Rapid Spread and Genetic Diversification of HIV Type 1 Subtype C in a Rural Area of Southern Mozambique

Abstract

In this study, we analyzed the human immunodeficiency type 1 (HIV-1) viruses circulating between 1999 and 2004 in antiretroviral-naive women from a rural area of southern Mozambique. Nucleotide sequencing of the HIV-1 long terminal repeat (LTR) U3, envelope (env) C2V3C3, and protease (pr) genomic regions was performed from women sera samples collected in 1999 and 2004. Phylogenetic analysis revealed that all amplified sequences belonged to subtype C. Although env sequences were predominantly CCR5-tropic (R5), CXCR4-tropic (X4) variants were also identified (13%). Both 1999 and 2004 sequences were widely dispersed across multiple clusters and were related to different reference sequences from neighboring countries. Sequences from 2004 showed significantly more nucleotide genetic diversity than sequences from 1999. Importantly, genetic diversification was also observed at the pr and env amino acid level, suggesting that positive selection forces were implicated in the viral diversification. These results indicate the rapid spread and diversification of subtype C virus in Mozambique where HIV-1 prevalence in the Manhiça antenatal clinic reached 23% in 2004.

HIV-1 Genetic Diversity and Transmitted Drug Resistance in Health Care Settings in Maputo, Mozambique

“…Maputo is the capital city of Mozambique and has the third highest HIV-1 prevalence rates in the country (23%, 18%-29%). 3 Unlike other studies investigating transmitted HIV drug resistance in Mozambique [27][28][29] and elsewhere in Africa, [21][22][23][24][25] the patients enrolled in our study could afford to pay for CD4 cell counts, for plasma viral load, and, eventually, for antiretroviral drugs. Moreover, they were, in general, severely immune compromised.…”

“…[27][28][29] Phylogenetic analysis revealed that the C viruses circulating in Maputo are highly divergent and probably have been introduced into this city from diverse geographic regions. These results are consistent with previous findings demonstrating the existence of many subtype C sublineages in southern Africa.…”

“…51 Unlike all other studies performed in Mozambique, we could detect in an important proportion (19.2%) of patients all other major African subtypes and untypable variants, either alone (subtype G) or in recombinant forms with subtype C (A, D, F, and U). [27][28][29] Notably, phylogenetic analysis has shown that a cluster of 7 patients was infected with a highly homologous strain that is closely related to CRF37_cpx, a recombinant originally found in Cameroon, 52 and to subsubtype A3, originally found in Senegal. 53 This type of clustering usually results from a founder effect and strongly suggests that these strains were recently introduced into Maputo.…”

“…54 In summary, our results indicate that the HIV-1 epidemic in Maputo is evolving rapidly to a greater epidemiological and virological complexity when compared to the rest of the country where subtype C prevails. [27][28][29] It will be important to monitor the potential impact of the multiple HIV-1 genetic forms in ART, especially now that it is being universally expanded, in diagnosis and in vaccination.…”

HIV-1 Diversity and Its Implications in Diagnosis, Transmission, Disease Progression, and Antiretroviral Therapy

“…Subtype C is the overwhelming prevailing strain in Southern Africa (Bartolo et al, 2009b;Gonzalez et al, 2010;Lahuerta et al, 2008;Papathanasopoulos et al, 2010), in India and neighbor countries (Neogi et al, 2009a;Neogi et al, 2009b) and in the southern region of Brazil (Monteiro-Cunha et al, 2011). Subtype D strains are found mainly in East Africa, and to a lesser extent in West Africa (Conroy et al, 2010;Harris et al, 2002;Laukkanen et al, 2000;Songok et al, 2004).…”