Complexity of the HIV strains circulating among the HIV infected individuals of Manipur
- Part 1 -

Dr Lisam Shanjukumar Singh *

World AIDS Day 2014 at 1st MR Parade Ground, Imphal on 1st December 2014 :: Pix - Arunkumar Thongam (DIPR)

The Cancer and Molecular Biology Division, Department of Biotechnology, Manipur University has recently conducted a research work to identify the HIV strains circulating among the HIV infected individuals of Manipur, funded by the Department of Biotechnology, Ministry of Science and Technology, Govt. of India (research project no. BT/PR-14081/MED/12/469/2010).

The findings of the research work suggested that more than half of the HIV infected individuals of Manipur are harbouring complex and drug resistant HIV strains indicating that the current situation of HIV epidemic in Manipur is alarming.

The results of the research work are summarized below:-

1). 38% of the HIV-1 circulating among the HIV infected individuals of Manipur belongs to subtype C, however 62% is new recombinant strains. HIV contains two copies of genetic material in the form of RNA. These RNA are the genome of HIV. Depending on the chemical composition of genome, HIV is divided in two main types, HIV-1 and HIV-2. HIV-1 can be further divided into three Groups: Group M (Major), Group O (Outlier), and Group N (Non-M or Non-O).

Group M is responsible of all the infections worldwide and is subdivided into nine pure subtypes (A, B, C, D, F, G, H, J, and K). Subtype C is predominant in India whereas subtype B is most prevalent in rich countries (USA, Europe and Australia).

New recombinant strains of HIV-1 arise when two or more pure subtypes (A, B, C, D, F, G, H, J, and K) are infecting an individual at the same time (co-infection) and fusion or recombination (a process similar to sexual reproduction and sometimes known as viral sex) between the two or more HIV-1 subtypes occurred in cells of the individual.

Then, the resulting recombinant strain having new genome derived from old HIV genomes so become new type of virus. Since the recombinant strains may have acquired more fitness for survival and transmissibility to another individual more easily, they cause many complications including
(a) for effective treatment of HIV infected individuals with antiretroviral therapy (ART),
(b) development of effective vaccination strategies and
(c) implications for diagnostic assays.

Drugs for AIDS treatments are developed by the rich countries where subtype B is the predominant HIV-1 virus and therefore antiretroviral drugs were developed and clinically tested for efficacy with subtype B viruses. The impact of antiretroviral drugs are yet to be fully assessed on these genetic differences or non-B subtypes. Therefore, emergence of recombinant strains is big challenge for effective management of HIV epidemic in any area. Recombinant strain and HIV drug resistant are mostly found in Africa, especially Central Africa and also in some part of Southeast Asia.

2). Again, among the recombinant forms of HIV which are found in Manipur, 61% contained unclassified genomes. This finding is the first report of detecting unclassified/unknown subtype (U) in India to the best of our knowledge. A particular fragment of HIV genome is defined as unclassified (subtype U) if the chemical composition (sequence) is considerably divergent from any sequences of HIV available in the worldwide HIV database.

These unclassified subtype have been reported mostly in African countries. Unclassified subtype may be the result of numerous recombination and/or mutation in the virus genome. Mutation is the change in the chemical compositions of genome due to environmental factors (treatment with ART is also an environmental factor). Mutation of HIV-1 genome may also lead to change in many characteristics of the virus like resistance to ART, more fitness for survival, easily transmissible with more virulent. The ability of HIV to undergo mutation and reproduce itself with new characteristics (escape from drug effect) during the treatment of antiretroviral drugs is called HIV drug resistance (HIVDR).

3). The consequences of HIVDR include
(a) treatment failure,
(b) need to start more costly second- and third- line treatments,
(c) increased health costs associated with these,
(d) spread of drug resistant HIV, and
(e) need to develop new anti-HIV drugs.

If HIV drug resistance becomes widespread, the drugs currently used to treat HIV infection may become ineffective. When prevalence of HIV drug resistant in Manipur was investigated, we found that more than 50% of the HIV infected population of Manipur are harbouring mutated HIV which are known to be resistance to ART.

Among these individual, 21%, 24%, 25%, 13%, 36% and 37% individuals were found to be having resistance to drugs 3TC (Lamivudine), AZT (Zidovudine), D4T (Stavudine), TDF (Tenofovir), EFV (Efavirenz) and NVP (Nevirapine) respectively. Finding further revealed that the resistance against the drugs that target to viral reverse transcriptase (RT) was very much high in Manipur. Most of mutated virus was found to have resistance to primary drug used in this state. Some individual are harbouring virus which are resistant to multiple drugs used in the state.

To date, levels of HIVDR emergence remain manageable in an area where ART program is running step by step. However, resistance is slowly increasing. To maximize the long-term effectiveness of first-line ART and ensure the sustainability of ART programmes, it is essential to minimize the further spread of HIV drug resistance. Therefore, World Health Organization (WHO) recommends assessment of drug resistance emergence and transmission robustly.

To be continued...