Frequency of Depression in Primary Caregivers of Older Adults
H IV Primary Care for Adults
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HIV Primary Care for Adults
Larry Boly, MDStaff Physician CCRMCDepartment of Internal Medicine
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Goals of Presentation
• Discuss screening recommendations for HIV • Review the initial evaluation and laboratory testing to be
performed in HIV infected patients • Identify DHHS 2013 preferred ARV regimens• Understand concept of designing ARV regimen• Discuss pros and cons of NNRTI, PI, or INSTI regimens
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What percentage of the HIV Population in U.S . is not aware of their HIV infection?
1) 0-5%2) 5-10%3) 15-20%4) 20-25%5) 25-30%
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Rates of Adults and Adolescents Living with Diagnosed HIV Infection 2010 – U.S.
• CDC estimates 1,148,200 persons in U.S. > 13 living with HIV
• CDC estimates 207,600 (18.1%) unaware
• (Prevalence is the number of people living with HIV infection at a given time, such as at the end of a given year)
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Which of the following is false?
1) The HIV incidence in black women is 0.24%2) The HIV incidence in black women in the U.S. is comparable
to adult incidence rates in Sub-Saharan Africa 3) Risks in U.S. women cluster with poverty and
disempowerment 4) In 2010 the estimated number of new HIV infections was
lowest among individuals age 25-345) Rates of HIV infection are increasing in MSM population in
the U.S.
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Incidence • Incidence is the number of new HIV infections that occur during a
given year.1) CDC estimates that approximately 50,000 people in the United States are newly infected with HIV each year.2) In 2010 (the most recent year that data are available), there were an estimated 47,500 new HIV infections.3) Nearly two thirds of these new infections occurred in gay and bisexual men.4)Black/African American men and women were also highly affected and were estimated to have an HIV incidence rate that was almost 8 times as high as the incidence rate among whites
• CDC Estimates of New HIV Infections in the US (www.cdc.gov/hiv/statistics/surveillance/incidence/index.html
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U.S. Preventative Services Task Force 2013• Routine testing once for everyone age 15-65 (Grade A recommendation)
• Paves the way for coverage under ACA
• Repeat testing recommended for • Those higher risk for HIV infection (yearly)• Those actively engaged in risky behavior • Those living in high- prevalence setting (seroprevalence >0.1% -
1/1000)
Moyer VA, Screening for HIV: U.S. Preventative Services Recommendation Statement Annals of Internal Medicine April 30, 2013
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Goals of the Initial Evaluation (1)
• Confirm HIV infection• Identify acute problems requiring immediate intervention to
prevent morbidity • Assure that the patient understands how to avoid transmitting
HIV • Identify chronic medical problems and troubling symptoms • Identify problems requiring referral (medical, housing,
psychological, social legal or financial)• Establish stage of HIV disease
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Goals of the Initial Evaluation (2)
• Establish a baseline of physical findings for comparison with future examinations
• Begin to discuss appropriate anti-HIV drug therapy • Identify indications for prophylaxis • Identify social support • Establish a plan based on findings for long term management
of identified problems • Communicate recommendations in a process that establishes
confidence and trust
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Case 40 yo female referred to positive health clinic as recently diagnosed HIV positive. Husband died several years ago from HIV complications, however patient previously not tested. History of meth use in past. Clean for past 18 months. Heterosexual, not sexually active in past 2 years. Has disclosed status to daughter (age 17) and to mother. Has stable housing is unemployed and is receiving SSI. She has NKDAHer history is significant for hyperlipidemia and bipolar illness which is well controlled. She is on the following medications:1) Trazadone 100 mg qhs2) Oxcarbazepine 1200 mg qhs3) Seroquel 200 mg qhs 4) Lorazepam 1mg qhs prn 5) Simvastatin 20 mg qd
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The Initial History • HPI• Estimation of time of infection, including likelihood of infection
