title: When should HAART be initiated in pregnancy to achieve an undetectable HIV viral load by delivery?
abstract: BACKGROUND
  HAART dramatically reduces mother-to-child transmission of HIV allowing vaginal delivery if the viral load is low. This study provides data for the optimum timing of short-term HAART in pregnancy.
  
  
  METHODS
  Retrospective multicentre cohort study of pregnant women commencing HAART in London and Brighton, UK. Demographics, gestation, drug class, CD4 cell count, and viral load results were collated. Survival curves for reaching a viral load less than 50  copies/ml were stratified by initial HIV viral load. Cox's proportional hazards regression model was adjusted for demographics and immunovirological parameters.
  
  
  RESULTS
  Viral load was less than 50  copies/ml in 292 of 378 pregnancies (77.2%) by delivery. Pretreatment viral load was associated with the time taken, and the proportion achieving a viral load less than 50  copies/ml at (P≤0.001). When baseline viral load was less than 10 ,000  copies/ml, gestational age at HAART initiation did not affect success up to 26.3 weeks gestation. When viral load was more than 10 ,000  copies/ml, deferring HAART past 20.4 weeks reduced the probability of reaching less than 50  copies/ml by delivery (P=0.011). When baseline viral load was more than 100, 000  copies/ml the likelihood of reaching a viral load of less than 50  copies/ml was low (37%: hazard ratio 0.31), and dependent on the length of time on HAART. The hazard ratio for a nonnucleoside reverse transcriptase inhibitor regimen achieving a viral load less than 50  copies/ml compared with a protease inhibitor was 0.7 (95% confidence interval 0.52-0.94).
  
  
  CONCLUSIONS
  With a viral load more than 10, 000  copies/ml and especially with a viral load more than 100 ,000  copies/ml, the probability of achieving either less than 50 copies/ml by the time of delivery is compromised by delaying initiation of short-term highly active antiretroviral therapy beyond 20.4 weeks gestation. Current UK and other guidelines for when to commence START may therefore limit the chance of vaginal delivery.
authors.affiliation: Guy's & St Thomas' NHS Foundation Trust, London, UK.
authors.forename: Phillip J
authors.initials: PJ
authors.lastname: Read
authors.forename: Sundhiya
authors.initials: S
authors.lastname: Mandalia
authors.forename: Palwasha
authors.initials: P
authors.lastname: Khan
authors.forename: Ursula
authors.initials: U
authors.lastname: Harrisson
authors.forename: Claire
authors.initials: C
authors.lastname: Naftalin
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Gilleece
authors.forename: Jane
authors.initials: J
authors.lastname: Anderson
authors.forename: David A
authors.initials: DA
authors.lastname: Hawkins
authors.forename: Graham P
authors.initials: GP
authors.lastname: Taylor
authors.forename: Annemiek
authors.initials: A
authors.lastname: de Ruiter
mesh_terms: D000293:Adolescent; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D036861:Delivery, Obstetric; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D008875:Middle Aged; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy* / Q000821:virology; D011480:Protease Inhibitors / Q000008:administration & dosage*; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage*; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load / Q000706:statistics & numerical data*; D055815:Young Adult
chemical_list: D011480:Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors