HIV-1 subtype B virus is the most prevalent subtype in Puerto Rico (PR), accounting for about 90% of infection in the island. Recently, other subtypes and circulating recombinant forms (CRFs), including F(12_BF), A (01_BF), and CRF-39 BF-like, have been identified. The purpose of this study is to assess the distribution of drug resistance mutations and subtypes in PR. A total of 846 nucleotide sequences from the period comprising 2013 through 2017 were obtained from our “HIV Genotyping” test file. Phylogenetic and molecular epidemiology analyses were performed to evaluate the evolutionary dynamics and prevalence of drug resistance mutations. According to our results, we detected a decrease in the prevalence of protease inhibitor, nucleoside reverse transcriptase inhibitor (NRTI), and non-NRTI (NNRTI) resistance mutations over time. In addition, we also detected recombinant forms and, for the first time, identified subtypes C, D, and CRF-24BG in PR. Recent studies suggest that non-subtypes B are associated with a high risk of treatment failure and disease progression. The constant monitoring of viral evolution and drug resistance mutation dynamics is important to establish appropriate efforts for controlling viral expansion.
Get full access to this article
View all access options for this article.
References
1.
StebbingJ, PattersonS, GotchF: New insights into the immunology and evolution of HIV. Cell Res, 2003; 13:1–7.
2.
HoDD, HuangY: The HIV-1 vaccine race. Cell, 2002; 110:135–138.
3.
Seillier-MoiseiwitschF, MargolinBH, SwanstromR: Genetic variability of the human immunodeficiency virus: Statistical and biological issues. Annu Rev Genet, 1994; 28:559–596.
4.
PeetersM, SharpPM: Genetic diversity of HIV-1: The moving target. AIDS, 2000; 14Suppl 3:S129–S140.
5.
CoffinJM: Genetic diversity and evolution of retroviruses. Curr Top Microbiol Immunol, 1992; 176:143–164.
6.
LealE, VillanovaFE: Diversity of HIV-1 subtype B: Implications to the origin of BF recombinants. PLoS One, 2010; 5:e11833.
7.
BuonaguroL, TorneselloML, BuonaguroFM: Human immunodeficiency virus type 1 subtype distribution in the worldwide epidemic: Pathogenetic and therapeutic implications. J Virol, 2007; 81:10209–10219.
8.
PlantierJC, LeozM, DickersonJE, et al.: A new human immunodeficiency virus derived from gorillas. Nat Med, 2009; 15:871–872.
9.
VidalN, MulangaC, BazepeoSE, LepiraF, DelaporteE, PeetersM: Identification and molecular characterization of subsubtype A4 in central Africa. AIDS Res Hum Retroviruses, 2006; 22:182–187.
10.
TaylorBS, SobieszczykME, McCutchanFE, HammerSM: The challenge of HIV-1 subtype diversity. N Engl J Med, 2008; 358:1590–1602.
11.
IsaacsT, AberaAB, MuloiwaR, KatzAA, ToddG: Genetic diversity of HHV8 subtypes in South Africa: A5 subtype is associated with extensive disease in AIDS-KS. J Med Virol, 2016; 88:292–303.
12.
BartoloI, RochaC, BartolomeuJ, et al.: Highly divergent subtypes and new recombinant forms prevail in the HIV/AIDS epidemic in Angola: New insights into the origins of the AIDS pandemic. Infect Genet Evol, 2009; 9:672–682.
13.
KazennovaE, LagaV, GromovK, et al.: Genetic variants of HIV type 1 in men who have sex with men in Russia. AIDS Res Hum Retroviruses, 2017; 33:1061–1064.
14.
LapovokI, LagaV, KazennovaE, BobkovaM: HIV type 1 integrase natural polymorphisms in viral variants circulating in FSU countries. Curr HIV Res, 2017; 15:318–326.
SchlubTE, SmythRP, GrimmAJ, MakJ, DavenportMP: Accurately measuring recombination between closely related HIV-1 genomes. PLoS Comput Biol, 2010; 6:e1000766.
17.
RagupathyV, ZhaoJ, WoodO, et al.: Identification of new, emerging HIV-1 unique recombinant forms and drug resistant viruses circulating in Cameroon. Virol J, 2011; 8:185.
18.
FangG, WeiserB, KuikenC, et al.: Recombination following superinfection by HIV-1. AIDS, 2004; 18:153–159.
19.
van der KuylAC, CornelissenM: Identifying HIV-1 dual infections. Retrovirology, 2007; 4:67.
20.
TaylorBS, HammerSM: The challenge of HIV-1 subtype diversity. N Engl J Med, 2008; 359:1965–1966.
