Faculty Bibliography

SETTING/METHODS:We conducted a retrospective study among HIV-infected adult suspects (≥18 years) with pulmonary tuberculosis (TB), who underwent Xpert MTB/RIF (Xpert) testing at McCord Hospital and its adjoining HIV clinic in Durban, South Africa. OBJECTIVE:To determine if Xpert testing performed at a centralized laboratory accelerated time to TB diagnosis. DESIGN/METHODS:We obtained data on sputum smear microscopy [acid-fast bacilli (AFB)], Xpert, and the rationale for treatment initiation from medical records. The primary outcome was "total diagnostic time," defined as time from sputum collection to clinicians' receipt of results. A linear mixed-effect model compared the duration of steps in the diagnostic pathway across testing modalities. RESULTS:Among 403 participants, the median "total diagnostic time" for AFB and Xpert was 3.3 and 6.4 days, respectively (P < 0.001). When compared with AFB, the median delay for Xpert "laboratory processing" was 1.4 days (P < 0.001) and "result transfer to clinic" was 1.7 days (P < 0.001). Among 86 Xpert-positive participants who initiated treatment, 49 (57%) started treatment based on clinical suspicion or AFB-positive results, whereas only 32 (37%) started treatment based on Xpert-positive results. CONCLUSIONS:In our setting, Xpert results took twice as long as AFB results to reach clinicians. Replacing AFB with centralized Xpert may delay TB diagnoses in some settings.

The distinctive feature of the human immunodeficiency virus (HIV) epidemic in Sub-Saharan Africa is the burden on women, in particular young women of reproductive age. Consequently, most late-phase effectiveness microbicide clinical trials are conducted in sub-Saharan Africa where fertility rates are high. Because late-phase clinical trials are conducted over prolonged periods of time, women participating in these trials may fall pregnant during the trial. Their unborn babies may be exposed to a drug whose teratogenic potential is unknown if the investigational drug is not withdrawn. High pregnancy rates in such trials may compromise statistical integrity, as women will be withdrawn from the study drug for the duration of the pregnancy. It is therefore imperative for microbicide trials to implement effective contraceptive and pregnancy management programmes that maintain low pregnancy rates and the safety of unborn babies while not compromising the conduct and statistical integrity of the trial.