HIV levels peak in semen 3 - 4 weeks after infection

HIV viral load is at its highest in semen three to four weeks after infection with HIV, according to a study published in the August 20^th edition of AIDS. The study also revealed that individuals with late-stage HIV infection also have high viral loads in their semen, and the investigators believe that their findings confirm earlier suggestions that individuals recently infected with HIV as well as those with advanced HIV disease, are particularly infectious and are driving the spread of HIV.

It is estimated that 80% of all HIV infections are acquired sexually. The transmission of HIV depends upon the infectiousness of the host and the susceptibility of the sexual partner, and both infectiousness and susceptibility can vary significantly over time.

Infectiousness can be directly correlated with viral load in blood, and blood viral load can serve as a surrogate marker of shedding of HIV in genital secretions.

Recent epidemiological research suggests that HIV-positive individuals are at their most infectious soon after they have become infected with the virus, a period often referred to as primary or acute HIV infection. (However a recent US researcher suggested that only 9% of HIV infections were due to individuals with primary infection. Although this model did acknowledge the high viral load present during primary infection, the short duration of primary infection and the small number of sexual contacts per individual during this time limited the contribution of individuals with acute infection to the epidemiology of HIV).

There have been no longitudinal studies of the dynamics of genital tract shedding of HIV during primary infection. However, investigators have recently developed a surveillance strategy that allows for the identification of individuals with primary HIV infection even before antibodies to HIV have developed. This has enabled clinicians to detect a significant number of patients with acute HIV infection in the US state of North Carolina, as well as in Malawi, South Africa, and Brazil.

A team of investigators from North Carolina, San Francisco, and Malawi designed a study which involved men identified with acute HIV infection from a sexually transmitted infections clinic in Malawi. The investigators focused on changes in viral load in both plasma and genital secretions in men with both acute HIV infection and advanced HIV disease.

The study was conducted between February 2003 and October 2004 and included men attending the Lilogwe sexually transmitted diseases clinic in Malawi. All the men attending the clinic were screened for HIV and other sexually transmitted infections.

Investigators estimated the date of primary HIV infection as occurring two weeks before the onset of symptoms of acute antiretroviral syndrome, including fever, headache and joint and muscle pain.

Of the 951 men who attended the clinic, 370 (39%) were HIV-infected. Of these 16 (2%) were confirmed as having acute HIV infection and 345 (37%), chronic HIV infection. The investigators’ prospective study included all 16 men with acute HIV infection and 25 men with chronic HIV infection. On enrolment, 44% of men with acute HIV, and 52% of those with chronic HIV, had gonorrhoea, NSU or chlamydia.

On entry to the study, the median duration of HIV infection for those with acute HIV was estimated to be 28 days. At the initial screening visit, blood viral load was significantly higher in men with acute HIV (1,000,000 copies/ml) than men with chronic HIV (100,000 copies/ml; p = 0.01). One week after enrolment, when semen samples were first obtained, the investigators found that although mean viral load in semen was higher in those with acute HIV infection (25,000 copies/ml), than those with chronic HIV infection (8,000 copies/ml), the difference was not statistically significant.

The investigators calculated that viral load peaked in the blood of acutely infected individuals 17 days after infection at well over 1,000,000 copies/ml and in semen four weeks after acquisition of HIV, at approximately 32,000 copies/ml. It then fell back steeply in both blood and semen, and by week ten was a mean of 125,000 copies/ml in blood and 1,000 copies/ml in semen, levels at which it remained stable through 28 weeks of follow-up. These changes in blood and semen viral load between peak levels and nadir levels were statistically significant (p < 0.001).

For patients with chronic HIV infection, the investigators found a statistically significant relationship between low CD4 cell count and high viral load in semen (p = 0.01). The investigators believe that this finding supports the theory that patients with advanced HIV disease are more infectious. They also found that each 1 log₁₀ drop in CD4 cell count was associated with a 2 log₁₀ increase in viral load in semen. However, peak viral load in the semen of patients with advanced HIV infection was a mean of 1.4 log₁₀ lower than the peak observed in patients with acute HIV infection, a statistically significant difference (p = 0.0168).

“In the current study, we found that HIV in the seminal plasma reached its peak 4 weeks after infection, and that this burst of HIV shedding was almost completely contained by week 10, most likely reflecting the host immune response”, write the investigators.

The investigators conclude that their evidence shows that models suggesting the importance of patients with acute and advanced HIV to the continued epidemiology of HIV “are likely correct, and help to explain the continued spread of HIV in different kinds of populations.” The investigators add, “the need for [the] development of prevention intervention(s) focused on patients in the very earliest stages of HIV infection and their exposed and at-risk sexual partners is urgent.”