Most heterosexual African HIV transmission may occur during primary infection

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A study of the way that HIV viral load in semen varies during early infection has led researchers to conclude that half or even more of all HIV transmission from men to women in sub-Saharan Africa occurs during the first two months of the men’s infection.

These observations could answer the paradox that heterosexual infection in Africa spreads rapidly despite there being documented low transmission rates during chronic infection (Chakraborty). Longitudinal studies of discordant couples produced transmission rates that could not possibly sustain an expanding epidemic (as low as a 20-40% chance of infection per stable couple from man to woman during the man’s lifetime) (Pinkerton). These findings have led some researchers to suggest that a large proportion of HIV infection in Africa must be occurring through routes other than vaginal sex, for example through unsterilised medical needles or anal sex (Gisselquist; Brody).

To assess the contribution of sexual intercourse during primary infection, Christopher Pilcher and colleagues from the University of North Carolina analysed seminal viral load measurements from two cohorts of patients diagnosed during primary infection.

Glossary

primary infection

In HIV, usually defined as the first six months of infection.

acute infection

The very first few weeks of infection, until the body has created antibodies against the infection. During acute HIV infection, HIV is highly infectious because the virus is multiplying at a very rapid rate. The symptoms of acute HIV infection can include fever, rash, chills, headache, fatigue, nausea, diarrhoea, sore throat, night sweats, appetite loss, mouth ulcers, swollen lymph nodes, muscle and joint aches – all of them symptoms of an acute inflammation (immune reaction).

sexually transmitted diseases (STDs)

Although HIV can be sexually transmitted, the term is most often used to refer to chlamydia, gonorrhoea, syphilis, herpes, scabies, trichomonas vaginalis, etc.

sample

Studies aim to give information that will be applicable to a large group of people (e.g. adults with diagnosed HIV in the UK). Because it is impractical to conduct a study with such a large group, only a sub-group (a sample) takes part in a study. This isn’t a problem as long as the characteristics of the sample are similar to those of the wider group (e.g. in terms of age, gender, CD4 count and years since diagnosis).

longitudinal study

A study in which information is collected on people over several weeks, months or years. People may be followed forward in time (a prospective study), or information may be collected on past events (a retrospective study).

Because detecting patients in primary infection is uncommon and measuring their seminal viral load even less so, the researchers only found 30 seminal viral loads taken during the first 12 weeks of infection. However, these gave a consistent picture: between the second and sixth week of infection, seminal viral loads averaged 12,500 copies/ml (4.1 logs). After week seven, they settled down to an average ‘set point’ of 3,100 copies/ml (3.49 logs). The peak of infectiousness was reached around the third week of infection, when seminal viral loads averaged 75,000 copies/ml.

Using the assumption that, in the absence of sexually transmitted infections, seminal viral loads would parallel those in blood, they then extrapolated these data to calculate the average infectiousness of men having vaginal intercourse during acute and chronic HIV infection.

They calculated that there would be one HIV infection from man to women per 213 acts of vaginal sex during his primary infection. In other words, if the man had vaginal sex with a regular partner every other day during the four-week period he was most infectious, there would be about a one in 16 chance that he would infect her.

This contrasts with one infection per 1,000-10,000 acts of vaginal sex during chronic infection. But since the period in chronic infection (in the absence of treatment) is usually in the order of 60-100 times longer than the period of acute infection, the overall contribution to transmission events that would occur during chronic infection would account for more than half the cases of heterosexual transmission if it is assumed that regular partners had been having sex for a period varying from six months to five years.

That is, as long as men in acute HIV infection have viral loads no more than five times higher than they do in chronic infection. But as the study authors point out, this is likely to be a conservative estimate of how infectious men are in primary infection.

They point out that African men, even in the absence of sexually transmitted infections, tend to have seminal viral loads three to four times higher than men in developed countries (Dyer). However, a quarter of the men studied in primary infection had seminal viral loads ten times higher than the median, of the order of 125,000 copies/ml. Men in this category would have a one in four chance of infecting their female partners during the month of primary infection at the highest frequency of sexual intercourse (16 acts per month).

Out of the 30 original semen studies sampled, five had even higher viral loads, in the order of 200,000 to 2 million.

The researchers specifically excluded seminal samples from men with a diagnosed acute sexually transmitted infection. Given that STIs are more common in Africa than the west and that studies have shown that African men with urethritis are eight times more likely to transmit HIV, the calculations add up to the possibility that more than half of heterosexually-transmitted HIV in Africa is passed on from men to women in the first six weeks of the man’s infection, say the authors.

References

Pilcher Christopher D et al. Brief but efficient: acute HIV infection and the sexual transmission of HIV. J Infect Diseases 189: 15 May 2004.

Chakraborty et al. Viral burden in genital secretions determines male-to-female sexual transmission of HIV: a probabilistic empiric model. AIDS 15:621-7. 2001.

Pinkerton SD et al. Secondary HIV transmission rates in a mixed-gender sample. Int J STD AIDS11:38-44. 2000.

Gisselquist D et al. HIV infections in sub-Saharan Africa not explained by sexual or vertical transmission. Int J STD AIDS13:657-66. 2002.

Brody, S., & Potterat, J. J. Assessing the role of anal intercourse in the epidemiology of AIDS in Africa. International Journal of STD & AIDS, 14, 431-436. 2003.

Dyer JR et al. High levels of human immunodeficiency virus type 1 in blood and semen of seropositive men in sub-Saharan Africa. J Infect Diseases177: 1742-6. 1998.