第一例在喀麦隆之外发现的N型HIV

         N型HIV罕见，就在2011年11月之前世界上诊断的也不过12例，而且都在喀麦隆。但是，去年11月份柳叶刀杂志在线发表了一个在法国发现的N型急性HIV感染患者。该患者从多哥共和国旅行归来8天发病，在多哥有性接触。用常用的抗体初筛及确证检测方法都是弱阳性，但病毒载量超过1万。因为治疗前做耐药检测时无法用目前方法扩增出逆转录酶和蛋白酶，作者团队才检测了病毒的基因序列，发现是N型。文章结论是：罕见的N型已经在喀麦隆之外发现，需要加大监测力度。但是，我认为，目前我们仍不必担心N型的问题。北京佑安医院性病艾滋病临床诊疗中心李在村

以下是原文，可以在柳叶刀网站上找到，需要注册，免费。

HIV-1 group N: travelling beyond Cameroon

Constance Delaugerre PhD a, Fabienne De Oliveira MSc c, Caroline Lascoux-Combe MD b, Prof Jean-Christophe Plantier PhD c, Prof François Simon MD a

On Jan 21, 2011, a 57-year-old man living in France attended our emergency unit with fever, rash, lymphadenopathy, and genital ulceration, 8 days after returning from Togo. He reported sexual contact with a Togolese partner, and HIV primary infection was suspected. Fourth-generation ELISA (ARCHITECT HIV Ag/Ab Combo, Abbott, Chicago, IL) was weakly positive, and HIV-1 western blot (New Lav Blot I, Biorad, Paris, France) showed weak reactivity with the p55 and p24 antigens. On Feb 1, 2011, his HIV-1 RNA load was 4?2 log10 copies per mL (Cobas TaqMan HIV-1 v2.0 assay, Roche Molecular Systems, Branchburg, NJ, USA). On Feb 9, 2011, he developed facial paralysis. At this time his CD4 cell count was 219 per μL and his plasma and CSF HIV-1 RNA concentrations were 4?4 log10 and 4?5 log10 copies per mL, respectively.

In keeping with French guidelines on new cases of HIV infection, we undertook resistance genotyping before starting treatment. We were surprised that we could not amplify the reverse transcriptase and protease genes with the ViroSeq HIV-1 genotyping assay (Abbott, Chicago, IL, USA) and the French National Agency for AIDS Research consensus primers, despite the high viral load. This finding prompted us to serotype the samples.1, 2 Clear reactivity against group-N-specific antigens was obtained and we therefore did full-length genome sequencing.3 Phylogenetic analysis confirmed that the new sequence clustered strictly within available group-N sequences (sequence designated N1.FR.2011, GenBank accession number JN572926). When last seen for follow-up after 4 weeks of antiretroviral combination therapy with tenofovir, emtricitabine, darunavir/ritonavir, raltegravir, and maraviroc, our patient"s plasma HIV-1 RNA load was below 20 copies per mL and his CD4 cell count was 483 per μL.

HIV-1 group N (non-M, non-O) was first identified in 1998 in a Cameroonian woman with AIDS.1 This highly divergent HIV variant is more closely related to SIV isolated from wild chimpanzees than to HIV-1 groups M (major), O (outlier), and P.1, 3 Group-N infection has previously been reported only in HIV-infected patients living in Cameroon.4 More than 12 000 HIV-infected patients living in Cameroon have been tested for group-N infection, but only 12 cases, including two couples infected by the same strains, have been identified.1, 2, 4, 5 Although our patient was diagnosed in Paris, the infection was probably acquired in Togo, which suggests that group-N viruses are now circulating outside Cameroon. This case of primary HIV-N infection is particularly important because of the severe clinical manifestations and early decline in the CD4 cell count. A five-drug antiretroviral combination showed good initial efficacy, but longer-term immunological and virological follow-up is needed. The viral load of this HIV-N infected patient was positive during the primary infection as assessed by the Cobas TaqMan HIV-1 v2.0 assay, but the validity of the quantitative result is uncertain. The viral load was also assessed using the Abbott RealTime HIV-1 assay (Chicago, IL, USA), but was under-quantified by about 1 log10. Whether other commercial assays can quantify these variants remains to be shown. Standard resistance genotyping methods used for group M failed to amplify the group-N virus, as happened with the first case of group-P virus detected in 2009.3 Discrepancies between the results of HIV viral load assays and molecular tests should alert clinicians and virologists to the possibility of infection by a variant virus, which has important implications for management of the patient. This case of HIV-1 group-N primary infection indicates that this rare group is now circulating outside Cameroon, which emphasises the need for rigorous HIV epidemiological monitoring.

Contributors

CD and FDO fully characterised the viral isolates, CL-C was in charge of clinical follow-up, J-CP overlooked the serotyping and molecular analysis, and CD, J-CP, and FS wrote the report. Written consent to publish was obtained.

References

1Simon F, Mauclère P, Roques P, et al. Identification of a new human immunodeficiency virus type 1 distinct from group M and group O. Nat Med 1998; 4: 1032-1037. CrossRef | PubMed

2Roques P, Robertson DL, Souquière S, et al. Phylogenetic characteristics of three new HIV-1 N strains and implications for the origin of group N. AIDS 2004; 18: 1371-1381. CrossRef | PubMed

3Plantier JC, Leoz M, Dickerson JE, et al. A new human immunodeficiency virus derived from gorillas. Nat Med 2009; 15: 871-872. CrossRef | PubMed

4Yamaguchi J, Coffey R, Vallari A, et al. Identification of HIV type 1 group N infections in a husband and wife in Cameroon: viral genome sequences provide evidence for horizontal transmission. AIDS Res Hum Retroviruses 2006; 22: 83-92. CrossRef | PubMed

5Vallari A, Bodelle P, Ngansop C, et al. Four new HIV-1 group N isolates from Cameroon: prevalence continues to be low. AIDS Res Hum Retroviruses 2010; 26: 109-115. CrossRef | PubMed