2. Objectives
Facts on Newly Diagnosed Older Patients
Older Adults Adherence
Women HIV Guidelines
Perinatal, Intrapartum and Postpartem HIV
Guidelines
Drug/Drug Interactions
3. Newly Diagnosed Older Patients:
Facts The proportion of older adults who are exposed to HIV through male-
to-male contact and injection drug use decreases with older age
groups. Exposure to HIV with heterosexual contact increases with
age
Over 30% of persons with HIV are > age 50
Sexual contact is the most common risk factor; IV drug use is next
Heterosexual contact accounts for the most rapid growth in infection.
Older adults who participate in risky behaviors are less likely than
younger adults who have the same risky behaviors to use HIV/AIDS
prevention methods
4. Clinical Question �
Relative to their younger counterparts,
elderly people diagnosed with HIV:
A. Have a shorter survival rate
B. Have fewer opportunistic infections
C. Have a less severe disease course
D. Have longer AIDS free survival intervals
5. Newly Diagnosed Older Patients
Relative to their younger counterparts, older adults living
with HIV/AIDS
have a more severe HIV disease course and a shorter survival rate;
have less desirable health indices at diagnosis (e.g., lower CD4+ cell
counts);
have shorter AIDS-free intervals;
have a higher number of opportunistic infections and
have earlier development of tumors and lesions
6. Newly Diagnosed Older Patients:
Guidelines
Older persons experience earlier development of conditions
associated with aging, such as cardiovascular disease and
neurocognitive impairment
Older persons may have dampened immunologic responses to ART.
ART initiation in older persons should not be delayed.
Current Guidelines recommend ART for all patients older than 50
years of age.
The efficacy, pharmacokinetics, adverse effects, and drug interaction
potentials of ART in the older adult have not been studied
systematically
7. Older Adults: Risky Behavior
Older adults are less likely to use a condom as a form of protection
Infection rate of older women surpasses older men, sexually active older
women who do not fear pregnancy and do not know about the risk of HIV
infection may not insist on using a condom
Older women who were infected through heterosexual contact were less
likely to have been tested for HIV
Many older men who have sex with men engage in practices that put them
at risk
Older adults who use condoms may not know how to store them properly
8. HIV and Older Women
The number of older women with HIV
infection is expected to increase for two
reasons:
the rate and incidence of new infections in this
age group are increasing,
And women already in care for HIV infection are
expected to live longer due to improved ART and
other treatment advances.
9. Treatment Experienced Patients
Nearly 25% of patients on ART are not virologically suppressed
Failure of virologic suppression often results in resistance mutation
Failure of first line regimens is usually caused by
1. suboptimal adherence
patient factors
2. transmitted drug resistance
ARV regimen factors
10. Clinical Question: �
What are some ways to monitor
adherence in older patients with HIV?
A. Pill counting
B. Checking Refill records
C. Checking viral loads (labs)
D. All of the above
11. Adherence and the Older Patient
Combination of these measurements is best
Pill count
Self report
Measurements of Viral Load (lab)
Measurements of therapeutic drug levels
Direct observed therapy
Refill records
12. Adherence and the Older Patient
Medication adherence >60 years old ranges from 26%-68%
Strongly related to factors related with aging (ie. Polypharmacy, cognitive
and physical limitations, social isolation, and access to medication)
Unstable housing is directly correlated with non adherence
Older AA men are less likely to be adherent then older white men
Perceptions that ART is effective and nonadherence of medications lead to
viral resistance predicts higher adherence
Men aged 50-67 years old listed the following reasons for nonadherence:
side effects, busy schedules, fatigue, stigmatization of HIV
13. HIV Infected Women: Guidelines
The indications for initiation of antiretroviral therapy (ART) and the goals of
treatment are the same for HIV-infected women (AI).
Women taking antiretroviral (ARV) drugs that have significant
pharmacokinetic interactions with oral contraceptives should use an
additional or alternative contraceptive method to prevent unintended
pregnancy (AIII).
Women of childbearing potential should undergo pregnancy testing before
initiation of efavirenz (EFV)
Alternative regimens that do not include EFV should be strongly considered
in women who are planning to become pregnant or sexually active and not
using effective contraception (BIII).
