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OBJECTIVE Determine the frequency of genital HIV-1 shedding in a large cohort of women on long-term suppressive antiretroviral therapy (ART) and its association with mucosal inflammation. DESIGN We measured levels of HIV-1 RNA and inflammation biomarkers in cervicovaginal lavage (CVL) from HIV-seropositive women enrolled in the Women's Interagency HIV Study (WIHS). METHODS HIV-1 was quantified (Abbott RealTime HIV-1 assay) from CVL samples of 332 WIHS participants with and without clinical evidence of genital inflammation at the time of CVL collection; participants had suppressed plasma viral load (PVL; limit of quantitation less than 20-4000 copies/ml depending on year of collection) for a median of 7.1 years [interquartile range (IQR) 3.4-9.8, Group 1] or for a median of 1.0 years (IQR = 0.5-1.0, Group 2). Twenty-two biomarkers of inflammation were measured in CVL to compare with clinical markers. RESULTS HIV-1 was detected in 47% of 38 pre-ART CVL samples (median 668 copies/ml) and detection in CVL was associated with higher pre-ART PVL. HIV-1 was detected in only 1 of 38 CVL samples from these women on suppressive antiretroviral therapy for 1 year. No HIV-1 RNA was detected in 294 CVL samples from a cross-sectional set of women with suppressed PVL for a median of 7 years. Clinical inflammation markers were correlated with inflammatory biomarkers in CVL specimens, although genital inflammation was not associated with measurable genital HIV-1 shedding in these WIHS participants on ART. CONCLUSION ART that suppresses HIV-1 in the plasma of women also prevents genital tract HIV-1 shedding, even in the presence of genital tract inflammation.

Background The Hologic Aptima HIV-1 Quant Assay that is currently available on the Panther system is FDA-cleared for plasma viral load monitoring. We compared to other assays for use with dried blood spots (DBS) and for early infant diagnosis (EID) using plasma and DBS. Methods Spiked dilution panels of plasma and DBS were made using negative donor blood and subtype B and subtype C HIV-1 stocks. Patient samples included plasma from HIV-1-infected adults, plasma from HIV-1-infected infants and exposed uninfected infants, and DBS from infected adults. Samples were run on Aptima Quant and either Abbott RealTime HIV-1 Quant assay or Hologic Aptima HIV-1 Qual assay. Results Aptima Quant and Abbott Quant were comparable: the 95% limit of detection was 42cp/ml for Aptima Quant and 91cp/ml for Abbott Quant. EID comparisons showed that Aptima Quant and Qual had 100% sensitivity and 98.9% specificity with overall agreement between the assays of 98.4%. Aptima Qual had a slightly lower limit of detection (95% limit of detection was 27cp/ml for Aptima Qual and 65 cp/ml for Aptima Quant). With spiked DBS, all 16 DBS with >30cp/ml on Aptima Quant were detected on Aptima Qual, 10/12 (83%) with ‘ Conclusion The Hologic Aptima HIV-1 Quant assay performed similarly for viral load and EID on both plasma and DBS samples. Our data suggest the ‘ Disclosure No significant relationships.

In light of highly prevalent resistance among previously unmonitored patients retained in care >2 years with virological failure in Malawi, differentiated care pathways with immediate switch to second-line antiretroviral therapy may be appropriate, maximizing clinical outcomes by avoiding treatment switch delays., We quantified resistance to first-line antiretroviral therapy among previously unmonitored patients in Malawi with viremia (≥1000 copies/mL). Ninety-five percent (n = 57/61) harbored nucleoside/tide reverse transcriptase inhibitor/non-nucleoside reverse transcriptase inhibitor resistance; resistance was more common comparing >2 (97%) versus ≤2 years (87%) on therapy. Immediate switch for persons retained in care may improve monitoring efficiency and maximize clinical outcomes.

OBJECTIVE The objective of this study is to assess nevirapine (NVP) resistance in infants who became infected in the three arms of the Breastfeeding, Antiretrovirals and Nutrition (BAN) study: daily infant NVP prophylaxis, triple maternal antiretrovirals or no extra intervention for 28 weeks of breastfeeding. DESIGN A prospective cohort study. METHODS The latest available plasma or dried blood spot specimen was tested from infants who became HIV-positive between 3 and 48 weeks of age. Population sequencing was used to detect mutations associated with reverse transcriptase inhibitor resistance. Sequences were obtained from 22 out of 25 transmissions in the infant-NVP arm, 23 out of 30 transmissions in the maternal-antiretroviral arm and 33 out of 38 transmissions in the control arm. RESULTS HIV-infected infants in the infant-NVP arm were significantly more likely to have NVP resistance than infected infants in the other two arms of the trial, especially during breastfeeding through 28 weeks of age (56% in infant-NVP arm vs. 6% in maternal-antiretroviral arm and 11% in control arm, P¼0.004). There was a nonsignificant trend, suggesting that infants with NVP resistance tended to be infected earlier and exposed to NVP while infected for a greater duration than infants without resistance. CONCLUSION Infants on NVP prophylaxis during breastfeeding are at a reduced risk of acquiring HIV, but are at an increased risk of NVP resistance if they do become infected. These findings point to the need for frequent HIV testing of infants while on NVP prophylaxis, and for the availability of antiretroviral regimens excluding NVP for treating infants who become infected while on such a prophylactic regimen.