Updated recommendations for prevention and treatment of HIV infection in adults has been released by the International Antiviral Society-USA Panel. The guidelines, published in the Journal of the American Medical Association (JAMA), holds importance as antiretroviral therapy (ART) is the cornerstone of prevention and management of HIV infection.
Michael Saag, director of the University of Alabama at Birmingham’s Center for AIDS Research, and colleagues drafted the guideline with an objective to evaluate new data and treatments and incorporate this information into updated recommendations for initiating therapy, monitoring individuals starting therapy, changing regimens, and preventing HIV infection for individuals at risk.
Recommendations for When to Start ART
- ART should be initiated as soon as possible after diagnosis, including immediately after diagnosis, unless patient is not ready to commit to starting therapy.
- Structural barriers that delay receipt of ART should be removed to allow newly diagnosed persons to receive ART at the first clinic visit after diagnosis, if they and their clinician determine that this approach is appropriate.
- Samples for HIV-1 RNA level; CD4 cell count; HIV genotype for NRTI (nucleoside reverse transcriptase inhibitor), NNRTI (nonnucleoside reverse transcriptase inhibitor), and PI (protease inhibitor); laboratory tests to exclude active viral hepatitis; and chemistries should be drawn before beginning ART, but treatment may be started before results are available.
- NNRTIs and abacavir should not be used for rapid ART start.
- ART should be started as soon as possible but within the first 2 weeks after diagnosis for most OIs (opportunistic infections).
- Primary MAC (Mycobacterium avium complex) prophylaxis is no longer recommended if effective ART is initiated.
- Primary prophylaxis for Pneumocystis pneumonia should be initiated for patients with CD4 cell counts below 200/μL.
- Prophylaxis for cryptococcal disease is not recommended in highly resourced settings with low prevalence of disease.
- ART should be implemented immediately in the setting of newly diagnosed malignancy, with attention to drug-drug interactions.
Recommendations for Initial ART Regimens
- Bictegravir/TAF/emtricitabine, Dolutegravir/abacavir/lamivudine, and Dolutegravir plus TAF/emtricitabine are the generally recommended initial regimens.
- Darunavir/cobicistat plus TAF (or TDF)/emtricitabine, Darunavir boosted with ritonavir plus TAF (or TDF)/emtricitabine, Efavirenz/TDF/emtricitabine, Elvitegravir/cobicistat/TAF (or TDF)/emtricitabine, Raltegravir plus TAF (or TDF)/emtricitabine, and Rilpivirine/TAF (or TDF)/emtricitabine (if pretreatment HIV RNA level is <100 000 copies/mL and CD4 cell count is >200/μL) are recommended if generally recommended regimens are not available or not an option.
- TDF is not recommended for individuals with or at risk for kidney or bone disease.
- Initial 2-drug regimens are only recommended in the rare situations in which a patient cannot take abacavir, TAF, or TDF.
- Pregnant individuals with HIV infection should initiate ART for their own health and to reduce the likelihood of HIV transmission to the infant.
Recommendations for When and How to Switch ART Regimens
- Review of the ART treatment history, regimen tolerability, comedications, and results of prior resistance tests is recommended before any treatment switches are made.
- In patients with NRTI mutations, switching from a boosted PI to a regimen containing a drug with a low genetic barrier to resistance (eg, NNRTI or raltegravir) is not recommended.
- HIV viral load should be checked 1 month after switching regimens to ensure virologic suppression has been maintained.
Switching When Virologically Suppressed
- Patients taking older ART drugs with known toxicity should be questioned carefully to identify subtle adverse effects of which they may be unaware or that they may not attribute to the drug. The presence of these toxicities should prompt a change in regimen.
- In general, if the older regimen is well tolerated without evidence of toxicity, there is little reason to switch to a newer regimen.
- Proactive switching from TDF to TAF is recommended for patients at high risk of renal or bone toxicity.
- Switching from 3-drug regimens to certain 2-drug regimens in the setting of viral suppression, using dolutegravir/rilpivirine, a boosted PI with lamivudine, or dolutegravir with lamivudine can be used in patients with no prior virologic failure or transmitted drug resistance.
- Patients who are co-infected with HIV and HBV should receive a regimen that contains 2 drugs active against HBV, usually TAF or TDF plus lamivudine or emtricitabine, in addition to a third ART drug (evidence rating AIIa). Such patients should generally not be switched to 2-drug ART.
- Monotherapy with boosted PIs or dolutegravir is not recommended.
Switching for Virologic Failure
- Resistance testing is recommended while taking the failing ART regimen or within 4 weeks of stopping.
- Virologic failure should be confirmed and, if resistance is identified, a prompt switch to another active regimen using results of current and past resistance testing to prevent accumulation of additional resistance mutations is recommended.
- Dolutegravir, plus 2 NRTIs (with at least 1 active by genotype) is recommended after initial treatment failure with an NNRTI.
- A boosted PI plus 2 NRTIs (with at least 1 active NRTI) are recommended for initial treatment failure of an InSTI (integrase strand transfer inhibitor)-containing regimen.
- Dolutegravir plus at least 1 fully active other agent may be effective in the setting of raltegravir or elvitegravir resistance. Dolutegravir should be dosed twice daily in this setting.
- A single active agent added to a failing regimen is not recommended.
- For multiclass resistance, the next regimen should be constructed using drugs from new classes if available.
Recommendations for Laboratory Monitoring
- All persons who have ever been sexually active should be tested for HIV at least once in their lives.
- Risk for HIV often changes over a person’s lifetime; risk evaluation is recommended at each routine clinical visit.
