©2009 International Medical Press 1359-6535 (print) 2040-2058 (online)401
Antiviral Therapy 14:401–411
Background: The rapid expansion of antiretroviral treatment
in resource-limited settings is raising concerns regarding the
emergence and transmission of HIV drug resistance (HIVDR).
We evaluated the extent of transmission of drug-resistant
HIV strains in four Central African countries: the Republic of
Congo, Central African Republic, Chad and Cameroon.
Methods: The World Health Organization (WHO) HIVDR
threshold survey was implemented in major treatment areas
in each country. Pregnant women who were aged <25 years,
who were at first pregnancy and who were HIV type-1-
positive were enrolled at each site in 2006–2007 for geno-
typing. HIVDR prevalence was categorized using the WHO
threshold survey binomial sequential sampling method.
Results: The prevalence of HIVDR in Brazzaville and Bangui
sites could not be classified because the eligible sample
number was not reached. HIVDR prevalence was low (<5%)
in N’Djamena for all drug classes. In Yaoundé, we found
one individual with the D67D/N mutation and two with
K103N. HIVDR prevalence was categorized as low (<5%)
for protease inhibitors (PIs) and nucleoside reverse tran-
scriptase inhibitors (NRTIs), and moderate (≥5–≤15%) for
non-NRTIs (NNRTIs). HIVDR prevalence in Douala was low
for PIs and NNRTIs, and moderate for NRTIs as we identi-
fied one individual with M184V plus K101E plus G190A
mutations and a second with D67D/N.
Conclusions: The moderate HIVDR prevalence found in
Yaoundé and Douala indicate that efforts should be made
in Cameroon to prevent HIVDR; however, additional sur-
veys are needed to confirm this trend. This study high-
lighted challenges presented by the WHO methodology,
such as additional costs, workload, difficulties in acquir-
ing even small sample numbers and the necessity for bet-
ter quality assurance of HIV testing and record keeping at
Two-thirds of >33 million people living with HIV/AIDS
worldwide are from sub-Saharan Africa and, as a con-
sequence, treatment needs in this region are high .
Reversing the curve of HIV infection in sub-Saharan
Africa requires intensive and innovative prevention
strategies to break the chain of new HIV transmissions,
and access to treatment for the estimated 7 million
patients in need will be essential to achieve this goal.
Of the people now receiving antiretroviral treatment
(ART) in low- and middle-income countries, 67% live
in sub-Saharan Africa compared with only 25% in late
2003 . This large and rapid scale-up of ART pro-
grammes in developing countries is characterized by
two key elements: firstly, the use of standardized and
simplified treatment protocols mainly consisting of
two nucleoside/nucleotide reverse transcriptase inhibi-
tors (NRTIs) plus a non-NRTI (NNRTI; zidovudine or
stavudine plus lamivudine plus nevirapine or efavirenz)
Evaluation of transmitted HIV drug resistance
among recently-infected antenatal clinic attendees
in four Central African countries
Avelin F Aghokeng1, Laurence Vergne2, Eitel Mpoudi-Ngole1, Madeleine Mbangue3, Noe Deoudje4,
Etienne Mokondji5, Wilfrid S Nambei6, Marlyse M Peyou-Ndi7, Jean-Jacques L Moka7, Eric Delaporte2 and
1Virology Laboratory CRESAR/IMPM/Institut de Recherche pour le Développement (IRD), Yaoundé, Cameroon
2UMR145, Institut de Recherche pour le Développement (IRD) and University of Montpellier 1, Montpellier, France
3Hôpital La Quintinie, Douala, Cameroon
4Programme National de lutte contre le Sida/IST, N’Djamena, Chad
5Laboratoire National de la Santé Publique, Brazzaville, Republic of Congo
6Laboratoire National de Biologie, Bangui, Central African Republic
7Organisation de Coordination pour la lutte contre les Endémies en Afrique Centrale (OCEAC), Yaoundé, Cameroon
*Corresponding author: E-mail: firstname.lastname@example.org
© 2009 International Medical Press
AF Aghokeng et al.
and second-line therapy (boosted protease inhibitors
[PIs] with ≥1 NRTI) [3,4]; and secondly, the absence
of virological monitoring at treatment start and switch
because of the limited laboratory facilities and the high
cost of virological testing, even immunological assess-
ments such as CD4+ T-cell counts are only available
in few reference centres . Even when capacities for
CD4+ T-cell counts are available, countries are faced
with challenges such as difficulties in servicing and
maintaining equipment, insufficient capacity to meet
the demand for testing and delays in returning results
on time. One major consequence of this strategy could
be the likely emergence of high-level resistance during
first-line therapy because many people will stay on a
virologically failing regimen for longer periods . Such
resistance emerging on first-line therapy might compro-
mise the efficacy of second-line therapy and increase the
risk of transmission of drug-resistant strains.
