Raphael W. Lihana, et al.: Update on HIV-1 Diversity in Africa: A Decade in ReviewAIDS Rev. 2012;14:83-100
Update on HIV-1 Diversity in Africa: A Decade in Review
Raphael W. Lihana1, Deogratius Ssemwanga2, Alash’le Abimiku3,4 and Nicaise Ndembi3
1Center for Virus Research, Kenya Medical Research Institute (KEMRI), Nairobi, Kenya; 2MRC/UVRI Uganda Research Unit on AIDS,
Entebbe, Uganda; 3Institute of Human Virology, University of Maryland School of Medicine, Baltimore, USA; 4Institute of Human Virology-
Nigeria, Abuja, Nigeria
Institute of Human Virology-Nigeria
Pent House, Maina Court, Plot 252, Herbert Macaulay Way
Central Business District
Background: HIV-1 strains have diversified extensively through mutation and recombination since their initial
transmission to human beings many decades ago in Central Africa in the first part of the 20th Century (between
1915 and 1941). The upward trend in global HIV-1 diversity has continued unabated, with newer groups,
subtypes, and unique and circulating recombinants increasingly being reported, especially in Africa.
Objective: In this review, we focus on the extensive diversity of HIV-1 over a decade (2000-2011), in
51 countries of the three African geographic regions (eastern and southern, western and central, and
northern Africa) as per the WHO/UNAIDS 2010 classification.
Methodology: References for this review were identified through searches of PubMed, conference
abstracts, Google Scholar, and Springer Online Archives Collection. We retrieved 273 citations, of which
200 reported HIV-1 diversity from Africa from January, 2000 to August, 2011. Articles resulting from these
searches and relevant references cited in those articles were reviewed. Articles published in English
and French were included.
Findings: There has been a high diversity of HIV-1 in its epicenter, west-central Africa. A few subtypes,
namely, A (A1, A2, A3, A4, A5), C, CRF02_AG, and D accounted for about 85% of new infections. Subtype
A and D have been stable in East Africa; C in southern Africa; A, G, CRF02_AG, and CRF06_cpx in
western Africa; and subtype B and CRF02_AG in northern Africa. Recently a new putative group,
designated P, was reported to be found in two Cameroonians.
Conclusion: The regional distributions of individual subtypes and recombinants are broadly stable,
although unique/circulating recombinant forms may play an increasing role in the HIV pandemic.
Understanding the kinetics and directions of this continuing adaptation and its impact on viral fitness,
immunogenicity, and pathogenicity are crucial to the successful design of effective HIV vaccines. There
is need for regular monitoring and review updates, such as the one presented here, to assist countries
to plan and anticipate complex forms that may be introduced with time. (AIDS Rev. 2012;14:83-100)
Corresponding author: Nicaise Ndembi, firstname.lastname@example.org
HIV-1. Genetic diversity. Subtypes. Africa.
people including children were infected with HIV by
the end of 2009. Of this number, 2.6 million were new
infections, with another 1.8 million deaths1. Sub-Saharan
Africa accounted for over 67% of the total population
that was living with the virus. Of the 7,000 new infec-
tions per day, 97% occurred in middle- and low-income
Africa has some of the poorest countries in the world
whose populations have been severely affected by
HIV. For example, by the end of 2009, nine African
countries had more than 10% of their adult population
infected with HIV1. In some countries the epidemic is
even higher, e.g. in Botswana, 24.8% of adults are now
Globally, the Joint United Nations Programme on
HIV/AIDS (UNAIDS) estimates show that 33.3 million
AIDS Reviews. 2012;14
infected with HIV, while in South Africa, 17.8% are
infected. Rates of acquiring new HIV infections are still
high in sub-Saharan Africa, with an estimated 1.9 million
people becoming infected in 20091.
HIV-1 is characterized by an extensive genetic di-
versity2-6. Mutational escape results in a remarkable
degree of viral diversity within HIV-1 and its adaptation
in response to both immune activity and antiretroviral
therapy (ART). However, not all escape mutations are
advantageous to the virus since some can severely
hinder viral fitness7,8. Nevertheless, HIV strains often
exhibit specific associations with particular geograph-
ic regions and/or modes of transmission9-11. Tracking
these dynamic associations through surveillance of
genetic diversity has facilitated epidemiological in-
vestigations and informed public health strategies
aimed at preventing viral spread5. Several studies
have demonstrated that HIV-1 subtypes are not ran-
domly distributed around the globe but show distinct
geographical distributions3,12-16. The resultant viral di-
versity has implications for possible differential rates of
transmission, disease progression, responses to ART
(including the development of resistance), and vaccine
The main objective of this review is to summarize the
current available data on HIV-1 subtype diversity in
Africa. It provides an update on the genetic diversity
of HIV-1 strains in Africa and by region. In particular,
it provides an overview of recent epidemiological re-
search findings on multiple infections and geographic
distribution of HIV subtypes in 51 of the 54 African
countries. The information provided by this review
could complement and update available knowledge
of HIV-1 diversity in Africa, and provide critical infor-
mation for diagnostic tools, vaccine development, and
possible clues for tracking similar transmission patterns
Origins of HIV
It has been postulated that HIV-1 originated from
three independent cross-species transmissions of
simian immunodeficiency virus (SIVcpzPtt) infecting
chimpanzees (SIVcpz; Pan troglodytes troglodytes)
in west-central Africa, giving rise to pandemic
(group M) and non-pandemic (groups N and O) clades
of HIV-1, while the SIV origin of group O (outlier) vi-
ruses has not been identified19-21 (Fig. 1). Recently,
one new putative group, designated P, was reported
to be found in Cameroonian patients6,22. The group P
viral sequences, RBF168 and 06CMU14788, form a
distinct HIV-1 lineage that includes SIV sequences
from western gorillas (SIVgor; Gorilla gorilla gorilla),
suggesting that group P originated from gorillas22-24.
On the other hand, HIV-2 is believed to have origi-
nated from SIVSm from the sooty mangabey monkey
(Cercocebus atys)25,26. The sooty mangabey is the
only primate species naturally infected with viruses
related to HIV-2 and is found in western Africa27. The
HIV-2 has continuously evolved out of the epicenter in
western Africa and formed recombinants28,29 including
a circulating recombinant form (CRF). The first HIV-2
CRF was described among recently isolated gen-
omes from Japanese patients (who were believed to
have had links with similarly infected individuals
from western Africa) based on three recently isolated
gen omes from Japan and 1990 isolate 7312A from
Evolution of HIV-1 and classification
Subtype designations have been powerful molecular
epidemiological tools to track the course of the HIV-1
pandemic. Evolutionary analyses have revealed an
origin of pandemic HIV-1 group M in the Congo River
basin in the first part of the 20th Century (between
1915 and 1941), but the patterns of historical viral
spread in or around its epicenter remain largely un-
explored30-34. Group M is the predominant circulating
HIV-1 group. It has been divided into the current nine
subtypes: A-D, F-H, J, and K2,3. Within some subtypes,
further distinct sequence clusters exist based on gen-
etic variation of 15-20% (variation between subtypes
is usually 25-35%), leading to the classification of virus
strains into sub-subtypes. For example, subtype A has
been subdivided into sub-subtype A1, A2, A3, A4, and
A5, and F has been subdivided into F1 and F2. Fur-
thermore, inter-subtype recombinant genomes are
common, but many of them are found only in the dual ly-
infected individual patient in which they arose. If an
inter-subtype recombinant virus continues to be trans-
mitted from one individual to another, it can be clas-
sified as a CRF. The CRF represent recombinant HIV-
1 genomes that have infected three or more persons
who are not epidemiologically related, so they can be
assumed to have an epidemiologically relevant contri-
bution to the HIV-1 M group epidemic. The CRF are
labeled with numbers rather than letters, and num-
bered in the order in which they were first adequately
described, e.g. CRF02_AG. At least 51 CRF along with
a myriad of unique recombinant forms (URF) have
Raphael W. Lihana, et al.: Update on HIV-1 Diversity in Africa: A Decade in Review
Group N is a very distinctive form of the virus that
has only been identified in a few individuals in Camer-
oon. Group N is sometimes referred to as Not-M, Not-
O, also sometimes as the “new” group, and is also
thought to have originated from a chimpanzee trans-
mission. Subtypes within the HIV-1 N group are not yet
clearly defined. Very few isolates have been identified
and sequenced from humans36-39.
