Primary Care for Persons Living with HIV

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Primary Care for Persons Living with HIV Brian Montague, DO MS MPH Assistant Professor of Medicine Division of Infectious Diseases Warren Alpert School of Medicine Brown University

Outline What constitutes primary care for persons with HIV Engagement/retention Mental health and substance abuse Kidney disease Liver disease

What Constitutes HIV Care? Screening and Testing Post-Testing Counseling Laboratory Monitoring Treatment and Prophylaxis Management of Complications Adherence counseling Secondary Prevention Primary Care Testing sites Primary care centers Urgent care Emergency departments Hospitals Opportunistic Infections Metabolic disease Cardiovascular Disease Renal disease Liver disease Cognitive changes Mental health, Substance abuse, Cancer screening, lung disease, etc.

Who manages HIV Role of generalist: provision of basic HIV prevention, diagnostic and treatment services. Integration of those services into overall plan of care for the patient Physician Nurse Pharmacist CHW Role of specialist: initiation of HIV care and opportunistic infection treatment, comanaging cases with significant comorbidities e.g. viral hepatitis or ESRD, 3 rd line and salvage regimen

Why is Primary Care Important With current ART regimens, life expectancy increased Other non-hiv related conditions became principal drivers of survival

CDC. HIV/AIDS Surveillance Report. 2008;18. 6

Increasing Survival

Turning the Tide Globally

HIV in an Aging Population Standardized Proportionate Mortalities by Condition and HAART Period Disease Pre- HAART Early HAART Septicemia 10.7 12.9 11.6 Kidney Disease 7.8 9.4 11.7 Liver Disease (excl viral hepatitis) 4.9 8 10.8 Viral Hepatitis 1.2 3.4 10.9 GI Bleed 1.5 2.1 1.8 Ischemic Cardiac Disease 0.7 0.9 1.9 In US, hepatitis C is primary cause of mortality due to viral hepatitis Contemporary HAART Hooshyar et al. AIDS. 2007 Oct 1;21(15):2093-100.

Key Elements in Improving Outcomes Retention/engagement Mental health and substance abuse treatment Kidney disease prevention Liver disease Cardiovascular risk reduction and Metabolic syndrome, HTN, DM Cancer screening incl. HIV related (cervical) and non-hiv related (colorectal,? prostate)

ENGAGEMENT AND RETENTION

The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com. The spectrum of engagement in HIV care in the United States spanning from HIV acquisition to full engagement in care, receipt of antiretroviral therapy, and achievement of complete viral suppression. Gardner E M et al. Clin Infect Dis. 2011;52:793-800

Treatment as Prevention HPTN 052 International cohort of discordant couples Near 100% prevention of transmission if infected partner started on antiretroviral therapy Failure to engage patients and retain patients in care is both an individual and public health concern

MENTAL HEALTH AND SUBSTANCE ABUSE

Links Between HIV and Mental Health High burden of untreated mental health disease in all populations Adjustment reactions related to diagnosis and related complications Ongoing challenge of addressing HIV related stigma HIV associated neuro cognitive disease Uncontrolled mental health disorders and active substance abuse are important risk factors for virologic failure, interruptions in care, and adverse outcomes

Substance Use and HIV Transmission Increased Risk Tasking Behavior Substance Use Failure to Access Treatment Lack of Adherence to Treatment High Viral Loads Increased Transmission

Mental illness Adjustment reaction / Depression Anxiety May be compounded by substance use and abuse PTSD Bipolar Severe persistent mental illness

HAND Behavioral Depression Apathy Inertia Cognitive Altered memory psychomotor speed Forgetfulness Difficulty sustaining concentration Motor Altered coordination Ocular dysmetria Fine motor disturbances Behavior Cognitive HAND Motor NCI/HAND significantly more common in the CART era (aging cohort) Consistent association between NCI with nadir CD4 Heaton et al, J. Neurovirol. 2011;17:3-16

