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Promoting ARV Adherence

Goals of Holistic HIV/AIDS Therapy Prolongation of life Improved quality of life Reduction in viral load Reconstitution of immune system Sequencing of drugs Reduce HIV transmission

Holistic Management of HIV/AIDS Risk factor analysis/education Psychosocial assessment Clinical examination Laboratory testing Drug therapy and adherence Symptom management

HIV Infection of a Cell

Pol Protease Integrase ReverseTranscriptase Non-Nucleoside Reverse Transcriptase Inhibitors Nucleoside Reverse Transcriptase Inhibitors Protease Inhibitors Nucleotide Reverse Transcriptase Inhibitors The HIV pol (polymerase) gene

HIV, Laboratory Tests and Adherence CD 4+ T-cell count – Adults: normal count = 1000 – Pediatrics 35% 12 – 35 months: >30% months: >25% >5 years: >500 cell/mm3

HIV, Laboratory Tests and Adherence CD 4+ T-cell count and ART – CD 4+ T-cell count Rises rapidly in 4 weeks after starting ART – Gradual increase thereafter – Average increase while adherent to ART During first year: approximately 150 Each year thereafter: approximately 80

HIV, Laboratory Tests and Adherence Viral Load – Quantity of virus in one milliliter of blood – Range: 1,000,000 copies – Goal: undetectable or <50 copies

HIV, Laboratory Tests and Adherence Viral Load – A ten-fold (1 log) drop within 8 weeks 1,000,000 drops to 100, ,000 drops to 10,000 50,000 drops to 5,000 – Undetectable weeks after starting ART – Patients whose VL fall and remain <50 are at lower risk for resistance Virologic Failure Rise in viral load by >1 log from the lower point Sustained increase >5,000 copies/ml

Natural History of HIV Infection

Pharmacology and HIV/AIDS Entry inhibitors stop HIV entering the cell (Fuzeon only) Nucleoside reverse transcriptase inhibitors disrupt the gene-copying process (drugs include abacavir, AZT, ddI, 3TC) Non-nucleoside reverse transcriptase inhibitors block the gene-copying enzyme (drugs include nevirapine and efavirenz) Protease inhibitors block the formation of the new virus (drugs include amprenavir, lopinavir, ritonavir, nelfinavir)

Pharmacology and HIV/AIDS

Adherence and Viral Suppression AIDS 2001;15:2109

Adherence is the Goal! Adherence below 95% – poorer suppression of viral load – reduced increased in CD4 count – development of resistance Once daily treatment – missing no more than 1 dose in a month Twice daily treatment – missing no more than 3 doses in a month Three times a day treatment – Missing no more than 4 doses in a month

HIV Resistance HIV makes mistakes when copying itself Mistakes = mutations Mutations in pol gene – Drug resistance

HIV Resistance VL Time Drug-sensitive HIVDrug-resistant HIV ART begins Viral load falls as sensitive virus disappears Drug resistant virus continues to grow despite ART

HIV Drug-Related Mutations

Adherence Case Study Number 1 Shana, a 35 year old female, works as clerk in a grocery store in her neighborhood. She started on ARVs in December 2006 and is currently taking d4T, 3TC and Stocrin. Her laboratory results are as follows: DateCD4Viral Load November ,443 February ,723 June ,245 She presents to iThemba today for a follow-up appointment. She says she is “doing okay” and “takes her meds.”

Adherence Case Study Number 2 Sizwe, a 43 year old male, has been on ARVs since November He was initially on d4T, 3TC and Stocrin but because of peripheral neuropathy, he was changed to AZT, 3TC, and Stocrin in March His laboratory results are as follows: DateCD4Viral Load September 2005 (pre-ARV)53156,982 February <50 October <50 June He comes to iThemba today for a renewal of his ARVs and prophylactic medications. In April and May, he went to the pharmacy about 15 days early to get his refill; he reports losing them in April and that they were stolen in May.

Poor Adherence Untreated depression Substance abuse and alcoholism Lack of insight Failure to disclose HIV status Adolescents and young adults

How do I know if my patient- partner is adherent? Pills counts Dates of picking up refills Asking the patient – caregiver – missed doses in preceding week Laboratory value analysis

Promoting Adherence Patient – provider communication – pre-ART education – negotiated treatment plan – listen to your patient Never rush starting ART Treating psychosocial risks “Treatment Buddy” Drug-induced symptom management Memory aids – pill boxes – household cues (same time of day, activity) Planning ahead