Adolescents in need of ART A growing challenge

Washington D.C., USA, 22-27 July 2012www.aids2012.org

Sustaining quality while scaling up adolescent ART

Findings from Zimbabwe’s largest adolescent cohort

Shroufi A, Dixon M, Gunguwo H, Nyathi M, Ndlovu M, Saint-Sauveur JF, Taziwa F, Ndebele W, Ferreyra C, Carmen Viñoles M


Adolescents in need of ARTA growing challenge

• Improved treatment means children with HIV are surviving longer

• This means that increasing numbers of adolescents in Southern African are in need of ART 1

• Less experience managing this age group• Adolescents usually managed in adult programmes• Adult programmes may not address specific needs

of adolescents

1. Ferrand et al. AIDS. 2009;23(15):2039-46.


Will services cope?Adolescents pose particular challenges

• Known challenges in managing chronic disease1

• More unhealthy / high risk behaviours2

• Poor adherence to ART previously documented3

• Sub-optimal virological responses documented4,5

• Present to services relatively late6

1. Sawyer et al. Lancet. 2007;369(9571):1481-9.2. Catalano et al. Lancet. 2012;379(9826):1653-64. 3. Murphy et al. AIDS Care. 2001;13(1):27-40.4. Flynn et al. AIDS Res Hum Retroviruses. 2007;23(10):1208-145. Markowitz et al. N Engl J Med. 1995;333(23):1534-9. 6. Marston et al. J Acquir Immune Defic Syndr. 2005;38(2):219-27.


• Limited evidence on outcomes in Southern Africa

• Can scale up be achieved successfully?

Will services cope?

1. Bakanda et al. PloS one. 2011;6(4):e192612. Nglazi et al. BMC Infect Dis. 2012;12:21.


Mpilo ART clinic BulawayoAdolescents were a challenge...

• Zimbabwe pop: 12.5 million HIV prevalence: 13.1% (2010)

• One of 1st OI ART sites in Zimbabwe. MSF has supported ART provision at Mpilo since it opened in 2004

• As adolescent numbers increased, management challenges arose.


Adolescent model of care• Adolescent clinic located in

separate space from adult & paediatric clinics

• Specifically tailored services:• Dedicated, highly trained

counsellors • Life skills training• Social activities, camp outside

clinic• Youth club, “Chill Room” • Defaulter tracing• Peer counselling

• Adolescents engaged in clinic management decisions through elected peer representatives

An adolescent counsellor counselling an adolescent at Mpilo Hospital in Bulawayo(Written consent for use provided)


Adolescent model of care• Psychosocial Support:

– Life skills support, pottery, income generating projects, expressing feelings and thoughts through art, Hero book (MMPZ)

• All Mpilo Clinic staff was trained in adolescent customer care

“Chill” Room


Scale up of ART Initiation

> 7 fold increase in initiations

> 3 fold increase in initiations


Methods

• Retrospective cohort study, 2004 - 2010• Data electronically recorded after patient

consultations • Cox proportional hazards model used• Age defined at time of ART initiation:

Adolescents 10-19, adults ≥ 19• LFU: appointment missed by ≥ 3 months • Compared adolescent and adult outcomes


OutcomesMore adolescents initiated late and ill

Adolescents AdultsInitiations, n 1,776 9,360Median age, years* 13.3 34.7Med duration on treatment, days (IQR)*

567 (222.5 – 1082)

490 (191 – 947)

Males, %* 47.9% 30.7%Stage IV disease, %* 32.4% 24.9%

Diagnosed following illness* 91.5% 60.7%

*Statistically significant

Retention at 24 months* 86.0% 78·5%


Adolescent outcomes maintained during scale up

*Adjusted for age, haemoglobin, CD4 and BMI.

Adolescents• No change in deaths over time• HR = 0.92*, p=0.59• No change in LFU over time• HR=1.02*, p=0.59

Adults• No change in deaths over time• HR=0.9*, p=0.131• Increase in LFU over time• HR=1.2*, p=0.004


Mortality and LFUAdolescent LFU lower than in adults

P=0.83 P<0.0001


Summary FindingsMuch adolescent HIV undiagnosed + untreated

• Diagnosis usually after clinical illness, consistent with estimates that 75% of adolescent HIV is undiagnosed1

• By the end of study period, 17% of all actively followed patients were adolescents (1,610 / 9,387*) compared to estimate of 5% nationally1

1. Ferrand et al. Bull World Health Organ. 2010;88(6):428-34


Summary FindingsGood retention and low LFU can be achieved

• Despite challenges, low LFU and high retention were achieved in adolescents

• Despite later presentation, survival in adolescents equalled adult survival


Conclusions• As more HIV positive children survive into

adolescence, scale-up of specific services is needed

• Need to increase case-finding efforts by incorporating innovative approaches to identify HIV-positive adolescents, then link them to care tailored to their needs.

