title: Emergence of lamivudine resistance hepatitis B virus mutations in pregnant women infected with HBV and HIV receiving antiretroviral prophylaxis for the prevention of mother-to-infant transmission in Malawi.
abstract: HIV/HBV co-infection is highly prevalent in sub-Saharan Africa. The aim of this study was to determine if the use of triple combination lamivudine-containing prophylaxis for the prevention of mother-to-infant HIV transmission was associated with the emergence of lamivudine HBV mutations. The study included 21 pregnant co-infected women in Malawi who received either zidovudine or stavudine plus lamivudine and nevirapine from week 25 of gestation until 6 months after delivery or indefinitely if they met the criteria for treatment (CD4+ <350/mm(3)). HBV-DNA was determined using the Roche COBAS assay. Resistance mutations were assessed by the Trugene assay (Siemens Diagnostics). At baseline 33% of the women were HBeAg positive and had HBV-DNA > 10(4) IU/ml. Median CD4 count was 237 cells/mm(3) and median HIV-RNA was 3.8 log(10) copies/ml. After a median of 259 days of treatment, HBV-DNA was detectable in 9 out of 21 patients (42.8%). In three cases the HBV-DNA level was >10(4) IU/ml. Resistance mutations (M204I in five cases and L180M + M204I/V in one case) were present in 6 (28.6%) patients. Women with a resistant virus had significantly higher baseline HBV-DNA levels than those not developing resistance (1.1 × 10(7) IU/ml vs. 20.8 IU/ml, P = 0.022). Levels of ALT and AST were higher in women with resistant viruses compared to those retaining a wild-type virus. A high rate of lamivudine resistance was seen in this cohort of pregnant women. Follow-up of these patients will clarify if the presence of resistance has a significant impact on liver disease.
authors.affiliation: Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Clementina
authors.initials: C
authors.lastname: Galluzzo
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Liotta
authors.forename: Mauro
authors.initials: M
authors.lastname: Andreotti
authors.forename: Richard
authors.initials: R
authors.lastname: Luhanga
authors.forename: Haswell
authors.initials: H
authors.lastname: Jere
authors.forename: Sandro
authors.initials: S
authors.lastname: Mancinelli
authors.forename: Martin
authors.initials: M
authors.lastname: Maulidi
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Sagno
authors.forename: Maria
authors.initials: M
authors.lastname: Pirillo
authors.forename: Fulvio
authors.initials: F
authors.lastname: Erba
authors.forename: Roberta
authors.initials: R
authors.lastname: Amici
authors.forename: Susanna
authors.initials: S
authors.lastname: Ceffa
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Marazzi
authors.forename: Stefano
authors.initials: S
authors.lastname: Vella
authors.forename: Leonardo
authors.initials: L
authors.lastname: Palombi
authors.forename: Marina
authors.initials: M
authors.lastname: Giuliano
mesh_terms: D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000494:pharmacology; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D018791:CD4 Lymphocyte Count; D004279:DNA, Viral / Q000097:blood / Q000235:genetics; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000517:prevention & control; D006509:Hepatitis B / Q000821:virology*; D006515:Hepatitis B virus / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control; D019259:Lamivudine / Q000008:administration & dosage* / Q000494:pharmacology; D008295:Malawi; D009154:Mutation; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy*; D012367:RNA, Viral / Q000097:blood; D019562:Viral Load; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D004279:DNA, Viral; D012367:RNA, Viral; D019259:Lamivudine