dr ia hiv dr for slcov

HIV Drug Resistance and Early Warning Indicators

Iyanthi Abeyewickreme

Goal of antiretroviral therapy

• To achieve and sustain viral suppression among all those who receive antiretroviral therapy.

Increasing antiretroviral therapy coverage% ART coverage

% of people eligible who are receiving ART (based on 2010 WHO guidelines)

Source: UNAIDS Global report 2013

100

80

60

40

20

0

Number of people receiving ART increasedfrom ~2 million in 2005 to ~13 million in 2013

Presenter

Presentation Notes

The more people are on therapy, the more people will fail therapy. The more people fail therapy, the more people are likely to fail therapy carrying a resistant virus, resulting in an increase in transmission of resistance to previously uninfected people. This means that the relative contribution to new infections from people that are failing ART with HIVDR will increase and we will have an increased proportion of new infections that are resistant among those which are not averted.

Why does HIV develop drug resistance?

• HIV drug resistance refers to the ability of the virus to replicate in the presence of drugs that usually suppress its replication

• HIV DR is caused by changes (mutations) in the virus’s genetic structure

• Mutations are very common in HIV– as the virus replicates very rapidly– does not contain proteins needed to correct the

mistakes it makes – need for lifelong treatment

Presenter

Presentation Notes

In the presence of drug selective pressure, emergence of some HIV drug resistance (HIVDR) is inevitable due to the error-prone replication of HIV, its high mutation rate, and the need for lifelong treatment.

Three categories of HIVDR relevant to public health

1. Acquired HIVDR (ADR): occurs when mutations are selected for by ARV drugs in populations receiving ART

• Suboptimal drug combinations or adherence, treatment interruptions

2. Transmitted HIVDR (TDR): occurs when previously uninfected populations are infected with drug-resistant virus (appropriately measured in recently infected populations)

3. Pre-Treatment HIVDR (PDR): detected in individuals starting ART in which DR can be either transmitted or acquired (previous ARVs: treatment, PMTCT, PrEP/PEP)

Presenter

Presentation Notes

Broadly, there are 3 categories of HIVDR. Acquired HIVDR occurs when resistance mutations are selected for by drug selective pressure in individuals receiving ART. In individuals receiving ART, acquired HIVDR may emerge because of suboptimal adherence, treatment interruptions, inadequate plasma drug concentrations, or the use of suboptimal drug or drug combinations. Transmitted HIVDR occurs when previously uninfected individuals are infected with drug-resistant virus. The term “transmitted HIVDR” is appropriately applied only to HIVDR detected in recently infected individuals. The third category is HIVDR detected in individuals with chronic infection in which drug resistance can be either transmitted or acquired.

Why should countries monitor HIV DR?

Surveillance of HIV DR and of conditions favouring the emergence of resistance is • key to preserving the effectiveness of ART

and• and protecting the efficacy of the limited

therapeutic options • Is essential for the sustainability of HIV

programmes

HIV DR Systematic review 2000-2011: SEAR

• Suggest current 1st and 2nd line regimens are appropriate for the cohorts studied

• Limitations:– Studies conducted in Thailand and India only– Urban settings, small sample sizes, mixed populations– Not representative of the national programmes in the country– Unlikely to be generalisable to the region– Lack standardised methods: cannot compare data

Survey type Number of studies Overall HIV prevalence

TDR 10 8 showed low HIVDR levels (<5%)

PDR 23 3 reported moderate levels (5-15%)20 reported low levels (<5%)

ADR 17 NRTI resistance: ranged from 52-92%NNRTI resistance: ranged from 43-100%

Trotter et al. Systematic Review of HIV Drug Resistance in the World Health Organization Southeast Asia Region, AIDS Rev, 2014.

Presenter

Presentation Notes

There are also other sources of data on HIVDR There are done as research at limited or single sites. Multiple limitations – and not representative nor generalisable to the national programmes Since the systematic review, there are several other research studies done in HIVDR from Thailand and India - These have the same limitations as previous studies More information emerging from other countries eg Indonesia (new study from Bandung published in 2014)

WHO 2012 HIV drug resistance surveillance and monitoring strategy

Monitoring of HIVDR

Early Warning

Indicators

Surveillance of Transmitted

HIVDR in Recently Infected

Populations

Surveillance of pre-treatment

HIVDR in Populations

Initiating ART

Surveillance of Acquired HIVDR in

Populations Receiving First-

Line ART

Surveillance of HIVDR in

Children <18 months of Age

Early Warning Indicators of HIV Drug Resistance

• WHAT? Quality of care indicators --- assess factors associated with virological failure and emergence of HIVDR

WHEN? Annual monitoring WHERE? All ART clinics HOW? Standardized definitions, targets and

extraction tools -- as part of routine M&E WHY? Results provide clinic specific information

offering an opportunity for corrective action

WHO HIV Drug Resistance EWIs 2010

HIVDR Early Warning Indicators (EWI)Proportion of Clinics Achieving WHO-Recommended Targets

85%

65%

58%

17%

67%

69%

75%

0% 10%

20%

30%

40%

50%

60%

70%

80%

90%

Viral load suppression 12 months ≥70%

Drug supply continuity 100%

On time appointment keeping ≥80%

On time drug pick-up ≥90%

Retention on first-line ART ≥70%

Loss to follow-up ≤20%

Prescribing practices 100%

2107 clinics (2004-2009), >131,000 people, >50 countries

Presenter

Presentation Notes

This summarizes the results from cohorts of people initiating ART between 2004 and 2009, assessing 131,000 people at 2107 clinics. Mostly clinics in African Region. Most countries have monitored EWIs in a convenient sample of sites. Therefore, the data are not nationally representative and does not help to assess regional or global trends. Nevertheless, they show important gaps in service delivery and programme performance.

WHO Updated HIV Drug Resistance EWIs and Targets - 2012

Presenter

Presentation Notes

In 2012, WHO revised the EWIs. They were simplified and harmonized with other monitoring processes such as UNGASS and PEPFAR. The no. of core indicators were reduced to 4: on time pill pick up, dispensing practices, drug supply continuity, and clinic retention at 12 . A 5th indicator, viral load suppression is recommended at sites where viral load testing is routinely performed at 12 months after starting Rx. Monitoring of EWIs is based on a scorecard approach to facilitate interpretation of data.

Example of an EWI target scored card

Presenter

Presentation Notes

Red – poor performance (below desired level) Amber – fair performance (not yet at the desired level) Green – excellent performance (achieving the desired level)

National EWI surveys, 2005-2014

Countries EWI surveys

India 2014: Pilot ongoing, ~19 sites

Indonesia 2007: Pilot in 5 sites in Jakarta2011: 17 hospitals (12 with complete data)2012: 51 hospitals (26 with complete data)

Myanmar 2011: Pilot in 2 sites (1 NGO, 1 govt)2013: 13 sites nation-wide, plan expansion to 51 sites (govt and NGO)

Nepal 2013: Pilot in 3 sites2014: Expanded to 15 out of 44 treatment sites, covering all regions

Thailand 2006-2007: Scale up 2006-2007 nationallyFrom 2009: Integrated into national programmes2011: Implemented in >700 hospitals across 76 provinces, Paediatric HIVQUAL-T in 200 hospitals in 30 provinces2014: 1027 (under universal health coverage scheme) which is > 98% of all government hospitals

Outcome of EWI monitoring in NepalJuly 2011 – July 2012

9(64%)

10(83%)

7(47%)

3 (21%)

2(14%) 2(17%)

5(33%)

3(20%)

15 (100%)

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

EWI-1 adults EWI-1 children EWI-2 Retention in ART care EWI-3 Drug stock out EWI-4 prescribing practices

Good

Moderate

Poor

Presenter

Presentation Notes

Early warning indicator monitoring, has been implemented in Nepal since November 2013. Data was available for 4 out of the 5 EWIs recommended by WHO for monitoring. The EWI on ‘viral load suppression at 12 months’ was not monitored as there was no systematic data collection on viral load suppression during the data collection period (16th July 2011 to 15th July 2012). Only 36 ART sites were eligible for inclusion in EWI monitoring (sites established before July 2011). Data abstractors in 15 of these sites were trained and EWI monitoring was conducted (45%). Based on the results, 60% of the sites had EWI 1 - On-Time Pill Pick-up for adults - at <80%. The situation with children was very unsatisfactory compared with adults: in 83% of the sites, on-time pill pick-up for paediatric cases was <80%. EWI 2 - Retention in Care: only 47% of sites reported <75%. None of the sites reported ‘pharmacy stock-out’ (EWI 3) of ARVs or mono or dual dispensing of ARVs (EWI 4 - pharmacy dispensing practices). '

Sri Lanka

Sri Lanka – Patients on ART by end 2013

ART regimen Number of patients

First line 406

Substituted 1st line 87

Second line 37

Total 519

Number of ART clinics– 12

Source – 2013 Annual Report of NSACP

Source – 2013 Annual Report of NSACP

EWIs in Sri Lanka

• Should consider monitoring EWIs• HIV DR suspected in more than 12 patients?• 2 samples sent to India for HIVDR testing, costing

SLR 75,000 per sample• 27 patients currently on second line • Limited therapeutic options available • Need to preserve long-term efficacy and

durability of available 1st line and 2nd line drugs• EWIs do not require laboratory testing

India:1. NARI Pune2. TRC Chennai

Nepal

Thailand:1. Siriraj Hospital, Bangkok2. National Institute of

Health, Department of Medical Sciences, Bangkok

Indonesia

Myanmar

WHO-designated national HIVDR laboratories: SEAR 2014

WHO-designated Regional HIVDR Laboratories:(i) DRVI, Beijing, China (ii) Burnet Institute, Melbourne, Australia (iii) NSW State Reference Laboratory, Sydney, Australia

HIV DR Surveillance

1. HIVDR surveillance is NOT a special research activity but must be integrated within national HIV strategic plan

2. Routine implementation of HIVDR surveillance is required as: – CRITICAL TO INFORM PROGRAMME

PERFORMANCE AND POLICY– EASIER TO IMPLEMENT– GOOD VALUE FOR MONEY !

Will HIVDR increase?

• Expansion of ART access (more people on ARV)• Expanded role of ART for both treatment and

prevention:– PMTCT Option B + : ART for life to asymptomatic

woman– Introduction of PreP

• Change in ART eligibility criteria : ART to asymptomatic people

23

Presenter

Presentation Notes

YES!

Thank you

dr ia hiv dr for slcov

Documents

hiv drug resistance

drugresistant virus

hivdr adr

transmitted hivdr tdr

term transmitted hivdr

resistance mutations

use of suboptimal drug

replication hiv dr