Dr Nneka Nwokolo from
the Chelsea and Westminster Hospital in London focused on some of the clinical
conundrums and questions that frequently come up in clinical settings around

serodiscordant couples (where one partner is HIV-positive and the other is
negative), the research clearly shows that the risk of infection comes from
sexual encounters outside the primary relationship and not from the
HIV-positive undetectable partner. Dr Nwokolo said it was important to
emphasise this when counselling patients and their partners.

Another clinical
question related to treatment adherence and viral load ‘blips’ — when the virus
briefly becomes detectable. When an individual has been virally suppressed for
a long period of time, an occasional missed dose, or even a viral load ‘blip’
does not negate U=U. This is was emphasised by both Drs Nwokolo and Vernazza.

However, it is not known exactly how many missed does do affect the risk of transmission.

This is also linked to
the exact threshold at which it can be said an individual is undetectable. The
studies that have provided the bedrock of evidence have generally used below
200-400 copies/ml as a definition of undetectability. However, viral load tests
with a lower limit of detection of 1000 copies/ml are used in some
resource-limited settings. She said it was not certain whether a viral load
below 1000 copies/ml equates to no transmission risk.

Additionally, while
current guidelines state that an individual must be undetectable for six months
before it can be assumed they can safely engage in condomless sex, Dr Nwokolo
stated that this area requires more research as the actual duration might be

Drs. Nwokolo and
Vernazza both stated that the presence of other sexually-transmitted infections
does not affect U=U, as there were high rates of STIs in PARTNER and other studies,
which did not affect infection rates.

Various speakers emphasised
that U=U is specifically related to sexual transmission of HIV. An undetectable
viral load does not prevent other sexually transmitted infections, and is not
necessarily as effective when considering other HIV infection routes. Thus,
there is still a chance — albeit very small, at around 0.3-0.6% — of infection
via other routes such as breastfeeding, needlestick injury and needle sharing
among intravenous drug users even when the HIV-positive individual is
undetectable. There are various clinical questions around managing these other
possible routes of infection, with different responses in different settings.

For instance, guidelines
differ from country to country regarding whether post-exposure prophylaxis
(PEP) should be made available after a needlestick injury from an undetectable
patient. In the US, it is routinely offered, whereas in the UK it is not. This
is indicative of different ways of managing low levels of risk from
undetectable patients. Patient choice and attitudes towards potential infection
are important factors as PEP is occasionally prescribed as a means of
alleviating anxiety instead of being based on the actual risk of infection. Dr
Nwokolo disagreed with this approach and felt that education about U=U and the
low risk of transmission was important.

In relation to breastfeeding, high-resource countries such as the US
tend to recommend formula-feeding for HIV-positive undetectable mothers whereas
in low-resource settings, the benefits of breastfeeding are judged to outweigh any
potential risks. In these settings, diarrhoeal
diseases, pneumonia and malnutrition are common as access to clean water may be
limited, with infant formula also being expensive or inaccessible. Thus, the very
small risk of infection from an HIV-positive undetectable mother is seen as an
acceptable level of risk in these settings.