21.
BretscherMT, AlthausCL, MullerV, BonhoefferS: Recombination in HIV and the evolution of drug resistance: For better or for worse?. Bioessays, 2004; 26:180–188.
22.
CortezKJ, MaldarelliF: Clinical management of HIV drug resistance. Viruses, 2011; 3:347–378.
23.
NadaiY, EyzaguirreLM, SillA, et al.: HIV-1 epidemic in the Caribbean is dominated by subtype B. PLoS One, 2009; 4:e4814.
24.
MagiorkinisG, AngelisK, MamaisI, et al.: The global spread of HIV-1 subtype B epidemic. Infect Genet Evol, 2016; 46:169–179.
25.
Rodriguez-DiazCE, AndrinopoulosK: HIV and incarceration in the Caribbean: The experiences of Puerto Rico and Jamaica. P R Health Sci J, 2012; 31:161–169.
26.
CDC: Available at https://gis.cdc.gov/grasp/nchhstpatlas/charts.html accessed April2017.
27.
Rico DdSdP: Perfil Epidemiológico Integrado para la Prevención del VIH en Puerto Rico, 2008–2014. Available at www.salud.gov.pr/Estadisticas-Registros-y-Publicaciones/Estadisticas VIH/Perfil Epidemiol%C3%B3gico/Perfil Epidemiol%C3%B3gico Integrado para la Prevenci%C3%B3n del VIH en Puerto Rico.pdf accessed April2017.
LopezP, Rivera-AmillV, RodriguezN, VargasF, YamamuraY: The genetic diversity and evolution of HIV-1 subtype B epidemic in Puerto Rico. Int J Environ Res Public Health, 2015; 13:ijerph13010055.
30.
KaoCF, ChangSY, HsiaKT, et al.: Surveillance of HIV type 1 recent infection and molecular epidemiology among different risk behaviors between 2007 and 2009 after the HIV type 1 CRF07_BC outbreak in Taiwan. AIDS Res Hum Retroviruses, 2011; 27:745–749.
31.
GiffordRJ, de OliveiraT, RambautA, et al.: Phylogenetic surveillance of viral genetic diversity and the evolving molecular epidemiology of human immunodeficiency virus type 1. J Virol, 2007; 81:13050–13056.
32.
Pineda-PenaAC, FariaNR, ImbrechtsS, et al.: Automated subtyping of HIV-1 genetic sequences for clinical and surveillance purposes: Performance evaluation of the new REGA version 3 and seven other tools. Infect Genet Evol, 2013; 19:337–348.
SallamM, SahinGO, IngmanM, WidellA, EsbjornssonJ, MedstrandP: Genetic characterization of human immunodeficiency virus type 1 transmission in the Middle East and North Africa. Heliyon, 2017; 3:e00352.
36.
FloresI, PieniazekD, MoranN, et al.: HIV-1 subtype F in single and dual infections in Puerto Rico: A potential sentinel site for monitoring novel genetic HIV variants in North America. Emerg Infect Dis, 1999; 5:481–483.
37.
ZhangM, SchultzAK, CalefC, et al.: jpHMM at GOBICS: A web server to detect genomic recombinations in HIV-1. Nucleic Acids Res, 2006; 34(Web Server issue):W463–W465.
38.
PosadaD, CrandallKA: MODELTEST: Testing the model of DNA substitution. Bioinformatics, 1998; 14:817–818.
39.
SalemiM, de OliveiraT, CiccozziM, RezzaG, GoodenowMM: High-resolution molecular epidemiology and evolutionary history of HIV-1 subtypes in Albania. PLoS One, 2008; 3:e1390.
40.
VergneL, PeetersM, Mpoudi-NgoleE, et al.: Genetic diversity of protease and reverse transcriptase sequences in non-subtype-B human immunodeficiency virus type 1 strains: Evidence of many minor drug resistance mutations in treatment-naive patients. J Clin Microbiol, 2000; 38:3919–3925.
41.
AlbertJ, BerglundT, GisslenM, et al.: Risk of HIV transmission from patients on antiretroviral therapy: A position statement from the Public Health Agency of Sweden and the Swedish Reference Group for Antiviral Therapy. Scand J Infect Dis, 2014; 46:673–677.
42.
HammerSM: HIV drug resistance: Implications for management. Top HIV Med, 2002; 10:10–15.
43.
MontagnaC, MazzutiL, FalascaF, et al.: Trends in drug resistance-associated mutations in a real-life cohort of Italian patients infected with HIV-1. J Glob Antimicrob Resist, 2015; 3:267–272.