14. HIV Infected Women
Hormonal contraception
Conflicting data; when drug interactions with ART occur, additional contraceptive
methods should be recommended
Metabolic complications
More likely to experience increases in central fat with ART, less likely to
have TG elevations
More likely to have osteopenia/osteoporosis after menopause
Lactic acidosis
Female predominance with prolonged NRTI use (stavudine, didanosine,
and zidovudine)
Nevirapine-associated hepatoxicity
Increased risk of rash-associated liver toxicity in ARV naïve individuals
Women with CD4>250cells/mm3 or elevated transaminases are
at greatest risk
15. Clinical Question: �
A treatment naïve, pregnant women comes into
your clinic and has just been diagnosed with HIV.
She is in her 1st
trimester. What is a reasonable
regimen to begin while waiting for resistance
results ?
A. TDF/FTC + ATV/r
B. ABC/3TC + ATV/r
C. EVG/cobi/TDF/FTC
D. TDF/FTC + T20
16. Treatment Naïve Pregnant
Women: Guidelines
The same regimens as nonpregnant adults should be
used in pregnant women (AIII)
Multiple factors must be considered when choosing a
regimen for a pregnant woman including comorbidities,
convenience, adverse effects, drug interactions,
resistance testing results, pharmacokinetics (PK)(AII)
PK changes may lead to lower plasma drug levels of
drugs and necessitate increased dosages, more frequent
dosing, or boosting, especially of protease inhibitors. (AII)
17. Treatment Naïve Pregnant
Women: Guidelines
All HIV-infected pregnant women should receive a potent
combination ARV regimen (AI)
The decision as to whether to start the regimen in the
first trimester or delay until 12 weeks’ gestation will
depend on CD4 count, HIV RNA levels, and maternal
conditions. (AIII)
Earlier initiation of a combination ARV regimen may be
more effective in reducing transmission,
Fetuses are most susceptible to potential teratogenic effects in
the first trimester.
18. Initial ART Recommendations:
Treatment naïve pregnant women
Preferred regimens for the treatment of ART-naive HIV-
infected pregnant :
A dual NRTI combination (abacavir/lamivudine,
tenofovir/emtricitabine or lamivudine, or
zidovudine/lamivudine)
+ either a ritonavir-boosted protease inhibitor
(ritonavir-boosted atazanavir or ritonavir-boosted lopinavir)
or an NNRTI (efavirenz initiated after 8 weeks of
pregnancy). (AIII)
Refer to Antiretroviral Drug Resistance and
Resistance Testing in Pregnancy
22. Clinical Question: �
A known HIV positive, treatment
naïve, mother comes into the hospital
to give birth. Which ART is
recommended to be given before birth
to help prevent perinatal HIV
transmission? Why?
A. Didanosine
B. Zidovudine
C. Efavirenz
D. Darunavir
23. Intrapartum ARV Therapy/Prophylaxis
Women should continue their antepartum combination
ARV drug regimen on schedule as much as possible
during labor and before scheduled cesarean delivery.
(AIII)
Intravenous (IV) zidovudine should be administered to
HIV-infected women with VL >1,000 copies/mL (or
unknown VL) near delivery (AI),
In nonrandomized studies of women on cART, addition of
intrapartem AZT appears to reduce risk of perinatal transmission
24. Clinical Question: �
A newborn baby with an HIV positive
mother was just transferred into the
NICU. How soon should the baby begin
receiving ART?
A. Immediately
B. In 6 months
C. After the baby is done breastfeeding
D. Within the first year
25. Infant ART Prophylaxis:
Guidelines The 6 week neonatal component of the AZT prophylaxis regimen is
generally recommended for all HIV exposure neonates to reduce
perinatal transmission of HIV (AI).
Zidovudine, at gestational age-appropriate doses, should be initiated
as close to the time of birth as possible, preferably within 6 to 12
hours of delivery (AII).
Infants born to HIV-infected women who have not received cART
should receive prophylaxis with zidovudine given for 6 weeks
combined with three doses of nevirapine in the first week of life (i.e.,
at birth, 48 hours later, and 96 hours after the second dose), begun
as soon after birth as possible (AI).
The National Perinatal HIV Hotline (1-888-448-8765) provides free
clinical consultation on all aspects of perinatal HIV, including infant
care.