- For sexually active men who have sex with men and for transgender women, people who inject drugs, and others at increased risk, testing is recommended at least annually and as frequently as every 3 months.
- Diagnosis of sexually transmitted infections and hepatitis C virus can help identify persons who should be tested more regularly for HIV and who might benefit from preexposure prophylaxis.
- HIV screening with assays that can detect recent HIV infection, either an instrument-based combination antigen/antibody assay or a combination of a stand-alone antibody assay and nucleic acid testing, is recommended.
- Persons with ongoing condomless sexual exposures or sharing of needles or works need to be tested with assays that can detect HIV RNA or with combination antibody + p24 antigen tests. Individuals with signs or symptoms of acute or primary HIV infection should be tested with HIV RNA assays.
- All available tests can have false-positive results, so additional testing with an HIV viral load is recommended before ART initiation, although treatment may be started before results are available.
- HIV genotype to assess transmitted NRTI and NNRTI resistance should be performed; InSTI genotyping at baseline is not recommended unless exposure to a partner with InSTI resistance is suspected.
- CCR5 (chemokine receptor 5) tropism testing is recommended each time when considering maraviroc and HLA-B*5701 testing (only needed once) before use of abacavir.
- Once HIV RNA level is below 50 copies/mL, monitoring is recommended every 3 months until virus is suppressed for at least a year.
- If the viral load has not declined, adherence and toxicity should be discussed with the patient. If adherence appears to be sufficient, a genotype assay is recommended.
Recommendations for Engagement in Care and ART Adherence
- Routine, opt-out HIV screening is recommended in primary medical care settings, emergency departments, and for all pregnant women.
- Routine screening and treatment for depression is recommended.
- Systematic monitoring of time to care linkage after initial HIV diagnosis, retention in care, reengagement in care, ART adherence, and rates of viral suppression is recommended in all care settings and at a population level.
- Brief, strengths-based case management is recommended after HIV diagnosis to facilitate linkage to care.
- Systematic monitoring of missed clinic visits and rapid intervention after a missed visit is recommended.
- Personal telephone and interactive text reminders in advance of scheduled appointments and shortly after missed appointments (eg, 24-48 hours) are recommended.
- Screening for and addressing housing instability, food insecurity, ongoing substance use, psychiatric disorders, medication adverse effects, and pill burden is recommended.
- Data-driven risk stratification to identify high-acuity, high-need patients for combination intervention strategies to improve care engagement and viral suppression is recommended.
- Use of public health surveillance in conjunction with clinic-level data to guide individual-level linkage and reengagement in care activities is recommended.
- Opioid substitution therapy for opioid-dependent patients is recommended.
Recommendations for Prevention of HIV Infection
- HIV-seropositive and -negative individuals should be reminded that condoms are required to prevent acquisition of non-HIV STIs.
- Quarterly screening for asymptomatic STIs is recommended for all populations with high rates of bacterial STIs and incomplete condom use.
- Abacavir-based PEP is not recommended unless the exposed patient is known to be negative for the HLA-B*5701 allele.
- PrEP is recommended for populations whose annual HIV incidence is at least 2% .
- Daily TDF/emtricitabine is the recommended regimen for men and women (evidence rating AIa) and transgender individuals at risk of sexual exposure and people who inject drugs.
- A 1-week lead-in time is recommended with daily dosing for rectal, penile, and vaginal exposures with daily TDF/emtricitabine to ensure adequate tissue levels are achieved.
- At PrEP discontinuation, TDF/emtricitabine should continue for 1 week after the last sexual exposure.
- For individuals with active HBV infection (detectable HBsAg), discontinuation of TDF/emtricitabine PrEP could lead to acute HBV flares or hepatic decompensation, particularly for patients with hepatic cirrhosis; careful monitoring of HBV infection and liver function is recommended after discontinuation of TDF/emtricitabine.
- Pericoital TDF/emtricitabine PrEP, also known as on-demand, event-driven, or “2-1-1” dosing may be considered as an alternative to daily PrEP for MSM with infrequent sexual exposures. This regimen is not recommended in other risk groups or in patients with active HBV infection because of the risk of hepatitis flare and hepatic decompensation.
- If intercourse is planned in the context of 2-1-1 PrEP regimen, the first (double) dose of TDF/emtricitabine should be taken closer to the 24-hour precoital time than the 2-hour time.
- TDF/lamivudine, TAF/emtricitabine, and TDF alone are not recommended for PrEP.
- TDF-based PrEP is not recommended in persons with creatinine clearance below 60 mL/min/1.73 m2.
- HIV testing, preferably with a combination antigen-antibody assay, to confirm HIV-seronegative status is mandatory at time of initiation of TDF/emtricitabine PrEP; HIV RNA testing should be obtained if acute HIV is suspected.
- Measurement of serum creatinine level, determination of estimated glomerular filtration rate, and HBsAg testing are recommended before initiation of PrEP but need not impede PrEP initiation.
- HCV serologic testing should be performed at least annually and more frequently in the case of elevated transaminase levels or in high-risk individuals.
- During PrEP, intervals of follow-up every 3 months are recommended to allow for HIV testing and STI screening.
- If during PrEP treatment, exposure to HIV is known to occur, intensification of treatment with an additional agent(s) is not recommended.
- For individuals being treated with a course of 3-drug PEP for a recent exposure who are likely to be at risk of ongoing exposure, a seamless transition from PEP to PrEP is recommended.
- Each PrEP visit should be used to assess and troubleshoot barriers to adherence to PrEP.
According to the article, all updated recommendations focus on adults 18 years or older with or at risk for HIV infection with availability to most antiretroviral drugs.
For more information follow the link: 10.1001/jama.2018.8431
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