Date Published: February 27, 2019
Author(s): C. K. Chauhan, P. V. M. Lakshmi, V. Sagar, A. Sharma, S. K. Arora, R. Kumar.
Antiretroviral treatment may lead to the emergence of HIV drug resistance, which can be transmitted. HIV primary drug resistance (PDR) is of great public health concern because it has the potential to compromise the efficacy of antiretroviral therapy (ART) at the population level.
To estimate the level of primary drug resistance among recently infected cases of HIV in 6 ART centres of North-Western India from September 2014 to June 2016.
The level of primary drug resistance was studied among 37 recently infected HIV cases identified by Limiting antigen (Lag) avidity assay based on modified Recent Infection Testing Algorithm (RITA). The reverse transcriptase region of HIV-1 pol gene (1-268 codons) was genotyped. The sequences were analyzed using the Calibrated Population Resistance (CPR) tool of Stanford University HIV drug resistance (DR) database to identify drug resistance.
Among 37 isolates studied, 6 (16.2%) samples showed primary drug resistance (PDR) against reverse transcriptase (RT) inhibitor. The proportion of primary drug resistance was 22.2% (2/9) among female sex workers, 14.3% (1/7) among men having sex with men, and 14.3% (3/21) among injecting drug users. Observed mutations were K219R, L74V, K219N, and Y181C. Injecting drug user (IDU) has showed resistance to either nucleoside/nucleotide reverse transcriptase inhibitors (NRTI) or nonnucleotide reverse transcriptase inhibitors (NNRTI).
Resistance to either NRTI or NNRTI among the recently is a new challenge that needs to be addressed. The fact that both Y181C isolates are IDUs is important and represents 2/21 (~10%) NNRTI drug resistance. Surveillance for primary drug resistance (PDR) needs to be integrated into next generation of HIV surveillance as access to ART is increasing due to introduction of test and treat policy.
ART is the main stay of treatment to delay the occurrence of AIDS. Nearly 9.7 million people were receiving antiretroviral therapy (ART) in low- and middle-income countries by the end of 2016 . A mix of multiple antiretroviral drugs has been recommended to suppress HIV replication, thus preventing HIV linked mortality and morbidity apart from enhancing the quality of life of HIV/AIDS infected people. The introduction of zidovudine in 1987 started the era of ART but India started its antiretroviral therapy program for the treatment of HIV/AIDS in 2004; ARV drugs used in first line ART regimens for adults and adolescents in the national ART program in India are Zidovudine, Tenofovir, Abacavir, Lamivudine, Efavirenz, and Nevirapine . The second-line ART regimens comprised of zidovudine (ZDV), lamivudine (3TC), tenofovir (TDF), and boosted lopinavir/ritonavir (LPV/r) have been introduced recently in a phase wise manner at various centres .
Out of 64 recently infected individuals, only 37 samples (who had CD4 count between 200 and 500 cells/μl) could be genotyped. Of the total 37 samples, 9 were female sex worker (FSW), 7 were men who have sex men (MSM), and 21 were injecting drug user (IDU) samples. The mean age of the respondents was 34.8 (SD=10) years. The median CD4 count was 332.5 cells/μl (IQ range 257-491). All 37 samples belonged to subtype C (Figure 1)
Drug resistance is a major challenge for achieving viral suppression. In this study, we have sequenced the amplified RT region of pol gene of HIV isolates from recently infected and treatment naïve high risk individuals in north-west India. Primary drug resistance mutations were identified as per Stanford DR database. In India first line of ART comprised of RTI drugs and a higher rate of DR mutations have been reported in the RT region in therapy naïve individuals in India . The most common subtype of HIV-1 in India is subtype C [17, 22]. In the present study primary drug resistance was observed 16.2% (95% CI: 6.8-30.7) recently infected individuals. According to WHO, the drug resistance prevalence in a geographical area can be categorized as <5%, 5–15% and >15% . Thus primary drug resistance in our study can be categorized as moderate to high prevalence according to World Health Organization (WHO) criteria.
In conclusion, our study indicates that a moderate to high level of primary drug resistance was focused after the rapid expansion of ART program in India. Primary drug resistance was detected among 16% treatment naïve HRGs in north-west India by genotyping assay. The treatment of HIV has become increasingly complex with the introduction of new ARVs drugs and need of the hour is to understand ARV drug resistance development in order to effectively combat HIV infections. Resistance to NNRTI among IDUs is a new challenge that needs to be addressed. National programs to monitor HIV drug resistance among HIV-infected population should be done through HIV genotyping in sentinel populations.