HIV-1 group O, sometimes referred to as the “out-
lier” group, is rare and contains very diverse viruses,
but is still relatively rarely found. It is thought to have
originated in a transmission to humans from wild
gorillas23. Subtypes within the HIV-1 O group are not
yet defined, although the diversity of sequences
within the HIV-1 O group is nearly as great as the
diversity of sequences in the HIV-1 M group. Unlike
group M viruses, phylogenetic analyses of the gag
and env genes do not reveal distinct subtypes in the
HIV-1 O group.
Impact of HIV diversity on HIV diagnosis,
treatment, and vaccine development
Preliminary data reveal a very heterogeneous distri-
bution and dominance of different genetic subtypes
depending on the country analyzed. In Africa, all known
HIV-1 genetic subtypes and groups, including groups
N, O, and P, are present. This diversity has an impact
on serological diagnosis, virologic follow up, and thera-
peutic monitoring40-44. Whether the various groups,
subtypes, and recombinant forms of HIV-1 have bio-
logical differences (for example, with respect to trans-
missibility and the course of disease progression) is
not known10,45,46. A relationship between genetic sub-
type and natural resistance against antiretroviral drugs
has been reported47,48. The degree to which vaccines
based on one subtype will elicit cross-protection
against other subtypes is still poorly understood; hence
the need to understand the geographic distribution of
HIV-1 Group N
HIV-1 Group M
HIV-1 Group “P”
HIV-1 Group O
Figure 1. Phylogenetic tree derived from nucleotide alignment of genome sequences. HIV-1 group M is represented by single sequences
for each subtype A through H and J; group N and group O are each represented by five sequences, with isolates YBF30, ANT70, and
MVP5180 indicated, and SIVgor is represented by three sequences, CP684, CP2135, and CP2139. The alignment consisted of 7,509 nucleotides
after gaps were stripped.
AIDS Reviews. 2012;14
the major HIV-1 subtypes for appropriate interpretation
of HIV vaccine trials.
A current area of some controversy is the association
of emerging mutations with viral subtype. For instance,
preferential emergence of the K65R mutation has been
described in subtype C-infected patients failing stavu-
dine/didanosine-based regimens in Botswana49. Also,
K65R was detected in subtype C viruses after a short-
er period of culture in vitro compared with subtype B
virus, and was attributed to the presence of polymor-
phisms at positions 64, 65, and 66 in reverse tran-
scriptase of subtype C viruses50, although this was not
confirmed51. Subtype C viruses also develop resis-
tance against nonnucleoside reverse transcriptase in-
hibitors through either the K103N or V106M mutations,
whereas subtype B viruses rarely develop V106M mu-
tations52. Nelfinavir resistance appears to occur pri-
marily through L90M mutations in subtype G and C and
other non-B subtypes, whereas subtype B acquires
either D30N or L90M nelfinavir-resistant mutations.
Lemey, et al. have shown important differences in the
evolutionary rates of different subtypes using Bayesian
Markov Chain Monte Carlo relaxed-clock phylogenetic
analysis. It was observed that CRF02_AG had a high-
er mean substitution rate than all other subtypes in
both pol and env, while subtype D had lower rates in
pol and env (along with subtype B in pol). Subtype G
showed a similar pattern to that for CRF02_AG53,54. The
differences in mean substitution rates between sub-
types can be due to differences in the generation time,
mutation rate, or (immune) selective pressure and may
suggest less accumulation of mutations in subtype D
compared to any other subtype55.
HIV-1 genetic diversity has long been identified as a
key challenge in the development of an effective, pre-
ventive HIV vaccine. No one knows if an effective vac-
cine would be dependent on conserved epitopes or on
conformational presentation. Therefore, many strate-
gies are being pursued to confront the issue of high
diversity among HIV isolates, including the use of con-
sensus sequences, the deployment of a combination
of immunogens from different subtypes, the creation of
mosaic immunogens assembled through computation-
al optimization from pieces of natural sequences, and
the construction of multi-subtype immunogens derived
from conserved regions of the HIV-1 consensus prote-
ome17,18,56,57. Though infected individuals mount im-
mune responses, there are reports of mutational es-
cape by viruses from responses by CD8+ cytotoxic
T-cells and neutralizing antibodies over time. Peptides
based on highly conserved HIV-1 consensus group M
sequences, which are phylogenetically closer to
most circulating strains, may provide potential alter-
native vaccine candidates in populations with diverse
Epidemiology of HIV
The original cross-species transmission of HIV is be-
lieved to have occurred in west-central Africa and has
been evolving in humans since at least the early
1900s59. Despite high diversity in its origin in west-
central Africa, a limited number of viruses have spread,
with four subtypes and two CRF being responsible for
90% of infections. Worldwide, it has been shown that
48% of infections are caused by subtype C; 12% by
subtype A; 11% by subtype B; 5% by subtype G; 2%
by subtype D; and 22% recombinants4. We present
below a detailed update of the literature of the HIV
epidemic in each African country, in alphabetical or-
der, within the three main regions: east and southern
Africa; west and central Africa; and north Africa.
East and southern Africa
Countries with the largest epidemics are in southern
Africa; in South Africa, Zambia, and Zimbabwe, the
subtype C epidemic has continued to predominate
and the HIV/AIDS prevalence has either stabilized or
has shown a sign of decline according to the UNAIDS
2010 report. In the past 10 years, data on HIV-1 sub-
types in southern Africa has significantly increased in
seven of the 10 southern African countries. Subtype
data has been published from Angola60-62, Botswa-
na49,63-67, Malawi68-71, Mozambique72-76, South Afri-
ca69,77-90, Zambia69,90-95, and Zimbabwe69,96-98; however,
very limited data is available from Lesotho99,100, Na-
mibia, and Swaziland99,101, despite reported high HIV
The heteroduplex mobility assay (HMA) and multi-
region hybridization assay (MHA) offered a more
affordable option for simple and rapid classification of
HIV-1 subtypes, and was used in many areas, such as
Tanzania, Uganda, and Ethiopia. However due to
cross-reactivity across subtypes, this method could not
define specific sequence differences between isolates
of the same or different subtypes. In an attempted
optimization, we developed and applied these assays
to detect inter- and intra-subtype dual infections (both
simultaneous coinfection and consecutive superinfec-
tion) and determined the prevalence of dual infection
within some couples known to have discordant HIV-1
Raphael W. Lihana, et al.: Update on HIV-1 Diversity in Africa: A Decade in Review
subtypes from 155 participants in a rural clinical cohort
in southwestern Uganda. Of these, 45 participants
were suspected to be either dually infected with HIV-1
subtypes A and D or to be infected with recombinants
viruses. Cloning and DNA sequencing confirmed the
evidence of only two dual infections (Ssemwanga and
Ndembi, unpublished data). Direct DNA viral sequenc-
ing of fragments greater > 1,000 base pairs has been
appropriate in characterizing infecting HIV-1 subtypes
or CRF/URF and has been used to monitor regional
and global HIV-1 spread4,102-105. Although DNA sequenc-
ing of a bulk PCR product remains less expensive and
faster to perform than a clonal DNA sequence analysis,
minor HIV-1 variants (frequency < 20-30%) cannot be
detected106. This has been a major drawback in sub-
type analysis in Africa, though it is proving to be a
dependable tool. Nonetheless, in southern Africa, sub-
types A, C, and D together with their recombinants are
the major subtypes and account for > 50% of infections.
