Increased prevalence of transmission of drug resistant HIV and reduced response in newly infected subjects in nine US cities
30 July 2001. Related: Conference reports, Drug resistance, Intl Drug Resistance Workshop 15 Sitges 2006.
Widespread use of antiretroviral drugs in less than maximally suppressive regimens has always generated concern for the wider transmission of drug-resistant HIV and cases of single class and multiple drug resistance have been well documented for all routes of transmission.
Early studies looking at prevalence rates found marked local and national differences, but recent reports have shown that this underlying concern is still well founded and that in both the US and the UK these rates may be rising. [1, 2]
Updated data from Susan Little and colleagues was presented at this meeting from their retrospective ongoing analysis from 389 people (newly infected between July 95-May00) from nine North American cities in both US and Canada. [3] In addition to evaluating drug susceptibility the study compared prevalence of drug resistance by phenotype and genotype and assessed the natural history of HIV and subsequent treatment response.
Reduced susceptibility was defined as >10-fold reduced susceptibility to one or more drugs. Suppression was defined as two sequential viral load results <500 copies/ml and failure as one viral load result >500 copies/ml while on treatment.
Table: >10-fold reduced susceptibility
| 96-8 | 99-00 | p value | |
| N | 226 | 86 | |
| Any one ARV | 3.8 | 14.1 | 0.0002 |
| % RTI | 3 | 7.6 | 0.07 |
| % NNRTI | 1.7 | 7.6 | 0.01 |
| % PI | 0.4 | 8.7 | 0.0002 |
| % ≥2 classes (MDR)1 | .3 | 6.2 | 0.02 |
| Prevalence of major drug resistant mutations by genotype: | |||
| ≥1 major mutation | 5.5 | 18. | 0.001 |
| Major mutation + 215 D/N/S | 7.2 | 21.7 | 0.0004 |
| ≥ 2 drug classes (MDR) | 1.3 | 5.4 | 0.04 |
Not surprisingly, among the 199 people who started treatment, time to viral response was longer in those people with >10-fold reduced susceptibility to at least one ARV (p=0.09) compared to people <2.5-fold susceptible. Time to first failure following first undetectable result was also greatest in people with reduced >2.5-fold susceptibility compared to those fully sensitive [approximately 20% vs 10% at 200 days and 40% vs 22% at 600 days, p = 0.08].
Interestingly, this study reported little geographical differences between cities, and two cases of phenotypic sensitivity to NNRTIs returning approximately 6 months post infection.
References:
- Little, SJ et al – Antiretroviral Drug Susceptibility and Response to Initial Therapy Among Recently HIV-Infected Subjects in North America. Abstract 756. 8th CROI, Feb 2001.
- Pillay, D – BMJ 2001, 322. 1870-1088.
- Little, SJ et al – Antiretroviral resistance and response to initial therapy among recently HIV-infected subjects in North America. Abstract 25. Antiviral Therapy 2001; 6 (Supplement1):21