Short-course Combivir after single-dose nevirapine reduces but does not eliminate the emergence of nevirapine resistance in women.

BACKGROUND: In the Treatment Options Preservation Study (TOPS) trial, 4 or 7 days of Combivir (CBV; zidovudine/lamivudine) with maternal single-dose nevirapine (sdNVP) significantly reduced the emergence of NVP resistance as determined by virus population genotyping. To detect NVP resistance with greater sensitivity, we analysed TOPS samples by allele-specific real-time PCR (ASP). METHODS: In a random subset of women from each arm of the trial, plasma samples from before and 6 weeks after sdNVP were analysed using ASP at codons 103, 181, 184 and 190. RESULTS: Samples were analysed from 27 women in the sdNVP arm and 24 each in the CBV 4-day (sdNVP/CBV4) and 7-day (sdNVP/CBV7) arms. ASP detected NVP-resistant variants in week 6 samples from 70% of women in the sdNVP arm, 29% in the sdNVP/CBV4 arm and 33% in sdNVP/CBV7 arm (P<0.01 for sdNVP/CBV4 or sdNVP/CBV7 versus sdNVP; P=1.0 for sdNVP/CBV4 versus sdNVP/CBV7). Lamivudine resistance was detected by ASP in only 1 of 51 women who received CBV. CONCLUSIONS: Short-course CBV significantly reduced but did not eliminate the emergence of NVP resistance after sdNVP. NVP-resistant variants were detected in about one-third of women despite CBV treatment, but the duration of persistence and clinical impact of these variants in response to antiretroviral therapy is uncertain.

Optimization of allele-specific PCR using patient-specific HIV consensus sequences for primer design.

Allele-specific PCR based on subtype consensus sequences is a powerful technique for detecting low frequency drug resistant mutants in HIV-1 infected patients. However, this approach can be limited by genetic variation in the region complementary to the primers, leading to variability in allele detection. The goals of this study were to quantify this effect and then to improve assay performance.

Percutaneous embolotherapy for life-threatening hemoptysis.

STUDY OBJECTIVES: The management of life-threatening hemoptysis frequently poses a therapeutic dilemma because such patients are often poor surgical risks. Less often, patients refuse surgical intervention. The value of percutaneous embolotherapy, a useful alternative in these situations, was assessed. DESIGN, SETTING, PATIENTS, INTERVENTIONS: Sixteen consecutive patients who underwent percutaneous embolotherapy for life-threatening hemoptysis in a tertiary-care hospital were evaluated retrospectively. The bronchial arteries, as well as other intrathoracic arteries, were evaluated and selectively embolized if they were considered to supply the pathologic area from which the hemoptysis arose. RESULTS: The most common cause for hemoptysis was posttuberculous bronchiectasis (n = 12) with or without mycetomas. Ten patients required blood transfusions before embolotherapy. Pleural disease was noted on the chest radiograph in 13 patients and was generally associated with the presence of nonbronchial systemic collateral vessels. In three patients, arteries other than the bronchial arteries were the only source of hemoptysis. Percutaneous embolotherapy was successful in controlling the hemoptysis in all patients. The only complication documented was a transient paraparesis in one patient. Six patients did not return for follow-up. Of the remaining 10 patients, 3 patients had minor episodes of hemoptysis that were treated conservatively with success. One patient had significant recurrent hemoptysis that was managed with radiotherapy. One patient subsequently underwent a lobectomy. CONCLUSION: Percutaneous embolotherapy is a useful therapeutic modality in the management of life-threatening hemoptysis. The contribution of nonbronchial systemic collateral vessels, particularly where there is evidence of coexistent pleural disease, should always be suspected. In experienced hands, this is a safe and potentially life-saving procedure.