An average viral load reduction of 0.74 log is needed in order to reduce the risk of HIV transmission by 50%, according to an analysis of the Partners in Prevention study of aciclovir as an HIV prevention measure. The finding was presented at the AIDS Vaccine 2009 conference, but also has important implications for future studies of HIV treatment as prevention.
The link between plasma viral load – the level of HIV in the blood – and sexual transmission of HIV is well established, and a number of studies have sought to establish the risk of HIV transmission at different levels of viral load.
However, until now there has been little information about the extent to which varying degrees of viral load reduction might correlate with reductions in the risk of HIV transmission.
This information could be important in designing studies of the impact of interventions such as antiretroviral treatment on new infections, or of vaccines that affect the post-infection viral load even if they do not prevent infection (so-called sterilising vaccines).
Dr. Jairam Lingappa of the University of Washington, Seattle, and colleagues from the Partners in Prevention study of aciclovir treatment in HIV-positive people with HSV-2 coinfection, presented an analysis of viral load in the partners of individuals who became infected during the study.
The Partners study, previously described in detail here, recruited 3408 individuals and monitored HIV-serodiscordant couples every three months to detect new HIV infections and to measure viral load in the HIV-positive partner.
If HIV infection was detected in previously seronegative partners, viral sequencing in both partners was carried out in order to determine whether the primary partner was the source of infection.
This analysis revealed 108 linked infections, with viral load measurements available from the transmitting partner within the preceding three months.
(An obvious limitation of this method is that it cannot account for temporary viral load increases due to infections such as malaria that would not be fully captured by the three-month window between measurements, or sexually transmitted infections that would not affect plasma viral load but which would nevertheless increase genital viral load).
In this study individuals with HIV and HSV-2 were randomised to receive aciclovir treatment or placebo, to test whether aciclovir prophylaxis reduced the risk of HIV transmission.
Although the researchers noted a median viral load reduction of -0.25 log in those who received aciclovir, this specific analysis was not looking at the effects on HIV transmission of any HIV viral load reduction as a consequence of aciclovir prophylaxis.
The researchers stratified individuals according to their viral load over time, and then calculated the HIV incidence per 100 person-years for each viral load stratum.
| Viral load stratum | 2 - 3log (<1000 copies) | 3 - 4log (<10,000 copies) | 4 – 5log (<100,000 copies) | 5 – 6log (<1 million copies) | 6 – 7log (<10 million copies) |
| Transmission events | 3 | 10 | 58 | 38 | 3 |
| Person-years of follow-up | 954 | 1382 | 1772 | 805 | 53 |
| Incidence per 100 PYs | 0.3% | 0.7% | 2.9% | 4.7% | 5.7% |
The vast majority of follow-up and transmission events occurred in the viral load range between 3 and 6 log (1000 to 1 million copies/ml), with evidence of substantial reductions in the risk of transmission between each stratum as viral load fell lower.
Combining data from all strata, the researchers calculated that regardless of the baseline viral load, an average viral load reduction of 0.74 log would result in a 50% reduction in the risk of HIV transmission across the whole cohort. Extrapolating from the data presented, this degree of reduction would clearly have the greatest prevention impact in people with higher levels of viral load, since this is where over 90% of transmission events occurred.
Jairam Lingappa noted that the 2.1% HIV incidence observed in this study population was vastly lower than the HIV incidence observed in recent population cohort studies in Uganda and Zambia, and was likely to be attributable to the intensive counselling and condom provision for study participants.
Thus, a reduction of 0.74 log might result in a much larger number of infections averted at higher levels of HIV incidence, even if the reduction in risk of transmission remained consistent at 50%.
However, that hypothesis would need to be tested in a population study. This study looked at viral load and transmission only in serodiscordant couples where transmission could be proved, in which the majority of sexual contacts were within couples throughout the study, and where intensive counselling took place, rather than in a population where much wider sexual mixing may occur.
A forthcoming meeting organised by the World Health Organization will review the research questions that need to be addressed in order to establish the prevention effects of viral load reductions due to antiretroviral treatment.
Lingappa J et al. HIV-1 plasma RNA and risk of HIV-1 transmission. AIDS Vaccine 2009, Paris, abstract OA01-06LB, 2009.