US adult treatment guidelines updated – January 2011

The Department of Health and Human Services (DHHS) HIV guidelines are recognised as the most important guidelines produced in the US. As with all updates, changes in this edition are highlighted in yellow throughout the PDF file.

A selected summary of the changes include:

Importance of research

An emphasis on “the importance of clinical research in generating evidence to address unanswered questions related to the optimal safety and efficacy of antiretroviral therapy (ART)”. This may be an acknowledgement of some of the community-based concerns to the 2010 guidelines, particularly in reference to the international START study.

Routine monitoring

For clinically stable patients with CD4 counts above the level of risk for opportunistic infections (figure not specified) the guidelines recommend less frequent CD4 count monitoring–every 6–12 months instead of every 3–6 months–unless there are changes in the patient’s clinical status or initiation of treatment with interferon, corticosteroids, or anti-neoplastic agents.

Virological failure is defined as confirmed viral load >200 copies/mL defining blips (in most cases) as <200 copies/mL.

Additional resistance testing is suggested for detection of integrase-related resistance in people failing on an integrase-based combination. While currently unlikely to be a significant issue, the guidelines recognise that it may become increasingly important to include testing for integrase mutations in naive and newly diagnosed individuals.

Phenotype tests are only recommended for co-receptor tropism (unlike European guidelines that now recommend genotype testing). This largely reflects different geographical access to testing technologies.

Treatment choices

Maraviroc is included as an “acceptable regimen” for initial therapy when used with AZT/3TC but only as “may be acceptable but more definitive data are needed” when used with tenofovir/FTC or abacavir/3TC.

Use of ritonavir-boosted saquinavir has been downgraded to a “regimens that is acceptable but should be used with caution.”

Combination therapy for all women in pregnancy

More significantly, combination therapy (rather than AZT monotherapy) is now recommended as standard of care for all HIV-positive women to prevent mother-to-child transmission, even when they do not meet CD4 criteria for starting treatment.

Additional testing (viral load, p24) for women who are HIV antibody negative when first accessing antenatal care is recognised as being practiced in some centres.

Therapeutic drug monitoring

The following median (range) trough concentrations from clinical trial data are now included for newer drugs, even though the clinical significance of these levels has not bee demonstrated.

ARV Median trough (range)
Darunavir (DRV) (600 mg twice daily) 3,300 (1,255–7,368)
Etravirine (ETR) 275 (81–2,980)
Raltegravir (RAL) 72 (29–118)

Hepatitis B (HBV)/HIV coinfection

This section has been revised to provide more specific recommendations for management of HIV patients coinfected with HBV, including recommendations for patients with 3TC/FTC-resistant HBV infection and for patients who cannot tolerate TDF-based regimens.

TB/ HIV coinfection

The guidelines recommend ARV treatment for all HIV-positive patients with diagnosed active TB.

The time for starting ARVs following starting TB treatment is within 2–4 weeks for patients with CD4 count <200 cells/mm3, and within 2–4 weeks for patients with CD4 count 200–500 cells/mm3 (definitely by 8 weeks). For patients with CD4 count >500 cells/mm3, most panel members also recommend starting ART within 8 weeks of TB therapy.

The guidelines also state that both TB and HIV medications should be continued in the context of Immune Reconstitution Syndrome (IRIS).

Side effects

A new simplified table is included for main side effects and associated drug/class (Table 13).

Injecting drug users

The section on injecting drugs users has expanded information on opiate substitution therapy is included below. We also include the useful table on interactions with antiretrovirals (Table 11).

Methadone and ART

Methadone, an orally administered, long-acting opioid agonist, is the most common pharmacologic treatment for opioid addiction. Its use is associated with decreased heroin use, decreased needle sharing, and improved quality of life. Because of its opioid-induced effects on gastric emptying and the metabolism of cytochrome P (CYP) 450 isoenzymes 2B6, 3A4, and 2D6, pharmacologic effects and interactions with ARV agents may commonly occur [13]. These may diminish the effectiveness of either or both therapies by causing opioid withdrawal or overdose, increased methadone toxicity, and/or decreased ARV efficacy. Efavirenz (EFV), nevirapine (NVP), and lopinavir/ritonavir (LPV/r) have been associated with significant decreases in methadone levels. It is necessary to inform patients and substance abuse treatment facilities of the likelihood of this interaction. The clinical effect is usually seen after 7 days of coadministration and may be managed by increasing the methadone dosage, usually in 5-mg to10-mg increments daily until the desired effect is achieved.

Buprenorphine and ART

Buprenorphine, a patial u-opioid agonist, is administrated sublingually and is often coformulated with naloxone. It is being increasingly used for opioid dependence treatment. The lower risk of respiratory depression and overdose compared with methadone allows it to be prescribed by physicians in primary care for the treatment of opioid dependency. This flexible treatment setting could be of significant value to opioid-addicted HIV-infected patients who require ART because it enables one physician or programme to provide both medical and substance abuse services. Limited information is currently available about interactions between buprenorphine and antiretroviral agents. Findings from available studies show a more favorable drug interaction profile than that of methadone.

