Article

Surveillance of Transmitted Drug-Resistant HIV Among Young Pregnant Women in Ouagadougou, Burkina Faso

Ministry of Health/BFA, HIV Surveillance, Ouagadougou, Burkina Faso.
Clinical Infectious Diseases (Impact Factor: 8.89). 05/2012; 54 Suppl 4(suppl 4):S317-9. DOI: 10.1093/cid/cir988
Source: PubMed

ABSTRACT

Burkina Faso began rapid antiretroviral therapy (ART) scale-up in 2003 and by December 2009, 26 448 individuals were on treatment.
With rapid scale-up of ART, some degree of human immunodeficiency virus transmitted drug resistance (TDR) is inevitable. Following
World Health Organization methods, between June 2008 and July 2009, Burkina Faso assessed TDR in primigravid pregnant women
aged <25 years attending antenatal care clinics in Ouagadougou, Burkina Faso. TDR was classified as moderate (5%–15%) for
both nucleoside reverse-transcriptase inhibitors and nonnucleoside reverse-transcriptase inhibitors. The observed moderate
TDR in Ouagadougou is a cause for concern and calls for closer monitoring of Burkina Faso's ART program.

Full-text

Available from: Fatima Mouacha, May 02, 2014
SUPPLEMENT ARTICLE
Surveillance of Transmitted Drug-Resistant HIV
Among Young Pregnant Women in
Ouagadougou, Burkina Faso
Antoine Somda,
1
Lassana Sangare,
2
Monique Soro,
2
Saydou Yameogo,
2
Babou Bazie,
3
Francxoise Bigirimana,
3
Silvia Bertagnolio,
4
Martine Peeters,
5
Fatima Mouacha,
6
Ana Maria Rivera,
6
Michael R. Jordan,
4,6
and
Marie-Joseph Sanou
1
1
Ministry of Health/BFA, HIV Surveillance, and
2
Ministry of Health–LNR HIV,
3
World Health Organization, Ouagadougou, Burkina Faso;
4
World Health
Organization, Geneva, Switzerland;
5
UMI233, Institut de Recherche pour le Development and Universite
´
de Montpellier 1, France; and
6
Tufts University
School of Medicine, Boston, Massachusetts
Burkina Faso began rapid antiretroviral therapy (ART) scale-up in 2003 and by December 2009, 26 448
individuals were on treatment. With rapid scale-up of ART, some degree of human immunodeficiency virus
transmitted drug r esistance (TDR) is inevitable. Following World Health Organization methods, between
June 2008 and July 2009, Burkina Faso assessed TDR in primigravid pregnant women aged <25 years
attending antenatal care clinics in Ouagadougou, Burkina Faso. TDR was classified as moderate (5%–15%)
for both nucleoside reverse-transcriptase inhibitors and nonnucleoside reverse-transcriptase inhibitors. The
observed moderate TDR in Ouagadougou is a cause for concern and calls for closer monitoring of Burkina
Faso’s ART program.
Burkina Faso is a landlocked country in West Africa with
274 200 square kilometers and an estimated population
of 15 224 780. The country is divided into 13 regions,
45 provinces, and 350 departments. Burkina Faso has
one of the world’s lowest gross domestic products per
capita and faces a generalized human immunodeficiency
virus (HIV) epidemic. In 2009 there were an estimated
130 000 individuals (63 429 women) infected with HIV
[1]. In the capital city Ouagadougou, HIV prevalence
among pregnant women is 4% [3.0% 5.3%], and the
prevalence in women aged 15–24 years is 2.4% [1.4%–
4.0%]. By December 2009, the national antiretroviral
therapy (ART) program estimates that 26 448 in-
dividuals were receiving ART [2].
Successful ART scale-up in Burkina Faso has been
possible because of the use of a standardized public
health approach to HIV care and treatment. Since 2010,
ART has been provided free of charge in the public
sector, and patients are predominantly prescribed
standardized first-line ART regimens and monitored
following World Health Organization (WHO) clinical
staging guidelines and CD4 cell count. The first-line
ART regimen and 3 alternate first-line regimens con-
sist of 2 nucleoside reverse-transcriptase inhibitors
(NRTI) combined with a non-NRTI (NNRTI). Pro-
tease inhibitor–based regimens are generally reserved
for second-line regimens. Despite Burkina Faso’s un-
precedented rapid ART scale-up, coverage of those pa-
tients in need is estimated at 52%, suggesting a large and
ongoing unmet treatment need.
Given the current economic situation, limited human
resources, and existing infrastructure within the country,