44.
FrentzD, BoucherCA, van de VijverDA: Temporal changes in the epidemiology of transmission of drug-resistant HIV-1 across the world. AIDS Rev, 2012; 14:17–27.
45.
MaggioloF, RipamontiD, AriciC, et al.: Simpler regimens may enhance adherence to antiretrovirals in HIV-infected patients. HIV Clin Trials, 2002; 3:371–378.
46.
JulgB, BognerJR: Atriplatrade mark—HIV therapy in one pill. Ther Clin Risk Manag, 2008; 4:573–577.
47.
CalvaJJ, LarreaS, Tapia-MaltosMA, et al.: The decline in HIV-1 drug resistance in heavily antiretroviral-experienced patients is associated with optimized prescriptions in a treatment roll-out program in Mexico. AIDS Res Hum Retroviruses, 2017; 33:675–680.
48.
Sepulveda-TorresLDC, RishishwarL, RogersML, et al.: A decade of viral mutations and associated drug resistance in a population of HIV-1+Puerto Ricans: 2002–2011. PLoS One, 2017; 12:e0177452.
49.
MillerV, Ait-KhaledM, StoneC, et al.: HIV-1 reverse transcriptase (RT) genotype and susceptibility to RT inhibitors during abacavir monotherapy and combination therapy. AIDS, 2000; 14:163–171.
50.
MolinaJM, MarcelinAG, PavieJ, et al.: Didanosine in HIV-1-infected patients experiencing failure of antiretroviral therapy: A randomized placebo-controlled trial. J Infect Dis, 2005; 191:840–847.
51.
EronJJJr., BoschRJ, BettendorfD, et al.: The effect of lamivudine therapy and M184 V on the antiretroviral activity of didanosine. J Acquir Immune Defic Syndr, 2007; 45:249–251.
52.
LarderBA, KempSD, HarriganPR: Potential mechanism for sustained antiretroviral efficacy of AZT-3TC combination therapy. Science, 1995; 269:696–699.
53.
GotteM, ArionD, ParniakMA, WainbergMA: The M184 V mutation in the reverse transcriptase of human immunodeficiency virus type 1 impairs rescue of chain-terminated DNA synthesis. J Virol, 2000; 74:3579–3585.
54.
FrostSD, NijhuisM, SchuurmanR, BoucherCA, BrownAJ: Evolution of lamivudine resistance in human immunodeficiency virus type 1-infected individuals: The relative roles of drift and selection. J Virol, 2000; 74:6262–6268.
55.
DialloK, GotteM, WainbergMA: Molecular impact of the M184 V mutation in human immunodeficiency virus type 1 reverse transcriptase. Antimicrob Agents Chemother, 2003; 47:3377–3383.
Database SUHDR: Available at https://hivdb.stanford.edu/dr-summary/resistance-notes/NRTI/ accessed April2017.
58.
HarriganPR, StoneC, GriffinP, et al.: Resistance profile of the human immunodeficiency virus type 1 reverse transcriptase inhibitor abacavir (1592 U89) after monotherapy and combination therapy. CNA2001 Investigative Group. J Infect Dis, 2000; 181:912–920.
59.
RheeSY, LiuT, RavelaJ, GonzalesMJ, ShaferRW: Distribution of human immunodeficiency virus type 1 protease and reverse transcriptase mutation patterns in 4,183 persons undergoing genotypic resistance testing. Antimicrob Agents Chemother, 2004; 48:3122–3126.
60.
EshlemanSH, JonesD, GalovichJ, et al.: Phenotypic drug resistance patterns in subtype A HIV-1 clones with nonnucleoside reverse transcriptase resistance mutations. AIDS Res Hum Retroviruses, 2006; 22:289–293.
61.
HarriganPR, MoT, WynhovenB, et al.: Rare mutations at codon 103 of HIV-1 reverse transcriptase can confer resistance to non-nucleoside reverse transcriptase inhibitors. AIDS, 2005; 19:549–554.
62.
MelikianGL, RheeSY, VargheseV, et al.: Non-nucleoside reverse transcriptase inhibitor (NNRTI) cross-resistance: Implications for preclinical evaluation of novel NNRTIs and clinical genotypic resistance testing. J Antimicrob Chemother, 2014; 69:12–20.
63.
De LucaA: The impact of resistance on viral fitness and its clinical implications. In: Antiretroviral Resistance in Clinical Practice (GerettiAM, ed.) London, Mediscript, 2006.
64.
