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News in brief

Gus Cairns
Published: 17 July 2011

HIV drugs may have caused premature ageing

People with HIV seem to age prematurely. Specific age-associated conditions such as cardiovascular problems and type 2 diabetes are more common in people with HIV; also, more people develop the so-called ‘frailty phenotype’ early. This is the syndrome experienced in late old age characterised by weakness, weight loss, fatigue, inactivity and falls.

Although HIV drugs were initially implicated in premature ageing, current opinion believes it is associated with HIV infection itself and its long-term immune effects.

Now a new study suggests that some HIV drugs may be implicated after all.1

Researchers found that people with HIV who have taken some nucleoside reverse transcriptase inhibitor (NRTI) drugs were 20 times more likely to be deficient in a chemical called COX-SDH in their muscles than people who have never taken NRTIs, HIV positive or negative. The degree of COX-SDH deficiency was strongly related to the time spent taking these NRTIs.

COX-SDH is a marker of muscular strength and the efficiency of the mitochondria, the parts of the cells that provide energy; lack of it implies cells are not functioning normally.

The early HIV drugs d4T, ddI ddC and, to a lesser extent, AZT cause mutations in the DNA of mitochondria which means they produce non-functional copies of themselves. Although this study was too small to distinguish between different NRTIs, the NRTIs mainly used these days (3TC, FTC, abacavir and tenofovir) cause little mitochondrial damage.

“An HIV-infected individual treated with NRTIs during their third decade is predicted to develop approximately 5% of COX-deficient cells by age 60,” comment the researchers. “This is similar to or exceeds that seen in the healthy very old.”

However, not all researchers in ageing agree with the view that genetic damage to the mitochondria is an important cause of ageing. This was a small study and needs to be replicated in larger populations where the researchers can control more carefully for previous medical history and for current health status.

Small gains in starting therapy with high CD4

An Australian study comparing death rates in patients who started HIV therapy at high CD4 counts (over 650 cells/mm3) has found small but significant reductions in mortality, even compared with starting at the comparatively high figure of 500 cells/mm3.2

The study recruited 432 patients new to therapy who started with CD4 counts over 350 cells/mm3, and divided them into three groups according to their baseline CD4 count: 350 to 500, 500 to 650, and over 650 cells/mm3. After six years on therapy, the average CD4 count in these three groups was statistically the same, namely 689, 746 and 742 cells/mm3 respectively.

However, there was a modest but significant reduction in mortality in those starting at higher CD4 counts. After six years, patients who started therapy at a CD4 count over 650 cells/mm3 were 8% less likely to have died than patients who started at CD4 counts between 350 and 500 cells/mm3, and 4% less likely to have died than patients starting between 500 and 650 cells/mm3.  In absolute terms, this means one less death a year in every 3000 and every 6000 patients respectively.

The investigators calculated that, over six years, patients who started therapy when their CD4 counts were over 650 cells/mm3 had a 14% lower chance of developing AIDS or dying than patients starting therapy at between 350 and 500 cells/mm3.

According to the recent HPTN 052 study (see http://bit.ly/ncGzrm), putting people on HIV therapy with near-normal CD4 counts at least does them no harm and may even confer clinical benefit. This will add to the debate about whether the prevention benefit of treatment is so great that all people testing HIV-positive should be invited to start therapy on diagnosis.

One-in-nine new US diagnoses due to expanded testing

An estimated 11% of people infected with HIV in the last three years in the US would not have been diagnosed without routine testing in clinical settings in high-prevalence areas, according to the US Centers for Disease Control (CDC).3

In 2006 the CDC recommended ‘opt-out’ HIV testing, in which a test is performed unless specifically declined by the patient, in regions where more than one in 1000 of the local population had HIV. In 2007, it launched the $111 million Expanded HIV Testing Initiative (EHTI), which targeted 25 districts with high rates of infection in African Americans.

Nearly 2.8 million HIV tests were performed as part of the EHTI between October 2007 and September 2010, yielding 18,432 positive results. The CDC estimates that approximately 56,300 people are infected every year in the US:4 this implies that about 10% of new infections were diagnosed due to the initiative.

