US investigators have found people with HIV aged 50 and over have weaker immune restoration after starting antiretroviral treatment, and recommend that earlier treatment should be a priority in this group.
The study, published in the
online edition of the Journal of Acquired
Immune Deficiency Syndromes, also showed that the majority of
patients had a CD4 cell count above 500 cells/mm3 after five or more
years of therapy and that 75% of individuals had an undetectable viral load.
Combination antiretroviral therapy became available in 1996
and rapidly transformed the prognosis of patients with HIV.
However, published data examining the long-term
effectiveness of such treatment is currently limited.
Therefore investigators from the Multicenter AIDS Cohort
Study (MACS) monitored the CD4 cell counts and viral load of 614 HIV-positive
gay men who had been taking potent antiretroviral therapy for between five and
The investigators were especially eager to see if any
factors were associated with longer-term outcomes, and hypothesised that age,
and HIV disease stage before the initiation of therapy, as well as CD4 cell
count and viral load during the first five years of treatment, would affect
immunological and virological responses in the longer term.
At the time HIV therapy was started, 47% of men were aged
under 40 and 12% were aged over 50.
A total of 4431 CD4 cell counts and viral load measurements
were obtained from patients between years five and twelve of treatment.
Just over half (53%) the patients were taking therapy based
on a protease inhibitor, and 70% of these individuals were treated with a
ritonavir-boosted drug. Non-nucleoside reverse transcriptase inhibitor
(NNRTI)-based treatment was taken by 42% of individuals, with efavirenz (Sustiva) the
most widely used drug (70%). A small proportion of patients (5%) were treated
with a triple nucleoside reverse transcriptase inhibitor(NRTI) combination, a
regimen which is now considered suboptimal.
Median CD4 cell count five to twelve years after starting
therapy was 585 cells/mm3.
In the first five years of therapy, significant increases in
CD4 cell count were observed regardless of baseline CD4 cell count. However,
CD4 cell counts stabilised after five years for patients who initiated therapy
when their CD4 cell count was in the region of 350 cells/mm3. There
continued to be modest increases for people who started treatment with
weaker immune systems.
Factors associated with poorer CD4 cell count gains after
five years were a lower baseline CD4 cell count (p < 0.01), and co-infection
with hepatitis B virus (p = 0.01).
Patients who had an undetectable viral load for at least 50%
of the first five years of therapy had higher CD4 cell counts in the longer
term (p < 0.01), as did individuals who remained on their first or second
combination of drugs (p = 0.03).
Age at the initiation of HIV therapy also predicted
longer-term outcomes. The mean CD4 cell count after five years of therapy was
significantly lower for men who started treatment when they were aged 50 or
over, compared to people who started treatment when they were aged under
Younger men who started therapy when their CD4 cell count
was in the region of 201 to 350 cells/mm3 had a mean CD4 cell count of
670 cells/mm3 after ten or more years of treatment.
In contrast, the mean CD4 cell count at this time point for
the over 50s who initiated therapy with a similar count was 578 cells/mm3,
a significant difference (p < 0.01).
To achieve a similar long-term CD4 cell count as the under
40s, older patients would have needed to start therapy when their CD4 cell
count was above 350 cells/mm3.
“Our data support using age in the guidelines for initiating
HAART [highly active antiretroviral therapy], such that persons who are older
than 50 years should start treatment at higher CD4 counts,” write the authors.
Investigators also found that long-term outcomes were
associated with total lymphocyte count.
A count above 1200 cells/mm3 at the time HIV
therapy was started was associated with a significantly higher CD4 cell count after five years of treatment (p <
“This finding supports the inclusion of TLC [total
lymphocyte count] in HIV treatment guidelines,” comment the investigators.
Overall, 78% of viral load measurements obtained after five
years of therapy were undetectable.
Viral load in the first five years predicted subsequent
outcomes, and virological control was significantly better in the long term for
patients who were undetectable in this period (p < 0.01).
Switching treatment on two or more occasions was associated
with poorer control of viral load in the longer term (p = 0.06).
Unsurprisingly, individuals who reported 100% adherence had
good control of virus after year five.
“In this study, several factors were found to be associated
with lower CD4 cell counts in men who received HAART for 5-12 years. Important
modifiable factors were older age and lower CD4 cell count at the time of HAART
initiation,” comment the researchers.
Nevertheless, they are encouraged by their overall findings,
writing “this study shows that the effectiveness of HAART persists for up to 12