Transmission Patterns of HIV-Subtypes A/AE versus B: Inferring Risk-Behavior Trends and Treatment-Efficacy Limitations from Viral Genotypic Data Obtained Prior to and during Antiretroviral Therapy

被引：10

作者：

Avidor, Boaz ^{[1
,2
]}

Turner, Dan ^{[1
]}

Mor, Zohar ^{[3
]}

Chalom, Shirley ^{[1
]}

Riesenberg, Klaris ^{[4
]}

Shahar, Eduardo ^{[5
]}

Pollack, Shimon ^{[5
]}

Elbirt, Daniel ^{[6
]}

Sthoeger, Zev ^{[6
]}

Maayan, Shlomo ^{[7
]}

Olshtain-Pops, Karen ^{[7
]}

Averbuch, Diana ^{[7
]}

Chowers, Michal ^{[8
]}

Istomin, Valery ^{[9
]}

Anis, Emilia ^{[10
]}

Mendelson, Ella ^{[11
,12
]}

Ram, Daniela ^{[11
]}

Levy, Itzchak ^{[13
]}

Grossman, Zehava ^{[12
]}

机构：

[1] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Crusaid Kobler AIDS Ctr, IL-69978 Tel Aviv, Israel

[2] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Lab Viruses & Mol Biol, IL-69978 Tel Aviv, Israel

[3] Minist Hlth, Publ Hlth Serv, Ramle Dept Hlth, Ramla, Israel

[4] Soroka Med Ctr, IL-84101 Beer Sheva, Israel

[5] Rambam Med Ctr, Haifa, Israel

[6] Kaplan Med Ctr, Rehovot, Israel

[7] Hadassah Med Ctr, IL-91120 Jerusalem, Israel

[8] Meir Med Ctr, Kefar Sava, Israel

[9] Hillel Yaffe Med Ctr, Hadera, Israel

[10] Minist Hlth, Dept Epidemiol, Publ Hlth Serv, Jerusalem, Israel

[11] Minist Hlth, Cent Virol, Publ Hlth Labs, Ramat Gan, Israel

[12] Tel Aviv Univ, Sch Publ Hlth, IL-69978 Tel Aviv, Israel

[13] Sheba Med Ctr, Infect Dis Unit, Ramat Gan, Israel

来源：

PLOS ONE | 2013年 / 8卷 / 03期

关键词：

VIRUS REVERSE-TRANSCRIPTASE; TYPE-1; DRUG-RESISTANCE; RESPONSE CURVE SLOPE; PROTEASE; INFECTION; MUTATIONS; EPIDEMIOLOGY; DIVERSITY; SUSCEPTIBILITY; EMTRICITABINE;

D O I：

10.1371/journal.pone.0057789

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Background: HIV subtypes A and CRF01_AE (A/AE) became prevalent in Israel, first through immigration of infected people, mostly intravenous-drug users (IVDU), from Former Soviet-Union (FSU) countries and then also by local spreading. We retrospectively studied virus-transmission patterns of these subtypes in comparison to the longer-established subtype B, evaluating in particular risk-group related differences. We also examined to what extent distinct drug-resistance patterns in subtypes A/AE versus B reflected differences in patient behavior and drug-treatment history. Methods: Reverse-transcriptase (RT) and protease sequences were retrospectively analyzed along with clinical and epidemiological data. MEGA, ClusalX, and Beast programs were used in a phylogenetic analysis to identify transmission networks. Results: 318 drug-naive individuals with A/AE or patients failing combination antiretroviral therapy (cART) were identified. 61% were IVDU. Compared to infected homosexuals, IVDU transmitted HIV infrequently and, typically, only to a single partner. 6.8% of drug-naive patients had drug resistance. Treatment-failing, regimen-stratified subtype-A/AE-and B-patients differed from each other significantly in the frequencies of the major resistance-conferring mutations T215FY, K219QE and several secondary mutations. Notably, failing boosted protease-inhibitors (PI) treatment was not significantly associated with protease or RT mutations in either subtype. Conclusions: While sizable transmission networks occur in infected homosexuals, continued HIV transmission among IVDU in Israel is largely sporadic and the rate is relatively modest, as is that of drug-resistance transmission. Deviation of drugnaive A/AE sequences from subtype-B consensus sequence, documented here, may subtly affect drug-resistance pathways. Conspicuous differences in overall drug-resistance that are manifest before regimen stratification can be largely explained in terms of treatment history, by the different efficacy/adherence limitations of older versus newer regimens. The phenomenon of treatment failure in boosted-PI-including regimens in the apparent absence of drug-resistance to any of the drugs, and its relation to adherence, require further investigation.

引用

页数：13