Start treatment at a CD4 cell count of 500 to reduce risk of serious non-HIV-related illnesses?

Treatment guidelines (such as those in Europe and the US) are now recommending that HIV treatment should be started when an individual’s CD4 cell count is around 350 cells/mm³. Previous guidelines recommended the initiation of treatment when a patient’s CD4 cell count was around 200 cells/mm³.

These were changed when studies showed that patients who started treatment at higher CD4 cell counts had much better long-term improvements in their immune system. Furthermore, results from the SMART treatment interruption study showed that a low CD4 cell count increased the risk of serious non HIV-related illness, such as some cancers as well as heart, kidney and liver disease.

But could treatment guidelines soon be recommending starting treatment at an even higher CD4 cell count? There is evidence from the UK that patients with a CD4 cell count of 350 cells/mm³ have more HIV-related illnesses and a greater risk of death than patients with a CD4 cell count of 500 cells/mm³.

Prof Andrew Phillips of London’s Royal Free Hospital analysed results from a number of studies showing that HIV may have an important role in some serious non-HIV-related illnesses. He suggested that the earlier use of antiretroviral therapy could reduce the risk of these illnesses.

“We need to be looking at whether antiretroviral therapy should be initiated earlier in patients with CD4 cell counts above 500 [cells/mm³]”, Prof Phillips told CROI delegates.

Drug level monitoring

Increasing doses of protease inhibitors after therapeutic drug monitoring does not improve the overall chance of treatment-experienced patients achieving and maintaining an undetectable viral load, according to a US study presented to CROI.

Although this strategy had no benefit for Caucasian patients, it did have a modest effect on the viral load of black and Hispanic individuals.

The study involved 194 patients who had experience of at least one protease inhibitor, but who still had a viral load above 1000 copies/ml.

Four weeks after changing treatment to a new protease inhibitor-based combination they had levels of medicines in their blood monitored. Patients with low blood concentrations of drugs were randomised to either continue with their current protease inhibitor dose or to have the dose of their protease inhibitor increased.

But 20 weeks later, viral load was more or less the same in both groups of patients.

When the researchers looked at the results in more detail, they found that increasing the dose of protease inhibitors had better results in black and Hispanic patients than in white patients.

The amount of resistance a patient had to protease inhibitors also seemed to be important. Those with least protease inhibitor resistance had the biggest reductions in viral load after the doses of their new protease inhibitor were increased.

Unwanted pregnancy common in women after starting anti-HIV treatment

A study in Uganda has found that many women are having unwanted pregnancies in the first two years after starting anti-HIV treatment.

The study involved 700 women who started anti-HIV treatment between 2003 – 2006. Although almost all the women (97%) said they did not want more children, 17% became pregnant. These pregnancies peaked a year after starting anti-HIV treatment.

Only 8% of women were using dual contraception and just 14% were using permanent or semi-permanent methods of birth control.

The researchers recommend that family planning services should be an essential part of HIV treatment programmes.

Replacement feeding does not increase risk of pregnancy

A study conducted in Cote d’Ivoire has shown that women who use replacement infant feeding do not have a higher risk of pregnancy than women who breastfeed.

The results are surprising as breastfeeding is traditionally thought to offer some protection against pregnancy.

All the women received a short-course of anti-HIV treatment during pregnancy to prevent mother-to-child transmission of HIV. After that, 54% of women breastfed their infants and 46% used replacement feeding.

During the next twelve month approximately 4% of women using each method of infant feeding became pregnant. And after 24 months, more of the breastfeeding women became pregnant.

HIV treatment reduces risk of HIV infections in women who breastfeed

Taking anti-HIV treatment for six months during breastfeeding significantly reduces the risk of a mother passing on HIV to her baby, a study conducted in Kenya and presented to CROI has shown.

Breastfeeding involves a risk of HIV transmission and it is recommended that women should not breastfeed if safe alternatives are available.

But in resource-limited settings breastfeeding is often a safer alternative to formula feeding, and HIV-positive mothers are therefore often advised to breastfeed their infant until the age of six months.

The Kenyan study involved 522 HIV-positive women who were provided with anti-HIV treatment from the 32^nd week of pregnancy and for six months after the birth of their child. They were encouraged to exclusively breastfeed their child for these six months and to then wean their infants.

A total of 6% of children became infected with HIV in the first twelve months of life, and the researchers estimated that 3.5% of infants were infected because of breastfeeding.

Extended infants prophylaxis reduces HIV transmission during breastfeeding

Other studies presented to CROI also looked at the ability of anti-HIV treatment to prevent mother-to-child transmission of HIV during breastfeeding.

These showed that providing nevirapine to the infants of HIV-positive mothers for six to 14 weeks after birth can reduce by half the rate of HIV transmission due to breastfeeding.

But there was also evidence that in infants who did become infected with HIV, extending the period of nevirapine treatment increased the risk of resistance to the drug developing.

Long-term benefits of successful hepatitis C treatment

Many people with HIV are also infected with hepatitis C virus (often called HIV/hepatitis C coinfection). Liver disease caused by hepatitis C is now an important cause of death in these coinfected patients.

Treatment for hepatitis C virus clears the infection in about two-thirds of HIV-positive individuals who have recent, or acute, hepatitis C infection and in about a third of HIV-positive patients with long-term, or chronic, hepatitis C.

A study presented to CROI shows that successful hepatitis C treatment has long-term benefits for coinfected patients. The Spanish study involved HIV-positive patients with chronic hepatitis C and 31% had a successful response to hepatitis C treatment.

The researchers compared rates of death from any causes as well as rates of liver-related illness and death in the patients who did well on hepatitis C treatment and in those who did not.

They found that the patients who responded to hepatitis C treatment were less likely to die of any cause and also had a greatly reduced risk of liver-related illness or death. But rates of HIV disease progression were equal in both groups of patients.

Vaccine failure

Last year, the study looking at Merck’s potential HIV vaccine, ad5, was stopped when it was shown that people who received the vaccine had a higher risk of infection with HIV than those who received the placebo.

A detailed analysis of the trial’s results was presented to CROI. This showed that the increased risk of HIV was almost entirely located in uncircumcised men who had unprotected insertive anal sex.

Researchers think that the vaccine may have interfered with the men's natural immune responses to HIV. This might have been related to the men’s immunity to adenovirus, a common cold-type virus, that was used as the vaccine’s “delivery vehicle.”