Life expectancy for South African patients who start HIV therapy with CD4 cell counts above 200 is 'near normal'

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HIV-positive patients in South Africa can have a near-normal life expectancy, provided that they start antiretroviral therapy promptly, investigators report in the open access journal PLoS Medicine. Individuals who started therapy when their CD4 cell count was above 200 cells/mm3 had a life expectancy of approximately 80% of that of matched HIV-negative individuals.

“These results are encouraging,” comment the authors. Even better life expectancy was associated with starting treatment after 2006 and longer duration of therapy. The investigators believe that the revision of South African treatment guidelines recommending the initiation of therapy at CD4 cell counts of 350 cells/mm3 and testing campaigns are likely to lead to further improvements in prognosis.

The investigators undertook their research because little is known about the life expectancy of patients taking anti-HIV drugs in low- and middle-income countries. Several studies have shown that the prognosis of many HIV-positive patients in richer countries is now normal or near normal. But it is open to question if similar gains have been achieved in less well resourced settings which often face significant challenges in the delivery of healthcare and HIV treatment. In particular, very late HIV diagnosis might be expected to moderate improvements in life expectancy.

Glossary

middle income countries

The World Bank classifies countries according to their income: low, lower-middle, upper-middle and high. There are around 50 lower-middle income countries (mostly in Africa and Asia) and around 60 upper-middle income countries (in Africa, Eastern Europe, Asia, Latin America and the Caribbean).

person years

In a study “100 person years of follow-up” could mean that information was collected on 100 people for one year, or on 50 people for two years each, or on ten people over ten years. In practice, each person’s duration of follow-up is likely to be different.

prognosis

The prospect of survival and/or recovery from a disease as anticipated from the usual course of that disease or indicated by the characteristics of the patient.

low income countries

The World Bank classifies countries according to their income: low, lower-middle, upper-middle and high. While the majority of the approximately 30 countries that are ranked as low income are in sub-Saharan Africa, many African countries including Kenya, Nigeria, South Africa and Zambia are in the middle-income brackets. 

sample size

A study has adequate statistical power if it can reliably detect a clinically important difference (i.e. between two treatments) if a difference actually exists. If a study is under-powered, there are not enough people taking part and the study may not tell us whether one treatment is better than the other.

A team of investigators therefore examined data obtained from six South African antiretroviral therapy cohorts. A total of 37,740 patients starting HIV therapy between 2001 and 2010 were included in the authors’ analysis. The large sample size and the diverse populations represented in these cohorts were major strengths of the study.

Mortality was estimated by linking patient records to the South African national population register. The excess mortality attributable to HIV was then estimated. The investigators took into account factors such as age, CD4 cell count at the initiation of HIV therapy and the duration of treatment.

Most of the patients were female (62%) and three-quarters were aged between 25 and 44 years. For most of the period of analysis, patients only became eligible for treatment when their CD4 cell count dropped below 200 cells/mm3. Therefore, 87% of patients had a baseline CD4 cell count below this threshold and only symptomatic patients with higher CD4 cell counts were eligible for therapy.

There were 5,782 deaths during 69,514 person-years of follow-up. The overall mortality rate was 83 per 1,000 person-years. It was substantially higher for men (100 per 1,000 person years) than women (73 per 1,000 person years). Mortality rates were highest during the first twelve months of HIV treatment and then fell to low levels with longer duration of therapy.

HIV-negative men and women aged 20 had an average life expectancy of a further 45 and 53 years respectively.

Overall, HIV-positive men and women aged 20 at the time they started antiretroviral drugs had average life expectancies of a further 28 and 37 years.

Life expectancy increased with baseline CD4 cell count. Overall, the life expectancy of patients with a count above 200 cells/mm3 when they started treatment was between 70% and 86% of those of their HIV-negative peers. However, patients whose CD4 cell count was below 50 cells/mm3 had a life expectancy of between 48% and 61% of those in HIV-negative individuals.

“South African patients starting ART have life expectancies around 80% of normal life expectancy,” write the authors.

Starting treatment after 2006 was associated with improvements in prognosis. Patients initiating therapy after that date with a baseline CD4 cell count above 200 cells/mm3 had average life expectancies between 82% and 88% of those in HIV-negative individuals of the same age and sex.

Further analysis showed that the life expectancy of patients who survived 24 months after the initiation of therapy was between 15%-20% higher than individuals who had just started treatment.

The authors note that treatment is now recommended for all patients before their CD4 cell count falls below 350 cells/mm3. Testing campaigns are also likely to have increased the proportion of patients able to start treatment before their CD4 cell count falls to dangerously low levels. The investigators therefore suggest: “Estimates of life expectancy for adults who have initiated ART with CD4 counts above 200 cells/mm3 may therefore be underestimates of the life expectancies in the future.”

However, they acknowledge that antiretroviral treatment programmes in resource-constrained settings still face formidable challenges. They conclude: “It is…critical that appropriate funding systems and innovative ways to reduce costs are put in place, to ensure the long-term sustainability of ART delivery in low- and middle-income countries.”

References

Johnson LF et al. Life expectancies of South African adults starting antiretroviral treatment: collaborative analysis of cohort studies. PLoS Medicine, 10:4. E1001418