In East Africa, HIV subtype diversity is characterized
by strains that are further dependent on human migra-
tory patterns. The majority of infections are due to
subtype A, with others being due to subtypes C and D
and a high proportion of CRF/URF.
Severe HIV/AIDS epidemic has been recorded in
Angola1, with the adult population shown to have di-
vergent HIV subtypes and recombinants60-62,107. Most
HIV subtype data in Angola has been derived from
sequencing of the pol gene60,62,107 or pol, gag and env
genes61,107. Early data from HIV-1 pol sequences
showed that subtype C and F were the most predom-
inant, while subtypes A, D, G, and H were also found60.
Similarly, unclassified sequences were also found,
suggesting they were unknown new subtypes or re-
combinants from unknown subtypes. Another subse-
quent study that analyzed 48 samples in the HIV gag
and env genes found a contrasting prevalence of sub-
type A1 being predominant (38%), followed by C (15%)
and several other subtypes: H (10%), J (6%), G (4%),
A2 (4%), F1 (2%), and D (2%)61. The subtype F1 in
Angola is thought to have originated from the Demo-
cratic Republic of Congo (DRC)108 and was introduced
into Brazil by emigrants during the late 1970s (1975-
1980), coinciding with the beginning of the Angolan
civil war in 1975109,110. One comprehensive study in
Angola analyzed almost 400 sequences from gag, pol,
and env genes of 159 HIV-infected patients derived
from eight provinces across Angola107 and found two
distinct sub-clusters within the subtype A, which were
defined as new A5 and A6 sub-subtypes107. In the
Angolan population, close to 50% of viruses were
recombinants, with predominance of subtype A and
CRF02_AG. In another study of transmitted drug
resistance among newly diagnosed HIV-infected
pregnant women, the same subtype distribution was
Although subtype data of most studies was derived
from small sample sizes using pol sequence data,
subtype C is the most predominant in Botswana49,63-67.
Data from a study based on 71 pol sequences from
11 representative districts of northern and southern
Botswana classified all but one (which exhibited pol
gene mosaicism) as subtype C66.
In Eritrea, epidemiological studies on HIV-1 subtypes
have been similar to reports in Ethiopia. This is be-
cause the two countries were originally one. Prolonged
civil war between the two countries led to their separation,
but population movements have remained the same.
HIV-1 subtypes reported from this region are mainly
Subtype C is predominant in Ethiopia; over 80% of
all reported subtypes are classified as C112. The sub-
type C found here has its origin in India and is believed
to have been introduced from South Africa and, through
founder effects, has spread through Djibouti, Eritrea,
and Ethiopia111, although others speculate entry from
several sources including neighboring countries like
Somalia, Sudan, and Djibouti where subtype C has been
Furthermore, within subtype C, there are sub-clusters,
hence the diversity into C and C’112,121-125.
HIV-1 subtype A was reported as the predominant
strain in southern Kenya, with over 30% recombi-
nants126-128. All along, studies have shown that subtype
A1 is predominant in Kenya, but subtypes A2, D, C,
and G together with their recombinants have also been
described126,129-135. Whereas subtypes A and D are
AIDS Reviews. 2012;14
believed to have been introduced into Kenya from
western Africa through Uganda, their recombinations
are thought to be as a result of founder effects128. This
has been shown by the detection of subtypes A, C,
and D together with CRF16_A2D recombinants136.
Kenyan subtype C has two distinct epidemics; one
from north Africa, believed to be Ethiopian C, where
this has been the major strain with links to India, while
another epidemic is from the south, believed to have
its origin in southern Africa where subtype C is pre-
dominant, as illustrated by the marked increase in
prevalence of subtype C in northern Kenya137. The
southern epidemic is thought to be as a result of
direct introduction from southern Africa through
Tanzania. As such, Kenya appears to have an array
of subtypes that co-circulate courtesy of increased
human migration in and around East and central
Africa. For instance, in a study among HIV patients
in Kilifi, phylogeographic analysis of 153 pol sequences
compared with those from other regions of Africa
showed that while many sequences were closely
related to sequences from Kenya, others were most
closely related to known sequences from other parts
of Africa, including West Africa128.
The first few known reports showed the dominance
of subtype C among migrant mine workers from Lesotho
in South Africa99, and since then, very limited data is
available. Subtype A was shown in a subsequent study
in a patient from Lesotho in South Africa100.
There has been an increase in the generation of data
on the HIV-1 subtype from Malawi over the years68-71.
The scaling up of ART has increased the pol gene
sequence data (used in laboratory monitoring of pa-
tients and ART success), with one study reporting
subtype C as the only subtype in Malawi68. Other
studies found envelope diversity during vertical trans-
mission of HIV-1 in mother-infant pairs and also re-
ported the predominance of subtype C in Malawi70. In
a study to determine subtype C diversity in Malawi,
Zambia, Zimbabwe, and South Africa in preparation
for vaccine trials in southern Africa, no evidence of
intersubtype recombination was reported69 and a recent
study also showed the predominance of subtype C in
drug-naive HIV-positive individuals in a rural population
In the recent past, most of the subtype data from
Mozambique has been derived from sequencing the
pol gene, in studies outlined below, to determine
prevalence of drug-resistant mutations among ART-
naive HIV-positive individuals. Several studies have
reported varying subtype distribution estimates, but
with subtype C being predominant72-76. A study among
treatment-naive individuals showed the predominance
of subtype C72. In southern Mozambique, a study to
determine HIV-1 diversity between 1999 and 2004 found
predominance of subtype C, with 2004 sequences
showing significantly more genetic diversity than
sequences from 199973. In yet another study among
75 HIV-positive drug-naive pregnant women, the ma-
jority of sequences were subtype C, with few subtypes
A, D, and some recombinants76. In addition to subtype
C, a few sequences were found that clustered with
subtype A, D, and some recombinants76. In Maputo, a
study to monitor viral loads and drug resistance among
individuals taking first-line therapy for at least 12 months
showed that among the 15 individuals with viral loads
> 1,000 copies/ml, of which 12 were sequenced, eight
were infected with subtype C, whereas the other four
had CRF08_BC75. Another study in Maputo to deter-
mine the subtype distribution and level of transmitted
drug resistance in a healthcare setting also found
predominantly subtype distribution as C (80.8%), G
(3.8%), CRF37_cpx (6.7%), unclassified (U) (1.0%),
and recombinant strains (7.7%) comprising the A, C,
D, F, and U clades74.
HIV-1 subtypes A and C have been reported to be
predominant in Rwanda. Studies among antenatal
clinic attendees in Kigali showed that subtype A to-
gether with its recombinants accounted for the majority
of infections138,139. Similarly, another study on samples
from urban Kigali documented subtype A as predomi-
nant90. The limited data on HIV subtypes in Rwanda
may be attributed to civil war and the 1994 Rwandan
genocide, which coincided with the up-scaling of gene
sequencing technologies in this region.
Seychelles and Madagascar
Seychelles and Madagascar are important tourist
destinations and offer a good opportunity in studying
HIV subtype spread since infections are known to
Raphael W. Lihana, et al.: Update on HIV-1 Diversity in Africa: A Decade in Review
spread with human migration. In a study of 40 HIV-in-
fected patients in Mahe hospital, Seychelles, it was
reported that besides recombinants, CRF01_AE and
CRF02_AG, subtype A was the most prevalent140. A
similar study in Madagascar found in addition the pres-
ence of complex HIV-1 strains (CRF02_AG, CRF06_cpx,
and CRF10_CD). Most viruses were related to those
detected in neighboring mainland countries and from
around the world141.
