Complexity of the HIV strains circulating among the HIV infected individuals of Manipur
- Part 2 -

Dr Lisam Shanjukumar Singh *

A painting at World AIDS Day 2013 at MFDC Auditorium on December 01, 2013 :: Pix - : Ashok Ningthoujam

WHO's HIVDR monitoring and surveillance strategy is composed of five key elements:

a) Monitoring of Early Warning Indicators of HIV drug resistance

b) Surveillance of HIVDR in recently-infected adult populations (transmitted HIVDR)

c) Surveillance of pre-treatment HIVDR in adult populations initiating ART (pre-treatment HIVDR)

d) Surveillance of acquired HIVDR in populations of adults and children receiving ART (acquired HIVDR)

e) Surveillance of HIV drug resistance in treatment-naive children less than 18 months of age

4). When the origin of the HIV circulating in Manipur was investigated by comparing all the genomes of Manipur HIV with all the HIV genome submitted to the worldwide HIV database from different part of the world, 81% originated from china, 11% from mainland India, and the rest from other countries. It suggests that Manipur HIV epidemic was possibly invaded mainly from China through Myanmar via heroin trafficking routes.

In China, Yunnan province which shares a border of 4,060 km with Myanmar in the west, Laos in the south and Vietnam in the southeast (closing it to the "Golden triangle" of Southeast Asia, the second largest opium producer in the world) is one of the provinces hardest-hit by HIV in China. In recent time, emergence of multiple recombinant subtype of HIV has been reported from this area.

5). Our study illustrated the emerging of extremely diversified and complicated genetic variable recombinant forms and drug resistance mutations in HIV-1 of Manipur which is an alarming situation. It is worth to note that the HIV epidemic which was once dominated among Injecting Drug Users (IDUs), has now penetrated into the general population through sexual route silently.

The emerging of new fusion or recombinant strains of HIV may change in their transmission ability and consequently spread the disease more rapidly especially in the remote areas. The study suggests that it is very important in Manipur where about half of the HIV patients harbouring drug resistance virus, to know whether a HIV infected individual is harbouring HIV drug resistance (HIVDR) or not before starting ART as well as before changing treatment regime (from first-line to second-line, second-line to third-line, so on) for effective and meaningful treatment.

Recombinant forms of HIV and drug resistant HIV emerge mainly in the area where areas with different prevalent subtypes meet. The China-Myanmar-India border region is a 'HIV recombinant hotspot" that serves as a key channel for illegal drug trafficking from the "Golden triangle" to other countries/regions.

6). The viral load testing is imperative when making decisions around clinical management of HIV patients. Although viral load testing remains a big question in Manipur since the facility for this test is currently not available and therefore only some samples (after scrutiny) are being sent to other state for testing, but the results of our study has raised a bigger question.

The HIV-1 viral load assays depend on the sequence (chemical composition) of the HIV genome. Most of the currently available commercially assay kits are developed based mainly on the sequence of subtype B virus which is predominant in rich counties and therefore, these assays are not necessarily as accurate or adequate for all non-B HIV-1 subtypes and specially recombinants strains (Reference: LeeAnne M. Luft, et.al. HIV-1 viral diversity and its implications for viral load testing: review of current platforms. International Journal of Infectious disease, Oct. 2011, Volume 15, Issue 10, Pages e661–e670).

Since we have found extremely diversified and complicated genetic variability recombinant strains of HIV in Manipur, the question raised is whether the currently available viral load assay kits will be accurate/adequate for all the strains of HIV circulating in Manipur or not. It is needed to be answered by conducting more research.

7). Our findings were anticipated due to the geographical location of Manipur, (an important gateway of India to "Golden triangle") but not as diversified and complicated genetic variability as illustrated by our study. As the Intravenous Drug Users (IDUs) used to share their injecting equipment, when a new strain enters into a drug network; it begins to recombine with existing strains and create new recombinants unique to that drug network.

Drug networks provide the ideal means for rapidly spreading HIV within core groups and represent an emerging threat for the introduction of novel or recombinant strains into larger heterosexually active communities. Therefore, in addition to the geographical location, high rate of addiction to drugs and social-structures may be the facilitating factors for accelerating the generation of highly diversified and complicated genetic variability of HIV-1 in Manipur.

Besides, clustering patterns of the Manipur HIV new recombinant forms into multiples groups displaying monophyletic lineages in the phylogenetic trees (that is; when their genetic similarities was analysed) strongly suggested that these new recombinant forms are not confining to few individuals but spreading to new individuals.

8). Although, Manipur has been the highest HIV prevalent state in India for decades, this research work of HIV molecular epidemiology studies with large HIV sample size from Manipur is the first of its kind. The HIV epidemiology of an epidemic area is not static but very dynamic with time.

Therefore, it is very necessary to investigate the nature of HIV drug resistance at the molecular level from time to time with large sample size so that policy makers and doctors can provide effective and meaningful management and treatment to the HIV infected population of Manipur and to prevent spreading of this deathly epidemic to general public silently. We are looking forward for collaborative works from any government or private Institutes/Centers of the state for further studies.

The research work was conducted by the research team of the Cancer and Molecular Division, Department of Biotechnology, Manipur University, Canchipur led by Dr. Lisam Shanjukumar Singh and assisted by Dr. Thiyam Ramsing Singh. Dr. Adhikarimayum Lakhikumar Sharma conducted all the experiments and thereafter he was awarded Ph.D. Degree in Biotechnology. Dr. Kh. Ranjana Devi, Department of Microbiology, RIMS and ART Center, RIMS provided samples.

Concluded..