Short Communication: Acquisition of Additional Nuclear Factor Kappa B Binding Sites in Long Terminal Repeat of Genetically Evolving HIV-1 Subtype C Viral Species in Host with Comorbidities.

HIV-1 causes millions of deaths around the world. Higher disease progression and mortality are seen in HIV positive individuals with comorbidities. Two of the most pertinent conditions are coinfection with Mycobacterium tuberculosis and Intravenous Drug abuse. The mechanisms involved, however, still remain unresolved. To elucidate the mechanisms involved, we evaluated the genetic alterations in terms of additional nuclear factor kappa B (NF-κB) sites in the long terminal repeat (LTR) of HIV-1 subtype-C isolates from infected human individuals from North India, supposedly acquired by the emerging viral quasi-species in the infected host in presence of these two comorbid conditions. Interestingly the results indicate higher number of NF-κB sites in the viral isolates from HIV-tuberculosis coinfected (n = 26, 16 isolates with 3 sites and 10 isolates with 2 sites) and intravenous drug users (n = 20, 13 isolates with 3 sites and 7 isolates with 2 sites) compared to the mono-infected hosts (n = 30, 10 isolates with 3 sites, 18 isolates with 2 sites, 2 isolates with 1 site). The biological relevance of these alterations in the NF-κB sites within the HIV-1 LTR with respect to viral replicative capacity and HIV disease progression needs to be studied further.

Human Immunodeficiency Virus-1 Subtype-C Genetically Diversify to Acquire Higher Replication Competence in Human Host with Comorbidities.

Unusual disease progression is observed in the HIV-1 infected patients who are either coinfected with Mycobacterium tuberculosis (Mtb) or concomitantly on intravenous drug use (IDU). The mechanism involved in the breakdown of host immune defense and the synergistic effect in both the conditions are still not well understood. In this study, we aimed to highlight the emergence of genetically diversified variants of virus in these two cohorts among HIV-1 subtype-C infected population from a Northern state of India. A cross-sectional study was performed on treatment-naïve HIV-1 subtype-C infected individuals constituting three different cohorts of HIV-1 monoinfected, HIV-1-M. tuberculosis (HIV-TB) coinfected, and HIV-1 infected individuals on substance abuse (HIV-IDU) for acquisition of genetic alterations in terms of frequency of drug resistance (DR) mutations in reverse transcriptase gene. The data reveal a significantly higher viral load, higher death rate, and higher frequency of major DR mutations in the genome of viral isolates from HIV-TB and HIV-IDU cohorts as compared with HIV monoinfected. Majority of the mutations found in the HIV-TB coinfected and HIV-IDU cohorts conferred high level of resistance to the first-line treatment regimen (Lamivudine with Tenofovir or zidovudine or Abacavir and Nevirapine or Efavirenz). Our findings support the hypothesis that the HIV-1 evolve while replicating in the host with Mtb coinfection or substance abuse, with the emergence and accumulation of genetically diversified quasi-species. Further studies are warranted to understand the association of such genetic variations with increased replication competence and faster rate of disease progression in such individuals.