Molecular Diversity of the Human Immunodeficiency Virus Type 1 in Metropolitan Cities in Central Africa: An Update of Data

The Human Immunodeficiency Virus (HIV) has a diversity that is equal to the complexity of its management. The group M (Major) is the dominant group in Sub-Saharan Africa and its distribution is very heterogeneous; the diversity of the virus is more heterogeneous in this region than elsewhere in the world which follows a complex and specific algorithm because of geographical positions and countries. This distribution is very dynamic, evolving and unpredictable. This review aimed to expose the specifics of the HIV Type 1 epidemic in Central Africa, in terms of the different molecular variants of HIV published for the region compared to the geographic location. Both Type 1 and Type 2 of HIV are prevalent in sub-Saharan Africa due to distinct geographical contexts. HIV-2 is mainly documented in West and Central Africa, particularly in Cameroon, Guinea-Bissau, Gambia, Senegal, Ivory Coast and Burkina-Faso however HIV-1 infection is widely distributed across the continent. The HIV-1 epidemic in Sub-Saharan Africa is dominated by the Group M. The different subtypes respect a certain geographical distribution across the continent. West Africa is dominated by subtype A, most commonly encountered; followed by the subtypes D, F, G, C, B, J, K and several Circulating Recombinant Forms that are not represented in all Central African countries.


Introduction
The Human Immunodeficiency Virus (HIV) has a diversity that is equal to the complexity of its management [1]. The classification of recombinant types, groups, sub-types, sub-sub-types and Recombinant Forms (CRFs-Circulating Recombinant Forms and URFs-Unkown Recombinant Forms) or mutant forms has led to a better understanding of the virus, the distribution and evolution of the epidemic [2] [3]. It has also helped to better guide the care of patients infected with HIV [4]. The group M (Major) is the dominant group in Sub-Saharan Africa and its distribution is very heterogeneous; the diversity of the virus is more heterogeneous in this region than elsewhere in the world [2] (Figure 1). It follows a complex and specific algorithm because of geographical positions and countries [1] [3] [5] [6]. This distribution is very dynamic, evolving and unpredictable.
According Sahara, where four out of every five infected adolescents aged between 15 and 19 years are girls [7]. Sub-Saharan Africa has been carrying the heaviest burden of the HIV epidemic for a long time; nearly 70% of the global epidemic is concentrated there [7] [8]. For the year 2018, about 6200 young women aged from 15 to 24 years were infected with HIV each week south of the Sahara [6] [7]. Central Africa is a region where the prevalence that is more or less stable and low for HIV-1 infection compared to other regions south of the Sahara; in 2015, the average prevalence was 2.6% for women and 1.8% for men [9] [10] [11] [12]. This region includes the following countries: Angola, Cameroon, Central African Republic (CAR), Chad, Democratic Republic of Congo (DRC), Equatorial Guinea, Gabon, Republic of Congo (RC), and Sao Tome and Principe ( Figure 2).
The purpose of this literature review was to expose the specifics of the HIV Type 1 epidemic in Central Africa, in terms of the different molecular variants of HIV published for the region compared to the geographic location. HIV-1 is divided into 4 groups: M (Major), O (Outlier), N (Non-major and non-outlier) and P [1] [2]. Group M is responsible for over 3/4 of the global epidemic of HIV/AIDS [2]. The major group (M), which is the majority, is subdivided into distinct sub-types called "pure" (A, B, C, D, F, G, H, J and K) and 48 Recombinant Circular Forms (CRFs). There are currently 98 recombinant subtypes (CRF and URFs) resulting from recombination phenomena between 2 or more different subtype viruses co-infecting the same individual [1]. The viral subtype B is the dominant subtype found in Europe, the Americas, Asia and Australia [3]. Subtype C is predominantly responsible for the global HIV/AIDS epidemic [13]. The other groups of HIV-1 (N, O, P), which represent only a minority of circulating strains, are more common in Cameroon and its neighboring countries in Central Africa [1] [2] [3].

