HIV: Screening and Treatment Related Issues

Leonard Anang Sowah, MBChB, MPH

Assistant Professor of Medicine

University of Maryland School of Medicine

Overview1. Quick overview of HIV epidemic global and local

2. Epidemiology of HIV focusing mostly on new infections in the city of Baltimore and surrounding counties

3. Routine testing how and why

4. Discussion of HIV continuum of care for the state of Maryland and problem areas in the continuum

5. Clinical issues in HIV care

6. Models of HIV Care in the primary care clinic

The HIV Virus• RNA virus belonging to the family of

retroviruses and sub-family lentiviruses

• Requires viral RNA dependent DNA polymerase enzyme to infect cells

• Rate of change in nucleotides that cause amino acid changes exceeds that favoring amino acid conservation - high dn/ds ratio

• Viral envelope proteins are highly variable and some conserved proteins occur in inaccessible surface pockets

• Cellular infection by virus in is dependent on the CCR5 co-receptor interaction

HIV/AIDS disease progression

Global HIV Epidemiology

Adult/Adolescent HIV Cases Alive on 12/31/2011, by ZIP Code

Source: http://phpa.dhmh.maryland.gov/OIDEOR/CHSE/Shared%20Documents/Baltimore-City.pdf , assessed 7/2/2015

HIV, Poverty and Race in the US

Denning P and DiNenno E, Communities in Crisis: Is There a Generalized HIV Epidemic in Impoverished Urban Areas of the United States? http://www.cdc.gov/hiv/pdf/statistics_poverty_poster.pdf

HIV Testing

• HIV-1/HIV-2 Ag/Ab combo immunoassay (4th generation)– Abbott Architect HIV Ag/Ab Combo Assay (Abbott Laboratories)

– GS HIV Combo Ag/Ab EIA (Bio-Rad Laboratories)

• HIV-1/HIV-2 antibody differentiation immunoassay– Multispot HIV-1/HIV-2 Rapid Test (Bio-Rad Laboratories)

• HIV-1 RNA assay– Aptima HIV-1 RNA Qualitative Assay (Hologic Gen-Probe)

HIV-1/HIV-2 Ag/Ab Combo-Assay

• Detects HIV-1 P24 Antigen and HIV-1 and HIV-2 antibodies

• The test therefore is capable of identifying HIV infection as early as 17 days

• Detects HIV in 89% of individuals with false negatives from an initial HIV antibody screen

Laboratory markers of HIV infection

Laboratory Testing for the Diagnosis of HIV Infection: Updated Recommendations, CDC; June 27, 2014

Maryland State Policy

http://stacks.cdc.gov/view/cdc/23447

Transmission Risk Across The Continuum

Skarbinski J et al, 2015, JAMA Internal Medicine, 175 (4) 588 - 596

HIV care continuum stages for HIV-infected partners.

Cope AB, Powers KA, Kuruc JD, Leone PA, Anderson JA, et al. (2015) Ongoing HIV Transmission and the HIV Care Continuum in North Carolina. PLoS ONE 10(6): e0127950. doi:10.1371/journal.pone.0127950http://127.0.0.1:8081/plosone/article?id=info:doi/10.1371/journal.pone.0127950

Awareness of Serostatus Among People with HIV and Estimates of Transmission

~25% Unaware of Infection

~75% Aware of Infection

Accounting for:

~55% of New Infections

~45% of New Infections

Marks G, Crepaz N., et al 2005; JAIDS Journal of Acquired Immune Deficiency Syndromes. 39(4):446-453

Date of download: 7/2/2015Copyright © 2015 American Medical

Association. All rights reserved.

From: Antiretroviral Therapy for Prevention of HIV Transmission in HIV-Discordant Couples

JAMA. 2013;310(15):1619-1620. doi:10.1001/jama.2013.278328

Risk of HIV Transmission in Serodiscordant Couples Treated vs Untreated With Antiretroviral Therapy in Observational StudiesSource: Figure adapted with permission from Cochrane HIV/AIDS Group.

aEffect estimates may not reflect raw counts due to confounder adjustment.bEstimated from median follow-up time.cHazard ratio.

Mean (+SE) Rate of Heterosexual Transmission of HIV-1 among 415 Couples, According to the Sex and the Serum HIV-1 RNA Level of the HIV-1–Positive Partner.

Quinn TC et al. N Engl J Med 2000;342:921-929.

Current FDA approved ART drugs

http://www.edurant.com/hcp/key-resources/hiv-patient-resources

When to Start ART (Current US GuidelinesWhen to Start ART (Current US Guidelines))

• ART is recommended for all HIV-infected individuals to reduce the risk of disease progression.

• ART also is recommended for HIV-infected individuals for the prevention of transmission of HIV.

• Patients starting ART should be willing and able to commit to treatment and understand the benefits and risks of therapy and the importance of adherence..

www.aidsetc.org29

Recommendations for Initiating Recommendations for Initiating ARTART

• “Patients initiating ART should be willing and able to commit to lifelong treatment and should understand the benefits and risks of therapy and the importance of adherence.”