In South Africa, there is rich data from many studies
that have documented subtype C as the predominant
subtype69,77-90. In Kwazulu-Natal, a region with an explo-
sive outbreak of HIV infection, analysis of 72 treatment-
naive patients in protease and C2V5 envelope regions
showed that all were subtype C that segregated with
other C viruses from southern Africa78. In Cape Town,
a study demonstrated some phylogenetic diversity
among treatment-naive HIV-positive patients; among
140 pol sequences analyzed, 133 (95%) were subtype
C, five (3.6%) subtype B, and one each subtype G and
CRF02_AG81. Several other studies across South Africa
in the Free State83, Kwazulu-Natal78,82, Cape Town69,84,90
and other areas have shown a high prevalence of
subtype C and very few representatives of the other
subtypes and recombinants84,86. The observed in-
crease in non-subtype C strains has been attributed to
immigration of people from countries with civil unrest
and also immigrant workers into South Africa86.
Since 1998, when some subtype C data from Swazi
migrant workers was reported99, limited data showing
predominance of subtypes C has been documented
among patients in Swaziland101.
In Tanzania, HIV-1 subtypes A and C have been
documented as major circulating strains142-146. Subtype
C is thought to have been introduced from southern
Africa, where it is the most common strain in circulation,
and through founder effects from Lubumbashi in the
DRC125. A study conducted among HIV patients in
Mbeya region found multiple infections (recombination,
dual infections, and triple infection using single genome
amplification) to account for 27%147. The proportion of
HIV subtype recombinants in the country has also been
increasing with new sequencing technologies148-151.
More than 60% of detected recombinants are those of
subtype C. This differs from the Kenyan epidemic,
which consists of mostly A and D recombinants128.
Tanzania also leads East Africa with the highest
prevalence of reported recombinants152. It is here that
CRF10_CD was reported among perinatally infected
infants, an indication that this CRF has been circulating
among the Tanzanian population148 for some time.
As far back as the mid-1980s153, multiple genetic
subtypes of HIV-1 were reported in Uganda, with A and
D as the most prevalent and with connections to their
cities of origin in central Africa11,103,105,125,154-159. The
prevalence of HIV-1 decreased from an estimated 14%
in the early 1990s to around 8% in 1999 as a result of
an aggressive prevention program and open discussions
on issues surrounding HIV160. Detailed and systematic
characterization of the HIV-1 epidemic in Uganda over
time showed that the distribution and degree of gen etic
diversity of the two predominant subtypes, A and D,
differed11,153. In an eight-year (1994-2002) interval, a
significant decrease of 8% in subtype D prevalence
was detected11. Subtype D was replaced with an in-
crease of subtype A and recombinant strains. It was
noted that subtype D is decreasing in Rakai, probably
as a consequence of faster disease progression and
lower infectivity of this subtype45,46. Recent studies
have confirmed an increase in prevalence of subtype
A1, with consistent detection of A/D recombinants and
Several studies in Zambia have reported predomi-
nance of subtype C69,90-95. Some earlier reports inves-
tigating the prevalence of drug resistance mutations
among ART-naive Zambians showed that 93% of all
infections were of subtype C91. In a study among 548
participants, 98% of sequences were found to be sub-
type C95. More recently, in a multicentre study includ-
ing Entebbe, Kigali, Kilifi, Lusaka, and Cape Town, a
significant increase in subtype C transmitted drug re-
sistance in Zambia was reported90.
Over the years, subtype data has been generated
from Zimbabwe69,96-98,161. Similar to other geographic
AIDS Reviews. 2012;14
regions, available subtype data from Zimbabwe is from
pol sequence data for estimation of ART resistance.
Subtype C was exclusively found in 21 Zimbabwean
patients who were failing ART96. In a recent study to
determine the virologic response to triple nucleoside/
nucleotide analogue regimens over 48 weeks among
Ugandan and Zimbabwean adults, subtype C was pre-
dominantly found in Zimbabwe, whereas A and D were
found in Uganda97. Based on Bayesian analysis from
177 pol subtype C sequences, the origin and evolutionary
history of subtype C in Zimbabwe was shown to have
been due to regional conflict and migration during the
Zimbabwean national independence, following a period
of socio-political instability161.
The observed lack of HIV diversity data from
Com oros, Lesotho, Mauritius, Namibia, and Swaziland
could not be explained, but it may probably be due to
cultural norms and laws that prohibit HIV research as
well as the population’s lack of knowledge on HIV/AIDS
resulting in heightened stigma. It could also be due to
lack of both technical and financial capacity of these
countries to carry out diversity studies. This therefore
highlights the existing gaps in HIV diversity data in
some of the sub-Saharan countries.
West and Central Africa
Subtype data from Benin has not been extensively
published162-164; earlier reports from Cotonou showed
a prevalence of 39% CRF02_AG as determined by the
gag HMA methodology162. Another study that was
done in a randomly selected general population and
sex workers in Kisumu (Kenya), Ndola (Zambia), Coto-
nou (Benin), and Yaounde (Cameroon) revealed that
70% of infections in Cotonou were subtype A by env,
but 50% of the env subtype A infections were found to
be CRF02_AG when the gag gene was analyzed163. In
Cotonou, CRF02_AG was found at a prevalence of
66%, subtypes G, A3, CRF06_cpx and other URF were
found in HIV-1-infected patients receiving ART in routine
A study to determine HIV-1 drug resistance among
newly diagnosed patients before scaling up ART in
Burkina Faso and Cameroon found that among the 97
samples from Burkina Faso, the subtype distribution
was CRF02_AG (n = 47; 48.5%), CRF06_cpx (n = 46;
47.4%), A (n = 3; 3.1%), and G (n = 1; 1.0%)165. A high
predominance of recombinant HIV-1 strains CRF06_
cpx 16/29 (55.17%), CRF02_AG 9/29 (31.03%), A1
2/29 (6.89%), G 1/29 (3.44%), and CRF09_cpx 1/29
(3.44%) was shown when 29 samples were sequenced
from non-HAART and HAART-treated patients from
Burkina Faso166. Another study on prevention of moth-
er-to-child transmission of HIV in 227 seropositive
women found that 221 were infected with HIV-1, four
with HIV-2, and two with mixed HIV infections; all three
children infected with HIV-1 had CRF06_cpx167. The
predominance of CRF02_AG (56.5%) and AGK/K/AK
(26.1%) was shown among patients on ART in Burkina
Faso and Mali168. Several studies have shown the pre-
dominance of CRF02_AG and CRF06_ cpx in Burkina
In Burundi, a study among HIV drug-naive individu-
als showed that subtype C was the most common
strain in Bujumbura172. However, a study by Vidal, et
al.273 found 28.6% to be recombinants. HIV-1 subtype
data in this country is limited due to conflicts, but is
thought to be influenced by prevailing subtypes in
Cameroon probably has the highest number of
HIV-1 subtypes found in any country in the world. HIV-1
group O is endemic to Cameroon and west-central
Africa, accounting for only 1-6% of all cases of HIV-1
infection in Cameroon (about 10,000 to 20,000 peo-
ple)173-175. HIV-1 N is extremely rare at present and
has only been found in Cameroon39. Recently a new
putative group, designated P, was reported to be
found in two Cameroonians6,22. To date only two group
P infections have been reported (Fig. 1). Studies con-
ducted in the major cities of Yaoundé and Douala in
1999 and 2002 evaluated the HIV strains present in
blood donors, patients with tuberculosis, and those
with sexually transmitted infections showed CRF02_
AG was the predominant strain, accounting for 60-
68% of HIV infections, with an additional 26% classi-
fied as URF. Subtypes, D, F2, and G, and CRF, 01,
11, 13, 22, 36, and 37 have been identified in Camer-
oon. Although there are regional differences in strain
prevalence, diversity is high throughout the country
in both urban and rural areas16,43,102,176-183. Moreover,
Brennan, et al. analyzed 676 HIV-infected blood
Raphael W. Lihana, et al.: Update on HIV-1 Diversity in Africa: A Decade in Review
donations collected from 1997 through 2004 at blood
banks in Douala and Yaoundé and found that group M
accounted for 97.3% (n = 658) of infections, whereas
group O was present in 2.2% (n = 15) and HIV-2 in
0.4% (n = 3). Within the group M infections, 14 sub-
types and CRF and URF were identified33,184. Overall,
CRF02_AG accounted for 58.2% of infections, URF
14.8%, and levels of subtypes, A, B, C, D, F2, and G,
and CRF, 01, 06, 09, 11, 13, 22, and 37, varied from
0.2 to 6.1%. Evaluation of HIV strains present in the
donor population over a nine-year period showed no
substantial changes in the proportion of infections
caused by each subtype and CRF, the percentage of
intersubtype recombinants, or the strain composition of
the URF. Multiple infections (dual and triple infection)
and recombination between highly divergent HIV-1
strains have been reported in Cameroon43,174,185-188.
