WEAB02: Antiretroviral resistance: clinical implications of drug resistance for people living with HIV. 

Moderators Charles Boucher and Michael Jordan began the session with an overview of several critical issues related to how drug resistance can affect the rollout of ARV in the developing world. The session then delved into a diverse array of topics bound by the common theme of drug resistance, but calling upon very different disciplines.

 WEAB0202: Association between acquired HIV drug resistance and HIV plasma RNA and CD4+ cell counts during early infection and during the set point phase, V. Jain, USA.

Jain et al. presented the results of one of the first analyses to investigate the clinical in vivo impact of transmitted drug resistance (TDR) on viral load (VL) and CD4 counts over time in untreated patients. This study used cubic spline modeling to examine the distinctly non-linear behavior of VL and CD4 over time. They found that VL is 0.4 logs lower during early HIV infection in patients with TDR vs. wild-type, but this difference waned with time and VL became similar between groups during the virologic set-point. They found CD4 counts were 50 cells higher in patients with TDR, but this difference was not significant either early or later in disease. Authors speculated that either the loss of TDR mutations, or the gain of compensatory mutations, may be responsible for the waning of early VL differences, but that overall it is reassuring that TDR does not appear to have significant clinical consequences on the progression of untreated HIV.

 WEAB0203: Suboptimal adherence associated with virologic failure and resistance mutations among patients on 1^st line HAART in Bangalore, India, M. Ekstrand, USA/India.

Ekstrand et al. explored adherence characteristics among persons in southern India who were taking ART, an important area with currently very limited known data. She found that 94% of patients self-reported a >95% adherence level, but 20% reported periodic interruptions of therapy. Not surprisingly, those with interruptions were found to have more viremia, and more detectable drug resistance. When the reasons for ART interruptions were explored via a focus group format many interesting items emerged including stigma, an inability of patients to confidentially visit their pharmacy to pick up medications, lack of leave from work, and difficulties related to not being able to disclose their HIV status to their families. Author detailed several planned intervention trials to address these issues of stigma aimed at improving adherence.

 WEAB0204: Dose-response curve slope is a missing dimension in the analysis of HIV-1 drug resistance, M. Sampah, USA.

Sampah et al. presented data on how examining the slope of the dose-response curve of antiretrovirals (an innovative yet not widespread subject of study) affects the impact of drug resistance mutations. The study’s first conclusion was that consideration of this parameter is important in assessing to what degree mutations will reduce susceptibility to particular drugs (and that the IC50 alone is not sufficient). The second conclusion was that the different drug classes showed fundamentally different behavior in terms of how resistance mutations affected the dose response curve. They state that this reflects the distinct mechanisms of drug action on resistant viruses.

 WEAB0205: Monitoring the emergence of resistance mutations in patients under salvage therapy with raltegravir in Rio de Janeiro, Brazil: a six month follow-up, C. Passaes, Brazil. This study prospectively examined the emergence of raltegravir (RAL) mutations (by a homebrew integrase genotyping process) among triple class ART-experienced Brazilian patients (n=4) who had been infected with HIV>10years, and now were beginning RAL-containing salvage regimens. Two of four patients had virologic failure on RAL, and 1/4 showed RAL mutations (Q148H and G140S). The second question was whether RAL mutations could be detected in proviral DNA prior to plasma, and whether this could be used to predict future RAL resistance. Only the patient with RAL mutations on plasma showed RAL mutations in proviral DNA (and this was in the same time point), so proviral DNA did not appear to help predict future plasma RAL mutations. Emphasis was placed on close monitoring of experienced patients being salvaged with RAL.