• Patients may choose to postpone ART

• Providers may elect to defer ART, based on patients’ clinical or psychosocial factors

October 201130

Consider Deferral of ARTConsider Deferral of ART

• Clinical or personal factors may support deferral of ART– If CD4 count is low, deferral should be considered

only in unusual situations, and with close follow-up

• When there are significant barriers to adherence

• If co-morbidities complicate or prohibit ART

• “Elite controllers” and long-term non-progressors

October 2011 www.aidsetc.org31

Recommended regimens for antiretroviral therapy (ART)-naive patients

Preferred RegimensINSTI based RegimensEpzicom plus Dolutegravir (DTG/ABC/3TC)(Patients must be negative for HLA-B*5701 (AI))Truvada plus Dolutegravir (TDF/FTC/DTG) (AI)Stribild (EVG/c/TDF/FTC) GFR must be >70 mL/min (AI)Truvada Raltegravir (TDF/FTC/RAL) (AI)

PI/r-Based RegimensPrezista and norvir plus Truvada (TDF/FTC/DRV/r)(AI)

Alternate RegimensTruvada plus Atazanavir/ritonavir (TDF/FTC/ATV/r) (BI)Truvada plus Efavirenz (EFV/TDF/FTC) (BI)

(ABC/3TC plus ATV/r, EFV plus ABC/3TC, and rilpivirine/TDF/FTC)

Modified from DHHS Guidelines 2015; https://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-treatment-guidelines/0 accessed 5/23/2015

NA-ACCORD: Risk of all cause on mortality on ART by baseline factor

Kitahata MM, Gange SJ, Abraham AG, et al. Effect of early versus deferred antiretroviraltherapy for HIV on survival. N Engl J Med. 2009;360:1815-1826.

START TRIAL (Strategic Timing of Antiretroviral Treatment)

http://www.nytimes.com/2015/05/28/health/hiv-treatment-should-start-with-diagnosis-us-health-officials-say.html?_r=0

Clinical Case • Presenting complaint

– 37 yr old female presents for a new primary care visit (Nov-2008)– No specific complaints per her except for occasional knee pain– Reports she just came into clinic for a physical because it was required in her

transitional house

• PMH– None

• FMH– Hypertension in mother and sister– Thyroid disease in sister

• Social Hx– Smoker ½ ppd– Occasional marijuana (no cocaine or heroin)– Living in transitional housing– 12 lifetime sexual partners– No partner in past 12 mths – One daughter

Clinical Case (contd)• Vitals

– T: 96.5, HR: 82, RR: 18, BP: 105/69, Wt: 150 lb, Ht:5ft 2in, Pulse Ox: 99%, BMI: 32.9 kg/m2

• Rest of Physical – A.A female healthy looking, obese, well groomed. – Rest of exam was remarkable

• Laboratory Investigations– HIV Counseling and testing CMP, CBC, TSH, RPR,

GC/Chlamydia, Fasting Lipids, Toxo titer, CMV titer, G-6-PD, Hepatitis Profile, Pap Smear, PPD

Follow-up• Rapid test was positive as well ELISA HIV 1 & II positive confirmed with

Western blot

• Initial CD4 count was 464 (29.1%)

• HIV viral load was 18,592 copies

• Genotype – R211K, L63P

• Dropped her CD4 count by about 200 cells over the next 6 months

• Discussed benefits of therapy in this situation

• Started patient on Truvada, and Kaletra 200/50 2 tabs BID

HIV viral load trend over time

Switched Prezista and Norvir for Kaletra

Started on Truvada and Kaletra

Changed all ARVs to Stribild

CD4 trend over time

HIV viral load has remained suppressed since starting therapy. Switched ARVs to Stribild on 5/30/2013 to reduce pill burden

Goals of HIV therapy

• Viral load reduction to below limits of assay detection (< 20, <40, <50, <75 copies/mm3) in a treatment-naïve patient usually occurs within the first 12–24 weeks of therapy.

• Predictors of virologic success include: – high potency of antiretroviral regimen

– excellent adherence to treatment regimen

– low baseline viremia

– higher baseline CD4 T-cell count

– rapid (i.e., >1 log 10 in 1 to 4 months) reduction of viremia in response to treatment

Goals of HIV therapy

• CD4 counts rise as a result of suppression of viral replication, not a direct result of antiretroviral drugs

• Monitoring of therapy:– CD4 count & Viral load measurements

– “safety labs”: CBC, renal/hepatic function, UA, CK

– Resistance testing

• Genotypic

• Phenotypic

Virologic Failure

• Review adherence, adherence, adherence!!– Explore changes in lifestyle– Significant losses, death, sexual partners, job loss, housing situation– Substance abuse and mental health

• Resistance testing– Test while on failing regimen– Requires VL of at least 1000 copies/mm3

– Genotypic: analysis of AA sequence of RT and PRO genes for known mutations that confer resistance

– Phenotypic: growth of sample virus compared with WT standard in presence of drugs in vitro

Genotype results

Phenotype resistance assays

http://www.vircolab.com/product-center

Models of HIV Care• Patient Centered Medical Home Model

– Encourages having most frequently required services around the patient– Ideal for patient new to the culture of longitudinal care– Having co-located services is gold-standard– Care Team –

• Primary HIV Provider• Case Management/Nursing/Social Work• Mental Health and Substance Abuse

• Specialty Care Models– PCP with Referral to Infectious Disease/HIV Specialist

• Patients with stable primary care already used to having a PCP and specialist may do better in this system

• Beneficial when providers are good with sharing information• Tends to benefit patients with high health literacy

Hybrid Primary/Specialty Care Model

• Involves ongoing collaboration between Infectious Disease/HIV specialist with Primary Care

– Encouraged with ACA on account of expectations of increase demand for HIV specialist beyond available resource

– Practiced to some extent by some Health Care Systems

– Primary Provider maintains most the care decisions of their patients

– Would have HIV Specialist consult on new patients

– Consults can occur at patient’s local clinic or at the specialist site but local site is encouraged

– Specialist can visit local site to see patients periodically based on specified agreements

– On-going mentoring between Specialist and PCP would assist the transition of stable patient into full PCP with specialist input periodically based on need.

Summary• Though new HIV infections are trending downwards total

number of people living with HIV continue to rise

• Early diagnosis and treatment reduces all cause mortality

• CDC and State of Maryland recommend routine screening to identify HIV infected individuals and also to reduce stigma

• Primary care offices are very important to the success of this initiative