Average CD4 cell count at time HIV therapy was started increased among young people in New York City after 2009

Prevalence of transmitted drug resistance also increased

Michael Carter
Published: 29 January 2014

The average CD4 cell count at which young people living with HIV in New York City started antiretroviral therapy increased significantly after US guidelines changed in late 2009 to recommend therapy at higher counts, investigators report in the online edition of Clinical Infectious Diseases. The study also showed that 18% of young people had transmitted drug resistance, potentially limiting their choice of anti-HIV drugs.

“We found a significant increase in the mean CD4 count at initiation of ART [antiretroviral therapy] after…guidelines changed in December 2009,” comment the authors. “Our findings demonstrate uptake of the 2009 ART initiation guidelines.”

HIV treatment recommendations for young people (adolescents and young adults aged 13 to 24 years) follow those for adults. US antiretroviral treatment guidelines have been revised on several occasions in recent years, each time recommending the earlier initiation of therapy compared to previous editions of the guidelines. In December 2009, people with CD4 counts between 350 and 500 cells/mm3 became eligible for treatment. In early 2013, guidelines were again revised, this time recommending treatment for everyone with HIV, regardless of immune status.

But relatively little is known about the timing of antiretroviral treatment initiation in young people. There are also important knowledge gaps concerning the prevalence of transmitted drug resistance in this patient group, with estimates ranging between 5 and 18%.

Investigators therefore designed a retrospective study involving 331 young people newly presenting for HIV care in New York City between 2007 and 2011. Data were gathered on CD4 cell count and viral load on entry to care and at the time treatment was started. Results of baseline genotypic resistance tests were available for a subset of 212 patients. None of the participants had taken pre-exposure prophylaxis (PrEP) or post-exposure prophylaxis (PEP) and all were antiretroviral naive. All the patients acquired HIV via sexual contact or as a result of injecting drug use.

Most (90%) of the patients were male and 78% were in the men who have sex with men (MSM) risk group.   

The mean CD4 cell count at the time of entry into care was 452 cells/mm3. Average CD4 cell count did not differ between people presenting for care during 2007-2009 vs 2010-2011.

In the earlier period, 33% of patients had a CD4 count below 350 cells/mm3 and thus qualified for HIV therapy. In 2010-2011, 57% of individuals had a CD4 count below 500 cells/mm3, fulfilling the revised criteria for the initiation of therapy.

Mean viral load at presentation was approximately 128,000 copies/ml. It was similar in both the earlier and later time periods.

A total of 191 patients (58%) started HIV therapy. Mean CD4 cell count at the time of treatment initiation in 2007-2009 was 261 cells/mm3 compared to 363 cells/mm3 in 2010-2011, a significant difference (p < 0.001).

In 2010-2011, patients with CD4 counts between 350 and 500 cells/mm3 had a fivefold increase in their odds of starting treatment compared to individuals with similar CD4 counts in 2007-2009 (OR = 5.2; 95% CI, 1.1-25.1).

Six months after starting treatment, 71% of patients had an undetectable viral load. The proportion of patients achieving this outcome did not differ between the two time periods.

The most commonly used (64%) HIV treatment combination was Atripla (efavirenz/FTC/tenofovir). A raltegravir (Isentress)-containing regimen was prescribed to 12% of patients and 20% were treated with a regimen containing a ritonavir-boosted protease inhibitor.

There were subtle changes in prescribing practices over the period covered by the study. Notably use of Atripla declined (early vs later time periods =  71 vs 60%, respectively), whereas prescribing of raltegravir become more common (early vs later time periods = 8 vs 15%, respectively).

Resistance tests were performed for 212 patients (64%). Patients starting treatment were more likely to undergo resistance testing than individuals who remained antiretroviral naive (78 vs 45%).

Overall, 18% of the tested patients had a major drug resistance mutation, indicating transmitted resistance.

Prevalence of transmitted resistance increased significantly from 12% in 2007-2009 to 25% in 2010-2011 (p = 0.02).

“Our data suggest an increasing rate of resistance in ART-naive individuals,” comment the investigators.

Mutations conferring resistance to non-nucleoside reverse transcriptase inhibitor (NNRTIs) were found in 60% of those with transmitted resistance. Four patients had resistance to drugs in two of the major antiretroviral classes.

“The drug resistance mutations have implications for choosing initial regimens for ART-naive adults and young adults,” conclude the authors. “Monitoring the epidemiology of HIV drug resistance mutations will inform future treatment guidelines and our findings reinforce the recommendation to perform HIV resistance testing upon entry into care.”

Reference

Gagliardo C et al. A multicenter study of initiation of antiretroviral therapy and transmitted drug resistance in antiretroviral naive adults and young adults with HIV in New York. Clin Infect Dis, 2014.