HIV subtype data from Cape Verde is very limited;
however, there has been a case report of a patient from
Cape Verde who was diagnosed with an extremely rare
HIV-2 with severe neurological disease in the USA189.
Central African Republic
The circulation of numerous HIV-1 subtypes have
been reported from the Central African Republic (CAR),
including subtypes A1, A2, A3, A4, B, C, D, CRF01_AE,
F, G, H, CRF06_cpx CRF11_cpx, CRF13_cpx, and
CRF19_cpx102,190,191. Several full-length CRF01_AE
viruses from the CAR have been characterized192.
HIV-1 in Chad has been documented, but little infor-
mation on subtypes exists193,194. Lasky, et al. identified
the genetic subtypes by env HMA of HIV-1 from two
individuals who were infected overseas on deployment
to Chad as subtype B. In the group of HIV-1-infected
individuals that was studied and who were deployed
overseas, 63.4% were infected with non-B strains. In
addition, subtype A, B, and C viruses in this population
were very heterogeneous. Vidal, et al. assessed the
molecular epidemiology of HIV-1 env and gag from
107 samples from patients attending the general hos-
pital in N’Djamena, which revealed that four subtypes
(A, D, G, and F) and three CRF were found to co-circulate,
and a minor proportion of the strains could not be
Several studies from Côte d’Ivoire have reported on
the HIV diversity and prevalence of HIV drug resis-
tance170,195-202. An earlier study in a cohort of 99 sero-
converts in Abidjan revealed that most of the isolates
(82/99, 83%) were CRF02 AG, nine strains were HIV-1
subtype A, one was a recombinant between A (pol)
and F2 (env), four clustered with CRF06_cpx, and three
isolates formed an isolated cluster195. A field evaluation
of a gag-based HMA in comparison with DNA se-
quencing on 108 samples in Abidjan showed that
(82%) were CRF02_AG, 14 (11%) were subtype A, five
(4%) were subtype G, three (2%) were subtype D, one
was CRF01_AE, and one was subtype H. Several
other studies in Côte d’Ivoire have documented the
predominance of CRF02_AG based on drug resistance
Democratic Republic of Congo
Numerous studies have assessed the extent of
gen etic diversity of HIV-1 group M viruses in the DRC
(formerly Zaire). The high number of co-circulating HIV-1
subtypes, high intra-subtype diversity, the high number
of possible recombinant viruses and unclassified
strains are all consistent with the presence of an old
and mature epidemic in the DRC, suggesting that the
region is the epicenter of HIV-1 group M31,203-209. Sev-
eral epidemiological surveys in both rural and urban
areas of the DRC have confirmed that all known HIV-1
subtypes are co-circulating. The proportion of CRF02_
AG among subtype A strains based on env sequences
decreases from west to central Africa, with an absence
of CRF02_AG in the DRC. Kita, et al. found that a high
proportion (16/27; 59.3%) of HIV-1 strains in Likasi
were intersubtype recombinants210. This was higher
than that reported in other regions of DRC (29-44%).
Interestingly, two HIV-1 strains from Likasi (00CD009
and 01CD208) significantly clustered with CRF02_AG
reference strains (with 97.4% bootstrap value). This
was the first report of CRF02_AG in the DRC, suggest-
ing that CRF02_AG is spreading into Central Africa.
CRF02_AG and subtype A represent 70-80% of circu-
lating HIV-1 strains in west and west-central Africa.
Vidal, et al. undertook an epidemiological survey
(247 samples) in three regions of the DRC: Kinshasa
(the capital city), Bwamanda (north), and Mbuyi-Maya
(south). All known subtypes were found to co-circulate,
and for 6% of the samples the subtype could not be
identified. Subtype A is predominant, with prevalences
AIDS Reviews. 2012;14
decreasing from north to south (69% in the north,
53% in the capital city, and 46% in the south). Sub-
type C, D, G, and H prevalences ranged from 7-9%,
whereas subtype F, J, K, and CRF01-AE strains rep-
resented 2-4% of the samples; only one subtype B
strain was identified. The highest prevalence (25%) of
subtype C was in the south, and CRF01-AE was seen
mainly in the north211. Yang, et al. looked at HIV-1
subtype distribution among commercial sex workers
from Kinshasa during the mid-1980s. The env ana-
lysis showed that of 24 samples, 37.5% were subtype
G, 21% subtype A, 12.5% sub-subtype F1, 8%
CRF01_AE, 4% subtype D, and 4% subtype H; 12.5%
Equatorial Guinea borders to the north with Camer-
oon, where different subtypes of group M and O simul-
taneously circulate. Analysis of 119 plasma samples
from HIV-1 seropositive individuals showed that
CRF02_AG accounted for 47%, sub-subtype A3, sub-
type C, subtype D, subtype F (clustered close to F2),
subtype G, CRF06_cpx, CRF09_cpx, CRF11_cpx,
CRF22_cpx, and CRF26_A5U have been reported213-215.
HIV-1 group O has also been identified in Equatorial
Besides HIV-1 group O being documented in Gabon,
HIV-1 group M, subtypes A, B, F, G, H, K, CRF01_AE,
CRF02_AG, and CRF11_cpx have also been reported
in three independent studies216,217. Phylogenetic
analysis of 31 strains from Gabon found two subtype
A, four subtype D, one subtype G, one subtype H,
eight CRF02_AG, six CRF MAL-like, six URF and one
After 16 years of HIV surveillance in western Africa
(1988-2003), it has been shown that the prevalence of
HIV-1 in the Gambia is increasing while HIV-2 is declin-
ing219. The HIV subtype distribution in the Gambia
based on full envelope sequences has shown presence
of a novel CRF (named CRF49_cpx) in addition to the
predominant CRF02_AG, a few HIV-1 subtypes B, C,
and D220. Another study among 20 patients showed
12 infections with HIV-2 and eight dual infections with
HIV-1 and HIV-2221.
Most studies in Ghana have documented CRF02_AG
as the predominant strain222,223. Phylogenetic analysis
of HIV-1 partial pol sequences from 207 Ghanaian
individuals revealed that 66% of infections were
CRF02_AG, whereas 25% were URF. CRF02_AG was
the parental strain in 87% of URF, forming recombinants
with genetic forms circulating in minor proportions:
CRF06_cpx, sub-subtype A3, CRF09_cpx and subtypes
G and D. Two triple recombinants (CRF02_AG/A3/
CRF06_cpx and CRF02_AG/A3/CRF09_cpx) were also
identified223. A study on 25 treatment-naive patients
from Ghana showed a predominance of CRF02_AG
strain (n = 22), but three (13.6%) of these were recom-
binants with HIV-1 subtype K and/or A1. Two patients
had unclassified/complex strains with D/CRF01_AE and
HIV-1 and HIV-2 have been reported to be prevalent
in Guinea224. In Conakry, a study on 99 ART-naive
patients found that 89% were infected with CRF02_AG
Guinea-Bissau and Liberia
In Guinea-Bissau, among 711 females, a high preva-
lence of HIV-1 (9.5%), HIV-2 (1.8%) and dual HIV-1 and
HIV-2 (1.1%) was reported among women attending
sexual health clinics225. In another study to assess the
prevalence of HIV-1 and HIV-2 before, during, and
after the civil war in Guinea-Bissau, it was found that
the prevalence of HIV-1 increased and that of HIV-2
decreased, and the risk of acquiring HIV-1 was more
than fourfold compared to HIV-2226. There is, however,
not much data on HIV diversity in Guinea-Bissau. In
Liberia, possibly due to the long civil war in the past
couple of years, there is no HIV diversity data that we
could include in our review.