Transmitted resistance has the potential to rapidly
reverse the effectiveness of first-line ART at both the
individual and population level, especially when a
standard regimen is used without any baseline moni-
toring of drug resistance. Individuals with transmitted
drug resistance start ART with a lower genetic barrier
to resistance, a higher risk of virological failure and a
higher risk of developing resistance, even to drugs in
their regimen that were originally fully active [6–8]. For
these reasons, the World Health Organization (WHO)
has recommended the surveillance of drug resistance in
areas where ART is being rapidly scaled-up in order to
supply information that can help minimize the devel-
opment and transmission of drug-resistant viruses and
to assess the effectiveness of first-line regimens used in
the area [9–11]. Previous studies evaluating the preva-
lence of drug resistance among ART-naive patients in
Africa have reported variable results ranging from <5%
in Gabon , Djibouti  and Cameroon [14,15] to
6% in Côte d’Ivoire  and recently >9% in Cameroon
again . However, the results of some of these and
other previous surveys are difficult to compare because
different treatment-naive populations were studied, the
statistical methods used differed and the drug resist-
ance mutations that were considered as relevant also
varied between studies . Standardized surveillance
of transmitted HIV drug resistance (HIVDR) is thus
necessary to provide comparable results and to follow
the trend of HIVDR transmission over years.
In this study, we evaluated the prevalence of trans-
mitted HIVDR among recently infected patients in
four Central African countries (the Republic of Congo,
Central African Republic, Chad and Cameroon) using
the WHO HIVDR threshold survey (TS) and assessed
the feasibility and challenges for the implementation
of this generic protocol in sub-Saharan countries. In
the four countries, access to ART had been scaled-up
recently and approximately 20–53% of patients in
need of ART were receiving treatment in 2007.
The survey of transmitted HIVDR in Central Africa
was conducted between the end of 2006 and mid 2007
in four countries: the Republic of Congo, Central Afri-
can Republic, Chad and Cameroon, all of which are
part of a regional public health organization called
Organisation de Coordination pour la lutte contre les
Endémies en Afrique Centrale (OCEAC).  In each
country, geographical settings with the oldest ART pro-
gramme, where ART was widespread, had been avail-
able for the longest period of time and where the major-
ity of eligible HIV-infected individuals in the country
were treated, were chosen as study areas for this first
regional HIVDR surveillance.
Study population and sampling
As recommended by the WHO Global Resistance
Network, the study population in each area included
participants in HIV sentinel serosurveys who were
likely to be newly infected and therefore at low risk
of previous ART exposure. As recommended by the
WHO, eligibility criteria were women whose age was
<25 years, in their first pregnancy and who had con-
firmed HIV type-1 (HIV-1)-positive tests . These
criteria limited the number of years of potential expo-
sure to HIV transmission and provided an indication
of strains that were recently transmitted. However,
despite the fact that the majority of the countries per-
form sentinel surveys among antenatal clinic attendees,
they target a wider age group (generally women aged
15–49 years) and thus the required sample size with
the applied eligibility criteria might not be reached in
all cases. We therefore organized specific HIV senti-
nel serosurveys focusing exclusively on women aged
<25 years in each study area to enrol more eligible
individuals. HIVDR TS laboratory forms were devel-
oped to collect minimum sociodemographic informa-
tion as well as essential variables from blood draw
site, national laboratory and genotyping laboratory.
A plasma sample collected from each patient was
tested on-site for the presence of HIV-1 antibod-
ies using the national HIV testing algorithms in each
country. Two simple and rapid assays, Determine®
HIV-1/2 (Abbott Laboratories, Tokyo, Japan) and
ImmunoComb® II HIV 1&2 BiSpot (Orgenics, Ltd.,
Yavne, Israel), were used at the sentinel sites. Eligible
plasma samples and accompanying HIVDR TS labora-
tory forms were shipped within the day or week from
the HIV sentinel serosurvey sites to the corresponding
national laboratory and later to the regional HIVDR
Transmitted HIV drug resistance in Central Africa
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Accepted for publication 12 January 2009