Naltrexone and ART

A once monthly extended-release intramuscular formulation of naltrexone was recently approved for prevention of relapse in patients who have undergone an opioid detoxification program. Naltrexone is also indicated for treatment of alcohol dependency. Naltrexone is not metabolised via the CYP 450 enzyme system and is not expected to interact with protease inhibitors (PIs) or non nucleoside reverse transcriptase inhibitors (NNRTIs).

Table 11 provides the currently available pharmacokinetic interaction data that clinicians can use as a guide for managing patients receiving ART and methadone or buprenorphine. Particular attention is needed concerning communication between HIV care providers and drug treatment programmes regarding additive drug toxicities and drug interactions resulting in opiate withdrawal or excess.

Methylenedioxymethamphetamine (MDMA), GHB, ketamine, and methamphetamine all have the potential to interact with ARV agents because all are metabolised, at least in part, by the CYP 450 system. Overdoses secondary to interactions between the party drugs (i.e., MDMA or GHB) and PI-based ART have been reported.

Table 11 (from DHHS guidelines) Drug interactions between antiretroviral agents and drugs used to treat opioid addiction



Antiretroviral class/drug Pharmacokinetic interactions

Recommendations/clinical comments

Buprenorphine EFV buprenorphine AUC ↓ 50%; norbuprenorphine* AUC ↓ 71%

No withdrawal symptoms reported. No dosage adjustment recommended; however, monitor for withdrawal symptoms.

ATV buprenorphine AUC ↑ 93%; norbuprenorphine AUC ↑ 76%; ↓ ATV levels possible.

Do not coadminister buprenorphine with unboosted ATV.

ATV/r buprenorphine AUC ↑ 66%;

norbuprenorphine AUC ↑ 105%

Monitor for sedation. Buprenorphine dose reduction may be necessary.

DRV/r buprenorphine: no significant effect,

norbuprenorphine AUC ↑ 46% and

Cmin ↑ 71%

No dose adjustment necessary.

TPV/r buprenorphine: no significant effect;

norbuprenorphine AUC, Cmax, and Cmin ↓ 80%

TPV Cmin ↓ 19%–40%

Consider monitoring TPV level.

3TC, ddI, TDF, ZDV, NVP,


No significant effect

No dosage adjustment necessary.


FPV +/- RTV, IDV +/- RTV,

SQV/r, RAL, MVC, T20

No data
Methadone ABC methadone clearance ↑ 22%

No dosage adjustment necessary.

d4T d4T AUC ↓ 23% and Cmax ↓ 44%

No dosage adjustment necessary.

ZDV ZDV AUC ↑ 29%–43%

Monitor for ZDV-related adverse effects.

EFV methadone AUC ↓ 52%

Opioid withdrawal common; increased methadone dose often


NVP methadone AUC ↓ 41%

NVP: no significant effect

Opioid withdrawal common; increased methadone dose often necessary.

ATV/r, DRV/r,

FPV/r, IDV/r,

LPV/r, SQV/r,


With ATV/r, DRV/r, FPV/r: R-methadone† AUC ↓ 16%-18%;

With LPV/r: methadone AUC ↓ 26%–-53%;

With SQV/r 1,000/100mg BID: R-methadone AUC ↓ 19%;

With TPV/r: R-methadone AUC ↓ 48%

Opioid withdrawal unlikely but may occur. No adjustment in methadone usually required; however, monitor for opioid withdrawal and increase methadone dose as clinically indicated.

FPV No data with FPV (unboosted)

With APV: R-methadone Cmin ↓ 21%, AUC no significant change

Monitor and titrate methadone as clinically indicated.

The interaction with FPV is presumed to be similar.

NFV methadone AUC ? 40%

Opioid withdrawal rarely occurs. Monitor and titrate dose as clinically indicated. May require increased methadone dose.

ddI (EC capsule), 3TC, TDF,


No significant effect

No dosage adjustment necessary.

FTC, MVC, T20 No data

*Norbuprenorphine is an active metabolite of buprenorphine. † R-methadone is the active form of methadone.


3TC = lamivudine
d4T = stavudine
T20 = enfuvirtide
ABC = abacavir
APV = amprenavir,
ATV = atazanavir
ATV/r = atazanavir/ritonavair
ddI = didanosine
DRV/r = darunavir/ritonavir
EFV = efavirenz
ETR = etravirine
FPV = fosamprenavir
FPV/r = fosamprenavir/ritonavir
FTC = emtricitabine
IDV = indinavir
IDV/r = indinavir/ritonavir
LPV/r = lopinavir/ritonavir
MVC = maraviroc
NFV = nelfinavir
NVP = nevirapine
RAL = raltegravir
RTV = ritonavir
SQV/r = sacquinavir/ritonavir
TDF = tenofovir
TPV = tipranavir
TPV/r = tipranavir/ritonavir
AZT = zidovudine


Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. January 2011.

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