Mali and Mauritania
The most prevalent HIV-1 strain in Mali is CRF02_AG;
other strains like CRF01_AE, CRF06_cpx, CRF09_cpx,
other HIV-1 subtypes and several recombinants between
CRF and known subtypes have been reported227-230.
Similar to other studies, most sequence data from Mali
has been generated from routine sequencing of the pol
gene for surveillance of drug resistance. A study to
Raphael W. Lihana, et al.: Update on HIV-1 Diversity in Africa: A Decade in Review
determine the prevalence of drug resistance among
98 ART-naive patients in Bamako showed that CRF02-
AG constituted 75% of cases, followed by the CRF06-
cpx subtype (20%), and intersubtype recombinants
between CRF02-AG, CRF01-AE, and CRF06-cpx
were also described in 5% of cases227. Analysis of
the pol gene among 198 ART-naive patients diag-
nosed with HIV-1 between 2005 and 2006 in Bamako
and Segou showed the prevalence of CRF02_AG in
Bamako (74%; 73/99) and in Segou (70%; 66/94).
Distribution of the other subtypes was: 22 CRF06_cpx
(11%), six A (3%), five CRF09_cpx (3%), two G (1%),
two F2 (1%), one CRF01_AE (0.5%), and one CRF18_
cpx (0.5%), with a greater diversity in Bamako than
in Segou228. Other studies showed similar prevalence
of CRF02_AG strain in Mali229,230. We did not have
sufficient data that described the diversity of HIV in
The CRF02_AG and CRF06_cpx have been reported
to be the most predominant strains in Niger231,232. Gen-
etic characterization of 110 HIV-positive samples in the
V3-V5 envelope region and p24 gag region showed
that the majority of the strains were CRF02_AG
(54.3%) or CRF06_cpx (18.1%) in env and gag; more
than 9% of the samples were recombinants between
CRF02_AG and CRF06_cpx; nine were CRF06_cpx in
env but CRF02 in gag, and for one sample the opposite
Significant data has been published to describe the
diversity of HIV in Nigeria, showing the presence of
CRF02_AG, HIV-1 subtype G, HIV-1 sub-subtype A3,
CRF06_cpx and other recombinants233-241. The differ-
ences in the geographic distribution of subtype A and
G was shown in a study where the overall prevalence
of subtype A and G was 61 and 39%, respectively233.
This study further showed that subtype A was pre-
dominant (70%) in the south (Lagos), subtype G was
predominant (58%) in the north (Kano), and both sub-
types were equally distributed in the northeast (Maidu-
guri ): A (49%) and G (47%)233. An earlier evaluation
of the protease gene among 10 ART-naive HIV-positive
patients in Nigeria showed that 80% of samples were
subtype A and the rest were unclassified divergent
strains234. In Oyo state, analysis of 50 ART-naive patients
showed the predominance of CRF02_AG (57%), subtype
G (26%), and CRF06_cpx (11%)235. Characterization of
transmitted resistance among 14 infants infected by their
HIV-positive mothers in Jos, Plateau State revealed
presence of CRF02_AG (n = 5), HIV-1 subtype G (n =
5), HIV-1 sub-subtype A3 (n = 2), CRF06_cpx (n =
1), and HIV-1 subtype D recombinant (n = 1)236. An-
other study has also shown a prevalence of CRF02_AG
(45%) and HIV-1 subtype G (38%) in an evaluation of
338 patients who were failing first-line therapy in Nige-
ria238. Evaluation of 28 HIV-positive patients in the env
and gag genes showed predominance of CRF02_AG
at 39% and HIV-1 subtype G at 32%239. Recently, the
prevalence of CRF02_AG (45%), subtype G (38%) and
other CRF and URF has been reported among Nigerian
patients failing first-line ART241.
Republic of Congo
Niama, et al. assessed the HIV molecular epidemiology
in the Republic of Congo242. Phylogenetic analysis of
HIV-1 gag p24 sequences showed the predominance
of subtypes A and G strains (36.5 and 30.8%, respec-
tively), followed by subtype D strains (12.5%). Subtype
H represented 3.85% of the strains, and 4.8% of the
samples could not be classified and were identified as
U (unclassified). Bikandou, et al. summarized the fre-
quency of the different subtypes (A, C, D, G, H) for the
env gene in three independent studies243-245. The per-
centage of subtype G in the first three studies was 29.4%
for samples collected in 1988-1992, 24.1 and 21.4% for
samples collected in 1996-1997, and 20.4% for sam-
ples collected in 1998-1999245 using HMA and direct
Studies in Senegal have shown the predominance
of HIV-1 CRF02_AG, other variants, URF170,246-249,
and HIV-2250. Data from studies on both treatment-
naive (n = 104) and experienced (n = 94) patients in
Senegal showed a predominance of CRF02_AG (64%),
with 10 other variants C [14/200 (7%)), B [10/200 (5%)],
CRF06-cpx [5/200 (2.5%)], D [4/200 (2%)], CRF11-cpx
[4/200 (2%)], A3 [3/200 (1.5%)], G [3/200 (1.5%)],
A [2/200 (1%)], A1 [1/200 (0.5%)], and CRF45
[1/200 (0.5%)] and 25 URF249. All HIV-1 group M
subtypes have earlier been documented to be present
in Senegal, with 84.6% of infections with subtype A251.
In the period between 1988 and 2001, the emergence
of sub-subtype A3 was reported among female sex
workers in Dakar, Senegal213,252. A surprising study
AIDS Reviews. 2012;14
among men who have sex with men in Senegal found
that 40% of infections were due to subtype C, CRF02_AG
(24.3%), B (18.6%), G (8.6%), CRF09_cpx (4.3%), and
There is not much data on the diversity of HIV in
Sierra Leone, probably due to the past political insta-
bility. However, there was a case report of a patient
that harbored a CRF02_AG with multi-NRTI-resistance254;
this report probably indicates that the CRF02_AG may
be co-circulating in Sierra Leone. In another case re-
port, the isolation of a new strain of HIV-2 (HIV2-
NWK08F) from a Sierra Leone immigrant was identified
in the USA255.
Togo is also an area where not much work has been
reported on HIV diversity; however, there is a study
that reported a high genetic diversity and prevalence
of drug resistance mutations among ART-naive pa-
tients256. In this study, phylogenetic analysis of HIV-1
pol and env showed that CRF02_AG (48.7 and 51.2%)
and G (12.8 and 16.2%) were predominant, followed
by A3 (6.4 and 6.2%), and CRF06_cpx (3.8 and
12.5%), respectively. One strain was identified as
CRF05 in pol and env. Two divergent subtype A
strains in env were unclassified (U) in pol but clustered
with a previously described complex recombinant
There is paucity of data on HIV subtypes in northern
Africa. This is due to constraints, such as cultural
norms and laws, the population’s lack of knowledge
about HIV/AIDS, and the bureaucratic health systems,
which hinder the development and implementation of
effective surveillance. This leads to possible perennial
underreporting of HIV prevalence and almost no re-
porting on subtype diversity. However, seroprevalence
studies among different HIV risk groups have been
reported in some countries257-259.
