• HIV disease progression: a high viral load and being very ill soon after infection with HIV are connected with poorer survival, a study has found; and HIV-positive people with mental health problems live just as long as those without, but take more anti-HIV drugs and spend more time in hospital.
• HIV and illness: people with a high viral load taking anti-HIV treatment are more likely to be admitted to hospital with bacterial pneumonia; and two new blood tests provide an accurate way of detecting latent infection with tuberculosis.
• HIV and hepatitis C: HIV-positive people with the easier-to-treat strains of hepatitis C may only need 24 weeks of treatment with full-dose anti-hepatitis C treatment to get good results, with blood tests after only four weeks predicting who is going to respond to treatment.
• Mother-to-child transmission of HIV: women who take a protease inhibitor during pregnancy appear to have an increased risk of having a premature baby, according to an American study. But some doctors think that there's a need for more studies before this is know for certain.
• Anti-HIV treatment - side-effects: a small study has found that efavirenz (Sustiva) causes only modest sleep disturbances; and people taking anti-HIV treatment who have a high viral load or who inject drugs are more likely to develop an early symptom of cardiovascular disease.
• Superinfection: the first confirmed case of superinfection in the UK is reported, involving a young gay man who was reinfected with a drug-resistant strain of HIV soon after first contracting the virus.

HIV disease progression

Primary HIV infection and disease progression

Last week’s HIV Weekly included a report of a French study which found that people who had a low CD4 cell count and large amounts of HIV’s genetic material in their blood experienced a rapid fall in their CD4 cell count.

Now a study which found that a high viral load and the severity of symptoms soon after infection with HIV are associated with poorer survival has been published. The study involved female sex workers in Kenya.

HIV-negative sex workers were recruited to the study and had monthly HIV tests to monitor how many became infected with the virus. A set of symptoms, including fever, headache, muscle pain, rash, sore throat and diarrhoea often develop soon after a person becomes infected with HIV (often called primary or acute infection) and the women were asked to say if they had experienced any of these symptoms.

The doctors found that the lower the viral load a woman had soon after infection with HIV, the longer she lived. For example, average survival was seven years in women whose early viral load was over 50,000, but increased to nine years if the first viral load was between 10,000 – 49,000. Very few deaths were seen in women who had a very low viral load – below 10,000 – when it was first measured.

Another predictor of worse survival was having severe symptoms of HIV primary infection. Each symptoms of primary infection a woman had increased the risk of death by 14%.

Although this study had the objective of looking at the rate of HIV disease progression in Africa, its findings could have wider implications. Effective anti-HIV treatment means a longer, healthier life, but there is still some uncertainty about the best time to start treatment. It is currently recommended that everybody who is ill because of HIV should start treatment, as should people whose CD4 cell count is around 250 – the point at which they start to have a real risk of becoming ill with a potentially life-threatening infection.

The value of treating HIV soon after infection has been much debated. Some doctors think that treatment at this time might offer a unique opportunity to restore the immune system and boost its ability to fight HIV, but other doctors are much skeptical. Because of this uncertainty, it is only recommended to take HIV treatment soon after infection as part of a clinical trial.

Mental health and survival

Good mental health is an important part of general good health, and is as important for people with HIV as anybody else. However, it is known that people with HIV are more likely to experience a range of mental health issues including depression. Some anti-HIV drugs and medicines used to treat other infections have also been associated with mental health problems.

As well as being illnesses in their own right, mental health problems might, it has been suggested, mean that people with HIV don’t do as well, having poorer adherence to their HIV treatment, and being more likely to become ill and die.

An Australian study has found that this isn’t the case, and that HIV-positive people with mental health problems live just as long as those without. They did, however, find that people with mental health problems took more anti-HIV drugs and spent more time in hospital.

Treatment for mental health problems, including depression, work well in people with HIV and many HIV treatment centres have mental health specialists. Talk to your doctor if you think you have mental health problems – there will be somebody who can help.

HIV and illness

Bacterial pneumonia

In countries like the UK there has been a dramatic fall in the amount of illness and death caused by HIV since effective anti-HIV treatment became available in the mid 1990s. But there are still about 400 new AIDS diagnoses a year in this country and approximately the same number of AIDS-related deaths, with the majority occurring in people whose HIV was diagnosed very late.

