Data on the prevalence of double infection (DI) in HIV individuals are lacking in Spain. To fill this gap, we analyzed the prevalence of DI in a cohort of men who have sex with men (MSM) and examined factors contributing to DI. We selected 81 MSM attending Centro Sanitario Sandoval, a sexually transmitted diseases clinic in Madrid. We obtained by ultra-deep sequencing the proviral sequences in gag and env genes and performed a phylogenetic analysis for the identification of DI. Clinical, behavioral, host, and viral factors were studied for its association with DI. We detected six individuals with DI and one case of superinfection with a global prevalence of 8.6%. The genetic distance among the subtype B viruses in monoinfected individuals (24.4%) was lower than the distance between the two viruses in subtype B DI individuals (29.5%). Individuals with a high number of sexual contacts (>25 partners/year) had an 8.66 times higher risk of DI (p = .017). In this MSM cohort the prevalence of HIV DI was estimated at 8.6%. DI was strongly associated with the number of sexual partners. Because of the pathogenic consequences of HIV DI, this high prevalence should promote public health programs targeted at high-risk population such as MSM for the control of HIV infection and DI. HIV DI should be considered for a better clinical management of these individuals.
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References
1.
JostS, BernardMC, KaiserL, et al.: A patient with HIV-1 superinfection. N Engl J Med, 2002; 347:731–736.
2.
ReddAD, QuinnTC, TobianAA: Frequency and implications of HIV superinfection. Lancet Infect Dis, 2013; 13:622–628.
Plan Nacional sobre el Sida—D.G. de Salud Pública CeICNdE-I. Unidad de Vigilancia de VIH y Comportamientos de Riesgo. Vigilancia Epidemiológica del VIH y sida en España 2018: Sistema de Información sobre Nuevos Diagnósticos de VIH y Registro Nacional de Casos de Sida. Madrid, 2019.
5.
BlackardJT, MayerKH: HIV superinfection in the era of increased sexual risk taking. Sex Transm Dis, 2004; 31:201–204.
6.
van der KuylAC, CornelissenM: Identifying HIV-1 dual infections. Retrovirology, 2007; 4:67.
7.
BarKJ, LiH, ChamberlandA, et al.: Wide variation in the multiplicity of HIV-1 infection among injection drug users. J Virol, 2010; 84:6241–6247.
8.
TempletonAR, KramerMG, JarvisJ, et al.: Multiple-infection and recombination in HIV-1 within a longitudinal cohort of women. Retrovirology, 2009; 6:54.
9.
PacoldME, PondSL, WagnerGA, et al.: Clinical, virologic, and immunologic correlates of HIV-1 intraclade B dual infection among men who have sex with men. AIDS, 2012; 26:157–165.
10.
Soares de OliveiraAC, Pessoa de FariasR, da CostaAC, et al.: Frequency of subtype B and F1 dual infection in HIV-1 positive, Brazilian men who have sex with men. Virol J, 2012; 9:223.
11.
LuanH, HanX, YuX, et al.: Dual infection contributes to rapid disease progression in men who have sex with men in China. J Acquir Immune Defic Syndr, 2017; 75:480–487.
12.
ZhangY, SuB, LiH, et al.: Triple HIV-1 infection is associated with faster CD4(+) T-cell decline. Front Microbiol, 2020; 11:21.
13.
HebberechtL, VancoillieL, SchauvliegeM, et al.: Frequency of occurrence of HIV-1 dual infection in a Belgian MSM population. PLoS One, 2018; 13:e0195679.
14.
PernasM, CasadoC, SandonisV, et al.: Prevalence of HIV-1 dual infection in long-term nonprogressor-elite controllers. J Acquir Immune Defic Syndr, 2013; 64:225–231.
15.
VesaJ, ChaillonA, WagnerGA, et al.: Increased HIV-1 superinfection risk in carriers of specific human leukocyte antigen alleles. AIDS, 2017; 31:1149–1158.
16.
CaetanoDG, CortesFH, BelloG, et al.: A case report of HIV-1 superinfection in an HIV controller leading to loss of viremia control: A retrospective of 10 years of follow-up. BMC Infect Dis, 2019; 19:588.
17.
GottliebGS, NickleDC, JensenMA, et al.: HIV type 1 superinfection with a dual-tropic virus and rapid progression to AIDS: A case report. Clin Infect Dis, 2007; 45:501–509.
18.
CornelissenM, PasternakAO, GrijsenML, et al.: HIV-1 dual infection is associated with faster CD4+ T-cell decline in a cohort of men with primary HIV infection. Clin Infect Dis, 2012; 54:539–547.
19.
WagnerGA, PacoldME, Kosakovsky PondSL, et al.: Incidence and prevalence of intrasubtype HIV-1 dual infection in at-risk men in the United States. J Infect Dis, 2014; 209:1032–1038.