In Algeria, the characterization of HIV-1 has shown
high subtype diversity258. Subtype B has been report-
ed as the predominant subtype, particularly in the
northern part of the country, but there is a high diver-
sity of the virus, including CRF02_AG, CRF06_cpx, and
CRF02_AG/CRF06_cpx, which tend to increase in the
southern part that borders sub-Saharan African
countries260. In a recent study among treatment-
experienced and treatment-naive patients, a similar
trend was observed, with subtypes B, CRF06_cpx,
CRF02_AG, G, D, A, F, C, and CRF09_cpx being
The earliest study of HIV-1 subtypes in Djibouti
among French military personnel on missions abroad
showed predominance of subtypes C (48%), B (33%),
A (15%), and CRF01_AE (3%)193. In a study of HIV-1
env isolates from African countries, subtypes A and C
were exclusively reported from Djibouti, though the
number of isolates was small115. It was shown in sub-
sequent studies that the majority of infections were of
subtype C, A, D as well as CRF02_AG recombinants,
consistent with previous findings120,262.
Besides seroprevalence studies257,259, very little is
known about the distribution of HIV subtypes in Egypt.
However, one study has reported HIV-1 subtype B as
predominant in Egypt263.
Libyan Arab Jamahiriya
In an analysis of HIV-1 and hepatitis C viruses among
children in Al-Fateh hospital in Benghazi, Libya, HIV-1
CRF02_AG was reported to have been circulating
among the Benghazi population, leading to vertical
transmission from mothers to their infants264. The find-
ings were contrary to the belief that these children were
infected by foreign health workers. The CRF02_AG
subtype detected among the children showed a single
CRF02_AG lineage with links to West African sequences.
This emphasized the importance of surveillance and
ruled out introduction of the infections by foreign health
HIV-1 subtype surveillance studies have reported
subtype B in Morocco266,267. In a study of HIV-1-in-
fected treatment-naive individuals in Casablanca, it
was established that subtype B predominated (74.6%),
Raphael W. Lihana, et al.: Update on HIV-1 Diversity in Africa: A Decade in Review
followed by CRF02_AG (15.5%), CRF01_AE (4.2%), C
(1.4%), G (2.8%), and F2 (1.4%)268. Among HIV-infected
treatment-naive patients from Rabat, it was established
that HIV-1 subtype B predominated (74%), followed by
CRF02_AG (15%), A1 (6%), C (2%), F1 (1%), CRF09_cpx
(1%), and CRF25_cpx (1%)269.
In Somalia, though no visible studies on HIV sub-
types have been done, the limited available data has
documented subtype A, C and their recombinants as
the most common116,117. In a study among HIV pa-
tients on the border between Kenya and Somalia, it
was reported that subtype A was common270. A study
on genetic diversity of the HIV env from isolates of
African origin reported presence of subtype C in
In Sudan, subtype D is the most common119. How-
ever, its introduction here might have been from two
fronts; from Central Africa and also from Uganda or
Kenya where this subtype is prevalent. Here the two
global subtype D lineages, one circulating in East
Africa and another in west-central Africa, are be-
lieved to mix119. Also found in Sudan is subtype C,
which probably originated in Ethiopia, Sudan’s neigh-
bor to the east. However, little is known about HIV-1
diversity in the greater part of this country due to civil
war. Like other Arab countries, northern Sudan is Mus-
lim and therefore abhors reporting on HIV. The south
has limited data, which has generally been obtained
from refugee camps in Kenya137. Southern Sudan
became independent on 9th July 2011 after more than
25 years of civil war with northern Sudan. So far it is
a country with the poorest health infrastructure. With
this independence, Southern Sudan joined the East
African community, United Nations, and the African
Union. It is hoped that there will be accelerated HIV
research and data dissemination for the majority who
may have missed out on the expanded treatment ac-
cess in Africa.
In Tunisia, the first HIV-1 subtype surveillance report
showed the presence of subtype B and CRF02_AG271.
Similarly, Karray-Hakim, et al. reported the same
Table 1 and 2, summarize HIV-1 subtype distribution
from selected peer-reviewed studies that have docu-
mented HIV subtype diversity in eastern, western,
southern and northern Africa.
In this review, we examined the trend of HIV-1 sub-
type diversity in 51 African countries over the last dec-
ade. This is also the period in which new technologies
in HIV research have been rolled out in middle- and
low-income countries, and collaborations with devel-
oped countries increased to cope with the increased
access to prevention strategies, treatment, and vac-
cine trials. The increased use of automated sequenc-
ing technologies has made it possible for many coun-
tries to monitor their HIV spread and prognosis. This is
critical for developing country strategies to contain the
epidemic. However, the sequence information was not
available from several countries (Comoros, Mauritius,
and Sao Tome and Principe). Overall, the regional dis-
tributions of individual subtypes and recombinants are
broadly stable, although URF/CRF may play an in-
creasing role in the HIV pandemic.
Nicaise Ndembi and Deogratius Ssemwanga were
supported by EDCTP Senior Fellowship award
TA.2007.40200.011. Additional funding was by Abbott
Research agreement # 7000-9611-1- 2010 to Nicaise
Supplementary data is available at AIDS Reviews
journal online (http://www.aidsreviews.com). This data
is provided by the author and published online to
benefit the reader. The contents of all supplementary
data are the sole responsibility of the authors.
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AIDS Rev. 2012;14:83-100 (Supplementary Data) Raphael W. Lihana, et al.: Update on HIV-1 Diversity in Africa: A Decade in Review (Supplementary Data)
Table 1. Selected studies that have documented HIV subtype diversity in eastern Africa
Population studied Site Gene sequenced Subtypes determined (%)
Kageha, et al. 20112008General patientsCentral Kenya Partial env 69.811.5 18.7
Hue, et al. 20112009Newly infected patientsCoastal Kenya Partial pol74 10718
Lihana, et al.20102005 Patients on ARTNairobiPartial pol, env42.9* 7.150
Khamadi, et al. 20092005HIV patients Coastal KenyaPartial env 86581
Khoja, et al.2008 2007General patients NairobiPartial gag56.510.118.8 2.911.6
Kiptoo, et al.20082006 ANC mothersNorth Rift, Kenya Partial pol74.3* 10.3 12.8 2.6
Khamadi, et al.20082005 General patients Northern KenyaPartial, pol, env57 2797
Land, et al. 2008 1996Commercial sex workers NairobiPartial env 7069 15
Steain, et al.2005 2004 ANC MothersWestern KenyaPartial gag, env4060†
Khamadi, et al.20052005 General patientsNorthern KenyaPartial, env 5039 11
Songok, et al.20032000 Antenatal clinic attendeesWestern KenyaPartial env63.33.3 6.7 3.3 23.3
Dowling, et al.20022000 Southern Kenya562.4 2.439
Mosha, et al.2011 2004-2005HIV drug-naive youths Dar es Salaam, Tanzaniapol 27 234 46
Nofemela, et al.20112009HIV patients Mbeya, TanzaniaSingle genome amplification18.1 414.5 36.4
Nyombi, et al. 2008 2005Drug-naïve ANC attendees Kagera, and Kilimanjaropol34 261921
Somi, et al.20082006 Dar es Salaam, Tanzania 33.333.3 10.323.1
Nyombi, et al. 2008 2005ANC mothers Kagera, TanzaniaPartial pol, env27.829.6 16.725.9
Nyombi, et al. 20081985-2005 HIV patients Northern TanzaniaPartial env2931 27 13
Herbinger, et al. 2006 2000 ANC, blood donors MHA8.5 40.8 3.8 46.9
Arroyo, et al.2005 2003 General populationMbeya, Tanzania18433 36
Arroyo, et al.20042001 Blood donors Mbeya, TanzaniaFull length15555 25
Kiwelu, et al.20032002 Bar and hotel workersMoshi, TanzaniaPartial gag, env 48208 25
Ndembi, et al 20112009-2010 Drug-naive VCT attendeesKampala UgandaPartial pol51.4 2.932.9 12.9
Kiwanuka, et al.2010 1997-2002General cohortRakai, Uganda Near full length 15.759.624.7
Lyagoba, et al.20102003-2004Cohort DART UgandaPartial pol 663 301
Eshleman, et al.20091993-2003Drug-naive adults Rakai, UgandaPartial pol, env251 63.59.6
Ndembi, et al20082007Drug-naive HIV patients Entebbe, UgandaPartial pol 50*2 399
Herbeck, et al.20071989-2000 Antenatal cohortUgandaPartial env 455419
Yirrell, et al. 20041990General cohortUgandaPartial env, gag254926
Eshleman, et al.20042000 Antenatal cohortHIVNET, UgandaPartial pol52.7 2.235.1 10
Hu, et al.2000 1997General patients Uganda49 2.548
Rayfield, et al. 19981997 Cross sectionalUganda Partial env57.40.542.1
Vidal, et al. 20072002Drug-naiveBujumbura, BurundiPartial pol, env0.868.91.7 28.6
Koch, et al.20011998 HIV-positive drug-naiveBujumbura, Burundi Partial pol, env11.188.9
Servais, et al.2004 2000ANC Kigali, RwandaPartial pol 79 144.7 2.3
Kassu, et al. 20072003Treatment-naive Northwest EthiopiaPartial gag, pol, env1.197.8 1.1
Hussein, et al. 20001997Commercial sex workersAddis Ababa HMA98.5 1.5
Hierholzer, et al.20021998-1999HIV patients and blood donorsKhartoum, SudanPartial env 6.73050 3.310
ART: antiretroviral therapy; ANC: antenatal clinic; HMA: heteroduplex mobility assay; MHA: multiregional hybridization assay.