Martinez-PicadoJ, SavaraAV, SuttonL, D'AquilaRT: Replicative fitness of protease inhibitor-resistant mutants of human immunodeficiency virus type 1. J Virol, 1999; 73:3744–3752.
65.
MenzoS, MonachettiA, BalottaC, et al.: Processivity and drug-dependence of HIV-1 protease: Determinants of viral fitness in variants resistant to protease inhibitors. AIDS, 2003; 17:663–671.
66.
DevereuxHL, EmeryVC, JohnsonMA, LovedayC: Replicative fitness in vivo of HIV-1 variants with multiple drug resistance-associated mutations. J Med Virol, 2001; 65:218–224.
67.
CraigC, RaceE, SheldonJ, et al.: HIV protease genotype and viral sensitivity to HIV protease inhibitors following saquinavir therapy. AIDS, 1998; 12:1611–1618.
68.
RheeSY, TaylorJ, FesselWJ, et al.: HIV-1 protease mutations and protease inhibitor cross-resistance. Antimicrob Agents Chemother, 2010; 54:4253–4261.
69.
VermeirenH, Van CraenenbroeckE, AlenP, et al.: Prediction of HIV-1 drug susceptibility phenotype from the viral genotype using linear regression modeling. J Virol Methods, 2007; 145:47–55.
70.
DandacheS, SevignyG, YelleJ, et al.: In vitro antiviral activity and cross-resistance profile of PL-100, a novel protease inhibitor of human immunodeficiency virus type 1. Antimicrob Agents Chemother, 2007; 51:4036–4043.
71.
BaxterJD, DunnD, WhiteE, et al.: Global HIV-1 transmitted drug resistance in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial. HIV Med, 2015; 16Suppl 1:77–87.
72.
FoxZ, PhillipsA, CohenC, et al.: Viral resuppression and detection of drug resistance following interruption of a suppressive non-nucleoside reverse transcriptase inhibitor-based regimen. AIDS, 2008; 22:2279–2289.
73.
WheelerWH, ZiebellRA, ZabinaH, et al.: Prevalence of transmitted drug resistance associated mutations and HIV-1 subtypes in new HIV-1 diagnoses U.S.-2006. AIDS, 2010; 24:1203–1212.
74.
WheelerVW, RadcliffeKW: HIV infection in the Caribbean. Int J STD AIDS, 1994; 5:79–89.
75.
HeslopOD, SmikleMF, DeerD, et al.: Human immunodeficiency virus type-1 (HIV-1) subtypes in Jamaica. West Indian Med J, 2005; 54:279–282.
76.
VaughanHE, CaneP, PillayD, TedderRS: Characterization of HIV type 1 clades in the Caribbean using pol gene sequences. AIDS Res Hum Retroviruses, 2003; 19:929–932.
77.
NoelRJJr., ChaudharyS, RodriguezN, KumarA, YamamuraY: Phylogenetic relationships between Puerto Rico and continental USA HIV-1 pol sequences: A shared HIV-1 infection. Cell Mol Biol (Noisy-le-grand), 2003; 49:1193–1198.
78.
BlancoM, MachadoLY, DiazH, RuizN, RomayD, SilvaE: HIV-1 genetic variability in cuba and implications for transmission and clinical progression. MEDICC Rev, 2015; 17:25–31.
79.
MachadoLY, BlancoM, DubedM, et al.: HIV type 1 genetic diversity in newly diagnosed Cuban patients. AIDS Res Hum Retroviruses, 2012; 28:956–960.
80.
CuevasMT, RuibalI, VillahermosaML, et al.: High HIV-1 genetic diversity in Cuba. AIDS, 2002; 16:1643–1653.
81.
WalkerPR, PybusOG, RambautA, HolmesEC: Comparative population dynamics of HIV-1 subtypes B and C: Subtype-specific differences in patterns of epidemic growth. Infect Genet Evol, 2005; 5:199–208.
82.
Martinez-CajasJL, Pant-PaiN, KleinMB, WainbergMA: Role of genetic diversity amongst HIV-1 non-B subtypes in drug resistance: A systematic review of virologic and biochemical evidence. AIDS Rev, 2008; 10:212–223.
83.
RiemenschneiderM, CashinKY, BudeusB, et al.: Genotypic prediction of co-receptor tropism of HIV-1 subtypes A and C. Sci Rep, 2016; 6:24883.
84.
WalterBL, ArmitageAE, GrahamSC, et al.: Functional characteristics of HIV-1 subtype C compatible with increased heterosexual transmissibility. AIDS, 2009; 23:1047–1057.
85.
MontanoSM, SanchezJL, Laguna-TorresA, et al.: Prevalences, genotypes, and risk factors for HIV transmission in South America. J Acquir Immune Defic Syndr, 2005; 40:57–64.
