Signals warning of the
transmission of drug-resistant HIV are growing in low- and
middle-income countries, and governments should step up surveillance
efforts as they scale up treatment, experts concluded today at the
Eighteenth Conference on Retroviruses and Opportunistic Infections (CROI) in Boston.
A World Health
Organization (WHO) survey of 'early warning indicators'
– levels of
performance that treatment services should be hitting in order to
minimise the risk of drug resistance – showed substantial problems
with drug stock-outs, loss to follow-up and patients picking up drugs
on time in nine African countries in 2008.
PharmAccess, a Dutch foundation that provides HIV treatment services
for the private sector in sub-Saharan Africa, shows that levels of
transmitted drug resistance across eleven countries showed that the risk
of identifying transmitted drug resistance increased by 38% for each
year that a country had been scaling up antiretroviral treatment.
Furthermore, a survey
of recently infected young people in Kampala, Uganda, showed that
8.6% had evidence of drug-resistant virus, with resistance to all
three classes of antiretroviral drug currently available in the
country detected among the sample.
In Latin America, rates
of transmitted drug resistance may run as high as 20% in some parts
of Brazil, and 6.8% in Mexico, researchers reported.
Transmission of drug
Viruses resistant to
drugs used in HIV treatment may be transmitted by people on treatment
that is failing, or by people who have stopped or interrupted
treatment. The best way of preventing the transmission of
drug-resistant virus, apart from consistent condom use during sex, is
to ensure that doses of medication are never missed.
in drug supply and difficulties in reaching the clinic to pick up
drugs, often due to poverty or fluctuating income, mean that even
patients with good adherence to treatment may be blocked in their
efforts to take medication consistently.
For this reason the
World Health Organization developed a set of early warning indicators
that are being monitored at a large sample of HIV clinics in
sub-Saharan Africa, in order to give advance notice of problems, and
to provide feedback to clinics on how they are doing.
A review of clinic
performance in sub-Saharan Africa in 2008 found that in respect to
indicators most likely to affect adherence, clinics needed to improve
substantially to minimise the risk of resistance.
Early warning indicators
Survey of 130 clinics in 9 countries, 2008
Proportion of clinics reaching target
100% prescription of WHO first-line recommended
< 20% loss to follow-up
>70% retention on appropriate first-line
>90% of patients picking up prescribed ARVs
>80% of clinic appointments attended as
100% of drugs available at pharmacy at all
PharmAccess carried out
a review of drug resistance in 2478 treatment-naive patients
commencing antiretroviral treatment at 13 sites in eleven countries, and
found an overall prevalence of 5.71% (95% confidence interval 4.82 to
6.70%). Resistance to all three drug classes was found (NRTIs 2.2%,
NNRTIs 3.41% and PIs 1.27%). The presence of resistance at a site was
significantly associated with the time since the initiation of ART
provision in that geographic area (odds ratio 1.56, p<0.001). The
researchers calculated that the risk of resistance increased by 38%
for each year of ART provision.
A survey conducted in
2009 and 2010 in Kampala, Uganda, which sought to identify young
people recently infected through voluntary counselling and testing
centres, found an apparent increase in transmitted drug resistance
when compared to a sample of young women tested through antenatal
clinics in 2007. Although the level of resistance identified was
somewhat higher than the 2007 sample, at 8.6%, the researchers said
that the prevalence of resistance was still low to moderate.
Nevertheless, they say
it is time to step up resistance surveillance in Uganda.
in Brazil using dried blood spot sampling and testing through a
central laboratory showed large regional variations, with prevalence
of transmitted resistance as high as 19.9% in Salvador province and
12.8% in Rio de Janeiro.
Unlike in Africa, where
the predominant form of transmitted drug resistance is non-nucleoside
reverse transcriptase inhibitor resistance relating to use of
nevirapine and efavirenz, resistance in Brazil is more likely to be
related to use of nucleoside analogues, and may reflect the past use
of unboosted protease inhibitors, leading to greater emergence of
NRTI resistance when those regimens failed.