Death Rate of HIV-Infected Youth Increased Thirty Fold

MedicalResearch.com Interview with:
Gayatri Mirani MD and
Tulane University School of Medicine
New Orleans, Louisiana

Paige L. Williams, PhD
Department of Biostatistics
Harvard T. H. Chan School of Public Health
Boston, MA 02115

Medical Research: What is the background for this study

Response: Combination antiretroviral therapy (cART) has resulted in a dramatic decrease in HIV-related opportunistic infections and deaths in US youth, but both continue to occur. IMPAACT P1074, a long-term US-based prospective multicenter cohort study funded through NIH was conducted from April 2008 to June 2014. We reviewed complications and mortality rates in HIV-infected US youth enrolled in this study. Comparisons were made with a previous observational cohort study, P219C. While P219C was conducted from 2000 to 2007, we restricted our analysis to 2004-2007 in order to evaluate changes over the past decade.

A total of 1201 HIV-infected youth were enrolled in the IMPAACT P1074 study, with most (1040, or 90%) infected with HIV at birth. The overall study population was 52% female, 58% black non-Hispanic and 28% Hispanic. Their mean age at the first chart abstraction was 17.4 (±5.4 Std. Dev.) years. The majority were on cART, had a stable CD4 count (baseline mean > 500 cells/mm3) and a suppressed viral load over a median follow-up of 3.7 years. The P219C group was younger, with a mean age of 11.9 (±5.0 Std. Dev.) years at the start of the 2004-2007 follow-up period.

Medical Research: What are the main findings?

Response: The most commonly reported comorbidities for the P1074 group were psychiatric and neurodevelopmental disorders, asthma, pneumonia, and genital tract infections. The incidence of pneumonia decreased compared to P219C group. However, the incidence of substance or alcohol abuse, latent tuberculosis, diabetes mellitus, atypical mycobacterial infections, vitamin D deficiency or metabolic bone disorders, anxiety disorders and fractures increased 5-fold or greater compared to the earlier cohort. Pregnancies occurred in 19% of females older than 12.5 years, and 25% of those had at least one subsequent pregnancy while on the study. Some of the increases in incidence rates are expected since P1074 participants were generally older than P219C participants. However, the majority of these increases persisted after adjustment for age. There were 28 deaths in P1074 (mortality rate of 0.66/100 person-years), which was similar to the mortality rate of 0.63/100 person-years observed from 2004-2006 in P219C study. Most deaths (86%) were directly linked to infection or other HIV-associated medical conditions. Subjects who died did not differ from survivors by socio-demographic background, but were older and had lower CD4 counts and higher viral loads at death. The mortality rate was 30 times the standardized general US population.

Medical Research: What should clinicians and patients take away from your report?

Response: While many infectious conditions may have become less common with cART, other non-infectious conditions including metabolic disorders and neurodevelopmental conditions have emerged. We found higher rates of dyslipidemia, asthma, eczema, hypertension, diabetes mellitus, thyroid hormone abnormalities, vitamin D deficiency or metabolic bone disorders and fractures in P1074 than in P219C. Multi-factorial causes are at the root of these metabolic problems. Neurodevelopmental problems, described below, have also increased. They not only directly contribute to morbidity but also have secondary consequences such as medication non-adherence, risk-taking behavior, and increased HIV transmission,. Even after age-adjustment, substance or alcohol abuse, anxiety disorders, trauma/stress related disorders, disruptive/impulse control disorders, and learning and communication disorders showed higher incidence rates in P1074 than in P219C. Monitoring strategies for perinatally-infected youth may need to be modified to capture these types of diagnoses and provide a more comprehensive approach to retaining these individuals in care.

Another contributing factor to increasing HIV transmission in this population is their higher rates of genital HPV infection and anogenital herpes, as well as substantial rates of syphilis, chlamydia, gonorrhea, trichomoniasis, and yeast infections. While these higher rates largely reflect an older age distribution in the P1074 population, they raise concerns for development of cervical dysplasia in women, penile squamous cell carcinoma in men, and anal squamous cell carcinoma in women and in men who have sex with men. Strategies to improve diagnosis, early and appropriate treatment, and prevention are key components of HIV care in this youth. While some of these conditions may not carry the same morbidity as opportunistic infections, the mortality rate remains substantially elevated as compared to similarly-aged youth without HIV.

Medical Research: What recommendations do you have for future research as a result of this study?

Response: Prospective longitudinal studies involving HIV-infected youth are important to understand the evolving long-term effects of HIV infection and cART. Monitoring of chronic inflammatory conditions, prevention of genital tract infections, addressing neurobehavioral problems, and achieving healthy pregnancies with prevention of mother-to-child transmission are key focus areas for HIV-infected youth.

Citation:

Clin Infect Dis. 2015 Aug 12. pii: civ687. [Epub ahead of print]

Changing Trends in Complications and Mortality Rates Among US Youth and Young Adults With HIV Infection in the Era of Combination Antiretroviral Therapy.

Mirani G, Williams PL, Chernoff M, Abzug MJ, Levin MJ, Seage GR 3rd, Oleske JM, Purswani MU, Hazra R, Traite S, Zimmer B, Van Dyke RB; IMPAACT P1074 Study Team.

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Gayatri Mirani MD , Paige L. Williams, PhD (2015). Death Rate of HIV-Infected Youth Increased Thirty Fold 

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