HIV CasesHIV Cases

Case 1Case 1 36-year-old AA male, healthy in the past 36-year-old AA male, healthy in the past

with no prior hospitalizationswith no prior hospitalizations

Presents to ER with Presents to ER with 2 week history of cough with clear 2 week history of cough with clear

sputum productionsputum production Dyspnea on exertion, progressiveDyspnea on exertion, progressive Associated with subjective feversAssociated with subjective fevers Myalgias, fatigue; weight loss 5-10 Myalgias, fatigue; weight loss 5-10

pounds last monthpounds last month 4-5 loose BMs per day last few weeks4-5 loose BMs per day last few weeks

PMHPMH Genital herpesGenital herpes

Case 1Case 1 Social history: lives with a friend,

unemployed, no recent travel or sick contacts; not sexually active for the last 2 months; smokes marijuana occasionally; social alcohol; no tobacco.

Current meds: none

Temp 39.7; Pulse 114, BP 148/62, RR 22, O2 sat 88% RA

Exam notable for bilateral basilar rhonchi Otherwise unremarkable

Nasopharyngeal swab negative for influenza/other viruses

Sputum gram stain reveals few PMNs, no organisms

Strep. pneumonia and legionella antigens negative

Rapid HIV ELISA +

HIV WB also + p17/18 + p51/55 + p24 + p66 + p31 + gp120/160 +/+ gp41 +

Patient started empirically on ceftriaxone and zithromax for community-acquired pneumonia, but has not improved a day later. What should be the next step in management?

1) Send CD4 cell count, HIV viral load and genotype; await results before changing therapy

2) Above answer + send sputum for PCP testing and start bactrim + steroids empirically

3) Add additional antibiotic therapy to cover MRSA and Pseudomonas

4) All of the above

Patient had been started empirically on Patient had been started empirically on ceftriaxone and zithromax for community-ceftriaxone and zithromax for community-acquired pneumonia, but has not improved. acquired pneumonia, but has not improved. What should be the next step in management?What should be the next step in management?

1)1) Send CD4 cell count, HIV viral load Send CD4 cell count, HIV viral load and genotype; await results before and genotype; await results before changing therapychanging therapy

2)2) Above answer + send sputum for Above answer + send sputum for PCP testing and start bactrim + PCP testing and start bactrim + steroids empiricallysteroids empirically

3)3) Add additional antibiotic therapy to Add additional antibiotic therapy to cover MRSA and cover MRSA and PseudomonasPseudomonas

4)4) All of the aboveAll of the above

Patient is started on bactrim and steroids; fever and oxygenation improve

CD4 count 4 c/mm3 (1%)

HIV RNA 63,100 cp/mL

Genotype PROTEASE GENE

Primary mutations: None. Secondary mutations: None.

REVERSE TRANSCRIPTASE (RT) GENE Mutations: K101Q, Y181C, G190A.

Do you want to start Do you want to start antiretroviral therapy now?antiretroviral therapy now?

1)1) Yes, but not until patient has Yes, but not until patient has completed his pneumonia treatment completed his pneumonia treatment (concern for Immune Reconstitution (concern for Immune Reconstitution Syndrome)Syndrome)

2)2) Start therapy now with Start therapy now with truvada/ritonavir/darunavirtruvada/ritonavir/darunavir

3)3) Start therapy now with Start therapy now with truvada/efavirenz (atripla)truvada/efavirenz (atripla)

4)4) Defer therapy until patient has Defer therapy until patient has established HIV care and compliance to established HIV care and compliance to follow-up can be assessed as an follow-up can be assessed as an outpatientoutpatient

Do you want to start Do you want to start antiretroviral therapy now?antiretroviral therapy now?

1) Yes, but not until patient has completed his pneumonia treatment (concern for Immune Reconstitution Syndrome)

2) Start therapy now with truvada/ritonavir/darunavir

3) Start therapy now with truvada/efavirenz (atripla)

4) Defer therapy until patient has established HIV care and compliance to follow-up can be assessed as an outpatient

ACTG A5164: Immediate Versus Deferred ACTG A5164: Immediate Versus Deferred HAART in the Setting of Acute AIDS-HAART in the Setting of Acute AIDS-

Related OIRelated OI 48-week, strategy trial48-week, strategy trial

Determine the optimal Determine the optimal timing of HAART initiation timing of HAART initiation in the setting of acute in the setting of acute AIDS-related OI or serious AIDS-related OI or serious bacterial infection (BI)bacterial infection (BI)

