Safety of tenofovir gel, a vaginal microbicide, in South African women: results of the CAPRISA 004 Trial.
BACKGROUND
Tenofovir gel, used vaginally before and after coitus, reduced women's acquisition of HIV by 39%. This is a safety assessment of tenofovir gel, including renal, bone, gastrointestinal, genital and haematological parameters.


METHODS
In the Centre for the AIDS Programme of Research in South Africa (CAPRISA) 004, a double-blind, randomized placebo-controlled trial, 445 of the 889 eligibly enrolled women were assigned to tenofovir gel. All participants were advised to use the gel vaginally only, with one dose of gel within 12 h before and a second dose as soon as possible after sex, with no more than two doses in 24 h. Clinical and laboratory safety data were collected at monthly and quarterly visits, respectively. Genital assessments were undertaken at enrolment and quarterly thereafter, or as indicated.


RESULTS
Women assigned to tenofovir gel were exposed to an average monthly vaginal dose of 240 mg of tenofovir (six applications). In total, six women, three in each group, had mild creatinine elevations, all of which occurred in July/August 2008. The incidence of anaemia was 3.5 and 3.8 per 100 women-years in tenofovir and placebo groups, respectively (P=0.80). Of the six women (four tenofovir and two placebo) experiencing bone fractures, none were associated with abnormal phosphate or calcium values. The proportion of women with diarrhoea was higher in the tenofovir gel group (17% versus 11%; P=0.026). There was no significant increase of any genital adverse event in the tenofovir group.


CONCLUSIONS
No significant renal, haematological, genital or bone effects were associated with the use of tenofovir gel. Aside from a puzzling increase in diarrhoea, tenofovir gel has an excellent safety profile.
FHI 360, Clinical Sciences Department, Durham, NC, USA.
David C
DC
Sokal
Quarraisha Abdool
QA
Karim
Sengeziwe
S
Sibeko
Nonhlanhla
N
Yende-Zuma
Leila E
LE
Mansoor
Cheryl
C
Baxter
Anneke
A
Grobler
Janet
J
Frolich
Ayesha Bm
AB
Kharsany
Nomsa
N
Miya
Koleka
K
Mlisana
Silvia
S
Maarshalk
Salim S Abdool
SS
Karim
D000225:Adenine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000282:Administration, Intravaginal; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects*; D000891:Anti-Infective Agents, Local / Q000008:administration & dosage / Q000009:adverse effects*; D001842:Bone and Bones / Q000187:drug effects; D005260:Female; D005500:Follow-Up Studies; D041981:Gastrointestinal Tract / Q000187:drug effects; D015658:HIV Infections / Q000097:blood / Q000517:prevention & control; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D063065:Organophosphonates / Q000008:administration & dosage / Q000009:adverse effects*; D013019:South Africa; D000068698:Tenofovir; D014622:Vaginal Creams, Foams, and Jellies
D019380:Anti-HIV Agents; D000891:Anti-Infective Agents, Local; D063065:Organophosphonates; D014622:Vaginal Creams, Foams, and Jellies; D000068698:Tenofovir; D000225:Adenine