KIDNEY DISEASE

Renal Disease in HIV Positive Patients Kidney disease is an important complication of HIV infection in the era of antiretroviral therapy 1 In a retrospective study of 487 consecutive HIV positive patients with normal renal function, the initial prevalence of CKD was 2% 2 After 5 years of follow-up, 6% had progressed to CKD Older age was a multivariate predictor of CKD for this cohort 1 Gupta SK, et al. Clinical Infectious Disease. 2005; 40:1559-1585. 2 Gupta SK, et al. Clinical Nephrology. 2004.; 61:1-6.

Risk Factors for Kidney Disease in the HIV Positive Population Age Ethnicity Family History HIV CKD Risk Hypertension ART Diabetes = Modifiable = Nonmodifiable Hepatitis C Gupta SK, et al. Clinical Infectious Disease. 2005; 40:1559-1585.

IDSA Initial Evaluation Recommendations Obtain baseline GFR: All patients at the time of HIV diagnosis should be assessed for existing kidney disease with a screening urinalysis for proteinuria and a calculated estimate of renal function Annual screening: If there is no evidence of proteinuria at initial evaluation, patients at high risk for the development of proteinuric renal disease should undergo annual screening Renal function should be estimated on a yearly basis to assess for changes over time When to consider nephrology consultation: Additional evaluations and referral to a nephrologist are recommended for patients with proteinuria of grade 1+ by dipstick analysis or GFR<60 ml/min per 1.73m 2 Gupta SK, et al. Clinical Infectious Disease. 2005; 40:1559-1585.

LIVER DISEASE

Importance of Liver Disease Disease Pre- HAART Early HAART Septicemia 10.7 12.9 11.6 Kidney Disease 7.8 9.4 11.7 Liver Disease (excl viral hepatitis) 4.9 8 10.8 Viral Hepatitis 1.2 3.4 10.9 GI Bleed 1.5 2.1 1.8 Ischemic Cardiac Disease 0.7 0.9 1.9 Contemporary HAART In US, impact is driven primarily by hepatitis C

Key Points Prevention: Immunization Counseling regarding ETOH and supplement use Diagnosis: screening guides HIV therapy & f/u even if specific hepatitis treatment is not available Treatment: If hepatitis B positive, choose drugs with hepatitis B activity Monitoring: ALT,? ultrasound

CARDIOVASCULAR RISK REDUCTION

Population Attributable Fraction by Risk Gaziano et al. Curr Probl Cardiol. 2010; 35: 72-115.

HIV and Cardiovascular Disease HIV is thought to be an independent risk factor for CVD, however clinical significance of association is controversial Contributes to more than 10% of deaths among HIV positive individuals Factors that affect CV risk are similar for HIV positive and negative individuals Risk may vary among ARV agents Framingham scores seem to underestimate risk in HIV + individuals Suggestive Evidence Case reports of early onset CVD/MI Radiologic documentation of advanced atherosclerosis in patients with limited other risk factors Basic science mechanisms demonstrating HIV associated endothelial activation Adverse impacts of ARV medications on lipid profiles

Diagnosis and Management of Insulin Resistance in HIV-Infected Patients Older NRTIs and PIs significantly associated with insulin resistance and DM (AZT, stavudine) Screening for DM At baseline and 3-6 months after starting HAART Yearly thereafter Lifestyle modification Diabetic education Self-monitoring of blood glucose Aerobic and resistance training Florescu, D. Antiretroviral Therapy. 2007. 12:149-162.

