Viral load critical in heterosexual transmission

A study of 415 couples in Uganda has confirmed that viral load is the most important factor in determining whether HIV is transmitted. But it is unclear how these findings can be translated into a Western setting where people are using antiretroviral drugs, experts warn.

How the study was conducted

415 couples in whom one partner was HIV-positive were identified in the Rakai district of Uganda. The couples were identified by confidential HIV testing. All couples were offered counselling in condom use and the opportunity to learn their HIV status at the beginning of the study, and access to free condoms throughout the study. People diagnosed HIV-positive were left to decide whether or not to inform their partners, a decision criticised in an accompanying editorial in the New England Journal of Medicine.

Glossary

person years

In a study “100 person years of follow-up” could mean that information was collected on 100 people for one year, or on 50 people for two years each, or on ten people over ten years. In practice, each person’s duration of follow-up is likely to be different.

voluntary male medical circumcision (VMMC)

The surgical removal of the foreskin of the penis (the retractable fold of tissue that covers the head of the penis) to reduce the risk of HIV infection in men.

virological suppression

Halting of the function or replication of a virus. In HIV, optimal viral suppression is measured as the reduction of viral load (HIV RNA) to undetectable levels and is the goal of antiretroviral therapy.

matched

In a case-control study, a process to make the cases and the controls comparable with respect to extraneous factors. For example, each case is matched individually with a control subject on variables such as age, sex and HIV status. 

circumcision

The surgical removal of the foreskin of the penis (the retractable fold of tissue that covers the head of the penis) to reduce the risk of HIV infection in men.

Sexually transmitted infection treatment was offered at regular intervals as part of another study to half the participants. The other half were required to seek free treatment if they experienced any symptoms. HIV antibody status and exposure to sexually transmitted infections was tested every ten months.

Viral load prior to transmission was determined by measuring the viral load of the HIV-positive partner at the check-up prior to seronversion of his or her partner. To estimate the relative risk, this viral load result was matched with one from another individual of similar age and sex who had not seroconverted.

How the results are explained

Every year of follow-up for an individual in this study counts as a person year. In this study 415 couples were enrolled and followed for a median of just under two years. This means that the study followed people for approximately 800 person years.

Key findings

  • 22% of all partners seroconverted during the follow-up period.
  • Men were just as likely to become infected as women at any given level of viral load.
  • Circumcision appeared to be protective: none of the circumcised male partners of HIV-positive women became infected, whereas 40 out of 197 uncircumcised men became infected.
  • Symptomatic sexually transmitted infections did not affect an individual's likelihood of catching HIV, but a history of genital discharge in the HIV-positive partner was associated with an increased risk of HIV infection (p<0.05)
  • Viral load above 50,000 copies in the HIV-positive partner was most strongly associated with the risk of transmission, at a rate of 23 infections per 100 person years
  • 5.6% of all transmission occurred in couples where the HIV-positive partner had a viral load between 400 and 3,499 copies, indicating that transmission can take place even from individuals considered to be at very low risk of disease progression. This translates into 2.2 cases per 100 person years, a tenfold lower risk than seen in couples where the HIV-positive partner had viral load greater than 50,000 copies.
  • No infections occurred in couples where the HIV-positive partner had viral load below 1500 copies.

Comment

Dr Marcia Angell, an editor at the New England Journal of Medicine asked in an accompanying editorial "[the study] found that the risk of heterosexual transmission correlated with viral load, but how will that information be used in Uganda? The very condition that justified doing the study in Uganda in the first place - the lack of availability of antiretroviral treatment - will greatly limit the relevance of the results there."

In a second editorial Dr Myron Cohen of the University of North Carolina noted that the findings did not necessarily support the view that lowering viral load with antiretroviral treatment would reduce HIV transmission rates:

"HIV-1 can still be cultured from the genital secretions of some patients who are receiving antiretroviral therapy and who have undetectable levels of HIV-1 RNA in blood, a finding that means that one cannot reassure patients that they are not contagious. Indeed, if the use of such therapy increased the likelihood that HIV-1-infected patients would practice unsafe sex in the mistaken belief they were unable to transmit the virus, it could offset the benefit of viral suppression", he wrote.

Reference

Quinn CT et al. Viral load and heterosexual transmission of human immunodeficiency virus type 1. New England Journal of Medicine 342 (12): 921-929, 2000.

Angell M. Investigators' responsibilities for human subjects in developing countries. NEJM 342:13

Cohen M. Preventing sexual transmission of HIV - new ideas from sub-Saharan Africa. NEJM 342:13