PMID- 23469241
OWN - NLM
STAT- MEDLINE
DCOM- 20130827
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 3
DP  - 2013
TI  - 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.
PG  - e57789
LID - 10.1371/journal.pone.0057789 [doi]
LID - e57789
AB  - 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 drug-naive 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.
FAU - Avidor, Boaz
AU  - Avidor B
AD  - Crusaid Kobler AIDS Center, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
FAU - Turner, Dan
AU  - Turner D
FAU - Mor, Zohar
AU  - Mor Z
FAU - Chalom, Shirley
AU  - Chalom S
FAU - Riesenberg, Klaris
AU  - Riesenberg K
FAU - Shahar, Eduardo
AU  - Shahar E
FAU - Pollack, Shimon
AU  - Pollack S
FAU - Elbirt, Daniel
AU  - Elbirt D
FAU - Sthoeger, Zev
AU  - Sthoeger Z
FAU - Maayan, Shlomo
AU  - Maayan S
FAU - Olshtain-Pops, Karen
AU  - Olshtain-Pops K
FAU - Averbuch, Diana
AU  - Averbuch D
FAU - Chowers, Michal
AU  - Chowers M
FAU - Istomin, Valery
AU  - Istomin V
FAU - Anis, Emilia
AU  - Anis E
FAU - Mendelson, Ella
AU  - Mendelson E
FAU - Ram, Daniela
AU  - Ram D
FAU - Levy, Itzchak
AU  - Levy I
FAU - Grossman, Zehava
AU  - Grossman Z
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130301
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Anti-HIV Agents)
RN  - EC 2.7.7.49 (HIV Reverse Transcriptase)
RN  - EC 3.4.23.- (HIV Protease)
SB  - IM
MH  - Adult
MH  - Anti-HIV Agents/pharmacology/*therapeutic use
MH  - Drug Resistance, Viral/drug effects/genetics
MH  - Drug Users/statistics & numerical data
MH  - Female
MH  - Genetic Variation
MH  - HIV Infections/*drug therapy/epidemiology/*transmission/virology
MH  - HIV Protease/genetics
MH  - HIV Reverse Transcriptase/antagonists & inhibitors/genetics
MH  - HIV-1/classification/drug effects/*genetics/isolation & purification
MH  - Humans
MH  - Israel/epidemiology
MH  - Male
MH  - Molecular Typing
MH  - Phylogeny
MH  - Prevalence
MH  - Risk-Taking
MH  - Substance Abuse, Intravenous/epidemiology/virology
MH  - Treatment Outcome
PMC - PMC3585963
COIS- Competing Interests: IL is a consultant for Jansen, Glaxo-SmithKline, MSD, and 
      BioTIS; provided expert testimony for Viif; has been a member of the speakers' 
      bureau for Jansen, GlaxoSmithKline, MSD, and BioTIS; and has received expense 
      reimbursement for travel/meetings from Jansen, GlaxoSmithKline, MSD, and BioTIS. 
      All other authors have declared that no competing interests exist. This does not 
      alter the authors' adherence to all the PLOS ONE policies on sharing data and 
      materials.
EDAT- 2013/03/08 06:00
MHDA- 2013/08/28 06:00
PMCR- 2013/03/01
CRDT- 2013/03/08 06:00
PHST- 2012/11/25 00:00 [received]
PHST- 2013/01/25 00:00 [accepted]
PHST- 2013/03/08 06:00 [entrez]
PHST- 2013/03/08 06:00 [pubmed]
PHST- 2013/08/28 06:00 [medline]
PHST- 2013/03/01 00:00 [pmc-release]
AID - PONE-D-12-37105 [pii]
AID - 10.1371/journal.pone.0057789 [doi]
PST - ppublish
SO  - PLoS One. 2013;8(3):e57789. doi: 10.1371/journal.pone.0057789. Epub 2013 Mar 1.