with resistant virus • HIV – associated symptoms
• PMH• Prior STDs, Hepatitis• TB exposure, TB test results • HO chicken pox or shingles • Vaccination status • Travel history: exposure to endemic pathogens
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The Initial PE • Overall: body habitus, vital signs• Skin: fungal infections, edema, pigmented lesions, nodules,
molluscum, folliculitis, psoriasis, condylomata, • HEENT careful eye and oral examination (thrush, OHL, ulcers,
gingivitis) • Lymphatics: generalized vs focal • Abdomen: HSM• Anogential warts, STDs, ulcerations• Neurologic: mental status, peripheral neuropathy ( decrease
vibratory sensation, absent ankle jerks)
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Case • Physical exam • VSS• HEENT no lesions no thrush edentulous • Neck no adenopathy thyroid wnl• Chest Clear to A+P• CV rr without mrg • Abd soft nontender without HSM • GU/Rectal deferred • EXT no edema • Neuro CN intact , reflexes =, strength =, no dysmetria • Skin no lesions
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CMV Retinitis
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Oral Thrush
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Oral Candidiasis – Hypererythematous
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Oral leukoplacia
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Oral Kaposi Sarcoma
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Kaposi sarcoma ( plaque and nodule phase)
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Molluscum Contagiosum
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Secondary Syphilis
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Baseline tests
All of the following should be obtained except:
1) CMV IgG2) G6PD3) HAV,HBV and HCV 4) Cryptococcal antigen 5) Toxoplasmosis IgG
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Baseline tests (1)
• HIV antibody test • Do if HIV infection not clearly documented
• CD4+ T lymphocyte cell count and percent • Estimates stage of HIV disease • Urgency of anti- HIV therapy
• Plasma HIV RNA (viral load) • Estimates risk of progression
• HIV Genotype • Upon initiation of care• In persons failing integrase strand transfer inhibitor (INSTI) – INSTI
resistance should be ordered
• Aberg JA, CID 2013
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Baseline tests (2)
• CBC and chemistry panel • G6PD ( AA, mediterranean descent)• Fasting lipid panel, HGA1C• UA (protein) and CrCl • PPD, Quantiferon (T spot) • Toxo IgG• HBsAG, HBsAB, HBcAB ( if HBcAB+ only – check HBVDNA)• HCV AB if + - HCV RNA • HAV ab • CMV IgG• RPR, Trich (women), GC, chlamydia at presentation and annually
Aberg JA, CID 2013
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Baseline tests (3)
• Cervical cancer screening
• PAP upon initiation of care, repeat in 6 months and annually thereafter if results are normal
• Women with ASC-US, ASC-H , atypical glandular cells , low grade or high grade squamous intraepithelial lesions or squamous Ca should undergo colposcopy and direct biopsy
• Screening for Anal HPV Annually (weak recommendation)
• HPV vaccination all females 9-26 and males 9-21 (22-26 if not previously vaccinated)
• Aberg JA, CID 2013
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Case • Patient is seen back in clinic in 2 weeks. She continues to feel
well. Her laboratory exam is significant for the following:• H/H 13.4/38.8 WBC 5.6 Plat 234,000• CD4 85 ( %) • HIV RNA 93,100 • HIV genotype – “wild type” virus (no significant mutations) • HGA1C 5.3 Chol 96 TG 179• Cr 0.9 UA no protein lytes normal• Quantiferon negative • G6PD 8.3• Toxo IgG < 0.91 • HBsAB, HBcAB, HBsAG neg, HCV AB neg, HAV AB neg • RPR negative
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Case
Which of the following is not indicated at this point in time?1) Begin PCP prophylaxis with TMP/SMX2) Begin MAI prophylaxis with Azithromycin3) Begin ARV regimen 4) Begin Toxo prophylaxis with TMP/SMX 5) Obtain T spot
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Recommended Prophylaxis PCP Toxo MAI
Initiating Primary Prophylaxis
CD4< 200 CD4 <100 CD4<50
Preferred regimen TMP/SMX DS qd TMP/SMX DS qd Azithromycin 1200 mg q week
Alternative regimen
Dapsone 100 mg qdAtovaquone 1500 mg qd with food
Dapsone 50 mg qd + pyrimethamine50 mg /leukovoran 25 mg q week
Rifabutin 300 mg qd
Discontinuing Primary Prophylaxis
CD4>200 for >3 months
CD4 > 200 for >3 months
CD4>100 for > 3months
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Patient wishes to start ARV
How are ARV regimens designed?