Randomized armsRandomized arms Immediate HAARTImmediate HAART

Initiated at time of acute OIInitiated at time of acute OI Deferred HAARTDeferred HAART

Initiated after treatment for Initiated after treatment for acute OI is completedacute OI is completed

HAARTHAART No restrictions on initial No restrictions on initial

regimenregimen Study recommended Study recommended

ritonavir-boosted PI or ritonavir-boosted PI or NNRTI plus 2 NRTIsNNRTI plus 2 NRTIs

Baseline CharacteristicsBaseline Characteristics

ImmediImmediateate

(n=141)(n=141)

DeferrDeferreded

(n=141(n=141))

Male (%)Male (%) 8585 8686

HIV RNAHIV RNA(log(log1010 copies/mL) copies/mL)

5.075.07 5.085.08

No prior HAARTNo prior HAART 9393 9191

Median CD4 Median CD4 (cells/mm(cells/mm33))

3131 2828

Mean time to Mean time to start HAART start HAART after OI/BI after OI/BI diagnosis (day)diagnosis (day)

1212 4545

OIs (%)OIs (%) PCPPCP Serious BISerious BI Crypto/HistoCrypto/Histo ToxoplasmosisToxoplasmosis OtherOther

6262121214146666

6363121218183344

Zolopa A, et al. 15th CROI. Boston, 2008. Abstract 142.

ACTG A5164: 48-Week Final ACTG A5164: 48-Week Final ResultsResults

ImmediatImmediate HAARTe HAART(n=141)(n=141)

DeferreDeferredd

HAARTHAART(n=141)(n=141)

Odds RatioOdds Ratio(95% CI)(95% CI) PP

ValueValue

Death/AIDS Death/AIDS progression (number progression (number of events)of events)

2020 3434 0.510.51(0.23, 1.15)(0.23, 1.15)

0.0350.035

Time to AIDS Time to AIDS progression/ death progression/ death (weeks)(weeks)

116116 9494 0.530.53(0.25, 1.09)(0.25, 1.09)

0.0230.023

Time to CD4 target Time to CD4 target (weeks)(weeks)

>50 cells/mm>50 cells/mm33

>100 cells/mm>100 cells/mm334.04.04.34.3

8.18.112.112.1

--------

<0.00<0.0011

<0.00<0.0011

HIV RNA <50 HIV RNA <50 copies/mL with no copies/mL with no progression (%)progression (%)

47.547.5 44.744.7 ---- 0.2150.215

Recommendation:Initiate “immediate HAART” (within 2 weeks of OI/BI diagnosis) in the setting of

acute-AIDS related opportunistic infections/serious bacterial infections,absent any major contraindications

Zolopa A, et al. 15th CROI. Boston, 2008. Abstract 142.

Low frequency of IRIS (6% to 8%) and no difference in IRIS observed.70% of PCP patients received steroids.

IRIS and Mortality when ART Given with OIsIRIS and Mortality when ART Given with OIsA5164 Follow up (N=282 median CD4 29 A5164 Follow up (N=282 median CD4 29

cells/mmcells/mm33)) Early vs. deferred therapy with an OIEarly vs. deferred therapy with an OI

IRIS in 7.6% of patients after median of 33 days on IRIS in 7.6% of patients after median of 33 days on ART ART

Lower than estimates in retrospective studiesLower than estimates in retrospective studies

HIV RNA decline at week 4 predicted IRIS; HIV RNA decline at week 4 predicted IRIS; CD4 change did notCD4 change did not

Steroids delayed but did not prevent IRISSteroids delayed but did not prevent IRIS

No difference in rates of IRIS whether treatment No difference in rates of IRIS whether treatment started early or laterstarted early or later

Overall mortality in trial linked to lower absolute CD4Overall mortality in trial linked to lower absolute CD4 ((PP=0.04)=0.04)

Grant P, et al. 16th CROI; Montreal, Canada; February 8-11, 2009. Abst. 775.

