average age of people with HIV in the United States is rising into the 50s, perhaps the most important finding involves the impact of age on CD4-count response to a first antiretroviral combination. Compared with people under 30 years old when they began treatment, those 30 to 39 had a lower chance of gaining at least 100 CD4 cells in the first 2 years of treatment. Chances of adding 100 CD4 cells fell more and more in each older age group considered. Older age lowered chances of gaining CD4 cells regardless of what other traits a person might have that affect CD4 response to antiertroviral therapy.

This strong finding suggests that people with HIV and their doctors might consider age when deciding when to start antiretroviral therapy. Right now, antiretroviral treatment guidelines say nothing about how age might be considered in treatment planning. The NA-ACCORD researchers offer this suggestion about the meaning of their age-CD4 finding:

"Although further research is needed to determine if guidelines for when to start [combination antiretroviral therapy] should differ by age, our observation that older individuals are less likely to have a robust immunologic [CD4] response suggests that the optimal time to start [treatment] might differ by age."¹

The finding on how age affects CD4-cell response reflects results of earlier studies.⁴⁻⁶ Previous studies also found that older people often have a better viral load response to treatment than younger people. Some research suggests that better adherence to antiretroviral pill-taking schedules by older people explains this tendency. But the new study did not confirm that older age when treatment begins improves chances of a good viral load response. The NA-ACCORD investigators note that rules for patient entry into their study could have resulted in a study group with overall good adherence, regardless of age.

A third important finding is that half of this study group changed their antiretroviral combination or stopped treatment for at least 1 month in the first 2 years of therapy. This high rate suggests that antiretroviral side effects bothered many study participants and made them switch or stop treatment. The study included people who started their first antiretroviral combination from 1998 through 2008. The researchers do not report whether the stop-or-switch rate fell in more recent years. In general, people find the more recent antiretroviral combinations easier to tolerate. But this analysis does not address the possibility that tolerability improved in more recent study years.

The study also found that people who began treatment with a nonnucleoside had a better chance of reaching a viral load below 500 copies than people who started with a Norvir-boosted PI. That result mirrors a finding in a large trial that compared combinations including the nonnucleoside Sustiva (efavirenz) and the PI Kaletra (Norvir-boosted lopinavir).⁷

Together, these new findings offer people with HIV and their physicians important data to consider in deciding when to start antiretroviral therapy and in evaluating respones to therapy. The study also offers important findings that may be considered by the experts who write antiertroviral treatment guidelines.

References

1. Althoff KN, Justice AC, Gange SJ, et al. Virologic and immunologic response to HAART, by age and regimen class. AIDS. 2010;24:2469-2479.

2. Luther VP, Wilkin AM. HIV infection in older adults. Clin Geriatr Med. 2007;23:567-583.

3. Centers for Disease Control and Prevention. HIV/AIDS Surveillance Report, 2006.

4. Greenbaum AH, Wilson LE, Keruly JC, Moore RD, Gebo KA. Effect of age and HAART regimen on clinical response in an urban cohort of HIV-infected individuals. AIDS. 2008;22:2331-2339.

5. Belanger F, Meyer L, Carre N, Coutellier A, Deveau C. Influence of age at infection on human immunodeficiency virus disease progression to different clinical endpoints: the SEROCO cohort (1988-1994). The Seroco Study Group. Int J Epidemiol. 1997;26:1340-1345.

6. Munoz A, Sabin CA, Phillips AN. The incubation period of AIDS. AIDS. 1997;11:S69-S76.

7. Riddler SA, Haubrich R, DiRienzo AG, et al. Class-sparing regimens for initial treatment of HIV-1 infection. N Engl J Med. 2008;358:2095-2106.