Anti-HIV treatment
Thanks to potent anti-HIV treatment, millions of HIV-positive people can look forward to a longer, healthier life. But there are still a lot of unanswered questions about anti-HIV therapy, not least when’s the best time to start treatment.
Current treatment guidelines say that everybody who is ill because of HIV should start taking a potent combination of anti-HIV drugs. It is also recommended that people with a weak immune system, indicated by a CD4 cell count of 200 or below, should start taking anti-HIV therapy.
But some doctors are now suggesting that treatment should be started sooner, when a person’s CD4 cell count is around 350. They point to studies showing that long-term increases in CD4 cell count were much higher in people who started HIV treatment when their immune systems were stronger, and also highlight the results of a treatment interruption study that showed that people with a CD4 cell count between 350 – 200 had an increased risk of developing some serious illnesses, like heart, liver, or kidney disease, that are not normally associated with HIV.
Now a study from the UK seems to add weight to suggestions that HIV treatment should be started at a higher CD4 cell count than is currently recommended. The study involved over 17,000 people who were not taking anti-HIV treatment. Researchers looked at how many people developed AIDS or died. As expected, they found that the lower a person’s CD4 cell count, then the higher their risk of becoming ill because of HIV or dying of any cause. They also found that people with a CD4 cell count between 500 – 649, which would normally be considered high, are 55% more likely to develop an AIDS-defining illness or die than people with a CD4 cell count above 650.
The researchers stress that people with a CD4 cell count above 350 have a much lower risk of AIDS or death than those with a CD4 cell count below 200, but they also write that “the risk [of AIDS] for higher CD4 cell counts is not negligible.” They hope that their findings will inform big clinical studies being considered to see what’s the best time to start anti-HIV treatment.
Treatment to prevent infections
A CD4 cell count of 200 or below shows that a person with HIV has a very real risk of developing the AIDS-defining infection pneumocystis jiroveci pneumonia, usually called PCP. This infection used to be a big cause of illness and death in people with HIV before effective anti-HIV treatment became available. It’s still one of the most common AIDS-defining illness seen in the UK, with 200 or so cases diagnosed each year.
Everybody with a CD4 cell count of 200 or less is recommended to start anti-HIV treatment because PCP pneumonia can be life-threatening.
Preventative treatment, often called prophylaxis, with special antibiotics like Septrin, can be used to reduce the risk of PCP developing in people with weak immune systems. When a person is taking anti-HIV treatment and their CD4 cell count increases to above 200 they can stop taking PCP prophylaxis because they no longer have a risk of developing the infection.
But some people, particularly if they started taking anti-HIV treatment when their CD4 cell count was very low, never experience an increase in their CD4 cell count to above 200. Therefore they need to keep on taking PCP prophylaxis as well as their anti-HIV drugs, meaning they have to take more pills everyday, with a greater risk of side-effects and possibly drug interactions.
Now a small Canadian study has found that as long as a person has an undetectable viral load, they can stop taking PCP prophylaxis, even if their CD4 cell count is below 200. The study involved 19 people who had had an undetectable viral load for at least three months. They stopped taking PCP prophylaxis, and although nobody’s CD4 cell count went above 200 for a sustained period of time, nobody developed PCP.
They think that a low viral load reduces the risk of infections, independent from CD4 cell count.
Side-effects
Like all medicines, anti-HIV drugs can cause side-effects. It is now well established that some anti-HIV drugs, including most of the protease inhibitors, can cause increases in blood fats (cholesterol). This can increase the long-term risk of heart disease.
Everybody can reduce their risk of heart disease by not smoking, eating lots of fresh fruit and vegetable, avoiding saturated fat (such as red meat and full-fat dairy produce), and by taking regular exercise. You can find out more about eating a good diet if you are worried about your risk of heart disease here.
But American researchers have found that people with HIV with increased blood fats are consuming more saturated fat and cholesterol than people in the general population, even though they don’t have a higher energy (or calorie) intake.
The researchers who conducted the study think that people with HIV could be eating more fat because of some of the side-effects of anti-HIV treatment, including metabolic changes, or altered taste.
HIV and hepatitis C
Many people with HIV are also infected with hepatitis C virus (HCV). This virus can cause serious, even fatal, damage to the liver.
Hepatitis C seems to progress more rapidly in people with HIV. Treatment for hepatitis C is available, and it is able to cure the infection in about two-thirds of people with HIV who take it soon after they contract hepatitis C, but it only cures hepatitis C in about a third of HIV-positive individuals who have had hepatitis C for over a year.
Spanish researchers have recently found that HIV/hepatitis C-infected people who have a high hepatitis C viral load (above 500,000 iu/ml) before they started hepatitis C treatment were more likely to experience a relapse of their hepatitis C after a seemingly successful response to treatment. They also found that those who still had a detectable hepatitis C viral load after four weeks of anti-hepatitis C treatment were also more likely to relapse.
A surprise finding was that people who took anti-HIV treatment at the same time as therapy for hepatitis C were more likely to relapse. They think that this is because some of the people who needed to take HIV treatment had very weak immune systems and were therefore unable to respond effectively to their anti-hepatitis C therapy.
In a separate study, Canadian researchers have found that HIV/hepatitis C-infected patients who develop an allergy to the anti-HIV drug nevirapine (Viramune) have a greatly increased risk of death.
Nevirapine allergy consists of a severe rash and liver problems. The risk of it happening is greatest in women who start taking the drug with a CD4 cell count of 250 or above, and in men with a CD4 cell count above 400. Because of this, nevirapine treatment should not be started in people with CD4 cell counts above these levels.
People with hepatitis B or C, because of changes in their liver function, also appear to be at a greater risk of having an allergic reaction to nevirapine.
None of the HIV/hepatitis C-infected people who experienced an allergic reaction to nevirapine in the Canadian study died because of it. Rather, they had an increased risk of death because they had to interrupt their anti-HIV treatment.
Viral load and infectiousness
Viral load is highest in semen three to four weeks after a man first becomes infected with HIV, researchers have found. They also found that men who have advanced HIV disease also have a high viral load in their semen.
A low CD4 cell count was also found to be linked to a high viral load in semen.
The study involved men attending a sexual health clinic in Malawi. An international team of researchers found that viral load peaked in the semen of men at around 1,000,000 copies/ml about a month after they first became infected with HIV. Such a high viral load suggests that recently-infected men are particularly infectious and likely to pass on the infection to others during unprotected sex.
About ten weeks after HIV infection, viral load in semen had fallen to around 1,000 copies/ml where it remained for the remainder of the six month study.
The investigators also looked at viral load in the semen of men who had had HIV for a long time. They found that, as a man’s CD4 cell fell, the viral load in his semen increased, and that men with very low CD4 cell counts had particularly high viral loads in their semen.
The researchers conclude that men who have recently been infected with HIV, and men who are very ill because of HIV, are particularly infectious.
A recent mathematical model developed in America suggested, however, that even though viral load is high soon after a person is infected with HIV, the short period of time it is at this peak means that only about 9% of all new infections are due to people with recent HIV infection. Other studies suggest that as many as half of all new HIV infections are due to people recently infected with HIV.
If you are taking anti-HIV treatment and have an undetectable viral load in your blood, this doesn’t necessarily mean that you are uninfectious. Viral load in semen is often lower than viral load in blood, but in some men, particularly if they have a sexually transmitted infection, it can be higher.