outcomes vary enormously among people taking antiretroviral therapy in
different resource-limited settings, according to research published in the
online edition of Clinical Infectious
Diseases. An international team of investigators monitored outcomes in
patients in five African and two south-east Asian countries 12 and 24
months after starting HIV therapy. World Health Organization (WHO) approaches
for the delivery and monitoring of antiretroviral therapy were used in all
seven countries. Rates of virological failure differed significantly between
settings, from a low of 3% to a high of 26%.
using the [WHO] public health approach varies significantly from one setting to
another,” comment the authors. “The differences in VF [virological failure]
cannot be explained by study populations, ARV [antiretroviral] regimes or
biological monitoring which were similar at all sites…other factors should
therefore be considered, and local programme factors or local management of
clinics and healthcare centres are most likely associated with the heterogeneity
of virological outcomes.”
antiretroviral therapy in resource-limited settings is expanding rapidly. This
has in part been possible due to the adoption of the WHO model for the delivery
and monitoring of treatment. This takes into account limited financial
resources of low- and middle-income countries and the logistical constraints of
their health systems. WHO recommends viral load monitoring where possible, but
this is not feasible in most settings.
soon after the introduction of ARV rollout programmes in low- and middle-income
countries showed that patient outcomes were at the very least equal to those observed
in richer countries. However, subsequent research has highlighted alarming high
rates of virologic failure accompanied by the development of drug-resistant
team of investigators therefore analysed 12- and 24-month outcomes among
patients who started HIV therapy in seven low- and middle-income countries in
Africa (Burkina Faso, Cameroon, Ivory Coast, Senegal and Togo) and south-east
Asia (Thailand and Vietnam).
Blood samples were
taken at routine clinic visits and sent for viral load testing. A viral load
above 1000 copies/ml was the threshold for virologic failure. Samples with a
viral load above this figure were subjected to genotypic resistance testing.
Viral load for
approximately 4000 patients taking first-line theray was sampled between
October 2009 and December 2011. Women represented 70% of patients from African
countries, whereas men were in the majority in the south-east Asia.
12-month outcomes were analysed for 2060 patients and 24-month outcomes for
included d4T (stavudine, Zerit) or AZT (zidovudine, Retrovir) with 3TC (lamivudine, Epivir) and either
efavirenz (Sustiva or Stocrin) or nevirapine (Viramune). A very small number of patients received tenofovir (Viread),
but none were treated with a protease inhibitor.
Overall, 11% of
patients experienced virological failure at month 12 and 12% at month 24.
however, revealed that outcomes varied significantly between countries.
Very low rates of
treatment failure at both month 12 and month 24 (3 to 5%) were observed in
Burkina Faso (group A countries). The frequency of treatment failure after one
or two years of treatment varied between 9 and 14% in Cameroon, Senegal and
Vietnam (group B). In group C countries (Ivory Coast and Togo), between 18
and 20% of patients had a viral load above 1000 copies/ml after twelve months
of treatment. This increased to between 14 and 26% at month 24.
Between 10 and
50% of patients had a viral load between 1000 copies/ml and 5000 copies/ml,
“indicating that using the current WHO threshold for failure at 5000 copies/ml
could lead to significant misclassification of failing patients”.
three-quarters (71%) of patients experiencing failure at month twelve developed
strains of drug-resistant virus, and there was an 86% prevalence of drug
resistance among patients with virological failure after two years of therapy.
The proportion of
patients with two or more resistance mutations varied between 7 and 24%. Most
of the mutations concerned the drugs used in first-line therapy, but a few
patients developed cross-resistance to similar drugs.
were encouraged by the low prevalence of resistance observed in group A
countries, which they note was “unexpected” and “similar, if not better than
those obtained from countries where patients obtain adequate treatment
monitoring, including viral load assessment, generally industrialised countries
or well monitored cohort studies”.
The authors stress
that the differences in outcomes between countries cannot be explained by
differences in study populations or HIV treatment regimens. Rather, they
suggest, “Other factors should…be considered, and local programme factors or
local management of clinics and healthcare centres is most likely associated
with the heterogeneity of virological outcomes.” The investigators call for
“better programme management and implementation of actions to improve factors
as patient adherence, drug stock-outs and lost to follow-up”.
The author of an
accompanying editorial does not believe that the high failure rates in observed
in some countries can be ascribed to lack of routine viral load monitoring and
stresses that the drug-resistance testing is not a feasible option in most
continue about balancing the cost of drugs, monitoring and heath systems…for
countries struggling against poverty and high burdens of HIV,” he concludes.