Intermediate Levels of Transmitted Antiretroviral Drug Resistance in Midwestern Brazil

Abstract

E ditor: The prevalence of primary HIV-1 transmitted drug resistance (TDR) varies from intermediate levels to high levels in Brazil.^1
–3 The subtype profiles of HIV-1 in Brazil include as a majority the subtype B of HIV-1, but other subtypes, such as F1, C, D, A, and divergent sequences, cocirculate in various frequencies in different geographic regions.¹ Blood samples of 82 consecutive untreated HIV-1-positive participants were collected between September 2005 and June 2008 at the Voluntary Counseling and Testing Center in Goiania, a major capital city located in the Central-west region of Brazil. Brazil is divided into five macrogeographic regions: North, Northeast, Central-west, Southwest, and South. The central region of Brazil has the lowest incidence of AIDS among all the regions; however, the number of AIDS cases in this region is growing as a result of the so-called AIDS interiorization process that is occurring in this country (www.aids.gov.br/publicacao/2011/boletim_epidemiologico_2011). Sera were subjected to the serologic testing algorithm for recent HIV-1 seroconversion (STARHS). Plasma viral RNA was extracted and the protease and reverse transcriptase genomic regions were sequenced for subtype assignment and genotypic correlates for antiretroviral resistance, evaluated according to published guidelines that excluded common polymorphism.⁴

Out of the 82 participants, 57 (69.5%) were males; their mean age was 36±12 years. Of the 82 participants, 14 (17.1%) were identified as having recent HIV infection (RI) and 68 (82.9%) as long-term infection (LSI). Pure clade B was detected in 69 individuals (85.3%). The non-clade B and recombinant profiles in the protease and reverse transcriptase regions were F/F (3.7%), B/F (3.7%), F/B (3.7%), and C/C (3.7%).

Six individuals (7.3%) were found to harbor resistance mutations to antiretrovirals (Table 1), two (2.4%) of those with RI. The mutation K103N, which has been associated with high levels of nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance, was found in one individual with LSI (1.2%). Nucleoside reverse transcriptase inhibitor (NRTI)-associated mutations were found in four individuals (4.9%); two of these had T215 revertants. Primary mutations associated with resistance to protease inhibitor (PI) were found in one individual (1.2%). A phylogenetic analysis using a neighbor-joining phylogenetic reconstruction excluding resistance-related codons revealed no clusterization between sequences harboring TDR as defined as <1.5% genetic distances between samples (data on file).

Table 1.

Subtypes of HIV-1 and Amino Acid Substitution in the Resistance-Related Codons of Recent or Long-Standing Infected Individuals with Transmitted HIV Drug Resistance

			Subtype	Amino acid substitutions
Infection status	Gender	Age	PR/RT	PR	RT
RI	M	26	BB	None	T215S
RI	M	22	BB	V32VI	None
LSI	F	35	BB	None	V75IMV
LSI	M	38	BB	None	T69N; T2151
LSI	M	39	BB	None	K219T
LSI	M	45	BB	None	K103N

PR, protease; RT, reverse transcriptase; RI, recent infected; LSI, long-standing infected.

Brazil is a very large country and variations in prevalence of TDR have been identified among different geographic regions. An intermediate level of TDR was observed in HIV-1 variants from the HIV-1-positive individuals diagnosed in eight different Brazilian states.³ These results contrast with the ones from certain geographic areas such as Bahia and the city of Santos in which a high prevalence of TDR was found among chronically or recently infected individuals.^1,2,5 Therefore, the prevalence of 7.3% found in our study is in accordance with the TDR prevalence of the majority of studies described from other cities in Brazil. It is conceivable that our study may have underestimated TDR due to the low proportion of recently infected individuals (17.1%), since TDR is usually lower among long-standing infected individuals. In this sense, it has been hypothesized that individuals with long-standing infection may have been infected at a time when antiretroviral resistance was less common and/or some low genetic barrier resistance-related mutations may have vanished without the selective pressure of antiretrovirals. As TDR prevalence may vary in distinct geographic areas, we consider this first TDR report in a large urban area in Central Brazil of importance, and the continuous surveillance may help in making decisions about including pretreatment genotype tests or in creating guidelines for an empiric first line regimen in a resource-limited setting.

Footnotes

Author Disclosure Statement

No competing financial interests exist.

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