Tipranavir may rarely be associated with bleeding in the brain.

Boehringer Ingelheim, the manufacturers of the protease inhibitor (PI), tipranavir (Aptivus) have issued a warning about a newly-discovered, potentially fatal side-effect after 13 of the 6,840 people who took ritonavir-boosted tipranavir in clinical trials developed bleeding within the skull, known medically as intracranial haemorrhage. Sadly, eight of these people died.

More than half of the people who developed this rare problem - which affected one person out of every 500 - had pre-existing risk-factors, however. These included problems with blood clotting, lesions on the brain, head injury, recent brain surgery, and high blood pressure. Alcohol abuse and other medicines known to increase the risk of bleeding were also a factor.

Tipranavir is only approved for treatment-experienced people with limited treatment oprions. At the time of licencingm in 2005, liver-related side-effects were noted to be of concern, and it is recommended that people taking the drug have their liver function regularly monitored. Since the bleeding developed an average of 525 days after people started tipranavir/ritonavir, it has taken this long after the drug was approved for this problem to appear.

The warning is particular pertinent to HIV-positive people with haemophilia, since they are already at risk of 'a bleed in the brain' regardless of HIV status. Some test-tube studies and animal experiments have found some reductions in the ability of blood clots to form in the presence of tipranavir, and Boehringer Ingelheim is carrying out more investigations into the link between tipranavir and bleeding. However, there have been case reports of this problem occurring with other PIs, and a 2001 study from the US Centers for Disease Control found that the risk of 'a bleed in the brain' was increased in HIV-positive haemophiliacs taking PIs.

Two weeks prior to this warning being issued, Boehringer-Ingelheim also announced that they had halted a study of tipranavir in people who had never previously taken anti-HIV drugs just over a year into a three-year study. This is because, compared to those receiving lopinavir/ritonavir (Kaletra), significantly fewer people taking lower-dose ritonavir-boosted tipranavir had a viral load below 50 copies/ml.

This study used a lower dose (100mg) of ritonavir to boost tipranavir than approved for treatment-experienced patients (200mg). This is because a previous study of tipranavir in treatment-naive individuals using the higher dose of ritonavir had been stopped due to a high rate of asymptomatic liver enzyme elevations.

It is now extremely unlikely that tipranavir will ever be approved for people who have never taken anti-HIV drugs before, but the drug company points out that these results do not change its suitability for people with few treatment options, for whom the PI is licensed. Anyone taking tipranavir who has any concerns about this drug should first talk to their doctor before stopping or changing any of their anti-HIV drugs.

A new drug and a new formulation receive US approval

The United States Food and Drug Administration (FDA) have approved a new protease inhibitor (PI), darunavir (TMC114, Prezista), for HIV-positive individuals whose infection is not responding to treatment with other anti-HIV drugs. The FDA has also approved a triple drug anti-HIV combination in one pill, marketed as Atripla, which contains efavirenz (Sustiva) and Truvada (tenofovir and FTC).

The US approval of darunavir was granted after the drug's manufacturer, Tibotec, presented data from two randomised studies known as POWER 1 and POWER 2, which examined the risks and benefits of the drug in people with substantial treatment experience. Together, these studies found that those taking ritonavir-boosted darunavir had significantly larger reductions in their viral loads and higher CD4 count increases than those taking other ritonavir-boosted PIs. Both groups of patients took their PIs with other anti-HIV drugs, including nucleoside reverse transcriptase inhibitors (NRTIs), chosen on the basis of genetic testing. In addition, almost half of the patients were taking the fusion inhibitor T-20 (enfuvirtide, Fuzeon). The main side-effects seen in the studies were diarrhoea, nausea and headache. Around 7% of the patients also had skin rashes which were serious in a few cases.

The US approval of Atripla is significant because it marks the first collaboration between drug companies to create a fixed-dose anti-HIV drug combination. The drug contains 600mg of Bristol-Myers Squibb's efavirenz and Gilead's Truvada, which contains 300mg of tenofovir and 200mg of emtricitabine (FTC). Atripla is a single tablet taken once a day, with or without food, and is one of the most frequently prescribed regimens worldwide for the treatment of people with HIV who have not previously taken any anti-HIV drugs.

The triple combination pill is not likely to be approved in Europe until 2007, however European approval of darunavir is expected later this year.

Further decline for UK's sexual health

2005 data from the UK's Health Protection Agency (HPA) saw a 3% increase in the number of sexually transmitted infections (STIs) diagnosed in genitourinary medicine (GUM) clinics in the UK.

Chlamydia remains the most commonly diagnosed STI in the UK, possibly as a result of the scaling-up of the National Chlamydia Screening Programme. In 2005, 109,832 new cases were diagnosed - a 5% increase on the previous year.

Genital warts were the second most commonly diagnosed STI in 2005, with an increase of 1% from the previous year to 81,203 cases. Genital warts are caused by human papilloma virus (HPV), which is also associated with cervical and anal cancers.

New diagnoses of syphilis continued to significantly increase in 2005, up by 23% in 2004 to 2,807. Sixty percent of syphilis cases were seen in gay and bisexual men, many of whom were also HIV-positive.

New diagnoses of genital herpes increased by 4% (from 19,074 in 2004 to 19,771 in 2005), although they have remained under 20,000 since they dramatically increased at the turn of the century.

Finally, some good news: the number of new cases of gonorrhoea fell by 13%, from 22,350 in 2004 to 19,495 in 2005, with fewer cases reported across all English regions.

Most people who transmit HIV unaware they are HIV-positive

HIV-positive individuals who are unaware of their infection may account for between 54% and 70% of all new sexually transmitted HIV infections in the United States, according to a "conservative" mathematical calculation from the US Centers for Disease Control and Prevention (CDC).

However, the CDC calculation does not take into account data published last year which suggest that in the five months immediately following seroconversion, HIV transmission risk is approximately ten times greater than during chronic infection.

In addition, the CDC's data are based on one-in-four individuals being unaware of their HIV infection. In the United Kingdom, it is estimated that one-in-three HIV infections remain undiagnosed, which suggests that the proportion of new HIV infections from undiagnosed HIV-positive individuals in the UK may be even higher here than in the US.

Understanding who is more likely to transmit HIV may be helpful in the debate around the criminalisation of HIV transmission, which tends to penalise people already aware of their HIV status.