Cheap tests good predictors of disease progression after starting HAART

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Inexpensive blood tests to measure total lymphocyte count, haemoglobin levels, and response to antigens can accurately predict the risk of HIV disease progression and could be used as a tool to monitor the effectiveness of HAART in resource-limited settings, according to a study published in the April 1st edition of the Journal of Acquired Immune Deficiency Syndromes. In particular, the study found that the response to HAART was poorer in women who started HAART with total lymphocyte counts below 850 cells/mm3.

In rich countries, CD4 cell counts and viral load tests are used to predict the risk of HIV disease progression and death after starting treatment with HAART. Although HAART is becoming less expensive in many resource-limited settings, both these diagnostic tests remain too expensive to be used in routine HIV care.

Investigators from the Women’s Interagency HIV Study (WIHS), a prospective US study involving over 2000 HIV-positive women, wished to see if some cheap and readily available blood tests could accurately predict the risk of HIV disease progression. The tests included total lymphocyte count (TLC), which has been shown to mirror CD4 cell count and predict HIV disease progression in untreated individuals. Individuals with a TLC below 1250 cells/mm3 are recommended by the World Health Organisation to commence treatment with HAART.

Glossary

disease progression

The worsening of a disease.

lymphocyte

A type of white blood cell that is important in the immune system. Includes B cells (B lymphocytes, which produce circulating antibodies) and T cells (T lymphocytes, which are responsible for cell-mediated immunity).

haemoglobin (HB)

Red-coloured, oxygen-carrying chemical in red blood cells.

multivariate analysis

An extension of multivariable analysis that is used to model two or more outcomes at the same time.

anaemia

A shortage or change in the size or function of red blood cells. These cells carry oxygen to organs of the body. Symptoms can include shortness of breath, fatigue and lack of concentration.

Other tests used by the investigators included checking for anaemia (haemoglobin below 10.6g/dl is a recognised indicator of an increased risk of disease progression), and looking at the response of the immune system to vaccines.

The investigators analysed data from 873 women who had a known date of HAART initiation. The median period of follow-up was 3.6 years, and during this period 106 women died and 345 developed an AIDS-defining condition. The investigators modelled three sets of results, one of which included CD4 cell count and viral load, with an additional model excluding CD4 cell counts, and a further model viral load.

TLC below 1250 cells/mm3 was found to be correlated with a CD4 cell count below 200 cells/mm3 (p<0.001) and DTH (no antigen response versus at least one response, p<0.001).

In further modelling and multivariate analysis, TLC below 850 cells/mm3, anaemia (a haemoglobin level below 10.6g/dl), pre-HAART response to DTH testing and a history of a prior AIDS-defining pre-HAART illness were all found to be predictive of HIV disease progression or death after HAART initiation.

The investigators comment, “in this large cohort of HIV-1-infected women who initiated HAART… TLC, HGB level, anergy to DTH testing, and report of an ADI prior to the initiation of HAART each independently predicted both death and AIDS-related morbidity. These are all markers of disease severity that are of relatively low cost and could be performed in resource-limited settings.”

In particular, they emphasise that this is the first study to find that TLC is not only a useful tool to predict when to start HAART, but that TLC prior to HAART initiation can predict clinical outcome after starting anti-HIV treatment.

DTH may prove less useful, because it is more labour intensive and requires patients to be seen three days after testing to examine the skin reaction. DTH may also vary due to factors other than HIV.

Further information on this website

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References

Anastos K et al. Total lymphocyte count, hemoglobin, and delayed-type hypersensitivity as predictors of death and AIDS illness in HIV-1-infected women receiving highly active antiretroviral therapy. JAIDS 35: 383 – 392, 2004.