What Is the Most Aggressive Strain of HIV?

Researchers identify a strain able to advance to AIDS in 3 years

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.

In a study published in 2015, one such variant was reported to have been isolated in Cuba, which is known to develop into AIDS within three years of initial infection—making it arguably the most aggressive strain identified to date.

According to this report, the research group 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.

HIV blood test tube
David Silverman / Getty Images

Study Findings

Fifty-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 33, 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 (chronic AIDS) and 577 (non-AIDS) 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% vs 29%). Additionally, no differences in HIV acquisition by sexual activity were noted for the rapid progression group (50% anal vs 50% vaginal).

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, the 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 0.29% (compared to 0.36 in the U.S.).

Public health authorities are concerned they 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 Africa.

4 Sources
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  1. Kouri V, Khouri R, Alemán‬ Y, et al. CRF19_cpx is an evolutionary fit HIV-1 variant strongly associated with rapid progression to AIDS in CubaEBioMedicine. 2015;2(3):244-254. doi:10.1016/j.ebiom.2015.01.015

  2. UNAIDS. Cuba, 2020.

  3. UNAIDS. United States of America, 2020.

  4. Casado G, Thomson MM, Sierra M, Nájera R. Identification of a novel HIV-1 circulating ADG intersubtype recombinant form (CRF19_cpx) in CubaJAIDS Journal of Acquired Immune Deficiency Syndromes. 2005;40(5):532-537. doi:10.1097/01.qai.0000186363.27587.c0

Additional Reading

By James Myhre & Dennis Sifris, MD
Dennis Sifris, MD, is an HIV specialist and Medical Director of LifeSense Disease Management. James Myhre is an American journalist and HIV educator.