Dual HIV infection in women associated with higher viral load

A study of 25 female sex workers in South Africa has found that viral load was significantly higher in women with dual infection. It also found one case of later superinfection with a third virus in one of the dually infected women.

The women were part of the microbicide trial that took place in four African countries between 1996 and 2000 which established that the spermicide nonoxynol-9 facilitated rather than blocked HIV transmission, and this latest paper is a ‘spin off’ from that study (Grobler 2004; Van Damme 2002).

As part of the trial protocol, all participants had HIV viral load tests taken every month to check for seroconversion. This substudy found 31 seroconversions in one site in South Africa, and followed 25 of them for signs of dual infection and subsequent superinfection for 24 months. All the women were infected with HIV-1 clade C, the type most common in the region.

Among the group of 25 there were six dual infections (24%). These were established by sampling the genetic variability of the env gene in each patient’s virus.

When this clustered at two points rather than centring at one, the researchers regarded it as a dual infection. One patient did not show evidence of two distinct viral subtypes, but her viral samples were more variable than any two randomly selected samples from the rest of the group; she too was regarded as having a dual infection.

Full clinical data including CD4 cell count and viral load measurements at six and twelve months were available for 19 of the women, four of whom had dual infections.

The viral load ‘set point’, defined as the viral load at twelve months post-infection, was lower than that seen in other cohort studies (averaging only 5000 copies/ml). The researchers suggest several explanations for this; a different assay, the bDNA assay, was used in this study than in comparable ones, which used the Amplicor or Gen-Probe assays. Women tend to have a lower viral load. Also, this frequently exposed group of sex workers may have built up mucosal immune responses that helped the immune system to control viral load after serconversion.

Three of the four women with dual infections were the only three seroconverters who had viral load set points defined as ‘high’. Two had set points around 40,000 copies/ml and one had a very high viral load of 321,040 copies/ml. She had a rapidly progressing disease course, dying two years after infection, and was one of the subjects covered in another paper on the disease burden of dual infection (Gottlieb 2004).

When CD4 cell counts were paired off against subjects with low, medium and high viral loads, the average counts of women in the ‘high’ viral load category were 50% of those with low and medium viral loads (252 vs. 512 cells/mm³) but as only two CD4 cell counts were taken from women with high viral loads this was not statistically significant.

The one dually infected woman who did not have a high viral load (her set point was 1359 copies/ml) nonetheless had a low CD4 count (279 cells/mm³).

The study provides some insights into both the difficulty of conducting microbicide trials and their necessity. Of the 19 women with full clinical data, seven had their seroconversion detected more than three months after their previous negative HIV blood test, despite the fact that they were supposed to be monitored monthly.

The researchers also comment: “Despite risk-reduction counselling and provision of condoms, these women continued high-risk behaviour, with estimated condom use of less than 25%, an average of 15 sex partners a week, and HIV prevalence [in the local population] of 56%. It is estimated that each individual had 327-437 HIV exposures a year.”