title: 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.
abstract: 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.
authors.affiliation: Crusaid Kobler AIDS Center, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
authors.forename: Boaz
authors.initials: B
authors.lastname: Avidor
authors.forename: Dan
authors.initials: D
authors.lastname: Turner
authors.forename: Zohar
authors.initials: Z
authors.lastname: Mor
authors.forename: Shirley
authors.initials: S
authors.lastname: Chalom
authors.forename: Klaris
authors.initials: K
authors.lastname: Riesenberg
authors.forename: Eduardo
authors.initials: E
authors.lastname: Shahar
authors.forename: Shimon
authors.initials: S
authors.lastname: Pollack
authors.forename: Daniel
authors.initials: D
authors.lastname: Elbirt
authors.forename: Zev
authors.initials: Z
authors.lastname: Sthoeger
authors.forename: Shlomo
authors.initials: S
authors.lastname: Maayan
authors.forename: Karen
authors.initials: K
authors.lastname: Olshtain-Pops
authors.forename: Diana
authors.initials: D
authors.lastname: Averbuch
authors.forename: Michal
authors.initials: M
authors.lastname: Chowers
authors.forename: Valery
authors.initials: V
authors.lastname: Istomin
authors.forename: Emilia
authors.initials: E
authors.lastname: Anis
authors.forename: Ella
authors.initials: E
authors.lastname: Mendelson
authors.forename: Daniela
authors.initials: D
authors.lastname: Ram
authors.forename: Itzchak
authors.initials: I
authors.lastname: Levy
authors.forename: Zehava
authors.initials: Z
authors.lastname: Grossman
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use*; D024882:Drug Resistance, Viral / Q000187:drug effects / Q000235:genetics; D055030:Drug Users / Q000706:statistics & numerical data; D005260:Female; D014644:Genetic Variation; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000635:transmission* / Q000821:virology; D016333:HIV Protease / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors / Q000235:genetics; D015497:HIV-1 / Q000145:classification / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D007557:Israel / Q000453:epidemiology; D008297:Male; D058889:Molecular Typing; D010802:Phylogeny; D015995:Prevalence; D012309:Risk-Taking; D015819:Substance Abuse, Intravenous / Q000453:epidemiology / Q000821:virology; D016896:Treatment Outcome
chemical_list: D019380:Anti-HIV Agents; D054303:HIV Reverse Transcriptase; D016333:HIV Protease