individual HIV drug resistance (HIVDR) testing is nei-
ther routinely available nor recommended. However, as
ART is scaled up in Burkina Faso, the emergence and
transmission of HIVDR remains a fundamental concern.
Beginning in 2008, following WHO recommendations,
Burkina Faso implemented a comprehensive national
HIVDR prevention and assessment strategy that includes
Correspondence: Antoine Somda, MD, MPH, Ministry of Health/BFA; HIV
Surveillance, Burkina Faso (toniosomda@yahoo.fr).
Clinical Infectious Diseases 2012;54(S4):S317–9
Ó The A uthor 2012. Published by Oxford University Press on behalf of the
Infectious Diseases Society of America. All rights reserved. For Permissions,
please e-mail: journals.permissions@oup.com.
DOI: 10.1093/cid/cir988
Transmitted HIV Drug Resistance, Burkina Faso
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assessment of HIVDR early warning indicators and surveys of
transmitted and acquired HIVDR [35]. This comprehensive
national strategy will provide Burkina Faso’s ART program with
standardized information evaluating HIVDR in the country and
how well the program is functioning to minimize its emergence
and transmission.
This report documents Burkina Faso’s pilot of the WHO
transmitted HIVDR (transmitted drug resistance [TDR]) survey.
The presence of HIVDR before ART initiation is an important
predictor of virological response to antiretroviral regimens [6, 7].
Therefore, the existence of significant population level TDR may
undermine the success of the national ART scale-up initiative.
WHO TDR surveys provide important programmatic infor-
mation regarding the likely efficacy of future first-line ART and
current pre-and postexposure prophylactic regimens and will
indirectly provide evidence of how well current HIV prevention
programs function in preventing new infections. Ouagadou-
gou, the capital of Burkina Faso, was chosen for this pilot
because it is a large urban area where ART had been available
since 1999.
The WHO TDR survey method supports classification of
TDR as low (,5%), moderate (5%–15%), or high (.15%) in
a specific population in a specific geographic region using
#47 specimens. The TDR mutations are determined using
the WHO TDR mutations list available through the Stanford
HIVDR Calibrated Population Resistance tool [8, 9].
METHODS
Burkina Faso adapted its TDR survey from the WHO generic
protocol. Between May 2008 and June 2009, specimens for
HIVDR testing were obtained from consecutively diagnosed
HIV-positive women attending 11 antenatal care sites in
Ouagadougou. Specimens consecutively identified as positive
were eligible for HIVDR testing if they were from primi-
gravidae (and therefore not previously exposed to antire-
trovirals for prevention of mother-to-child transmission),
aged ,25 years (and therefore more likely to be recently
infected with HIV) and with no previous history of HIV
infection. Remnant diagnostic plasma specimens from
women meeting TDR survey inclusion criteria were trans-
ported within 72 hours to the University Hospital Center–
Yalgado Ouedraogo (CHU Yalgado), frozen at 220°C, and
then shipped on dry ice to the Institut de Recherche pour le
Developpement, a WHO-accredited HIVDR testing labora-
tory in Montpellier, France.
HIV reverse-transcriptase and protease were amplified
by means of previously published methods [10]. TDR mu-
tations were identified using the 2009 WHO TDR mutations
list [6], and TDR was classified following WHO TDR guid-
ance [2]. HIV subtypes and circulating recombinant forms
(CRFs) were determined by phylogenetic tree and recombination
analysis [11].
RESULTS
In total, 52 HIV-positive specimens meeting eligibility criteria
were obtained between June 2008 and July 2009. Among the
first 47 specimens, 3 had detected HIVDR: the first specimen
had the NRTI mutations M184I and G190A, the second had
the NNRTI mutation Y181C, and the third had both NRTI
(K70R, M184I, T2115I/T, K219E) and NNRTI mutations
(K103N, Y181C). To exclude erroneous inclusion of ART-
exposed women, eligibility criteria were double-checked
for specimens with HIVDR. The observed HIV subtype dis-
tribution was CRF 06_CPX (34%), CRF 02_AG (10.6%),