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ART Basic Rules
•3 Drugs from 2 drug classes
•Backbone of regimen 2 Nucleosides
•Anchor of Regimen • NNRTI • PI • INSTI
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Backbone: Nucleoside Analogs
• Preferred • Tenofovir (TDF)• Emtricitabine (FTC) • (Truvada = TDF/FTC)
• Alternative • Abacavir (ABC)• Lamivudine (3TC) • (Epzicom =ABC/3TC)
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Preferred Regimens • Have shown potent virologic efficacy as measured by the
proportion of subjects achieving and maintaining viral suppression in comparative clinical trials
• In two comparative clinical trials TDF/FTC was more effective than ABC/3TC
• Sax PE, NEJM. 2009;361(23):2230-2240• Post FA, JAIDS. 2010;55(1): 49-57
• In a third comparative clinical trial TDF/FTC and ABC/3TC showed comparable efficacy
• Smith KY, AIDS.2009;23(12):1547-1556
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Clinical Findings with Tenofovir Toxicity
• Reductions in GFR ( not seen in clinical trials but these studies excluded individuals with baseline reduced GFR)
• Proteinuria (can precede GFR reduction)• Kelly, AIDS 2013 Jan 28:27(3) 479-81
• Proximal tubule dysfunction/Fanconi’s syndrome • Aminoaciduria • Phosphaturia• Glucosuria
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How should we monitor for tenofovir toxicity ?
1) Monthly renal panel (Cr + lytes) +UA2) Q3 month renal panel + UA3) Q6 month renal panel + UA4) Q6 month renal panel + UA + phosphate excretion 5) Something else
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AJKD Guidelines • Measure eGFR pre-treatment • Reduce dose if eGFR < 60 ml/min
• Assess risk factors for kidney toxicity • Age • Body weight
• Measure every 3 months for one year then biannually• GFR• Fractional excretion of phosphate • Urine protein/creatinine ratio• Urine glucose • Tubular proteinuria if available
• Am J Kidney Dis 57(5):773-780. 2011
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Anchor of Regimen
•NNRTI (Non nucleoside reverse transcriptase inhibitor) Efavirenz (EFV)
•PI (Protease inhibitor) Atazanavir/r (ATV/r)
Darunavir/r (DRV/r)
•INSTI (Integrase Inhibitor) Ralegravir (RAL)
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What Percentage of the HIV population in US has achieved goal of therapy ? (complete virological suppression )
1) 82%2) 66%3) 50%4) 33%5) 25%
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CDC “vital statistics” July 2012
• 82% - Diagnosed • 66% - Linked to care • 37% - Retained in care • 33% - Prescribed ART• 25% - Virally suppressed
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NNRTI (EFV)– Pros and Cons
• PROS • Lower pill burden (Atripla = TDF/FTC/EFV)• Generally well tolerated
• CONS • Lower genetic barrier to resistance • CNS side effects • Rash • Dyslipidemia • Differing pharmacokinetics from Nucs• Potential teratogenicity
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NNRTIs -EFV- Pros and Cons Atripla (TDF/FTC/EFV)PROS• Atripla has been studied in the greatest number of clinical
trials• Available in single tablet once daily formulation • Generally well tolerated CONS• CNS side effects • Higher incidence of rash (including severe skin reactions)• Dyslipidemia • Lower genetic barrier to resistance (differing
pharmacokinetics)• Potential teratogenicity (animal studies and some human case
reports)
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PI (ATZ/r ; DRV/r) Pros and Cons
• PROS• High genetic barrier to resistance • Reasonable pill burden
• CONS • Metabolic Effects (elevated lipids)• GI side effects • Ritonavir boosting (drug drug interactions p450/CYP3A)
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If using a PI boosted regimen which of her drug(s) is/are contraindicated?