*Total A1 and A2. †Including dual infections.
Update on HIV-1 Diversity in Africa: A Decade in Review
Raphael W. Lihana1, Deogratius Ssemwanga2, Alash’le Abimiku3,4 and Nicaise Ndembi3
1Center for Virus Research, Kenya Medical Research Institute (KEMRI), Nairobi, Kenya; 2MRC/UVRI Uganda Research Unit on AIDS, Entebbe, Uganda; 3Institute of Human Virology, University of Maryland School of Medicine, Baltimore, USA; 4Institute of Human Virology-Nigeria, Abuja, Nigeria
AIDS Reviews. 2012;14 Raphael W. Lihana, et al.: Update on HIV-1 Diversity in Africa: A Decade in Review
Table 2 A. Selected studies that have documented HIV subtype diversity in southern Africa
Site Gene sequenced Subtypes %Circulating recombinant forms (CRF) %Others %
ABCDFGHJ 0208 09 13 37 URFU
Bartolo, et al.2005 2001Patients Luanda/Kabinda, Angola Partial env, gag42 15224 106 172
Bartolo, et al. 20091997, 2001Patients AngolaPartial env, gag, pol80.8 3.86.7 7.71
Castelbranco, et al.20102008-2009 Pregnant womenLuanda, Angola Partial env 14.2 17.18.5 22.88.5 5.78.5 2.9 220.127.116.11
Bussmann, et al.2005 2001 PatientsBotswana partial pol 100
Petch, et al. 20051996-2001Patients MalawiPartial pol 100
Bellocchi, et al.20052003Patients MozambiquePartial poll 98.3 1.7
Lahuerta, et al.20081999-2004Patients Southern MozambiquePartial LTR, env, pol 100
Maldonado, et al.2009 2006Patients Maputo, MozambiquePartial pol 66.7 33.3
Bartolo, et al. 20092002-2004 PatientsMaputo, Mozambique Partial pol 80.8 3.8 6.77.7 1.0
Gordon, et al.2003 2001-2002Patients KwaZulu-Natal, South AfricaPartial env, pol100
Jacobs, et al.2008 2002-2004 PatientsCape Town, South AfricaPartial pol3.6 950.7 0.7
Huang, et al. 20092006 Patients Free State, South AfricaPartial pol100
Marconi, et al.20082005-2006 PatientsKwaZulu Natal, South Africa Partial pol0.9 0.997.4 0.9
Jacobs, et al. 20092000-2001Patients Cape Town, South Africa Partial env3.1 6.9 89.10.3 0.30.3 0.3
Fish, et al.20102009Patients South AfricaPartial pol97.3 2.7
Papathanasopoulos, et al.20102004-2007PatientsSouth AfricaPartial pol973
Romani, et al.20092002-2004 PatientsSouth AfricaPartial vpr937
Scriba, et al. 20011998 Patients South AfricaPartial vif, vpr, vpu100
Deho, et al. 2008 2002-2003PatientsSwaziland Partial pol100
Hamers, et al.20102007-2008 PatientsLusaka, ZambiaPartial pol0.5 98 0.20.4 0.50.4
Handema, et al.2003 2000 PatientsZambiaPartial env, gag, pol 100
Kantor, et al. 2002 2001Patients Zimbabwe Partial pol100
Kassaye, et al. 20072000-2001 Pregnant womenZimbabwePartial pol100
Dalai, et al.2009 1991-2006Antenatal womenZimbabwePartial pol100
AIDS Reviews. 2012;14Raphael W. Lihana, et al.: Update on HIV-1 Diversity in Africa: A Decade in Review (Supplementary Data) Download full-text
Table 2 B. Selected studies that have documented HIV subtype diversity in western Africa
Subtypes % Circulating recombinant forms (CRF) %Others %
ABCDFG 010205 06 09 11 1345U URF
Marjorie Monleau, et al.2011 2008PatientsCotonou, BeninPartial pol 3.1 6.365.6 3.121.9
Vergne, et al.20062003 PatientsBurkina FasoPartial pol 3.11 48.547.4
Nadembega, et al. 20062003-2004PatientsOuagadougou Burkina Faso Partial pol6.9 3.4 31 55.2 3.4
Simpore, et al. 20072004-2006Mother- infant pairs Burkina FasoPartial pol100
Tebit, et al. 20082004-2006 Patients Ouagadougou, Burkina FasoPartial pol1.3 1.340 48 1.38
Tebit, et al. 2009 2004-2006Patients Ouagadougou, Burkina FasoPartial pol3.8 37.544.2 1.912.5
Adje-Toure, et al. 2003 1998-2000 PatientsAbidjan, Cote d’IvoirePartial pol 100
Chaix, et al.2005 2000-2003ChildrenAbidjan, Cote d’Ivoire.Partial pol94.7 2.6 2.6
Toni, et al. 20072002-2006 Patients Abidjan, Cote d’Ivoire Partial pol7 8826
Delgado, et al.2008 2002-2004 PatientsGhana Partial pol 2.40.5 1.465.73.91 25.1
Charpentier, et al. 20112009PatientsConakry, GuineaPartial pol311 8941
Derache, et al. 20072005 Patients Bamako, MaliPartial pol75 205
Haidara, et al.2010 2007-2008Patients MaliPartial pol2 5.9432 71.3 7.9211
Imamichi, et al.20092003-2005Patients Mali Partial pol13 69.6 8.7 8.7
Mamadou, et al.2002 1997-2000PatientsNigerPartial env, gag 54.318.1 27.6
Ajoge, et al.2011 2007Pregnant womenNorth-central Nigeria Partial env, gag 3.63.6 32.139.321.4
Ajoge, et al. 20112007 Pregnant womenNorth-central Nigeria Partial pol 3.6 3.639.950 3.6
Chaplin, et al.20112004-2009Patients NigeriaPartial pol3.6 37.9 45 4.49.2
Hawkins, et al.2009 2005Patients NigeriaPartial pol 3.637.944.9 4.4 9.2
Ojesina, et al. 20072003-2004 Mother-infant pairsNigeria Partial pol 15.430.8 38.5 7.77.7
Peeters, et al.2000 1996 FSW, patients,
Nigeria 18.104.22.168 37.5
Vicente, et al. 20011996 PatientsNigeria Partial pol8020
Diop-Ndiaye, et al.20101998-2001Patients SenegalPartial pol3572 1.5642.52 0.512.5
Yaotse, et al.2009 2006-2007Patients Lome, TogoPartial pol6.4 12.848.7 22.214.171.124 24.4
FSW: female sex workers.