• Good adolescent results are feasible with dedicated services in resource-constrained settings


Acknowledgements

• We acknowledge the work of all patients, MoHCW and MSF staff at Mpilo OI ART clinic

• We also acknowledge the work of Million Memory Project Zimbabwe (MMPZ)

• And the Contact Counselling Trust of Bulawayo

Conflict of Interest• The authors declare that they have no conflicts of interest


Supplementary information


Death rates + LFU ratesCrude and adjusted for LFU

Overall Adults Adolescents p-value

(logrank test)

Unadjusted death rate, per 100 person years (95% CI)

2·9 (2·7-3·2) 2·8 ( 2·5 – 3·0) 3·8 (3·2 – 4·5) 0·0007

Rate of loss to follow up, per 100 person years (95% CI)

8·5 (8·2-8·9) 9·2 (8·8 – 9·6) 4·8 (4·1 – 5·6) <0·00005

30% of those LTFU assumed dead

5·4 (5·1-5·.8) 5·4 (5·1-5·8) 5·5 (4·8-6·4) 0·8271


7·2 (6·8-7·5) 7·3 (6·9-7·7) 6·4 (5·6-7·3) 0·753


8·9 (8·5-9·3) 9·2 (8·8-9·6) 7·3 (6·5-8·3) 0·0011

At the most plausible levels of death among those lost to follow up no difference in death rates between groups


Adolescents, n

Mortality Loss to follow up

Retention 24 months

Mpilo cohort. Zimbabwe

1,776 3.8 (3.2 – 4.5)

4.8(4.1 – 5.6)

86%

Bakanda et al. Uganda (1)

575 3.6 (2.6-4.7)

- -

Nglazi et al. South Africa (2)

65 1.2 (0.3-4.8)

7.2 (4.1 –12.6)

-

Results


Entry to ART servicesFew adolescents came from VCT services

• Most adolescents referred from hospital after becoming unwell, subsequently being offered provider initiated testing and counselling (PITC)


Regimen infoMost common regimens used at initiation

Adults Adolescents (D4T-3TC-NVPp)Stavudine, Lamivudine, Nevirapine

7,412 1,543

FDC (AZT-3TC-NVP) Zidovudine, Lamivudine, Nevirapine

839 16

EFV+FDC (D4T30-3TC) Efavirenz, Stavudine, Lamivudine

705 85


ResultsMore adolescents initiated late

Adolescents AdultsInitiations, n 1,776 9,360Median age, years 13.3 34.7Males, % 47.9% 30.7%Stage IV disease, % 32.4% 24.9%VCT referrals 2.8% 17.5%Med duration on treatment, days (IQR)

567 (222.5 – 1082)

490 (191 – 947)

Mortality rate / 100 p yrs* 5.5 (4.8-6.4) 5.4 (5.1-5.8)LFU rate / 100 p yrs 4.8 (4.1-5.6) 9.2 (8.8 - 9.6)Retention at 24 months 86.0% 78·5%

*30% of those lost to follow up assumed to have died


Full references used slides 3+4

• Ferrand RA, Corbett EL, Wood R, Hargrove J, Ndhlovu CE, Cowan FM et al. AIDS among older children and adolescents in Southern Africa: projecting the time course and magnitude of the epidemic. AIDS. 2009;23(15):2039-46.

• Sawyer SM, Drew S, Yeo MS, Britto MT. Adolescents with a chronic condition: challenges living, challenges treating. Lancet. 2007;369(9571):1481-9.

•Murphy DA, Wilson CM, Durako SJ, Muenz LR, Belzer M, Adolescent Medicine HIV/AIDS Research Network. Antiretroviral medication adherence among the REACH HIV-infected adolescent cohort in the USA. AIDS Care. 2001;13(1):27-40.

• Flynn PM, Rudy BJ, Lindsey JC, Douglas SD, Lathey J, Spector SA et al. Long-term observation of adolescents initiating HAART therapy: three-year follow-up. AIDS Res Hum Retroviruses. 2007;23(10):1208-14.


Full references used slide 4

• Markowitz M, Saag M, Powderly WG, Hurley AM, Hsu A, Valdes JM et al. A preliminary

study of ritonavir, an inhibitor of HIV-1 protease, to treat HIV-1 infection. N Engl J Med.

1995;333(23):1534-9.

Marston M, Zaba B, Salomon JA, Brahmbhatt H, Bagenda D. Estimating the net effect of HIV

on child mortality in African populations affected by generalized HIV epidemics. J Acquir

Immune Defic Syndr. 2005;38(2):219-27.


Full references usedslides 5 and 14

Bakanda C, Birungi J, Mwesigwa R, Nachega JB, Chan K, Palmer A et al. Survival of HIV-infected adolescents on antiretroviral

therapy in Uganda: findings from a nationally representative cohort in Uganda. PloS one. 2011;6(4):e19261.

Nglazi MD, Kranzer K, Holele P, Kaplan R, Mark D, Jaspan H et al. Treatment outcomes in HIV-infected adolescents attending a

community-based antiretroviral therapy clinic in South Africa. BMC Infect Dis. 2012;12:21.

Ferrand R, Lowe S, Whande B, Munaiwa L, Langhaug L, Cowan F et al. Survey of children accessing HIV services in a high

prevalence setting: time for adolescents to count? Bull World Health Organ. 2010;88(6):428-34


Full references used

Catalano RF, Fagan AA, Gavin LE, Greenberg MT, Irwin CE, Ross DA et al. Worldwide

application of prevention science in adolescent health. Lancet. 2012;379(9826):1653-64.

Nachega JB, Hislop M, Nguyen H, Dowdy DW, Chaisson RE, Regensberg L et al.

Antiretroviral therapy adherence, virologic and immunologic outcomes in adolescents

compared with adults in southern Africa. J Acquir Immune Defic Syndr. 2009;51(1):65-71.


Full references used• Fox, M. P., & Rosen, S. (2010). Patient retention in antiretroviral therapy programs

up to three years on treatment in sub-Saharan Africa, 2007-2009: systematic

review. Tropical medicine & international health : TM & IH, 15 Suppl 1, 1-15.

doi:10.1111/j.1365-3156.2010.02508.x

Rosen S, Fox MP. Retention in HIV care between testing and treatment in sub-

Saharan Africa: a systematic review. PLoS Med. 2011;8(7):e1001056.

Adolescents in need of ART A growing challenge

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