Viral load and sexual transmission risk

There is a clear relationship between lower viral loads and reduced risk of HIV transmission. Whereas a high viral load can significantly increase the risk of sexual transmission, a low viral load significantly reduces sexual transmision risk.

This page will cover the studies that have looked at the impact of viral load on sexual transmission risk, regardless of the use of antiretroviral therapy.  Then, the following two sections – Treatment and heterosexual transmission risk and Treatment and sexual transmission risk between men – will cover the studies that have examined the specific impact that HIV treatment has had on sexual transmission risk.

The meta-analyses referred to in these sections include some of the same studies, but examine the impact on sexual transmission risk in different ways: some according to viral load regardless of treatment, and some according to treatment’s impact on viral load.

In 2009, a meta-analysis examining the impact of viral load on transmission risk (whether or not someone was on treatment) found that a high viral load can significantly increase the risk of transmission, and that a low viral load significantly reduces the risk.¹ The meta-analysis estimated that out of 1000 HIV-positive individuals with a viral load below 400 copies/ml regularly engaging in vaginal sex with an HIV-negative partner, only one transmission could be expected to occur in the course of a year. In contrast, among 1000 HIV-positive individuals with a viral load above 50,000 copies/ml, at least 90 transmissions could be expected to occur in the course of a year.

It is currently unknown whether there is a viral load threshold below which transmission is not possible. The meta-analysis estimated that the transmission rate for people with a blood plasma viral load below 400 copies/ml is 1 in 6250. The lowest recorded threshold of sexual transmission in an individual not on ART included in the meta-analysis occurred at a viral load of 362 copies/ml.

There may, however, be a difference in the risk of transmission between people who have low viral loads who are not on treatment, and people who have low viral load while on antiretroviral therapy. In untreated people, viral load in blood plasma is less reliably correlated with viral load in the genital tract, and this may be related to the penetration of antiretrovirals into seminal and vaginal fluid and rectal secretions.²

Nevertheless, there have since been case reports of suspected sexual transmission between men even when the blood plasma viral load was below the limit of detection due to antiretroviral therapy.³

This may be due to the imperfect correlation between viral load as measured in the blood, and the amount of virus in other body fluids, including those exchanged during unprotected sex: semen, cervico-vaginal fluids and/or rectal secretions.  This is covered in the section on Viral load in semen, cervico-vaginal fluid and rectal secretions.

A study of heterosexual couples in Uganda, published in 2000, and is often considered to be the benchmark study confirming that viral load measured in the blood is the most important factor in determining whether or not HIV is transmitted following sexual exposure. It found that no HIV transmission was observed over a 30-month period in the 51 couples where the HIV-positive partner had consistent viral load measurements in the blood below 1500 copies/ml.⁴

In May 2009, Attia and colleagues published a systematic review and meta-analysis examining all known prospective studies published or presented between January 1996 and February 2009 on the risk of HIV transmission through unprotected sexual intercourse according to viral load.¹ All were in heterosexual couples.

Of note, the review did not include studies examining the relationship between viral load and risk of transmission in sex between men, nor during anal sex, which is also practised by a significant minority of heterosexual couples, and which is often not reported, particularly in Africa where the practice is often considered to be taboo.⁵

• Studies: sex between men

Of the ten studies that included HIV-positive individuals not receiving antiretroviral therapy they calculated that amongst people with a viral load below 400 copies/ml the transmission rate was 0.16 per 100 person-years (0.0016 or 1 in 6250).

The most recent analysis of risk of heterosexual transmission according to blood plasma viral load comes from the Partners in Prevention study, published in 2012.⁶ This involved 3297 serodiscordant couples in sub-Saharan Africa who were not on antiretroviral therapy.

There were 151 new HIV infections during the two-year study (which was originally designed to assess whether or not the anti-herpes drug, aciclovir, taken by the HIV-positive partner reduced sexual transmission risk). Of these, 108 originated from the main partner, as determined by phylogenetic analysis. For this sub-study, 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 the study said they used condoms) and 15 in couples who claimed to have had no sex since the last visit.

The investigators found that each tenfold increase in viral load in the transmitting partner multiplied the risk of infection 2.89-fold.

This can be summarised as follows:

Viral load in transmitting partner                           Per-act infection risk

1000 copies/ml                                                         0.00028 (One in 3571)

10,000 copies/ml                                                      0.00082 (One in 1220)

100,000 copies/ml                                                    0.0024 (One in 416)

1,000,000 copies/ml                                                 0.0068  (One in 147)

The Attia review also included new information concerning a prospective observational study involving 393 monogamous heterosexual couples in Spain to determine HIV transmission risks, originally published in 2005. It revealed that there had been one case of sexual transmission when a HIV-positive partner, who was not on treatment, had a viral load of 362 copies/ml.⁷

Two further studies have also reported HIV transmission when viral load was below 1500 copies/ml (again in untreated individuals): at viral loads of 600 copies/ml⁸ and 1497 copies/ml.⁹