One in three new diagnoses took place in hospital emergency departments; the rate of positive results here was 0.8%. One in five took place in STI clinics and one in nine at community venues and organisations. Although community venues only carried out 6% of tests, their positive result rate was almost double that of other settings, indicating the importance of supporting community-based testing.

Coffee helps hepatitis C treatment

People with hepatitis C who drink a lot of coffee are nearly twice as likely to be cured after taking treatment, a study has found.5

People who drank more than three cups of coffee a day were 80% more likely to achieve a sustained virological response (SVR – defined as no detectable virus six months after the end of therapy) than people who drank none.

It is not clear why coffee helps with hepatitis C therapy or whether it will help people who have HIV as well as hepatitis C: this study was only conducted in people with hepatitis C alone.

The study looked at 855 patients who had already taken one course of unsuccessful hepatitis C treatment. Eighty-five per cent of patients said they drank coffee but only 15% had three or more cups each day.

Coffee drinkers had a higher hepatitis C viral load at baseline, but after twelve weeks of therapy, ones who drank three or more cups a day had an average hepatitis C viral load of 100 copies/ml compared to 40,000 copies/ml in non-coffee drinkers. 

Over a quarter (26%) of those drinking three or more cups of coffee a day achieved an SVR compared to 11% of those who did not drink coffee.

Abacavir heart attack risk still unclear

Studies in Denmark and amongst US forces personnel have produced contradictory findings on whether the NRTI drug abacavir (Ziagen – also in Kivexa) is associated with heart attacks and strokes.

The apparent link between abacavir and cardiovascular events was first uncovered by the D:A:D cohort study in 2008.6 Other studies, however, have failed to find a link.7

The Danish study8 looked at 5031 people accessing HIV care and contrasted their risk of having a stroke or other cerebrovascular event with the risk in 45,279 people in the general population. In this study, people taking abacavir were 66% more likely to have a cerebrovascular event.

However, a study by the Veteran’s Administration in the USA,9 following over 19,000 patients who received care between 1994 and 2004, while finding initially a slightly raised risk of heart attack in people taking abacavir, found that this increase may also be explained by kidney disease, a known risk factor for heart attacks.

Patients taking abacavir were 27% more likely to have hearts attacks than average, but they were also 25% more likely to have kidney disease than patients taking tenofovir.

Because tenofovir can cause kidney failure, mainly in people with pre-existing disease, people with kidney problems are both more likely to have heart attacks and to be prescribed abacavir.

References

  1. Payne BAI et al. Mitochondrial aging is accelerated by anti-retroviral therapy through the clonal expansion of mtDNA mutations. Nature Genetics, advance online publication, 26 June 2011.
  2. Wright ST et al. CD4 cell responses to combination antiretroviral therapy in patients starting therapy with high CD4 cell counts. JAIDS, online edition, doi: 10.1097/QAI.0b013e318225ba62.
  3. Viall AH et al. Results of the Expanded HIV Testing Initiative – 25 jurisdictions, United States, 2007-2010. Morbidity and Mortality Weekly Report 60 (24), June 24, 2011.
  4. See www.cdc.gov/hiv/resources/factsheets/us.htm
  5. Freedman ND et al. Coffee consumption is associated with response to peginterferon and ribavirin therapy in patients with chronic hepatitis C. Gastroenterology 140: 161-69, 2011.
  6. Sabin C et al. Do thymidine analogues, abacavir, didanosine and lamivudine contribute to the risk of myocardial infarction? The D:A:D study. 15th Conference on Retroviruses and Opportunistic Infections, Boston, abstract 957c, 2008.
  7. Bozzette SA et al. Long-term survival and serious cardiovascular events in HIV-infected patients treated with highly active antiretroviral therapy. J Acquir Immune Defic Syndr 47: 338-341, 2008.
  8. Rasmussen LD et al. Risk of cerebrovascular events in persons with and without HIV: a Danish nationwide population-based cohort study. AIDS 25: online edition, doi: 10.1097?QAD.0b013e3283493fb0, 2011.
  9. Bedimo RJ et al. Abacavir use and risk of acute myocardial infarction and cerebrovascular events in the highly active antiretroviral therapy era. Clin Infect Dis 53: 84-91, 2011.
This content was checked for accuracy at the time it was written. It may have been superseded by more recent developments. NAM recommends checking whether this is the most current information when making decisions that may affect your health.