26. Neonatal ART Drug Dosing: Guidelines
Zidovudin
e (ZDV)
Dosing Duration
≥35 weeks’ gestation at birth:4 mg/kg/dose PO twice
daily, started as soon after birth as possible and
preferably within 6–12 hours of delivery (or, if unable to
tolerate oral agents, 3 mg/kg/dose IV, beginning within 6–
12 hours of delivery, then every 12 hours)
Birth through 4-6
weeks
≥30 to <35 weeks’ gestation at birth:2 mg/kg/dose PO (or
1.5 mg/kg/ dose IV), started as soon after birth as
possible, preferably within 6–12 hours of delivery, then
every 12 hours, advanced to 3 mg/kg/dose PO (or 2.3
mg/kg/dose IV) every 12 hours at age 15 days
Birth through 6
weeks
<30 weeks’ gestation at birth:2 mg/kg body weight/dose
PO (or 1.5 mg/ kg/dose IV) started as soon after birth as
possible, preferably within 6–12 hours of delivery, then
every 12 hours, advanced to 3 mg/kg/dose PO (or 2.3
mg/kg/dose IV) every 12 hours after age 4 weeks
Birth through 6
weeks
All HIV-Exposed Infants
*initiate as soon as possible after delivery*
30. Clinical Question: �
Which of the following drugs interact with
protease inhibitors and needs to be monitored?
A. Nicardipine
B. Voriconazole
C. Simvastatin
D. All of the above
34. Drugs that interact with ART
Fusion Inhibitor Drugs that interact
Enfuvirtide
35. Drugs that interact with ART
PK Boosters Drugs that interact
Ritonavir Amiodarone, atorvastatin, benzos,
bupropion, clarithromycin, diltiazem,
piroxicam, quinidine, zolpidem
Cobicstat (cobi)
*potent inhibitor of CYP450 3A4 and
2D6*
Rifampin, dihydroergotamine,
cisapride, St. John’s Wort,
lovastatin/simvastatin, pimozide,
triazolam, oral midazolam
36. Key Points
Older patients are less likely to be screened for HIV and more likely to
experience severe side effects from ART
HIV infected women on hormonal contraceptives should be monitored and
use back up methods
Efavirenz should not be prescribed in HIV infected women who are trying to
become pregnant
Protease Inhibitors have multiple drug/drug interactions
Many drugs used prophylactically against opportunisitic infections have drug
interactions with ART, monitor carefully!
IV Zidovudine is recommended 3 hours before labor for HIV positive,
treatment naïve mothers or mothers with viral loads over 1000
Patients who are older (age &gt;50) and those with lower baseline CD4 cell counts are more likely to have blunted CD4 count responses. For monitoring purposes, the CD4 count should be repeated approximately every 3-6 months both in stable untreated patients and in patients on ART
Several studies have shown a higher risk of morbidity and mortality in older patients. When followed from seroconversion, older patients demonstrate faster disease progression compared with younger patients (see Table 3).
Older patients also are found to have a less robust increase in the CD4 count in response to ART and may have a higher rate of nonAIDS-related morbidities.
Older individuals may have a poorer response to therapy; earlier initiation of therapy may be considered for older patients.
Patient factors= higher pre-treatment HIV RNA, lower pretreatment CD4, comoribidities, drug resistance, suboptimal adherence, interruptions in access to ART
ARV factors= toxicity and AE, pharmacokinetic problems, suboptimal ARV potency, prior exposure to nonsuppressive regimens, food requirements, high pill burden/dosing frequency, D/D interactions, prescription errors
Assessment and Predictors of ART Adherence in Older HIV Infected Patients. Wutoh, AK, Elekwachi, O., Clarke-Tasker, V., Daftary, M., Powell, NJ., Campusano, G.
Journal of Acquired Immune Deficiency Syndromes. 33: S106-S114. 2003
forgetting
No gender differences in virologic responses to ART, there is possibly some pharmacokinetic difference such as body weight, plasma volume, gastric emptying time, plasma protein levels, CYP450 activity, and excretion activity
Safe and effective reproductive health and family planning services to reduce unintended pregnancy and perinatal transmission of HIV are an essential component of care for HIV-infected women of childbearing age. Counseling about reproductive issues should be provided on an ongoing basis. Providers should be aware of potential interactions between ARV drugs and hormonal contraceptives that could lower contraceptive efficacy. Several protease inhibitors (PIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs) have drug interactions with combined oral contraceptives (COCs). Interactions include either a decrease or an increase in blood levels of ethinyl estradiol, norethindrone, or norgestimate (see Tables 18a and 18b), which potentially decreases contraceptive efficacy or increases estrogen- or progestinrelated adverse effects (e.g., thromboembolism).
