HIV: Increase of recombinant forms over time, in the different regions, is an additional challenge to develop vaccines, says Dr. Mariza Morgado

From a regional distribution standpoint, Central Africa, birthplace of the epidemic, presented the greatest diversity of viral subtypes, unique and circulating recombinants

A study published in The Lancet Infectious Diseases, in November 30, the eve of World AIDS Day, showed the extraordinary global genetic diversity of the HIV and highlighted the great challenge of developing a vaccine to combat its global spread.

Considered one of the most comprehensive recent studies of HIV around the world, Hemelaar et al. entitled Global and regional epidemiology of HIV-1, molecular, 1990 a systematic review, global survey, and trend analysis is based on the systematic review of molecular epidemiology studies of the virus in different countries and regions of the world, published in the literature and accessed by multiple sources, in addition to the access to new information, unpublished data, based on a questionnaire sent to different leaders of researches in this area and members of the network for HIV isolation and characterization of the World Health Organization/United Nations joint programme On HIV/AIDS (WHO-UNAIDS Network for HIV Isolation and Characterisation), who were listed as co-authors of the article.

Dr. Mariza Morgado, a researcher at the AIDS and Molecular Immunology Laboratory of the Oswaldo Cruz Institute, explains that based on these informations about the HIV-1 subtypes distribution, the Unique Recombinant Forms (URFs) and the Circulating Recombinant Forms (CRFs), adjusted for the number of people living with HIV-1 in each region per year, it was possible to estimate the frequency of these subtypes and recombinants per region, distributed in four periods: 1990-1999; 2000-2004;2005-2009 and 2010-2015. From the comparative analysis between these periods we performed a trend analysis, which demonstrated that the distribution of subtypes and recombinant forms changed over time in countries, regions and globally, she notes.

The publication also points out that, in the period between 2010 and 2015, subtype C accounted for 46.6% of HIV-1 infections worldwide, while subtype B accounted for 12.1% and subtype A was equivalent to 10.3%. For this same period, an overall expansion of subtype B, URFs CRF01_AE and other CRFs was identified, while other subtypes remained stable (A and D), or decreased (C, G and CRF02_AG), when compared to periods prior to the global level. Regional variations have also been identified, showing that the diversity of HIV-1 is complex and is continually evolving, says Dr. Morgado. Still according to her, it calls attention the increase of recombinant forms through time, in different parts of the world, what represents an additional challenge for vaccine development.

She says that from a regional distribution standpoint, as the birthplace of the epidemic, Central Africa presented the greatest diversity of viral subtypes, URFs and CRFs, in the four assessed periods, whereas in the southern region, subtype C is predominant. A differentiated distribution of viral subtypes was also observed in countries from East to West Africa, with a predominance of CRF02_AG in West Africa and subtype A in East Africa. On the other hand, North America and Europe (Central and West) have predominance of subtype B, while Eastern Europe and Central Asia have a prevalence of subtype A, with an important increase of recombinant forms throughout the four assessed periods, she details.

The article also reveals that in Latin America, the predominant form is subtype B, with an increase of subtype C and of recombinant forms since the year 2000. Attention is drawn to the presence of infections with the F1, sub-subtype, whose frequency, although decreasing over time (7.8% 1990-1999 vs. 4.4% 2010-2015), is also seen in similar proportions in Central Africa, says the researcher while pointing out that in the global epidemic, sub-subtype F1, along with H, J and K corresponds to 0.9% of the overall infections. In South Asia, subtype C predominates in India, whereas in Southeast Asia, the predominant form is CRF01_AE, with subtype B increasing its frequency in the period 2010-2015.

Another point discussed in the paper is the distribution dynamics of subtypes and recombinant forms throughout time in the different regions and globally, which is multifactorial, both reflecting local epidemiological differences, new infections frequency, most affected groups, access to treatment and pathogenesis associated to infections by the different subtypes and recombinant forms. Also, socioeconomic factors, travels, migrations, urbanization, founding effect, transmission networks, among several factors that may favor these changes in the dynamics of the epidemic over time affects the distribution. The researcher acknowledges that these data are of great relevance to understand the global and regional HIV-1 epidemic and, reinforces the need to maintain a continuous surveillance system for viral diversity associated with the socio-demographic, clinical and behavioral characteristics of the populations at highest risk.

The scientist is emphatic in stating that the occurrence of this large variety of HIV-1 subtypes and recombinant forms continually evolving and varying their distribution over time in different regions of the world presents a major challenge. This challenge is not only for the development of vaccines, diagnostic and therapeutic methods that depend essentially on virus-specific molecular targets: Mutations in these regions can have an impact on the efficacy of vaccines and drugs, as well as on the sensitivity and specificity of diagnostic and viral quantification methods, reinforcing the importance of continued monitoring of circulating HIV-1 variants at local, regional and global levels, she concludes.

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