Results on Drug Resistance Mutations in Patients with HIV Who Failed First-Line Antiretroviral Therapy in a Public Hospital in Lima,Peru,2008

Abstract

Editor: Currently, it is known that one of the causes of antiretroviral treatment failure in HIV is the presence of mutations that confer resistance to certain drugs.¹ Compared with the United States, in Peru a genotyping study is not carried out before the start of antiretroviral therapy (ART),² so it is foreseeable that the drug resistance-related mutations will accumulate and cause a virological failure.³

The objective of this letter is to show the results obtained on the occurrence of drug resistance mutations in patients with HIV who failed first-line ART in a public hospital in Lima, Peru. To this end, a genotyping database of the National Institute of Health (NIH) and information on ART of patients belonging to the recognized National Hospital Arzobispo Loayza between 2008 and 2018 was used. This information contributes to the article “Changes from 2000 to 2009 in the Prevalence of HIV-1 Containing Drug Resistance-Associated Mutations from Antiretroviral Therapy-Naive, HIV-1-Infected Patients in the United States” and, in addition, to Latin American data.

The analysis shows that, out of a total of 191 patients who had failed first-line ART from 2008 to 2018, the most used initial scheme was composed of AZT/3TC/EFV in 34%. Most frequently, 58% used AZT/3TC as nucleoside reverse-transcriptase inhibitor (NRTI), 61% efavirenz (EFV) as non-NRTI (NNRTI), and 8% ATV/rtv, LPV/rtv, and DRV/rtv as protease inhibitor (PI) in the initial scheme.

In contrast, from Table 1, the most common mutations in the NRTI group are the discriminatory mutations M184V and K65R followed by the thymidine analog mutation (TAM) T215Y/F in 66.5%, 9.9%, and 17.8%, respectively. The K103N mutation is the most common in NNRTIs (28.8%) and M46I (3.7%) with D30N (2.6%) in PIs. The M184V mutation is the most common mutation in all cases, as it is observed in 64.9% of those who used AZT/3TC, 66.7% of those who used TDF/3TC, and 79.1% of those who used D4T/3TC in the first-line scheme. In addition, this mutation is the most frequent in the most used initial scheme AZT/3TC/EFV in 71.9%. The K65R mutation was observed mostly (36.3%) in patients exposed to TDF/3TC. The first-line scheme that includes AZT/3TC is the one with the highest number of mutations, both discriminatory (69.4%) and TAMs (55%).

Table 1.

Resistance Mutations: Percentage Occurrence According to First-Line Antiretroviral Regimen

ART regimen		No.	Discriminatory mutations		Thymidine analog mutations
NRTI	NNRTI/PI		K65R	M184V	M41L	T215Y/F	D67N	K70R	K219Q/E
AZT/3TC	EFV	64	2	46	6	14	5	4	5
	NVP	42	2	24	5	9	4	5	4
	PI	5	1	2	0	0	0	0	0
Total		111
TDF/3TC	EFV	32	12	22	1	1	1	0	2
	NVP	0	0	0	0	0	0	0	0
	PI	1	0	0	0	0	0	0	0
Total		33
D4T/3TC	EFV	10	1	8	2	2	2	1	1
	NVP	13	0	10	0	4	2	3	2
	PI	1	0	1	0	0	0	0	0
Total		24
Other regimens^a		23	1	14	3	4	3	2	4

ABC/3TC/EFV, AZT/3TC/NFV, DDI/3TC/PI, ABC/3TC/PI, DDI/3TC/NVP, TDF/FTC/EFV, TDF/EFV/PI, TDF/NVP/PI, ABC/EFV/PI, ABC/EFV/INI, and 3TC/EFV/PI.

3TC, lamivudine; D4T, estavudine; ABC, abacavir; ART, antiretroviral therapy; AZT, zidovudine; DDI, didanosine; EFV, efavirenz; INI, integrase inhibitor; NFV, nelfinavir; NNRTI, non-nucleoside reverse-transcriptase inhibitor; NRTI, nucleoside reverse-transcriptase inhibitor; NVP, nevirapine; PI, protease inhibitor; TDF, tenofovir.

It is concluded that patients who failed first-line ART in this public hospital have a considerable rate of mutations that cannot be compared with a genotyping study before the start of treatment because in Peru this practice has not yet been implemented. However, in case of a patient with virological failure, a timely and accessible genotyping study will be necessary, since the adequate control of the disease will depend on establishing a therapeutic scheme that guarantees virological suppression.⁴

References

Afani

, Gallardo

: Resistance to antiretroviral therapy in human immunodeficiency virus infection. Rev Chil Infectol, 2011; 28:461–469.

Norma Técnica de Salud N° 097-MINSA/DGSP-V.03. Norma Técnica de Salud de Atención Integral del Adulto con Infección por el Virus de la Inmunodeficiencia Humana (VIH). Ministerio de Salud, Lima, 2018. Available at ftp://ftp2.minsa.gob.pe/normaslegales/2018/R.M_215-2018-MINSA.PDF, accessed October 20, 2018 .

Boender

, Kityo

, Boerma

, et al.: Accumulation of HIV-1 drug resistance after continued virological failure on first-line ART in adults and children in sub-Saharan Africa. J Antimicrob Chemother, 2016; 71:2918–2927.

US Department of Health and Human Services. Guidelines for the use of antiretroviral agents in adults and adolescents living with HIV. 2018. https://aidsinfo.nih.gov/contentfiles/lvguidelines/adultandadolescentgl.pdf, accessed November 10, 2018 .

Results on Drug Resistance Mutations in Patients with HIV Who Failed First-Line Antiretroviral Therapy in a Public Hospital in Lima,Peru,2008–2018

Abstract

References