High drug resistance prevalence among vertically HIV-infected patients transferred from pediatric care to adult units in Spain

Abstract

Background: Antiretroviral treatment (ART) has contributed to increased life expectancy of HIV-1 infected children. In developed countries, an increasing number of children reaching adulthood are transferred to adult units. The objectives were to describe the demographic and clinical features, ART history, antiviral drug resistance and drug susceptibility in HIV-1 perinatally infected adolescents transferred to adult care units in Spain from the Madrid Cohort of HIV-1 infected children.

Methods: Clinical, virological and immunological features of HIV-1 vertically infected patients in the Madrid Cohort of HIV-infected children were analyzed at the time of transfer. Pol sequences from each patient were recovered before transfer. Resistance mutations according to the InternationaI AIDS Society 2011 list were identified and interpreted using the Stanford algorithm. Results were compared to the non-transferred HIV-1 infected pediatric cohort from Madrid.

Results: One hundred twelve infected patients were transferred to adult units between 1997 and 2011. They were mainly perinatally infected (93.7%), with a mean nadir CD4+-T-cells count of 10% and presented moderate or severe clinical symptoms (75%). By the time of transfer, the mean age was 18.9 years, the mean CD4+T-cells count was 627.5 cells/ml, 64.2% presented more than 350 CD4+T-cells/ml and 47.3% had ≤ 200 RNA-copies/ml. Most (97.3%) were ART experienced receiving Highly Active ART (HAART) (84.8%). Resistance prevalence among pretreated was 50.9%, 76.9% and 36.5% for Protease Inhibitors (PI), Nucleoside Reverse Transcriptase Inhibitors (NRTI) and Non-NRTI (NNRTI), respectively. Resistance mutations were significantly higher among transferred patients compared to non-transferred for the PI+NRTI combination (19% vs. 8.4%). Triple resistance was similar to non-transferred pediatric patients (17.3% vs. 17.6%).

Conclusion: Despite a good immunological and virological control before transfer, we found high levels of resistance to PI, NRTI and triple drug resistance in HIV-1 infected adolescents transferred to adult units.

Figure 1. Predicted resistance level to antiretroviral drugs in pretreated patients from the two studied cohorts.

Resistance level was estimated according to the HIVdb Interpretation Algorithm (Stanford University, Palo Alto, CA, USA) . PI, protease inhibitors: nelfinavir (NFV), saquinavir/r (SQV/r), indinavir/r (IDV/r), atazanavir/r (ATV/r), fosamprenavir/r (FPV/r), lopinavir/r (LPV/r), tipranavir/r (TPV/r) and darunavir/r (DRV/r), where “/r” indicates co-administration with low-dose ritonavir (RTV) for pharmacological “boosting”. NRTI, nucleoside reverse transcriptase inhibitors: zidovudine (AZT), stavudine (d4T), lamivudine (3TC), emtricitabine (FTC), didanosine (DDI), abacavir (ABC), tenofovir (TDF). NNRTI, non-nucleoside reverse transcriptase inhibitors: efavirenz (EFV), nevirapine (NVP), rilpivirine (RPV), etravirine (ETR). **Statistical differences (p<0.05) in resistance levels have been found between transferred and non-transferred patients for these drugs.