Partners study expands our knowledge of HIV transmission risk

Gus Cairns
Published: 03 March 2011

A prevention study in which the intervention being tested failed is turning out to be a fertile source of information about HIV transmission risk in heterosexuals.

Three substudies from the Partners in Prevention (PinP) prevention trial presented at the 18th Conference on Retroviruses and Opportunistic Infections (CROI) shed more light on the risk of transmission at specific viral load levels, how genital viral load influences infectiousness, and whether the viral load in the partner who transmits HIV influences viral load in the one who is infected.

PinP involved 3297 serodiscordant couples. It gave the anti-herpes drug aciclovir to the partners with HIV, all of whom also had the genital herpes virus HSV-2, to see if this would reduce the chance of their transmitting HIV to their HIV-negative partner. It did not, but HIV treatment, which was started by 349 of the HIV-positive partners during the study, did, reducing the likelihood of transmitting HIV by 92%.

Blood plasma viral load and infectiousness

James Hughes of the University of Washington in Seattle (UWS) presented findings on the relationship between HIV viral load in blood and the chance of transmission.

There were 151 new HIV infections during the two-year study, 108 of them originating from the main partner, as determined by phylogenetic analysis of their viruses. For this substudy, 86 linked transmissions with full viral load data from the transmitting partner were included.

The HIV-positive partner of each couple had their viral load tested every three to six months during the study and the HIV-negative partner took an HIV test every three months. Each time they came to the study centre they were asked about their sexual behaviour since the previous visit.

Of note, there were 56 transmissions between partners where 100% condom use was claimed (the majority of couples in PinP said they used condoms) and 15 in couples who claimed to have had no sex since the last visit.

The risk of HIV transmission per sex act derived from these figures was one per 526 sex acts from men to women, and one per 1000 from women to men. The male-to-female risk was higher because transmitting men tended to have a higher viral load and infected women were more likely to have herpes and be younger. Adjusting for these factors produced a roughly equal risk of transmission regardless of the sex of the transmitting partner.

Each tenfold increase in viral load in the transmitting partner multiplied the risk of infection 2.8-fold. This may be summarised as follows:

Viral load in transmitting partner                   Per-act infection risk                      

1000 copies/ml                                               One in 3571

10,000 copies/ml                                            One in 1220

100,000 copies/ml                                          One in 434

1,000,000 copies/ml                                       One in 149

There was an 18% lower risk of transmission per every five years older in the HIV-negative partner. HSV-2 in the HIV-negative partner more than doubled the risk of infection, and genital ulcer disease more than tripled it. Circumcision, if the negative partner was a man, halved his risk of infection – roughly in line with the circumcision trials – and self-reported 100% condom use made transmission 78% less likely, also in line with other meta-analyses of condom use.

Genital viral load and transmission

Having said this, viral load in semen and vaginal fluids probably influences the risk of transmission more than blood plasma viral load. Jared Baeten, also from UWS, presented a substudy of 2521 of the HIV-positive partners which measured the viral load in cervical swabs from the women and in semen from the men, and related them to the chance of transmission.  

Cervical samples from 1805 women, including 46 who transmitted HIV to their partner, and semen samples from 716 men, including 32 who transmitted HIV, were tested.

Each tenfold increase in genital viral load was associated with a 2.2-fold increase in the likelihood of transmission by women, and a 1.8-fold increase in the likelihood of transmission by men, roughly in line with the results from James Hughes’s study above.

After adjusting for blood plasma viral load, genital viral load was independently associated with the risk of transmission. What this means is that if we discount the influence of blood plasma viral load, there was still an additional 70% increased risk in the chance of transmission per tenfold increase in genital viral load. This suggests that genital viral load is, as anticipated, a better guide to the likelihood of transmission than viral load in blood.

Of note however, genital viral load is more often undetectable, and there were seven female-to-male and four male-to-female HIV transmissions from people with undetectable genital viral load but detectable HIV in their blood. There were no transmissions from someone with an undetectable viral load in blood and detectable genital viral load.

Relationship between partners’ viral load

Finally, Jairam Lingappa of UWS presented findings that showed there was a link between the viral load in the transmitting partner and the eventual viral load in chronic infection (the viral ‘set point’) in the infected partner. This has already been shown to apply in studies in gay men.

This has important implications for treatment as prevention as it may mean that if people with low viral loads on treatment do nonetheless transmit HIV, viral load could be lower and disease progression slower in those infected.  

A substudy of 101 linked transmission pairs, where it could be shown that the primary partner passed on HIV to their negative spouse, showed that for each tenfold increase in the blood plasma viral load in the transmitting partner there was a 2.5-fold increase in the viral load set point in the infected partner – very similar to the per-act increase in the chance of infection per tenfold increase in viral load.

If the transmitting partner took aciclovir rather than placebo, then their average viral load was 45% lower and the set point in the infected partner was 60% lower.

In cases where the source partner was a circumcised man, then the average viral load in the infected women was 80% lower.

Lingappa also looked at the transmissions that came from non-primary partners and found that there was a mysterious correlation between viral load in the primary partner – even though they were not the source of the infection – and the infected partner’s viral load. For each tenfold increase in the primary partner’s viral load, the infected spouse’s set point viral load doubled.

Lingappa speculated that immune reactions to regular partners with high viral loads might make people more susceptible to infections by unfamiliar viruses.  

He also found that pregnancy posed a big additional progression risk for women infected by non-regular partners; their viral load set point was 14 times higher than in other people.

References

Hughes J et al. Determinants of Per-act Infectivity of HIV-1 in the Partners in Prevention Study. Eighteenth Conference on Retroviruses and Opportunistic Infections, Boston, abstract 135, 2011.

Baeten J et al. Genital HIV-1 RNA Levels Predict Risk of Heterosexual HIV-1 Transmission. Eighteenth Conference on Retroviruses and Opportunistic Infections, Boston, abstract 154, 2011.

Lingappa J et al. Infected Partner's Plasma HIV-1 RNA Level and the HIV-1 Set Point of Their Heterosexual Seroconverting Partners. Eighteenth Conference on Retroviruses and Opportunistic Infections, Boston, abstract 134, 2011.

Abstracts and webcasts

You can view the abstracts from this research on the official conference website:

Abstract 135: www.retroconference.org/2011/Abstracts/41932.htm

Abstract 154: www.retroconference.org/2011/Abstracts/40117.htm

Abstract 134: www.retroconference.org/2011/Abstracts/41592.htm

You can also watch webcasts of presentations made at the conference.

The webcast from the conference session HIV transmission: old problems and new insights, includes the speakers James Hughes and Jairam Lingappa.

The webcast from the conference session Factors important in HIV transmission includes the speaker Jared Baeten.

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