Antiretroviral Therapy Does Not Completely Eliminate the Risk of HIV Transmission between Heterosexual Couples

By Liz Highleyman

Sue, 37, HIV positive for 15 years / Jeff, 38, HIV negative.

It is well known that by lowering HIV viral load in the blood and genital fluids, effective combination antiretroviral therapy can dramatically lower the risk of transmitting the virus. Some researchers, in fact, have suggested that expanded use of early therapy might significantly reduce HIV incidence on a population basis.

This past January, the Swiss Federal Commission for HIV/AIDS ignited a firestorm of controversy when they issued a consensus statement that an HIV positive person fully adherent on antiretroviral therapy with completely suppressed viremia for 6 months, and who does not have another sexually transmitted infection, "is not sexually infectious," that is, cannot transmit HIV through sexual contact.

The Swiss experts based their conclusion on a review of research looking at transmission between monogamous serodiscordant heterosexual couples, including relatively small and short-term studies showing no cases of transmissions among heterosexual couples trying to conceive if the HIV positive partner was on HAART and had an undetectable viral load.

But very low risk does not mean no risk, according to an analysis published in the July 26, 2008 issue of The Lancet.

David Wilson and colleagues with the National Centre in HIV Epidemiology and Clinical Research at the University of New South Wales in Sydney, Australia, conducted an analysis to quantify the small risk of transmission under circumstances described in the Swiss statement.

"The Swiss statement has the potential to allay exaggerated fears of transmission when the risk is actually extremely small, and could have particular value in situations such as heterosexual couples with discordant HIV status who are attempting conception," the study authors wrote as background. "But although the risk of transmission from people on effective therapy is low, it is unlikely to be zero. Factors such as incomplete adherence to therapy or the presence of other sexually transmitted infections could increase the risk of HIV transmission."

The Australian investigators used a mathematical model to estimate the risk of sexual transmission per unprotected sex act, as well as the cumulative risk over many exposures, among couples who are initially discordant for HIV status, and in which the HIV positive partner is on effective treatment with HIV RNA < 10 copies/mL over a prolonged period.

They used results from a study of HIV transmission between heterosexual couples in Rakai, Uganda, to derive a mathematical relation between viral load and the risk of HIV transmission per unprotected penetrative sexual act.
On the basis of that data, each 10-fold increment in viral load is associated with a 2.45-fold increased risk of transmission per sex act.

For heterosexual couples, they assumed vaginal not anal sex, and for gay men, they ignored "strategic positioning" (in which the HIV negative partner consistently takes the penetrative role and the positive partner the receptive role in order to minimize the risk of transmission). They further assumed that the effectiveness of antiretroviral treatment in reducing the risk of HIV transmission was about the same as for condoms.

Results

• Assuming that each couple engaged in 100 sexual acts per year, the model showed that the cumulative probability of transmission to the serodiscordant partner is:

• 0.22% or 0.0022 per year (uncertainty range 0.0008-0.0058) for female-to-male transmission;

• 0.43% or 0.0043 per year (0.0016-0.0115) for male-to-female transmission;

• 4.3% or 0.043 per year (0.0159-0.1097) for male-to-male transmission.

• In a population of 10,000 serodiscordant couples, the expected number of seroconversions over 10 years would be:

• 215 cases (range 80-564) for female-to-male transmission;

• 425 cases (range 159-1096) for male-to-female transmission;

• 3524 cases (range 1477-6871) for male-to-male transmission.

• This corresponds to a 4-fold increase in incidence compared with incidence under current rates of condom use.

Based on these findings, the study authors concluded, "Our analyses suggest that the risk of HIV transmission in heterosexual partnerships in the presence of effective treatment is low but non-zero and that the transmission risk in male homosexual partnerships is high over repeated exposures."

"If the claim of non-infectiousness in effectively treated patients was widely accepted, and condom use subsequently declined, then there is the potential for substantial increases in HIV incidence," they added. "Although we agree that effective antiretroviral treatment which leads to undetectable viral load is likely to have a substantial effect on reducing infectiousness, our analyses suggest that it should not replace condoms."

In an accompanying editorial, Geoffrey Garnett from Imperial College London and Brian Gazzard from Chelsea and Westminster Hospital suggested that while the Swiss experts may well have been too optimistic, the Australian authors were too pessimistic and did not give effective therapy enough credit for dramatically reducing HIV transmission risk.

"In many ways, the Swiss statement provides the opportunity for positive public-health messages, by promoting adherence to treatment and concern over other sexually transmitted infections," they wrote. "The use of condoms, in addition to antiretrovirals, to further reduce risk and prevent other sexually transmitted infections can then also be promoted."

8/01/08

References

DP Wilson, MG Law, AR Grulich, and others. Relation between HIV viral load and infectiousness: a model-based analysis. The Lancet 372(9635): 314-320. July 26 2008. (Abstract)

GP Garnett and B Gazzard. Risk of HIV transmission in discordant couples. The Lancet 372(9635): 270-271. July 26 2008