1) Trazadone 100mg qhs2) Oxcarbazepine 1200 mg qhs3) Seroquel 200 mg qhs 4) Lorazepam 1 mg qhs prn 5) Simvastatin 20 mg qd 6) All of the above
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Boosted PI (Drv/r ; Atv/r)
• Initial treatment with ritonavir (RTV) boosted PI containing regimens is unique from the resistance perspective, as virologic failure rarely selects for PI-resistance and NRTI resistance is uncommon • Consider for patients at higher risk for virological failure due to
suboptimal adherence/ inconsistent follow-up• No fully powered clinical trials that compare virologic efficacy of
DRV/r and ATV/r• ATV/r – cons indirect hyperbilirubinemia, needs acid
environment for absorption – dosing guidelines for acid reducing agents
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Integrase Inhibitor (RAL) Pros and Cons
• Pros• Low pill burden • Well tolerated • Better lipid profile
• Cons • Lower genetic barrier to resistance • Well tolerated • BID dosing
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Single Pill Regimens
NN anchoring regimen• Atripla (TDF/FTC/EFV) • Complera (TDF/FTC/ ) Not indicated if HIV VL >100,000
INST anchoring regimen • Stribild • ABC/3TC/Dolutegravir
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Which regimen would be least recommended?
1) Atripla (TDF/FTC/EFV) - single pill 2) Complera (TDF/FTC ) - single pill 3) Truvada (TDF/FTC) Darunavir 800 mg /100 mg Norvir qd 4) Truvada (TDF/FTC) Darunavir 600mg/100 mg Norvir bid5) Truvada (TDF/FTC) Atazanavir 300 mg/100mg Norvir qd
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Case
• Patient elects Atripla as she prefers a one tablet daily regimen• CNS side effects discussed with patient • Patient placed on TMP/SMX for PCP prophylaxis • Patient started on HAV and high dose HBV vaccine • Patient returns to clinic for 2 week follow up • No significant side effects noted • Patient adherent with regimen • HIV VL 1,010 copies (baseline 93,100)
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Case • Patient returns to clinic for cervical and anal Pap
• Patient adherent with medications and denies SE • HIV VL 23 copies/ml (week 12) • CD4 135 (15%)• Urine prot/cr ratio 0.10• Cr 0.8
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Case • Patient returns for follow up week 24 – adherent with
medications. Complains of bad dreams but denies worsening of her depressive symptoms
• CD4 198 (16%) • HIV VL < 20 copies/ ml • Pap reveals – ASCUS • Anal Pap reveals – SIL • Uprot/cr ratio 0/16 • Cr 0.8
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Case • You receive a message in your inbox that the patient was
5150ed for suicidal ideation • What would you do ?
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Case • Patient called and asked to come to clinic to discuss suicidal
ideation • Patient currently states no longer suicidal • At this point in time you would A) Continue Atripla B) Change regimen truvada isentress (bid regimen)C) Change regimen to Complera D) Change regimen to Truvada Darunavir Norvir
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Case
• Patient elects Truvada Raltegravir • She is sent for colposcopy• She is sent for high resolution anoscopy • She is followed up in clinic in 2 weeks to access adherence• Her HIV VL is < 20 copies/ml• Her CD4 count is 228 (21%)
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How often should we check her CD4 count?
1) Every 3-4 months 2) Every 3-4 months until her CD4 count is > 3003) Every 6 months 4) Every year
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DHHS Guidelines 2013
• Revised 2/2013 “for the patient …whose CD4 cell count has increased well above the threshold for opportunistic infection risk, the CD4 count can be measured…every 6 to 12 months, unless there are changes in the patient’s clinical status…”
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How often should we check her HIV VL
1) Every 3-4 months2) Every 3-4 months until her CD4 count is > 3003) Every 6 months4) Every year
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DHHS Guidelines 2013 – VL Monitoring
• 2-8 weeks after initiation of care • Every 3-4 months once virally suppressed • If suppressed for 2-3 years, then q6 months can be considered
• At treatment failure or when “clinically indicated”• Along with repeat resistance testing
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Case • Patient last seen in clinic 3 weeks ago• No longer having suicidal ideation • Adherent with regimen• No significant side effects to medications• U prot/cr ratio 0.16 ( upper limits of normal 0.15)• Cr 0.9• HIV VL < 20 copies/ml• CD4 228 (21%)• Colposcopy – benign
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Patient with mildly elevated Uprot/Cr ratio – you recommend
1) Continue current regimen of truvada isentress2) Obtain HLA B57013) Stop tenofovir if significant and sustained changes in eGFR, or fractional excretion of phosphate, or urine prot/cr ratio, or urine glucose 4) All of the above
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Thank you for your attention
ANY QUESTIONS?