More generally, people with HIV still experience illness, and French doctors recently conducted a study to see how often people who were taking potent anti-HIV treatment developed bacterial pneumonia requiring admission to hospital and what the risk factors for this were.

A total of 1203 people were included in the study and there were 29 cases of bacterial pneumonia. This meant that it occurred with a frequency similar to that seen in the general European and US population.

Having a viral load above 10,000 was strongly linked with the risks of developing bacterial pneumonia, with people whose viral load was above this level being five times more likely to experience the illness than those with a viral load below 10,000. Having a high viral load when taking HIV can be the result of not taking HIV treatment properly, and the doctors found that poor adherence to anti-HIV treatment increased the risk of bacterial pneumonia. Older people and injecting drug users also had an increased risk of bacterial pneumonia.

Unsurprisingly, not smoking reduced the risk of bacterial pneumonia significantly.

These findings, the French researchers suggest, could help decide who to target with pneumonia vaccinations.

Diagnosis tuberculosis

Tuberculosis (TB) is one of the most common AIDS-defining illnesses in the UK and the biggest cause of illness and death amongst people with HIV around the world.

TB can make a person unwell – this is called active TB – causing symptoms such as fever, chest pain, cough and weight loss. Many people, however, are infected with TB which isn’t causing illness, and this is called latent TB. At a later stage, latent TB can become active TB.

One of the standard tests for diagnosing latent TB is the tuberculin skin test. Unfortunately, often it’s not very reliable, and often produces false-negative results in people with HIV and doesn’t work well if you received the BCG TB vaccination as a child.

Two new blood tests have now been developed which provide a more accurate tool than the old skin test for diagnosis latent TB.

HIV and hepatitis C

Liver disease caused by hepatitis B or hepatitis C virus is now one of the leading causes of illness and death amongst people with HIV in countries like the UK where anti-HIV treatment is available. Although treatment for hepatitis C is available, it is less effective in people with HIV than it is in people who only have hepatitis C.

Concerns about side-effects sometimes mean that people with HIV are treated with lower doses of hepatitis C treatment than are used in people who only have hepatitis C. A study conducted by Irish doctors has found that using the full dose of the anti-hepatitis C drugs pegylated interferon and ribavirin can “cure” hepatitis C after only 24 weeks of treatment in HIV/hepatitis C-infected people, provided that they have the easier-to-treat strains of hepatitis C, genotypes 2 and 3.

Unfortunately, a disappointing response to treatment was seen in people who had the harder-to-treat genotypes 1 and 4.

The doctors used the drug erythropoietin (EPO) and blood transfusions in some patients to help make treatment more tolerable. Nevertheless, 90% of people reported ‘flu-like symptoms, 22% reported depression and 40% had blood disorders.

There are some points that need highlighting about this study. First of all, it was small, involving only 45 people. It also needs to be seen within the context of doctors trying to develop treatment strategies to improve the response to hepatitis C treatment in people with HIV. The standard duration of treatment for people with HIV and hepatitis C is 48 weeks, but some doctors have suggested that people with genotypes 1 or 4 may need up to a year and a half of treatment to stand any real chance of having a successful response. There has also been some interest in increasing the dose of ribavirin.

Another important finding of the Irish study was that you could predict four weeks into treatment who was going to respond to treatment – this might spare people who ultimately fail on hepatitis C treatment months of unpleasant side-effects.

Mother-to-child transmission of HIV

HIV can be passed on from a mother to her baby in the womb, during delivery, or by breastfeeding. There is an 8% risk of this happening, but this risk can be cut to less than 1% by the use of anti-HIV drugs, using a caesarean delivery if a mother has a detectable viral load, and by not breastfeeding.

Not all anti-HIV drugs can be used during pregnancy. The non-nucloeside reverse transcriptase inhibitor (NNRTI), efavirenz (Sustiva) should not be taken by pregnant women, or women who are thinking of becoming pregnant, because it has been associated with severe birth defects. Some, but not all, studies have found that the use of a protease inhibitor during pregnancy increased the risks of having a low weight or premature baby.

Now, an American study has been published which also shows that women who took a protease inhibitor during pregnancy were more likely to have a premature baby than those who took AZT monotherapy (an option for women who are in good health and have a low viral load), or an NNRTI .