20.
SmithDM, RichmanDD, LittleSJ: HIV superinfection. J Infect Dis, 2005; 192:438–444.
21.
SmithDM, WongJK, HightowerGK, et al.: HIV drug resistance acquired through superinfection. AIDS, 2005; 19:1251–1256.
22.
JurriaansS, KozaczynskaK, ZorgdragerF, et al.: A sudden rise in viral load is infrequently associated with HIV-1 superinfection. J Acquir Immune Defic Syndr, 2008; 47:69–73.
23.
PernasM, CasadoC, ArconesC, et al.: Low-replicating viruses and strong anti-viral immune response associated with prolonged disease control in a superinfected HIV-1 LTNP elite controller. PLoS One, 2012; 7:e31928.
24.
VandergeetenC, FromentinR, MerliniE, et al.: Cross-clade ultrasensitive PCR-based assays to measure HIV persistence in large-cohort studies. J Virol, 2014; 88:12385–12396.
25.
BelloG, CasadoC, SandonisV, et al.: A subset of human immunodeficiency virus type 1 long-term non-progressors is characterized by the unique presence of ancestral sequences in the viral population. J Gen Virol, 2005; 86:355–364.
26.
BolgerAM, LohseM, UsadelB: Trimmomatic: A flexible trimmer for Illumina sequence data. Bioinformatics, 2014; 30:2114–2120.
27.
ZhangJ, KobertK, FlouriT, StamatakisA: PEAR: A fast and accurate Illumina Paired-End reAd mergeR. Bioinformatics, 2014; 30:614–620.
28.
EdgarRC, FlyvbjergH: Error filtering, pair assembly and error correction for next-generation sequencing reads. Bioinformatics, 2015; 31:3476–3482.
29.
OlivaresI, Casado HerreroC, Iglesias-UsselMD, DietrichU, Lopez-GalindezC: Complete sequence of an infectious molecular clone derived from a Spanish HIV type 1 isolate. AIDS Res Hum Retroviruses, 1998; 14:1649–1651.
JensenMA, LiFS, van ‘t WoutAB, et al.: Improved coreceptor usage prediction and genotypic monitoring of R5-to-X4 transition by motif analysis of human immunodeficiency virus type 1 env V3 loop sequences. J Virol, 2003; 77:13376–13388.
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.
34.
PernasM, Tarancon-DiezL, Rodriguez-GallegoE, et al.: Factors leading to the loss of natural elite control of HIV-1 infection. J Virol, 2018; 92:1805–1817.
35.
FirthD: Bias reduction of maximum likelihood estimates. Biometrika, 1993; 80:27–38.
36.
R Core Team (2017). R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. https://www.R-project.org/
37.
Ayerdi-AguirrebengoaO, Vera-GarciaM, Puerta-LopezT, Raposo-UtrillaM, Rodriguez-MartinC, Del Romero-GuerreroJ: To whom is HIV pre-exposure prophylaxis proposed?. Enferm Infecc Microbiol Clin, 2017; 35:299–302.
38.
ThomsonMM, DelgadoE, ManjonN, et al.: HIV-1 genetic diversity in Galicia Spain: BG intersubtype recombinant viruses circulating among injecting drug users. AIDS, 2001; 15:509–516.
39.
de MendozaC, CabezasT, CaballeroE, et al.: HIV type 2 epidemic in Spain: Challenges and missing opportunities. AIDS, 2017; 31:1353–1364.
40.
PernasM, CasadoC, FuentesR, Perez-EliasMJ, Lopez-GalindezC.: A dual superinfection and recombination within HIV-1 subtype B 12 years after primoinfection. J Acquir Immune Defic Syndr, 2006; 42:12–18.
41.
GerhardtM, MlokaD, TovanabutraS, et al.: In-depth, longitudinal analysis of viral quasispecies from an individual triply infected with late-stage human immunodeficiency virus type 1, using a multiple PCR primer approach. J Virol, 2005; 79:8249–8261.
42.
KozaczynskaK, CornelissenM, ReissP, ZorgdragerF, van der KuylAC: HIV-1 sequence evolution in vivo after superinfection with three viral strains. Retrovirology, 2007; 4:59.
43.
McCutchanFE, HoelscherM, TovanabutraS, et al.: In-depth analysis of a heterosexually acquired human immunodeficiency virus type 1 superinfection: Evolution, temporal fluctuation, and intercompartment dynamics from the seronegative window period through 30 months postinfection. J Virol, 2005; 79:11693–11704.
44.
MarkhamRB, WangWC, WeissteinAE, et al.: Patterns of HIV-1 evolution in individuals with differing rates of CD4 T cell decline. Proc Natl Acad Sci U S A, 1998; 95:12568–12573.
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