Consistent use of male or female condoms to prevent transmission of HIV and protect against other sexually transmitted diseases (STDs) is recommended for all HIV-infected women and their partners, regardless of contraceptive use.
to reduce the risk of perinatal transmission of HIV.
Reducing HIV RNA to undetectable levels lowers the risk of perinatal transmission, lessens the need for elective C-section to reduce risk of HIV transmission, and reduces risk of ARV drug resistance in the mother.
Individualize ARVs based on factors such as:
Woman’s ARV history
Possible ARV resistance
Comorbidities
PK changes in pregnancy, placental ARV transfer
Potential adverse effects on woman and on fetus
Experience in pregnancy
Rationale for continuing EFV in pregnancy:
1st-trimester exposure is not definitely associated with increased risk of neural tube defects.
The risk of neural tube defects is limited to the first 5-6 weeks of pregnancy, before most pregnancies are recognized.
Unnecessary ARV changes during pregnancy may increase the risk of loss of virologic control and transmission to infant.
More frequent VL monitoring in pregnancy is recommended to identify women in whom the decline in VL is slower than expected.
Viral suppression generally achieved in 12-24 weeks in ARV-naive adherent individuals; rare cases take longer.
However, a 4-week neonatal chemoprophylaxis regimen can be considered when the mother has received standard combination antiretroviral therapy (cART) during pregnancy with consistent viral suppression and there are no concerns related to maternal adherence (BII).
The 6 week neonatal component of the AZT prophylaxis regimen is generally recommended for all HIV exposure neonates to reduce perinatal transmission of HIV (AI).
Zidovudine, at gestational age-appropriate doses, should be initiated as close to the time of birth as possible, preferably within 6 to 12 hours of delivery (AII).
Infants born to HIV-infected women who have not received cART should receive prophylaxis with zidovudine given for 6 weeks combined with three doses of nevirapine in the first week of life (i.e., at birth, 48 hours later, and 96 hours after the second dose), begun as soon after birth as possible (AI).
The National Perinatal HIV Hotline (1-888-448-8765) provides free clinical consultation on all aspects of perinatal HIV, including infant care.
Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States
Antiretroviral Prophylaxis Agents for HIV-Exposed Infants of Women who Received No Antepartum Antiretroviral Prophylaxis (initiated as soon after delivery as possible)
In addition to ZDV as shown above, administer NVP Birth weight 1.5–2 kg: 8 mg/dose PO Birth weight &gt;2 kg: 12 mg/dose PO 3 doses in the first week of life • 1st dose within 48 hrs of birth (birth–48 hrs) • 2nd dose 48 hrs after 1st • 3rd dose 96 hrs after 2nd
A rifamycin is a crucial component in treatment of drug-sensitive TB. However, both rifampin and rifabutin are inducers of the hepatic cytochrome P (CYP) 450 and uridine diphosphate gluconyltransferase (UGT) 1A1 enzymes and are associated with significant interactions with most ARV agents including all PIs, nonnucleoside reverse transcriptase inhibitors (NNRTIs), maraviroc (MVC), and raltegravir (RAL). Rifampin is a potent enzyme inducer, leading to accelerated drug clearance and significant reduction in ARV drug exposure. Despite these interactions, some observational studies suggest that good virologic, immunologic, and clinical outcomes may be achieved with standard doses of efavirenz (EFV)13-14 and, to a lesser extent, nevirapine (NVP)15-16 when combined with rifampin. However, rifampin is not recommended in combination with all PIs and the NNRTIs etravirine (ETR) and rilpivirine (RPV). When rifampin is used with MVC or RAL, increased dosage of the ARV is generally recommended. Rifabutin, a weaker enzyme inducer, is an alternative to rifampin. Because rifabutin is a substrate of the CYP 450 enzyme system, its metabolism may be affected by the NNRTI or PI. Tables 17, 18a, 18b, 18d, and 18eoutline the magnitude of these interactions and provide dosing recommendations when rifamycins and selected ARV drugs are used concomitantly. After determining the drugs and doses to use, clinicians should monitor patients closely to assure good control of both TB and HIV infections. Suboptimal HIV suppression or suboptimal response to TB treatment should prompt assessment of drug adherence, subtherapeutic drug levels (consider therapeutic drug monitoring [TDM]), and acquired drug resistance.