Case 2Case 2 27 y.o. Caucasian woman referred from ER after 27 y.o. Caucasian woman referred from ER after

positive rapid HIV test (came for sutures to positive rapid HIV test (came for sutures to laceration suffered in bike accident)laceration suffered in bike accident)

No other medical conditionsNo other medical conditions Risk factor: unprotected sex with menRisk factor: unprotected sex with men No tobacco; social ETOH; no illicit drugsNo tobacco; social ETOH; no illicit drugs Works as a waitress; lives with 2 roommates; no kidsWorks as a waitress; lives with 2 roommates; no kids Interested in starting meds for HIVInterested in starting meds for HIV Baseline labs performed (2 months ago)Baseline labs performed (2 months ago)

CD4 525 c/mmCD4 525 c/mm33, VL 35,000, no mutations by genotype, VL 35,000, no mutations by genotype RPR negative, Urine GC/CT negativeRPR negative, Urine GC/CT negative HCV Ab negative, HBV sAb positive, HAV Ab positiveHCV Ab negative, HBV sAb positive, HAV Ab positive CBC and metabolic panels normal, U/A normalCBC and metabolic panels normal, U/A normal Last week: CD4 510 c/mmLast week: CD4 510 c/mm33 (20%), VL 33,000 (20%), VL 33,000

Which selection would be a Which selection would be a poor choice?poor choice?

1. Defer therapy at present2. Initiate therapy with Truvada/Efavirenz

(atripla)3. Initiate therapy with Ritonavir-boosted

PI (darunavir or atazanavir) and 2 NRTIs

4. Initiate therapy with Raltegravir and 2 NRTIs

5. Initiate therapy with Maraviroc and 2 NRTIs

Which selection would be a Which selection would be a poor choice?poor choice?

1. Defer therapy at present2. Initiate therapy with Truvada/Efavirenz

(atripla)3. Initiate therapy with Ritonavir-boosted

PI (darunavir or atazanavir and 2 NRTIs4. Initiate therapy with Raltegravir and 2

NRTIs 5. Initiate therapy with Maraviroc and 2

NRTIs

Recommendations for Recommendations for Initiating ART Initiating ART

* Treatment with fully suppressive drugs active against both HIV and HBV is recommended.

DHHS. Available at: http://aidsinfo.nih.gov/Guidelines.

New Studies Supporting New Studies Supporting Earlier Antiretroviral Earlier Antiretroviral

TherapyTherapy Low CD4+ nadir associated with

Increased rates of HIV-associated neurocognitive disorders[1]

Arterial stiffness contributing to CV risk[2]

Increased risk of fracture[3]

Patients with acute opportunistic infection 2-fold higher risk of clinical progression in patients

who deferred HAART vs those started immediately[4]

Improved immunologic outcomes in patients starting early vs deferred HAART during acute opportunistic infection[5]

1. Ellis R, et al. CROI 2010. Abstract 429. 2. Ho J, et al. CROI 2010. Abstract 707. 3. Dao C, et al. CROI 2010. Abstract 128. 4. Miro J, et al. CROI 2010. Abstract 529. 5. Sanchez A, et al. CROI 2010. Abstract 509.

Immunodeficiency, HIV-1 RNA, Immunodeficiency, HIV-1 RNA, and and

Risk of Non-AIDS–Defining Risk of Non-AIDS–Defining CancersCancers Recent HIV-1 RNA levels not significantly associated with

non-AIDS–defining cancer risk (infection related or non-infection related)

Silverberg M, et al. CROI 2010. Abstract 28.

Adjusted HR*Adjusted HR* HIV Infected, CD4+ Cell Count, cells/mmHIV Infected, CD4+ Cell Count, cells/mm33

< 200< 200 201-499201-499 ≥ ≥ 500500 PP Value Value

Any infection Any infection relatedrelated

12.812.8†† 5.95.9†† 3.23.2†† < .001< .001

AnalAnal 164.2164.2†† 83.183.1†† 34.234.2†† < .001< .001

Hodgkin’s Hodgkin’s lymphomalymphoma

55.055.0†† 11.011.0†† 11.611.6†† < .001< .001

Oral/pharyngealOral/pharyngeal 3.13.1†† 1.91.9‡‡ 0.80.8 .030.030

Any infection Any infection unrelatedunrelated

1.81.8†† 1.21.2 1.11.1 .002.002

MelanomaMelanoma 1.31.3 1.91.9‡‡ 1.91.9‡‡ .71.71

LungLung 2.12.1‡‡ 1.01.0 1.21.2 .083.083

ColorectalColorectal 2.22.2‡‡ 1.01.0 0.90.9 .050.050*Adjusted for age, sex, smoking, overweight, alcohol/drug abuse, viral hepatitis; reference = uninfected cohort. †P < .001 relative to uninfected. ‡P < .05 relative to uninfected.

HIV Transmission Risk in HIV Transmission Risk in Heterosexual Serodiscordant Heterosexual Serodiscordant

Couples Initiating ARVCouples Initiating ARV

92% lower risk of HIV transmission in African 92% lower risk of HIV transmission in African serodiscordant couples when HIV-infected serodiscordant couples when HIV-infected partner receiving antiretroviral therapypartner receiving antiretroviral therapy 102 of 103 cases of confirmed HIV transmission occurred 102 of 103 cases of confirmed HIV transmission occurred

in couples with HIV-infected partner not receiving ARV in couples with HIV-infected partner not receiving ARV therapytherapy

Unadjusted relative risk: 0.17 (95% CI: 0.004-Unadjusted relative risk: 0.17 (95% CI: 0.004-0.94; 0.94; PP = .037) = .037)

Adjusted relative risk: 0.08 (95% CI: 0.002-Adjusted relative risk: 0.08 (95% CI: 0.002-0.57; 0.57; PP = .004) = .004) Adjusted for visit and CD4+ cell count at initiationAdjusted for visit and CD4+ cell count at initiation

Donnell D, et al. CROI 2010. Abstract 136.

Case 2Case 2

1 year later (therapy had been 1 year later (therapy had been deferred)deferred) CD4 375 c/mmCD4 375 c/mm33

VL 36,000 cp/mLVL 36,000 cp/mL

AsymptomaticAsymptomatic

What would you do?

1. Defer therapy at present, continue to monitor CD4 every 3-4 months

2. Initiate therapy3. Initiate therapy, but since

asymptomatic now can stop when CD4 again greater than 500

What would you do?

1. Defer therapy at present, continue to monitor CD4 every 3-4 months

2. Initiate therapy3. Initiate therapy, but since

asymptomatic now can stop when CD4 again greater than 500

CASE 3CASE 3

A 48 y.o. HIV-infected white male presents to you for treatment

He weights 140 lbs and is 5’11” tall He smokes 1 ppd and drinks moderately He presents with an HIV-1 RNA of

110,000 copies per mL and a CD4+ cell count of 210 cells/mm3

He wants to start antiretroviral treatment

What is his risk of underlying What is his risk of underlying osteopenia and osteoporosis?osteopenia and osteoporosis?

1.1. < 1%< 1%

2.2. 5-10%5-10%

3.3. 20% to 40%20% to 40%

4.4. 50-70%50-70%

5.5. > 90%> 90%

What is his risk of underlying What is his risk of underlying osteopenia and osteoporosis?osteopenia and osteoporosis?

1.1. < 1%< 1%

2.2. 5-10%5-10%

3.3. 20% to 40%20% to 40%

4.4. 50-70%50-70%

5.5. > 90%> 90%

ACTG 5224ACTG 5224Baseline characteristicsBaseline characteristics

N=269 *N=269 *Age, median (IQR)Age, median (IQR) 38 (31,44)38 (31,44)Male (%)Male (%) 85%85%White non-Hispanic Race (%)White non-Hispanic Race (%) 47%47%

HIV RNA logHIV RNA log1010 c/mL, median c/mL, median (IQR) (IQR)

4.62 4.62 (4.24,4.90)(4.24,4.90)

HIV RNA ≥ 100,000 c/mL (%)HIV RNA ≥ 100,000 c/mL (%) 41%41%

CD4 cells/mmCD4 cells/mm33, median (IQR), median (IQR)233 233

(106,334)(106,334)CD4 < 200 cells/mmCD4 < 200 cells/mm3 3 (%)(%) 43%43%Lumbar spine T score ≤-1 (%)Lumbar spine T score ≤-1 (%) 35%35%

BMI, Median (IQR)BMI, Median (IQR)24.9 (21.8, 24.9 (21.8,

28.2)28.2)

Limb fat kg, Median (IQR)Limb fat kg, Median (IQR)7.4 7.4

(4.7,10.1)(4.7,10.1)

Baseline prevalence of osteopenia/osteoporosis 35%

McComsey G, et al. CROI 2010. Abstract 106LB.

Osteopenia related to HIV Osteopenia related to HIV itself: itself:

Bones in HAART-naïve HIV Bones in HAART-naïve HIV individualsindividuals

TDF+3TC+ETDF+3TC+EFVFV

(n=299)(n=299)

D4T+3TC+ED4T+3TC+EFVFV

(n=301)(n=301)

TotalTotal(n=600)(n=600)

NormalNormal 221 (74%)221 (74%) 206 (68%)206 (68%) 427 (71%)427 (71%)

OsteopeniaOsteopenia 70 (23%)70 (23%) 83(28%)83(28%) 153(26%)153(26%)

OsteoporosisOsteoporosis 8 (3%)8 (3%) 12 (4%)12 (4%) 20 (3%)20 (3%)

Powderly et al. CROI 2005, Abstract 823.

16%

-1Gilead Study 903, pre-HAART

Would you do a DEXA scan Would you do a DEXA scan before starting before starting

antiretroviral therapy?antiretroviral therapy?

1. Yes2. No3. I do not know

Would you do a DEXA scan Would you do a DEXA scan before starting before starting

antiretroviral therapy?antiretroviral therapy?

1. Yes2. No3. I do not know

NOF: Indications for BMD NOF: Indications for BMD Testing for General Testing for General

PopulationPopulation Women > 65 and men > 70 years of ageWomen > 65 and men > 70 years of age Younger women and men (50 to 69 y of age) at riskYounger women and men (50 to 69 y of age) at risk

Women in the menopausal transition if there is a Women in the menopausal transition if there is a specific risk factorspecific risk factor

Adults who have a fracture after 50 y of ageAdults who have a fracture after 50 y of age Adults of any age with fragility fractureAdults of any age with fragility fracture Adults with a condition (eg, rheumatoid arthritis) Adults with a condition (eg, rheumatoid arthritis)

or taking a medication (eg, glucocorticoids) that or taking a medication (eg, glucocorticoids) that predispose them to osteoporosis. predispose them to osteoporosis. I would include I would include HIV here.HIV here.

Anyone being considered or on treatment for Anyone being considered or on treatment for osteoporosis. Women that discontinue estrogens.osteoporosis. Women that discontinue estrogens.

National Osteoporosis Foundation. Clinician’s Guide to Prevention and Treatment of Osteoporosis. Available at: http://www.nof.org/professionals/pdfs/NOF_ClinicianGuide2009 v7.pdf.

CROI 2010: Fracture CROI 2010: Fracture studiesstudies

HOPS cohort VA aging cohort

Dao C, et al. CROI 2010. Abstract 128. Womack J, et al. CROI 2010. Abstract 129.

CASE 3CASE 3

The patient’s labs are otherwise The patient’s labs are otherwise normal normal

Genotype is wild typeGenotype is wild type He prefers a simple treatmentHe prefers a simple treatment You prescribe atripla once dailyYou prescribe atripla once daily The patient tolerates his The patient tolerates his

medicine wellmedicine well

What do you expect to happen What do you expect to happen to his BMD after starting ART to his BMD after starting ART

treatment?treatment?

1.1. It will increase because his level It will increase because his level of chronic inflammation will be of chronic inflammation will be reducedreduced

2.2. It will stay the sameIt will stay the same

3.3. It will decrease by 3%-5%It will decrease by 3%-5%

4.4. It will decrease by 10%It will decrease by 10%

What do you expect to happen What do you expect to happen to his BMD after starting ART to his BMD after starting ART

treatment?treatment?

1. It will increase because his level of chronic inflammation will be reduced

2. It will stay the same3. It will decrease by 3%-5%4. It will decrease by 10%

A5224s design: Metabolic A5224s design: Metabolic

substudy of A5202substudy of A5202

A5224s

Mean (95% CI) percent change in lumbar spine BMD

A5224s

* -linear regressionNo significant interaction of NRTI and NNRTI/PI components (p=0.63)

**

McComsey G, et al. CROI 2010. Abstract 106LB.

Mean (95% CI) percent change in hip BMD

A5224s

*

*

McComsey G, et al. CROI 2010. Abstract 106LB.

Bone Conclusions of 5224s

HIV infection itself is associated with an HIV infection itself is associated with an increased risk of bone lossincreased risk of bone loss

All regimens appeared to produce an initial bone All regimens appeared to produce an initial bone loss with subsequent stabilization or even loss with subsequent stabilization or even improvement after Week 48improvement after Week 48

TTDF/FTC led to greater BMD loss in hip and DF/FTC led to greater BMD loss in hip and lumbar spine than ABC/3TClumbar spine than ABC/3TC

ATV/r led to greater BMD loss in lumbar spine ATV/r led to greater BMD loss in lumbar spine (but not hip) than EFV(but not hip) than EFV

Fractures were similarly distributed among Fractures were similarly distributed among study armsstudy arms

McComsey G, et al. CROI 2010. Abstract 106LB.

CASE 3CASE 3

After 4 years, he is doing well on his regimen

CD4+ cell count is now 526 cells/mm3 and his viral load is undetectable

While walking his dog, he fell and fractured his wrist.

Would you change his antiretroviral regimen?

1. Yes, definitely 2. No, this was a traumatic fracture3. No, look first for secondary causes of

osteoporosis

Would you change his antiretroviral regimen?

1. Yes, definitely 2. No, this was a traumatic fracture3. No, look first for secondary causes of

osteoporosis

N=125; subjects on antiretrovirals for mean of 3.4 years; 46% with low BMD at baseline. Independent predictors of low BMD were history of smoking, steroid use, or wasting; low current weight, and longer duration of HIV infection (p<0.05 for all).

Bone mineral density appears to Bone mineral density appears to improve/stabilize over timeimprove/stabilize over time

Mondy et al. CID 2003;36:482-90

25 OHD25 OHD

StudyStudy NN SexSex AgAgee

CDCD44

ARVARV SeasonSeason DefDef InsuInsuffff

NormNormalal

StephenseStephensen (REACH, n (REACH, US) 2006US) 2006

238 238 HIV+HIV+121 121 HIV-HIV-

25% M25% M10% W10% W

2020 ?? ?? Winter-Winter-SpringSpring

87%87%87%87%

Yin (WIHS Yin (WIHS cohort) cohort) 20092009

100 100 HIV+HIV+68 68 HIV-HIV-

100%F100%F29% W29% W

3838 434388

59%59% AllAll 81%81% 87%87%

19%19%13%13%

Bang Bang (Sweden) (Sweden) 20042004

115 115 HIV+HIV+

100% 100% M, M, 100% W100% W

4444 484800

62%62% Fall-Fall-WinterWinter

20%20% 36%36% 40%40%

Rubin Rubin (NYC) (NYC) 20052005

62 62 HIV+HIV+

100% M100% M34% W34% W

4848 545400

92%92% Fall-Fall-WinterWinter

42%42% 34%34% 24%24%

Rodriguez Rodriguez (Boston) (Boston) 20052005

57 57 HIV+HIV+

77% M,77% M,60% W60% W

4646 434300

81%81% Winter-Winter-SpringSpring

48%48% ?? ??

Van Den Van Den BoutBout(Holland) (Holland) 20082008

252 252 HIV+HIV+

75% M,75% M,73% W73% W

4141 424200

79%79% Jan-AugJan-Aug 29%29% ?? 71%71%

Dao (SUN Dao (SUN cohort) cohort) 20102010

672 672 HIV+HIV+

77% M77% M30% B30% B

4141 474711

80%80% AllAll 72%72% 38%38%

Broderi Broderi (ICONA) (ICONA) 20102010

856 856 HIV+HIV+

71% M71% M95% 95% EuroEuro

3636 ?? 96%96%

AllAll 7%7% 54%54% 39%39%

Mueller Mueller (Swiss (Swiss cohort) cohort) 20102010

211 211 HIV+HIV+

75%M75%M88%W88%W

3737 222266

100100%%

Spring Spring (Fall)(Fall)

42% 42% (14%)(14%)

53%53%(63(63%)%)

5%5%(23%)(23%)

Vitamin D and HIV

Courtesy of Michael Yin, MD

Case 3Case 3 DEXA scan results:DEXA scan results:

Hip T-score: -2.4Hip T-score: -2.4 L-spine T-score: -2.2L-spine T-score: -2.2

Vitamin D: 12ng/mLVitamin D: 12ng/mL Initiated on high dose vit D and calciumInitiated on high dose vit D and calcium

50,000 IU/wk X 12 weeks THEN 2,000 50,000 IU/wk X 12 weeks THEN 2,000 IU/dayIU/day

Optimizes nutrition/weight; stops smokingOptimizes nutrition/weight; stops smoking 1yr later1yr later

Hip T-score: -1.5Hip T-score: -1.5 L-spine T-score: -1.2L-spine T-score: -1.2