86.
HaggblomA, SvedhemV, SinghK, SonnerborgA, NeogiU: Virological failure in patients with HIV-1 subtype C receiving antiretroviral therapy: An analysis of a prospective national cohort in Sweden. Lancet HIV, 2016; 3:e166–e174.
87.
SutherlandKA, GhosnJ, GregsonJ, et al.: HIV-1 subtype influences susceptibility and response to monotherapy with the protease inhibitor lopinavir/ritonavir. J Antimicrob Chemother, 2015; 70:243–248.
88.
EasterbrookPJ, SmithM, MullenJ, et al.: Impact of HIV-1 viral subtype on disease progression and response to antiretroviral therapy. J Int AIDS Soc, 2010; 13:4.
89.
BousheriS, BurkeC, SsewanyanaI, et al.: Infection with different hiv subtypes is associated with CD4 activation-associated dysfunction and apoptosis. J Acquir Immune Defic Syndr, 2009; 52:548–552.
90.
VasanA, RenjifoB, HertzmarkE, et al.: Different rates of disease progression of HIV type 1 infection in Tanzania based on infecting subtype. Clin Infect Dis, 2006; 42:843–852.
91.
RaymondS, DelobelP, ChaixML, et al.: Genotypic prediction of HIV-1 subtype D tropism. Retrovirology, 2011; 8:56.
LauKA, WongJJ: Current trends of HIV recombination worldwide. Infect Dis Rep, 2013; 5(Suppl 1):e4.
94.
DelgadoE, ThomsonMM, VillahermosaML, et al.: Identification of a newly characterized HIV-1 BG intersubtype circulating recombinant form in Galicia, Spain, which exhibits a pseudotype-like virion structure. J Acquir Immune Defic Syndr, 2002; 29:536–543.
95.
HarrisB, von TruchsessI, SchatzlHM, DevareSG, HackettJJr.: Genomic characterization of a novel HIV type 1 B/G intersubtype recombinant strain from an injecting drug user in Germany. AIDS Res Hum Retroviruses, 2005; 21:654–660.
96.
EstevesA, ParreiraR, PiedadeJ, et al.: Spreading of HIV-1 subtype G and envB/gagG recombinant strains among injecting drug users in Lisbon, Portugal. AIDS Res Hum Retroviruses, 2003; 19:511–517.
97.
OrisatokiRO, OguntibejuOO, TruterEJ: The contributing role of tourism in the HIV/AIDS epidemic in the Caribbean. Niger J Med, 2009; 18:143–148.
98.
PadillaMB, Guilamo-RamosV, BourisA, ReyesAM: HIV/AIDS and tourism in the Caribbean: An ecological systems perspective. Am J Public Health, 2010; 100:70–77.
99.
Guilamo-RamosV, JaccardJ, McCarthyK, et al.: Taxonomy of Caribbean tourism alcohol venues: Implications for HIV transmission. Drug Alcohol Depend, 2013; 132:238–243.
100.
SurrattH: Sex work in the Caribbean Basin: Patterns of substance use and HIV risk among migrant sex workers in the US Virgin Islands. AIDS Care, 2007; 19:1274–1282.
101.
DerenS, KangSY, ColonHM, RoblesRR: The Puerto Rico-New York airbridge for drug users: Description and relationship to HIV risk behaviors. J Urban Health, 2007; 84:243–254.
102.
WolfersME, van den HoekC, BrugJ, de ZwartO: Using Intervention Mapping to develop a programme to prevent sexually transmittable infections, including HIV, among heterosexual migrant men. BMC Public Health, 2007; 7:141.
103.
CleghornFR, JackN, CarrJK, et al.: A distinctive clade B HIV type 1 is heterosexually transmitted in Trinidad and Tobago. Proc Natl Acad Sci U S A, 2000; 97:10532–10537.
104.
YebraG, de MulderM, MartinL, et al.: Most HIV type 1 non-B infections in the Spanish cohort of antiretroviral treatment-naive HIV-infected patients (CoRIS) are due to recombinant viruses. J Clin Microbiol, 2012; 50:407–413.
105.
CandottiD, Adu-SarkodieY, DaviesF, et al.: AIDS in an HIV-seronegative Ghanaian woman with intersubtype A/G recombinant HIV-1 infection. J Med Virol, 2000; 62:1–8.
106.
ZhangM, FoleyB, SchultzAK, et al.: The role of recombination in the emergence of a complex and dynamic HIV epidemic. Retrovirology, 2010; 7:25.