CVD Risk in HIV Cohorts Observational Studies of Coronary Heart Disease in HIV Infection Authors Population Patients (n) Bozette et al. Fris-Moller Mary-Krause et al Carrier et al Veterans Affairs Hospital System Data Collection of Adverse Drug Effects of Anti- HIV Drugs (DAD) French Hospital Database California Medicaid Study Years 34976 1992-1999 23468 1999-2005 34976 1992-1999 28513 1994-2000 HIV infected compared with controls No Controls Increased SMR for MI in Pt > 30 months compared with general French population: risk ration2.9 (1.5-5) No diff in those on PI Increased relative risk of CHD in men < 35y and women < 45y Effect of HAART No significant increase in CHD admissions or mortality compared with US population Increased rate of MI increased with > 6 years. PI 6.01 vs 1.53 events per 1000 py after adjustment for lipids, relative rate 1.10 (1.04-1.18) Incidence MI increased with > 30 m PI vs < 18m exposure: 33.8 vs 10.8 events per 10000 py Increased relative risk of CHD in those on HAART vs no HAART: 2.06 p<0.001 (covariate adjusted) Ho & Hsue. Heart 2009; 95: 1193-1202.

Events per 1000 Person-Years MI Rates in HIV Positive and HIV Negative Patients 100 80 60 AMI rate by age group HIV+ HIV 40 20 0 18-34 35-44 45-54 55-64 65-74 Age Group (Years) Cohorts (HIV+ =3851, HIV- =1,044,589) were identified in the Research Patient Data Registry. The primary outcome was AMI. Triant VA,et al. J Clin Endocrinol Metab. 2007;92:2506-2512.

Algorithm for Lipid Tx in HIV Ho & Hsue. Heart. 2009; 95:1193-1202.

CANCER SCREENING

Cancer Screening ADC Kaposi s Sarcoma Primary CNS Lymphoma HIV Associated but non ADC Cervical cancer and other HPV assoc squamous cell cancers Lymphoma (NHL) hepatocellular carcinoma (particularly hepatitis coinf) Non small cell lung cancer Other malignancies Breast cancer, colon cancer, prostate cancer, skin cancers Crum-Cianflone N, et al. AIDS. 2009;23:41-50.

Main Findings 23-year Tri-Service AIDS Clinical Consortium HIV Natural History Study analyzed ADCs Median time from HIV diagnosis to ADC: 5.6 years (IQR: 3.6-7.9) Most common ADC: Kaposi s sarcoma (73%) nadcs Median time from HIV diagnosis to nadc: 6.0 years (IQR: 2.8-11.7) Most common NADC: skin cancer (47%), usually basal cell carcinoma Rate of ADCs significantly increased from early to late pre-haart era and then significantly decreased following introduction of HAART Rates of nadcs stable during pre-haart eras and then significantly increased following introduction of HAART Proportion of nadcs significantly increased from 20% in pre-haart era to 36% in early post-haart era to 71% in late post-haart era (P <.0001) Crum-Cianflone N, et al. AIDS. 2009;23:41-50.

Key Findings Currently, incidence of ADCs continues to decline whereas incidence of nadcs increases nadcs account for majority of cancers in HIVinfected individuals Development of nadcs significantly associated with older age and white race HAART associated with reduced risk of ADCs, but not nadcs Crum-Cianflone N, et al. AIDS. 2009;23:41-50.

Summary With effective antiretroviral therapy patients can live relatively normal lives Key to survival is engaging patients and sustaining them on care With sustained virologic suppression, management of comorbid health risks determines longterm outcomes Effective systems of primary care are essential to achieving long-term outcomes

QUESTIONS? brianmontaguedo@gmail.com

EXTRA SLIDES

HAART and Mortality in US Palella FJ, et al. JAIDS. 2006;43:27-34. 40

Prevalence (%) Prevalence of Chronic Kidney Disease in the General Population Increases with Age Eight year cross-sectional Norwegian survey subjects 20 yrs of age 50 GFR (ml/min/1.73 m 2 ): 45-59 30-44 <30 40 N = 65,605 30 20 10 0 20-29 30-39 40-49 50-59 60-69 70-79 80-89 90+ Age (Years) Adapted from Hallan SI, et al. BMJ. 2006; 333:1047-1050.