HIV screening and treatment in as changes occur in our healthcare system. Targeted towards specific healthcare centers in Baltimore. Features some data from the Department of health and mental hygiene and new data on HIV transmission across continuum of HIV care.

1. HIV: Screening and
Treatment Related Issues
Leonard Anang Sowah, MBChB, MPH
Assistant Professor of Medicine
University of Maryland School
of Medicine

2. Overview
1. 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

3. 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

4. HIV/AIDS disease progression

5. Global HIV Epidemiology

8. 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

9. 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

12. 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)

13. 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

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

15. Maryland State Policy

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

21. Transmission Risk Across The
Continuum
Skarbinski J et al, 2015, JAMA Internal Medicine, 175 (4) 588 - 596

22. 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.0127950
http://127.0.0.1:8081/plosone/article?id=info:doi/10.1371/journal.pone.0127950

23. 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

24. Date of download: 7/2/2015
Copyright © 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.

25. 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.

27. Current FDA approved
ART drugs
http://www.edurant.com/hcp/key-resources/hiv-patient-resources

28. 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

29. Recommendations for InitiatingRecommendations 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

30. 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

31. Recommended regimens for antiretroviral therapy
(ART)-naive patients
Preferred Regimens
INSTI based Regimens
Epzicom 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 Regimens
Prezista and norvir plus Truvada (TDF/FTC/DRV/r)(AI)
Alternate Regimens
Truvada 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

32. 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 antiretroviral
therapy for HIV on survival. N Engl J Med. 2009;360:1815-1826.

33. 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

35. 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

36. 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

37. 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

38. HIV viral load trend over time
Switched Prezista and
Norvir for Kaletra
Started on Truvada and
Kaletra
Changed all
ARVs to Stribild

39. 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

40. 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

41. 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

42. 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

43. Genotype results

44. Phenotype resistance assays
http://www.vircolab.com/product-center

45. 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

46. 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.

47. 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