But an editorial accompanying the study highlights how doctors looking at the risks of premature birth have often come up with different results. This could be because they aren’t using the correct trial design to identify the true risk. They suggest that the real risk of premature delivery can only be shown by the use of a randomised, controlled trial. The studies so far have just looked at, or observed, outcomes and their ability to provide definite answers is therefore limited. To find out more about the design of clinical trials click here.

Anti-HIV treatment – side-effects

Anti-HIV treatment means a longer and healthier life, in fact many HIV doctors are now so optimistic about the effectiveness of HIV treatment that they think that provided a person with HIV starts treatment with HIV soon enough, takes their treatment properly, and can tolerate it, they will live just as long as an HIV-negative person.

But all the currently available anti-HIV drugs have unwanted side-effects. Many of these are short-term and fade or go away completely after the first few weeks of treatment with the drug, but others become a permanent feature of life with the drug. One of the main reasons why people have to change their HIV treatment is side-effects, and some side-effects are not only unpleasant, but can increase the risk of longer-term health problems occurring.

Efavirenz and sleep

The non-nucleoside reverse transcriptase inhibitor efavirenz (Sustiva) is a very widely used anti-HIV drug and in combination with other anti-HIV drugs it is one of the options recommended by UK doctors for people who are starting HIV treatment for the first time.

One of its chief advantages is that it is easy to take, a single pill being taken once-a-day with or without food.

However, efavirenz does cause side-effects. The drug is very good at getting into the brain and because of this it can cause side-effects such as sleep disturbances including insomnia, vivid dreams and nightmares, depression, and day time sleepiness. These side-effects are often worst during the early weeks of treatment with the drug. It is thought that about 1% of people who start treatment with efavirenz have to stop treatment with the drug because they find these side-effects unbearable.

A small British study has looked at changes in sleep patterns caused by efavirenz. Doctors electronically monitored the sleeping patterns of ten men before they started treatment with the drug, then after two weeks of therapy with efavirenz and again after three months. They found that starting treatment with efavirenz was associated with a reduction in the amount of the type of sleep associated with daytime alertness, but an increase in the amount of deep sleep when people dream. The doctors conclude that efavirenz only had a “modest” impact on sleeping patterns.

Interesting as this study is, it is worth noting that it did only include ten people – if you experience any side-effects after starting HIV treatment report them to your doctor. Anti-HIV treatment is meant to make you better, so don’t put up with side-effects just for the sake of them, the chances are that something can be done about them.

Risk of cardiovascular disease

Anti-HIV treatment can cause of collection of side-effects known as lipodystrophy. This can include a change in body shape, increased levels of fat in the blood, or a combination of the two.

The body fat changes caused by anti-HIV drugs can be distressing and stigmatising, and it is thought that the increases in blood fats can increase the long-term risk of health problems such as heart disease and diabetes.

But other factors may also mean that people with HIV might have an increased risk of heart problems. It is known that HIV can have an inflammatory effect and it is thought that this might contribute to a risk of heart problems. In addition, several studies have shown that people with HIV are more likely to have lifestyle factors that increase the risk of heart disease, such as smoking.

Now an American study has found that HIV-positive people with damage to the linings of their blood vessels, an early sign of cardiovascular disease, are more likely to have a high viral load an inject drugs.

Superinfection

Questions about superinfection are frequently asked of doctors and others working in health promotion, but it’s an area where speculation is rife. Few clinics have been able to carry out careful research on the subject, but one centre that did, the Royal Free Hospital in London, recently identified the UK’s first confirmed case of superinfection with drug-resistant HIV.

The clinic identified a case of superinfection that appears to have taken place approximately five months after initial seroconversion. This finding in itself is unsurprising, and should reinforce the need to counsel recent seroconverters about the increased risk of superinfection that seems to exist during the early months of HIV infection, before the immune response strengthens and/or diversifies.

However the case also reinforces the observation that when people become superinfected with drug-resistant viruses, it can change the balance between the immune system and the virus that was achieved after primary infection, leading to faster disease progression.

The case report can’t tell us anything about the frequency of superinfection, but it’s quite possible that such cases of rapid progression during the early months of infection will be observed more frequently as HIV antibody testing becomes more frequent and routine in the United Kingdom and the United States.

For more on superinfection, click here.