What Is the Most Aggressive Strain of HIV?

Researchers Identify a Variant in Cuba Known to Advance to AIDS in 3 Years

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While there is no set course in the way that HIV progresses from one person to the next, there are strains (variants) that are associated with rapid progression. These variants result from genetic mutations that typically develop initially within a specific region, oftentimes spreading beyond that region to become a predominant—if not the predominant—strain.

A study published in the medical journal EBioMedicine has reported that one such variant has been isolated in Cuba, which is known develop into AIDS within three years of initial infection—making it arguably the most aggressive strain identified to date.

According to the report, researchers from University of Leuven in Belgium have positively identified the strain as CRF19, a recombinant variant of HIV comprised of three different subtypes, A, D, and G.

Wherein HIV generally progresses to AIDS within five to ten years without therapy, CRF19 appears to progress so rapidly as to place an individual at greater risk of illness and death before treatment is even started.

Study Findings

Seventy-two patients were identified by researchers as being rapid progressors (RP), exhibiting either a precipitous drop in their CD4 count to below 200 cells/mL or exhibiting an AIDS-defining condition (or both). The median age of the patients was 34, while the average CD4 count at the time of diagnosis was 276 cells/mL. By contrast, a matched cohort of HIV patients without the CRF19 variant had an average CD4 count of between 522 and 577 at the time of diagnosis.

Moreover, rapid progressors had HIV viral loads one- to three-fold higher than non-rapid-progressors.

As a result, patients with confirmed CRF19 had median time between seroconversion and AIDS of only 1.4 years compared to 9.8 years for their non-CRF19 counterparts.

Explanations for Rapid Progression

The researchers were able to exclude several co-factors that may have explained the rapid progression to AIDS.

In terms of demographics, there were surprisingly more heterosexual rapid progressors than non-rapid-progressors (49% vs28%). Additionally, no differences in HIV acquisition by sexual activity (anal, vaginal) were noted.

Based on their findings, the investigators believe that rapid changes in the CRF19 variant may explain the phenomenon.

Generally speaking, there are two types of co-receptors on the surface of white blood cells that allow HIV entry into a cell: CCR5 and CXCR4. CCR5 is the co-receptor that HIV generally uses in early stage infection, while CXCR4 is the one used in later stage infection.

With the CRF19 variants, the virus switches from using CCR5 to CXCR4 far more quickly than other strains of HIV.  In doing so, progression of the disease is also speeded up, leading to the premature development of AIDS.

The findings will likely demand an increase in HIV surveillance in Cuba, which currently has a prevalence rate of 0.2% (compared to 0.9% in the U.S.) and  just over six thousand confirmed cases.

What is concerning is that, with the average time from infection to diagnosis ranging from 37 months to 55 months, public health authorities may not be able to identify individuals with the CRF19 variant quickly enough to stave the rapid spread of the virus.

While public health alarms have only now been raised, the variant was isolated in Cuba as far back as 2005 and may have likely originated in Central Africa, where a spattering of cases had been reported in Angola, Burkino Faso, Cameroon, and Togo.

Sources:

Khouri, V.; Khouri, R.; Alemán, Y.; et al. "CRF19_cpx is an Evolutionary fit HIV-1 Variant Strongly Associated With Rapid Progression to AIDS in Cuba." EBioMedicine. January 28, 2015; doi:10.1016/j.ebiom.2015.01.015.

Casado, G.; Thomson, M.; Sierra, M.; et al. "Identification of a Novel HIV-1 Circulating ADG Intersubtype Recombinant Form (CRF19_cpx) in Cuba." Journal of Acquired Immune Deficiency Syndromes (JAMA). December 15, 2005; 40(5):532-537.

Garrido, C.; Zahonero, N.; Fernandés, D.; et al. "Subtype variability, virological response and drug resistance assessed on dried blood spots collected from HIV patients on antiretroviral therapy in Angola." Journal of Antimicrobial Chemotherapy. January 24, 2008; 61(3):694-498.

Tebit, D.; Ganame, J.; Sathiandee, K.; et al. "Diversity of HIV in Rural Burkina Faso." JAMA. October 1, 2006; 43(2):144-152.

Machuca, A.; Tang, S.; Shixing, D.; et al. "Increased Genetic Diversity and Intersubtype Recombinants of HIV-1 in Blood Donors From Urban Cameroon." JAMA. July1, 2007; 45(3):361-363.

Yaotsè, D.; Nicole, V; Fabien Roche, N.; et al. "Genetic characterization of HIV-1 strains in Togo reveals a high genetic complexity and genotypic drug-resistance mutations in ARV naive patients." Infections, Genetics and Evolution. July 2009; 9(4):646-652.

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