The 8th Southern African HIV Drug Resistance and Treatment Monitoring Workshop

Summary Thursday 21 Nov

Raph Hamers

Opening session• South Africa largest HIV epidemic and ART program (2.1M)• “The best way to prevent HIV resistance is to prevent infection” (Cloete

van Vuuren) • Science translated into national policy and clinical practice• Broad variety of HIV topics “ geeky” mutations to adherence to clinical

cases• SATuRN 4 pillars (Tulio de Oliveira):

– advanced diagnostics– PHC clinics– Surveillance & research– Collaboration and capacity building

• Donor perspective RNE: to stimulate collaboration and research translating into policy

If you want to go fast, go alone. If you want to go far, go together.

We need to go very far, very fast.

“A modified African proverb applicable to the African HIV treatment expansion...”

Tulio de Oliveira

Keynote 1:Is understanding HIVDR still relevant? Mark Wainberg

Dolutegravir data

Results were confirmed in per protocol analysis: 91% DTG versus 84% DRV/r, ∆ (CI): 7.4 (1.4 - 13.3)

Proportion (95% CI) of Individuals With HIV-1 RNA <50 c/mL Over Time – Snapshot

(Flamingo)

Clotet et al. EACS 2013; Brussels, Belgium. Abstract LBPS4/6.

DTG: 90%

DRV/r: 83%

WeekBL 4 8 12 16 3624 48

Prop

ortio

n (%

) 95% CI for differencea

FavoursDRV/r

FavoursDTG

-20% 0 20%

7.10.9 13.2

-12%

Test for superiority: P=0.025

Dolutegravir resistance• Resistance mutations selected in vitro with dolutegravir are:

R263K or G118R plus H51Y (low-level resistance)– Addition of H51Y increases resistance against DTG but also

further decreases viral fitness

• No compensatory mutations in regard to restoring viral fitness have developed over more than two years in culture. – These findings help to explain why resistance against

dolutegravir in INSTI-naïve patients has not been observed

• “DTG monotherapy in ARV-naive patients?”

Keynote 2: Addressing adherence challenges – what

does the evidence say? Catherine Orrell

Barriers to Adherence in sub-Saharan Africa–ETOH/substance use–Depression –Memory

– Side effects–Pill burden/dosing

frequency

–Adolescence

–Transportation to clinic–Food security–Stigma

–Stock-outs and substitutions–Unfriendly service

Mill PLoS 2006, Oyugyi AIDS 2007, Tuller AIDS Beh 2010, Weiser JAIDS 2003; McCurdy CROI 2010, Nachega AIDS 2008, JAIDS 20090

What works in RLS?

• Review of recent literature - 27 studies from resource-limited settings identified by early 2012.• studies with comparator arms (case-control or randomised) and an adherence or biological marker as

an outcome.

Bärnighausen, Lancet ID 2011Thompson, Annals Int Med 2012

• Peer-driven group pre-treatment education (BIII).• Peer support (BIII)

• DOTS – benefit in terms of adherence, but not biological outcomes

• Monthly food supplementation packages (BII)• Electronic adherence reminder devices (AI)• Task-shifting no negative impact (3 RCTs)

Adherence interventions are successfulStudy Year n Intervention Outcome

Berki-Benhaddad

2006 15 Personal adh support Ave decrease VL by 2.3 log

Calmy 2007 232

Counseling, pill boxes, support group, treatment partner

77% achieved VL<400

DeFino 2004 45 Counseling, pill boxes, alarm reminders, repeat education…

Ave decrease VL by 0.6 log

Khan 2013 40 Structured adh counseling, including families

78% achieved resuppression

Orrell 2007 43 Pill box, dosing diaries, counseling, home visit

54% achieved resuppression

Parker 2013 200

Intensive adh counseling 48% achieved resuppression

Pirkle 2009 56 1 month mDAART, weekly f/u visits 36% decreased VL by >1 log

Wilson 2009 40 Counseling and education 90% resuppression

Bonner, JAIDs 2013

Develop your adherence toolkit:

• Medication factors - – OD, FDC, simplify

• Service / provider factors – – Education, peer support– Measure adherence: SR and

pharmacy refill– Interactive communication devices

• Patient factors -– Use VL– Be friendly and flexible

Panel discussion 1: Clinical Case Review.

Ava Avalos

• Successful with good retention, viral success and low levels of resistance

• Financial challenges: – International donor funding ending, clinical

training & mentorship programme are now experiencing setbacks

– Efforts to more effective and cost-efficient ways to ensure the long-term financial sustainability

Botswana National Program

• The long-term sustainability of the Botswana ART Program will depend largely on our ability to prevent HIV-DR through the capacity to detect and promptly address virological failure and sub-optimal adherence.

• Failure Management is the KEY– Routine VL monitoring– ART Failure Management Team & Protocols– Good retention, viral success and low levels of

resistance

• Clinical cases: holistic view – psychosocial, hypertension, diabetes,

neoplasma, etc.

Keynote 3: HIVDR impact and significance in context of

generalized epidemics. Deenan Pillay

• ART works, with or without resistance testing

• Resistance is relative not absolute: – Residual activity of the drug– Fitness cost

(Consensus statement Pillay-Wainberg)

• Resistance is a function of roll-out of treatment

The utility of resistance testing is determined by• Optimal use of VL tests• Availability of therapies• Health systems and costs

“Better alive with drug-resistant virus, than dead with drug-susceptible virus”

(Kevin de Cock, WHO)

Outcome of ART after 24 months of ART in PASER-MPascale Ondoa

• First (n=2755) and second-line ART (n=253) good retention and viral suppression up to 24 months– Early mortality first-line

• Limited accumulation of DRMs between 12 and 24 months of ART• Limited bPI mutations on 2nd line

• VL results may not be adequately used for clinical decision-making Causes to be further explored

Pediatric HIVDR: the case of Uganda

Cissy Kityo

• MARCH – Study: only pediatric cohort in Uganda currently assessing HIVDR

• Important barriers to care remain for children: – Late presentation (median age 4 yrs)

• Extensive resistance at switch (46% multiple TAMs) due to delayed switching fear of exhausting treatment options in children?

• Risk factors for baseline HIVDR:– PMTCT exposure, maternal ART use and breastfeeding

• HIV drug resistance among children is underreported, surveillance data necessary to inform pediatric guidelines

Pretherapy HIVDR: what’s next?Raph Hamers

• Pre-ART resistance and TDR are on the rise, particularly in southern and East Africa, mostly confined to NNRTI, associated with duration and coverage of national ART programs

• Currently, measured levels are of concern, but not at unexpected levels and rates, far majority of patients receive effective regimens– Lack of routine HIVDR surveillance data not up-to-date

• Strengthening of program functioning, retention and adherence, VL monitoring, access to 2nd line ART

• Modelling suggests that risk of TDR may be outweighed by HIV prevention– Implementation of novel TasP strategies (Option B+) will

need to be closely monitored to assess the consequences for retention-adherence-HIVDR

Panel discussion 2: Clinical Case Review.

Jan Loot Pretorius

• First-line failure and resistance due to GI malabsorption, biopsy: MAC

• Single-drug substitutions in patient with detectable VL burn drug options

• bPI plus residual activity of NRTI backbone can effectively resuppress VL – Sigaloff JID2012; Houseinipour HIVMed2011

Sponsors:

We would like to thank to our sponsors:

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