G (6.38%), and A1 (2.1%). Following WHO truncated
sequential sampling guidance [2], TDR was classified as
moderate (5%–15%) for both NRTIs and NNRTIs.
DISCUSSION
ART scale-up began rapidly in Burkina Faso in 2003. Some
degree of HIVDR is inevitable even when appropriate regi-
mens are prescribed and optimal adherence to treatment is
supported. Routine surveillance of TDR provides important
public health information regarding the efficacy of current
pre- and postexposure prophylaxis and may predict the
population-level efficacy of first-line regimens when recently
infected populations require ART.
Burkina Faso is one of the first countries in sub-Saharan
Africa to report moderate TDR using the WHO TDR survey
method. Notably, a previous TDR survey conducted in 2005
following WHO guidance in Bobo Dioulasso, the second largest
city in Burkina Faso, classified TDR as ,5% for all drug classes
[11], and much of the published literature suggests low rates of
TDR in sub-Saharan Africa [1318]. The findings of moderate
(5%–15%) TDR for NRTIs and NNRTIs in young primi-
gravidae with no previous antiretroviral exposure merit concern
and warrant further investigation. Rigorous quality assurance of
both laboratory and epidemiological data were performed to
ensure that each specimen came from a woman meeting eligi-
bility criteria. This was of particular importance, given that the
third specimen had multiple NRTI and 2 NNRTI mutations,
which raised concern for possible acquired HIVDR.
Results of TDR surveys cannot be interpreted adequately in
isolation and require a programmatic context for interpretation;
therefore, the Burkina Faso ART program is implementing early
warning indicators, such as rates of lost to follow-up, retention
rates on first-line ART at 12 months, on-time pill pick-up, and
drug supply continuity at ART clinics. The routine monitoring
of these indicators will provide important clinic and program
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information about factors contributing to emergence of
HIVDR in populations receiving ART in Ouagadougou and
throughout the country. Additionally, the result of this TDR
survey reinforces the need to strengthen prevention and ad-
herence support interventions for those receiving ART.
To further investigate the relationship between clinic and site
factors that may be leading to emergence of HIVDR, Burkina
Faso has implemented WHO surveys of acquired HIVDR in
2 ART clinics and plans to repeat the TDR survey in the same
population in Ouagadougou and expand it to other areas of the
country in the near future.
CONCLUSIONS
In conclusion, although the findings of moderate TDR are of
concern, they should be treated with caution. Present findings
are insufficient to change current ART guidelines in Burkina Faso
but do signal the importance of routine robust programmatic
monitoring of factors know to be associated with the emergence
of HIVDR at all treatment sites and the need for ongoing routine
surveillance of transmitted and acquired HIVDR.
Notes
Acknowledgements. We thank the staff of the Service of Bacteriology-
Virology of the Centre Hospitalier Universitaire Yalgado Oue
´
draogo and
the participants at the various study sites.
Disclaimer. The conclusions and opinions expressed in this article
are those of the authors and do not reflect those of the World Health
Organization.
Financial support. This work was supported by The Bill & Melinda
Gates Foundation and the National Institutes of Health (grants 5 T32
AI007438-18 to A. M. R. and NIH K23 AI074423-05 to M. R. J.).
Supplement sponsorship. This article was published as part of a sup-
plement entitled ‘‘The World Health Organization HIV Drug Resistance
Prevention and Assessment Strategy: Global, Regional, and Country
Progress,’’ sponsored by The Bill & Melinda Gates Foundation (38180).
Potential conflicts of interest. All authors: No reported conflicts.
All authors have submitted the ICMJE Form for Disclosure of Potential
Conflicts of Interest. Conflicts that the editors consider relevant to the
content of the manuscript have been disclosed.
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  • Source
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