French study finds older patients are diagnosed later and have slower immune reconstitution

A French study of 3015 patients on first-line highly active antiretroviral therapy (HAART), of whom 401 (13%) were over 50, has found that CD4 T-cell recovery is slower in older patients and that the risk of progression to AIDS or death after starting treatment is greater. This was despite the fact that older patients in the study had a better virological response to HAART. The findings are reported in the October 21^st issue of the journal AIDS, now available online.

The 3015 patients studied were patients in the French Hospital Database on HIV (FHDH), which collected data from 68 French hospitals. The study was a longitudinal one looking at all patients enrolled in the FHDH between 1997 and 2001 who initiated HAART. It excluded patients with prior treatment experience.

It only included patients who had three or more CD4 cell counts taken during the follow-up period, which averaged 31 months.

Among the characteristics of patients over 50 isolated by the study were:

• A third of the older patients had an AIDS diagnosis at the time of enrolment to the database compared with one in five of the under-50s (p
• Their median CD4 cell count on enrolment was 193 cells/mm³, compared with 252 cells/mm³ in younger patients (p
• They had a higher median viral load on enrolment: 45% had viral load over 100,000 copies/ml compared with 35% of the younger patients (p
• They were more likely to be male and their risk factor for HIV was more likely to be heterosexual sex (47% vs. 37%) or unknown (17% vs. 8%). Virtually none were injecting drug users compared with one in seven of the younger patients.

The risk of disease progression after starting HAART was almost 50% higher in over-50s during the five year follow-up period. All deaths, including ones unrelated to HIV, were included, which must inevitably bias the death rate toward the older patients; but the over 50s also had a 50% greater chance of developing a new AIDS-defining event. This difference remained almost unchanged after five years on HAART which suggests that the risk was not solely related to lower baseline CD4 cell counts in the over-50s but was a genuinely greater likelihood of progression while on HAART.

The higher rate of clinical progression in older patients may be explained by poorer immune reconstitution, the authors suggest. CD4 cell count recovery in older patients was slower. Their average increase in the first six months was 14.1 cells/mm³ a month compared with 17.3 in the under 50s, and 9.8 cells/mm³ a month compared with 11.1 after the first six months (both differences p 3 was just under 18 months in the older patients and 15 months in the younger.

This was despite the fact that the older patients were 23% more likely to achieve undetectable viral loads, and 77% of the older patients had reached a viral load below 500 copies/ml by six months of HAART compared with 71% of the under-50s. The investigators comment that they could not determine whether this was due to better adherence or some other factor.

Although nearly all AIDS-defining illnesses were more common in the over-50s, certain specific opportunistic infections were much more common. Cytomegalovirus (CMV) disease was five times more common in over-50s, even though the average CD4 cell count at which it was diagnosed was the same for over-50s and under-50s. The authors do not offer a clear explanation for why this is so, merely citing “inadequate CD4 cell response”.

The results lead the investigators to conclude that although atrophy of the thymus gland with age may be the cause of the slower immune recovery seen in older patients, delayed diagnosis could also contribute to the higher rates of AIDS and death seen. They suggest that French doctors are less likely to suspect that older patients have HIV, as are the patients themselves, and recommend awareness campaigns targeting patients over 50.