Classification of HIV Isolates
HIV-2 is divided into 8 groups named A to H, with groups A and B being the most represented [14]. HIV-2 infection is much rarer and is confined mainly to West Africa [13] [15]. In addition, the progression of the disease is much slower than for HIV-1 and this virus is transmitted with difficulty [16]. In general, because of its lower infectivity and slow progression, viral load in individuals infected with HIV-2 is significantly lower than in those infected with HIV-1 [14] [15] [16] [17]. In addition, the arrangement of coding regions on the genome is not identical for both types of virus ( Figure 3).

HIV Diversity in Sub-Saharan Africa
Both Type 1 and Type 2 of HIV are prevalent in sub-Saharan Africa due to distinct geographical contexts. HIV-2 is mainly documented in West and Central Africa, particularly in Cameroon, Guinea-Bissau, Gambia, Senegal, Ivory Coast and Burkina-Faso however HIV-1 infection is widely distributed across the continent [13] [15]. Group O infection of HIV-1 is particularly described in Cameroon, Chad, Gabon, Equatorial Guinea and Gabon, but also sporadically in other West African countries in the case of Niger, Nigeria, Senegal and Togo [18]. Infection with the N and P group has been documented to date in some Cameroonian patients [19] [20] [21].
The HIV epidemic in Sub-Saharan Africa is dominated by Group M of the Type 1 in general [22]. The different subtypes respect a certain geographical distribution across the continent, particularly in several regions of sub-Saharan Africa: West Africa is dominated by subtype A, East and South Africa are dominated by subtype C, while Central Africa is dominated by strains A, C, D, F, H, J, CRF01-AE and CRF02-AG [6] [23].

HIV Diversity in Central Africa
A literature search as conducted to identify the different strains of HIV Type 1 in  Figure   6). Another study has been carried out at the Lucrecia Paim Maternity Clinic always in Luanda (Table 1)  (3%) and CRF13_cpx (3%) ( Figure 5 & Figure 6) [41].
In 2015, a study was conducted in Pointe Noire, Republic of Congo, to prevent mother-to-child transmission of HIV-1 and to determine the prevalence of different subtypes and transmitted mutations related to drug resistance (Table  1) [46]. Ninety-five (95) plasma samples were initially collected and 68/95 (71.6%) samples were sequenced successfully. In particular, 35% of the sequences were classified as URFs, 11.7% as the sub-type A, 10.3% as CRF45_cpx, 8.8% as the sub-type G, 7.4% as CRF37_cpx, 5.9% as CRF18_cpx, 4.4% as the sub-type D, 2.9% as the sub-type B, 2.9% as the sub-type H, 2.9% as CRF02_AG, while the subtypes C and J, subtypes F1 and F2, and CRF25_cpx were found only in one sample each ( Figure 5 & Figure 6). Major mutations of NRTIs, NNRTIs and PIs were detected in 8.8% viral sequences. NNRTIs mutations were found in 3 patients (4.4%).
In Chad, the type of HIV that has been circulating since the onset of HIV infection is mainly HIV-1 (Table 1) [47]. Among groups circulating throughout the country, only the M group is found to date with mainly 4 sub-types (A, D, F and G) which co-circulate with 3 major recombinant forms (CRF01_AE, CRF02_ AG and CRF11_Cpx) ( Figure 5 & Figure 6) [47]. In 2017, in a study published by Adawaye C et al. (Table 1), conducted between 2011 and 2012 at N'Djamena National General Referral Hospital in 116 PVV on ARV, the following sub-types were identified after sequencing protease-RT 43: J (30%), CRF02_AG (30%), G (16%), A (9%), D (9%) and F (5%) ( Figure 5 & Figure 6) [48]. A few rare cases of Group O have been presented, but Group N as well as Type 2 HIV have not yet been seen in Chad [49].
Data on the diversity of HIV-1 group M for Sao Tome and Principe were not   available. This is the same observation made by Raphael WL and al. in 2012, in her bibliographic review on the genetic diversity of HIV-1 in Africa [49]. This situation may play a growing role in the HIV/AIDS epidemic.

Conclusion
The increased use of automated sequencing technology has made it possible to monitor the spread of HIV and its prognosis for several countries. Circulating

Recombinant Form CRF02_AG and subtypes A and G are present in all Central
African countries and are also the most commonly encountered; followed by the D, F, G, C, B, J, K subtypes and several Circulating Recombinant Forms that are not represented in all Central African countries.