Protease inhibitors are drugs used to treat HIV infection
and include indinavir, ritonavir, saquinavir, nelfinavir, fosamprenavir,
lopinavir, atazanavir and darunavir. Other classes of drugs used in HIV are the
nucleoside reverse-transcriptase inhibitors (NRTI) and the non-nucleoside
reverse-transcriptase inhibitors (NNRTI).
Treatment for HIV infection is started using the
first-line drugs before the CD4 cell counts drop to less than 200 cells/µL or
when they range between 200 and 350 cells/µL with an AIDS-defining illness. If resistance
develops to the first-line drugs, the patient is shifted on to a second-line
regimen. Those who develop resistance to these drugs as well will require a
Due to lack of plasma viral load monitoring
facilities in India, resistance to the first-line drugs is detected late,
resulting in a large number of resistant viruses. These patients are then
started on a protease-inhibitor based regimen, which consists of
ritonavir-boosted protease inhibitors like atazanavir, saquinavir, lopinavir or
indinavir, in combination with two nucleoside reverse-transcriptase inhibitors
(NRTI). (In ritonavir-boosted regimens, low doses of ritonavir are added to
improve the effect of the protease inhibitor in the regimen).
The HIV virus can develop resistance to the protease
inhibitors due to mutations on the protease enzyme. Exposure to a particular
protease inhibitor results not only in resistance to the particular drug; it
also results in resistance to all other protease inhibitors as well.
A study was conducted at YRG Centre for AIDS
Research and Education (YRG CARE), Voluntary Health Services (VHS), Chennai to
study the patterns of protease resistance mutations in South Indian patients
who had received protease inhibitors as a part of second-line treatment for HIV
The study was carried out in 107 HIV positive
patients whose first-line treatment has failed and who received second-line
ritonavir- boosted protease inhibitors for more than 6 months. HIV genotyping
was done in those with a plasma viral load of more than 2000 copies/mL.
Nearly half the patients in the study were started
on an atazanavir -containing regimen, closely followed by those taking an
indinavir-containing regimen. The tenofovir-emtricitabine regimen constituted
the NRTI backbone in most cases.
A total of 77 patients showed a detectable viral
load in the plasma. Sequencing was done in 45 of these samples. Among these, protease inhibitor mutations
were observed in 73% patients, NRTI mutations in 91% patients, NNRTI mutations
in 73% patients and both NRTI and NNRTI mutations in 66.7% patients.
Resistance to all the three classes of drugs was seen in 53% patients.
The study reported a high incidence of protease
inhibitor resistance of 73%, more than other studies conducted in India. The predominant
protease mutations observed in the study were M46I (22 samples; 49%), I54 V/A
(17; 38%), V82A (17; 38%), and L90M (14; 31%).
All the 45
sequences were susceptible to the protease inhibitor darunavir. Though some mutations to
darunavir were noted in the study, none of the patients had more than 3
darunavir resistance mutations, which is necessary to confer resistance to the
drug. The next protease inhibitor with least resistance of 2% was tipranavir.
Resistance to other protease inhibitors ranged between 47% and 60%.
indicates that mutations to protease inhibitors occur in majority of patients
receiving second-line treatment for HIV infection. Resistance to darunavir is
the least; thus, with limited other options available, it may be preferred in
third-line treatment for HIV infection in India.
1. Shanmugam Saravanan et al. Viremia and HIV-1 Drug Resistance
Mutations Among Patients Receiving Second-Line Highly Active Antiretroviral
Therapy in Chennai, Southern India. Clinical Infectious Disease DOI: