# Presentation: 697000

## A Fire in our House: Why do we not have a more effective response to the AIDS Pandemic?

-              Timothy Flanigan MD
-              Professor of Medicine
-              Brown Medical School

## Slide 2

## Reaching out: HIV Community based interventionsfor active substance users. Timothy P. Flanigan, MDProfessor of MedicineBrown Medical School

## Why Reaching out?

- HIV is the leprosy of our time! Stigma is overwhelming and can never be underestimated.
- Alienation, family disintegration, hopelessness, mental illness, violence, multiple medical ills, homelessness, spiritual desolation...in short terrible suffering is the rule not the exception
- This can only be addressed by going to the communitythe street, detox and treatment centers, jails and prisons... and this must be done by a person with care and compassion.

## HIV Testing, Prevention, and Treatment are interlinked! 

- These may be distinct academic disciplines...but that has NO relevance to the community we serve.
- There can be no realistic prevention without testing...no treatment without testing...they are intertwined and to the community that we serve must be promoted in a holistic fashion
- They are synergistic and support each other

## HIV treatment is prevention!

- Among HIV + men in treatment on ART:
-  Marked decrease in unprotected sex
-  ART decreases HIV in the blood, semen, and other body fluids with decreased transmission
- CDC study in Uganda estimated a >90% reduction in risk among men on ART
- In RI among substance users on a community based ART program very low risk taking behaviours

## PLASMA HIV RNA PREDICTS LIKELIHOOD OF TRANSMISSION

- 0

- 5

- 10

- 15

- 20

- 25

- 30

**Viral load (HIV-1 RNA copies/ml) and HIV transmission**

**Transmission rate per 100 Person-Years **

*Source: **Quinn N,** et al,** **N Eng J Med 2000*

**All subjects**

**Male-to-Female**
**Transmission**

**Female-to-Male**
**Transmission**

## HIV Testing

- New technologies: rapid testing
- New approach to decouple HIV testing with risk reduction counseling in many settings

## Slide 9

## Denial and Stigma are common and fuel the  flames of HIVIn the U.S., 250,000 of the 1,000,000 infected persons are unaware of their infectionKaiser Permanente Study: “1/2 of patients sought an AIDS test because they were feeling ill”African Americans and substance users are more likely to enter care later

## Spectrum of Disease at Time of Diagnosis

- CD4 Count at Diagnosis (n=27)

## Missed Opportunities for HIV Screening

**65% of study patients: NO identifiable risk factors**
***How do we know who to test***
*** ******with no identifiable risk factors?***
***Physicians, other care providers and PATIENTS all routinely underestimate the risk of HIV!***

## Feasibility and Acceptability of Rapid HIV Testing in Jail

- Curt G. Beckwith
- Sarah Atunah-Jay
- Jonathan Cohen
- Michelle Lally
- Michael Poshkus
- Josiah D. Rich
- Timothy P. Flanigan

## Slide 16

## Results

- _Participation:_
- 113 inmates were asked to participate
- 100 (88%) participated
- _Demographics:_
- Median age 29 (18-60)
- Race:
- 46% White
- 25% Black
- 17% Hispanic
- 10% Native American
- _Incarceration History:_
- Median  # lifetime incarcerations = 5 (range 1-43)
- Median # incarcerations in previous 12 months = 2 (range 1-7)

## HIV Risk Assessment

| Do not consider themselves at risk for HIV infection |  | 76% (75/99) |
| --- | --- | --- |
|  |  |  |
| Sexual History  | Multiple sex partners within six months prior to incarceration | 44% (44/99) |
|  | Condom Usage |  |
|  |                  Never/Rarely | 52% (52/99) |
|  |                  Sometimes | 21% (21/99) |
|  |                  Almost always/Always | 23% (23/99) |
|  | Self-reported History of STD | 33% (33/99) |
|  | Median # Lifetime sex partners | 10 (1-500) |

## Study Enrollment and Rapid Test Results

| Selected to participate | 113 |
| --- | --- |
| Participated | 88% (100/113) |
| OraQuick® testing | 95% (95/100) |
| Rapid Test Results |  |
|              Negative | 99% (94/95) |
|              Positive | 1% (1/95) |
| Received rapid test results | 100% |
| Received risk reduction counseling | 100% |

## Attitudes Toward Routine HIV Testing and Partner Notification

| Agreed RIDOC is a good place to offer routine HIV testing | 96% (96/100) |
| --- | --- |
| In hypothetical situation, if HIV test was positive, subject agreed to talk with counselor in order to inform contacts of the need for HIV testing | 95% (90/95) |
| In follow-up question, agreed that counselor could be a health counselor from the State Dept. of Health | 92% (83/90) |

## RI DOH & Miriam Databases

## Project Bridge: Retaining Ex-Offenders in Care

- The Miriam Hospital
- Supported by grant #H97HA00190
- from the Health Services and Resources Administration (HRSA) Special Projects of National Significance (SPNS) Program

## The Road Home

## Program Design

- Community based
- 2 person teams of social workers assigned to each case
- Daily contact first month
- Weekly contact weeks 5-12
- Monthly contact thereafter
- Accompany during medical exams

## Evaluation Findings

- 95% of eligible people enroll in program
- 90% have clinic visit in first month
- Increase in CD4 and decrease in PVL
- Continuity: 87% clinic visits at 24 months
- 84% complete 18-month enrollment

## Adherence

- Treatment can be simply and effectivenow 1 pill/day...”Atripla”
- Adherence of 95% is not absolutely necessaryexcellent viral suppression is achieved with rates of 80%
- Prior substance use does not predict poor adherencecurrent substance use, missed appointments, etc predict poor adherence

## Background

- Directly observed therapy (DOT), which has been so successful in the treatment of tuberculosis (TB) is currently being adapted for the treatment of HIV in multiple diverse settings
- These community based programs are called “modified DOT” “MDOT” “Directly administered ART” “DAART” “Accompagneur”...they all use a community based person or family member to deliver ART.
- The goal of these interventions is to decrease the long term morbidity and mortality from HIV/AIDS and limit the development and transmission of resistant virus, particularly in high risk communities

## MDOT at The Miriam Hospital

- Provision of observed therapy with once daily medications since 1999
- MDOT intervention
- Single arm pilot projects
- Randomized controlled trial (AARTS)
- Qualitative work with special populations
- Pregnant and post-partum women
- Individuals leaving prison

## MDOT intervention – methods

- Participants were recruited from both community and hospital-based clinics in Rhode Island and southeastern Massachusetts
- Primary care providers (PCPs) referred patients to the MDOT program if:
- patients had persistent viremia despite multiple attempts at clinic-based adherence counseling; or
- patients reported active substance use within the previous 6 months

## MDOT intervention – methods 

- Participants were placed on a once-daily antiretroviral regimen recommended by the study team and their PCP after considering toxicity profiles, genotype results, and prior HIV medications
- All participants kept at least a one-week supply of medications with them so that they could self-administer their medications if an outreach visit was missed

## MDOT intervention – methods

- Initially, a “near-peer” outreach worker (ORW) delivered medications to participants 5-7 days per week (intensive MDOT stage)
- After the intensive MDOT stage, outreach worker visits were gradually tapered to 1-3 days per week

## The Experience of 69 Participants Receiving MDOT

- Analysis of first 69 participants who have received MDOT using a once-daily regimen
- 80% had a history of substance use in the last 3 months and 71% had been incarcerated.
- 9% were employed and 93% were ART experienced

## PVL and CD4 Changes Among Participants Receiving MDOT

- PVL (log10)
- 1 month: median individual decrease of 1.56
- 3 months: median individual decrease of 2.34
- 6 months: median individual decrease of 2.7
- CD4
- 1 month: median individual increase of 42 cells/mm3
- 3 months: median individual increase of 57 cells/mm3
- 6 months: median individual increase of 64 cells/mm3
- 2/3 on MDOT at 3 months and 1/2 at 6 months...high instability
-  								JAIDS 2005

## MDOT Randomized Controlled Trial (AARTS) 

- Specific Aims
- To determine whether directly observed once-daily HAART (intervention) is more effective than self-administered once-daily HAART (control) in the suppression of plasma HIV RNA among current drug users
- To evaluate and compare patterns of adherence in the DOT arm and the standard of care (SOC) arm during all phases of the study
- To compare the development of antiretroviral resistance between the DOT and standard of care arms

## Proportion of participants achieving viral load suppression (PVL<=50 or  >2 log decrease from baseline) at 3 months, by baseline HAART experience

| Trial arm | All participants |  | HAART experienced |  | HAART 
naive |  |
| --- | --- | --- | --- | --- | --- | --- |
|  | Proportion | n success | Proportion | n success | Proportion | n success |
| SOC | 0.41 | 15 | 0.34 | 10 | 0.63 | 5 |
| DOT | 0.64 | 25 | 0.67 | 20 | 0.56 | 5 |
|  | p=0.07 |  | p=0.02 |  | p=1.00 |  |

- Deaths were considered unsuppressed viral loads – remaining missing data not included (n=11)

## Conclusions

- 	MDOT works for HAART experienced individuals with active substance users as shown in an  intent to treat analysis.

## Conclusions

- Patients with active substance use disorders are able to successfully engage in MDOT with significant viral load responses
- However, MDOT is not acceptable for everyone; by 6 months, almost half of those enrolled dropped out
- A sizable percentage of the attrition was due to structural changes, such as movement to a correctional facility, hospital, drug treatment facility, or assisted living facility

## DAART in New Haven

- Altice et al - IAS Conference on Pathogenesis and Treatment 2003
- Randomized controlled trial of DAART among 130 HIV+ individuals with active heroin or cocaine use
- Medications were administered on a community Health Care Van which travels in tandem with Syringe Exchange Program
- Pager device to remind participants of visits and unobserved doses
- Training Program for outreach workers

## DAART in New Haven - results

- 64% male, 79% racial minorities
- 66% of participants reported both cocaine and heroin use at baseline
- 57% had major depression
- Intention to treat analysis among 86 participants, looking at changes from baseline to 6 month
- viral load log
- DAART – decrease of 2.08
- SOC – decrease of 0.17
- p=.01
- CD4
- DAART – increase of 107
- SOC – increase of 12
- p=.01

## Lucas GM et al (CID 2006)

- Four year clinical trial of DAART, in which treatment outcomes are compared with outcomes of concurrent cohort comparison patients who took self-administered HAART
- DAART participants were recruited at 3 methadone clinics (n=82)
- Participants received supervised doses of HAART each morning they attended the methadone clinic, and other doses were self-administered
- Median duration of DAART – 10.3 months
- Comparison group
- Individuals who self-administered HAART were selected from the Johns Hopkins HIV Cohort
- IDU-methadone group (n=75)
- IDU-nonmethadone group (n=244)
- non-IDU group (n=490)

## Lucas GM et al (CID 2006)

## Lucas GM et al (CID 2006)

- DAART, when given in conjunction with methadone therapy, was feasible and was associated with improved virologic and immunologic outcomes compared with results from 3 groups of cohort comparison patients self-administering HAART

- THE END!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!

## Acknowledgements

- Jody Rich
- Grace Macalino
- Joe Hogan
- Jennifer Mitty
- Helen Loewenthal
- Cindy MacLeod
- Curt Beckwith

- Xiomara Paulino
- Marie Varella-Taylor
- Pam Varella
- Stephanie Zuba
- Lauri Bazerman
- Chuck Carpenter
- Immunology Center

- Special thanks to all of the individuals who have participated in MDOT projects at The Miriam Hospital

## Financial support

- National Institute of Drug Abuse (R01DA013767 and K23DA017622)
- Lifespan-Tufts-Brown Center for AIDS Research (NIH grant AI42853)
- Tufts Nutrition Collaborative, a Center for Drug Abuse and AIDS Research (NIH grant DA13868)
- Gilead Sciences
- Bristol-Myers Squibb