The link between sexually transmitted infections and HIV

The link between HIV and other STIs might seem obvious. After all, the same sorts of risk behaviour are involved. However, numerous studies seem to indicate that there is a stronger association between HIV and other STIs than would be expected simply from a behavioural link. Infection with STIs (including syphilis, gonorrhoea and herpes) seems to increase the risk of both acquiring and transmitting HIV over and above a behavioural link. So does bacterial vaginosis, a condition not formally classed as an STI, since it appears not to be transmitted, but which is associated with poor sexual health generally.

Depending on the STI involved and the population, studies have reported that having an STI magnifies the risk of acquiring HIV by anything from two to eight times or more. In the case of people with HIV, having an STI increases viral loads both in the blood and genital secretions, thus making people more infectious – even when taking antiretroviral treatment.

In a meta-analysis of studies calculating the HIV per-act transmission risk during heterosexual intercourse, Marie-Claude Boily and colleagues found that the risk appeared to be greater in higher-income countries than in lower-income countries. One possible explanation of the divergence is to do with rates of sexually transmitted infections.¹

In higher-income countries, the risk of transmission from men to women was estimated to be 1 per 1250 acts of intercourse, and from women to men 1 per 2500 acts of intercourse.

The studies conducted in lower-income countries (mainly in Africa) indicated a much higher transmission risk. Furthermore, the risk appeared higher from women to men, the opposite way round to higher-income countries and less biologically plausible. The risk in lower-income countries from men to women was 1 per 525 acts of intercourse and from women to men 1 per 115 acts. However, the 95% confidence intervals were very wide (for instance, the ‘real’ risk from men to women could, on the basis of the studies collated, be anything up to 1 infection per 38 acts).

The authors suggested that the differences seen were caused by much higher rates of STI infection in lower-income countries, especially in men. The per-act transmission risk when one partner had genital-ulcer disease (GUD) was 2.8% or 1 per 36 acts of intercourse – roughly an order of magnitude higher than the general transmission rate observed, and 50 times higher than the rate in higher-income counties. (GUD is a term that covers any visible external ulcer or sore, which can be caused by herpes, syphilis, chancroid, candida or several non-sexually transmitted conditions).

In the developed world, a study in Sydney, Australia, of 1427 gay men who were initially HIV-negative found that specific STIs were strongly associated with HIV acquisition.² In particular, anal gonorrhoea was associated with a sevenfold increased risk of HIV and having anal warts with a threefold increased risk, even after controlling for sexual behaviour.

Ulcerative STIs, such as syphilis, herpes and chancroid, cause lesions on the genitals and anus that may serve as ports of entry or exit for HIV. Inflammatory ones, such as gonorrhoea, chlamydia and bacterial vaginosis, cause the mucosa of the urethra, cervix and rectum to become inflamed. This makes it not only more fragile and likely to tear and bleed, but greatly increases the numbers of HIV-receptive or HIV-productive immune cells in the area. Inflammation also increases levels of circulating cytokines, immune-stimulating chemicals that activate T-cells.

One STI that has caused particular interest, leading to large trials to see if prophylactic treatment could reduce HIV acquisition/transmission, is herpes or, more precisely, herpes simplex virus 2 (HSV-2). This is for two reasons: firstly, it is by far the most common cause of genital ulcers, especially in the developing world, and indeed the most common STI; and secondly, because numerous studies have shown a strong link between even asymptomatic, subclinical herpes infection and the acquisition and transmission of HIV.

STI treatment is, of course, a good thing in itself, especially as some STIs such as syphilis are lethal if left untreated, while others can cause infertility. Moreover, another motive for treating STIs as an HIV-preventative measure is that it could be, if efficacious, very cost-effective. Drugs such as aciclovir, for herpes, are cheap, safe and easily available. (Aciclovir is the international spelling of this drug; in the US it is usually spelt acyclovir).

Therefore, reducing STIs in a population, or in the HIV-positive members of that population, could be a valuable additional way of reducing HIV infection.

This could involve:

• Treating HIV-negative people when they have STI symptoms.
• Treating all HIV-negative people in a population.
• Treating HIV-positive people when they have STI symptoms.
• Treating all HIV-positive people in a population.