HIV Screening and Treatment Guidelines
HIV Screening Recommendations
All persons aged 15-65 years should be screened for HIV at least once in their lifetime using routine opt-out screening in primary care settings, emergency departments, and for all pregnant women. 1, 2
Universal Screening Protocol
- Adolescents and adults aged 15-65 years should undergo routine HIV screening regardless of perceived risk, with younger adolescents and older adults screened if at increased risk 1, 2
- All pregnant persons must be screened for HIV, including those who present in labor or delivery with unknown HIV status 1, 2
- Screening should use fourth-generation HIV antigen/antibody combination assays that detect both HIV antibodies and p24 antigen, allowing detection of acute infection approximately 2 weeks earlier than antibody-only tests 1, 3, 4
High-Risk Populations Requiring Frequent Screening
High-risk individuals should be tested every 3 months as long as risk continues, including: 1
- Men who have sex with men (MSM) and transfeminine persons
- People who inject drugs
- Persons newly diagnosed with sexually transmitted infections or hepatitis C
- Sexual partners of HIV-infected persons
- Persons who exchange sex for money or drugs
Informed Consent Requirements
- Informed consent must be obtained before HIV testing is performed, with some states requiring written consent 5, 6
- Opt-out screening is recommended, meaning patients are notified that testing will be performed unless they decline 1, 2
Diagnostic Testing Algorithm
Initial Screening
Begin with a fourth-generation HIV antigen/antibody combination assay (such as ELISA or rapid HIV test) as the initial screening test. 1, 6, 3
Confirmatory Testing Protocol
All reactive screening tests must be confirmed before diagnosis using the following algorithm: 1, 6
If initial fourth-generation assay is reactive: Perform HIV-1/HIV-2 antibody differentiation immunoassay 1, 6
If differentiation assay is positive: HIV infection is confirmed 6
If differentiation assay is negative or indeterminate: Perform qualitative or quantitative HIV RNA testing (nucleic acid amplification test) to rule out acute HIV-1 infection 1, 6
If HIV RNA is positive with negative antibody differentiation: This indicates acute HIV infection 6, 3, 4
If both differentiation assay and HIV RNA are negative: Follow-up testing should be performed on a blood specimen collected 4 weeks after the initial reactive test 6
Traditional Algorithm (Still Valid)
- Initial enzyme immunoassay (EIA/ELISA) for HIV-1/HIV-2 antibodies, followed by Western blot or indirect immunofluorescence assay (IFA) if repeatedly reactive 5, 6
- A positive Western blot confirms HIV infection; a negative Western blot indicates the person is uninfected unless acute infection is suspected 6
- Indeterminate Western blot results require follow-up testing at 4-6 weeks and consideration of HIV RNA testing 6
Critical Testing Pitfalls
- Never diagnose HIV based on a screening test alone—false-positive screening results can occur with devastating psychological and social consequences 6
- Antibody tests cannot rule out infection that occurred less than 6 months before the test, as HIV antibody is detectable in ≥95% of patients within 6 months of infection 5, 6
- The "window period" (recent infection within 6 months) can produce false-negative results, which is why fourth-generation tests detecting p24 antigen are preferred 6, 3
Special Population Considerations
Infants Born to HIV-Positive Mothers
- For infants <15 months of age, standard antibody tests are unreliable due to transplacental passage of maternal HIV antibody 5, 6
- Definitive diagnosis requires laboratory evidence of HIV in blood or tissues by culture, nucleic acid detection (HIV RNA PCR), or antigen detection on two separate specimens 5, 6
- Passively acquired maternal HIV antibody falls to undetectable levels in most infants by 15 months of age 5
HIV-2 Testing
- HIV-2 testing should be considered in persons from endemic regions (West Africa), their sexual partners, or when clinical evidence suggests HIV disease but HIV-1 tests are negative 6
- The Multispot rapid test is FDA-approved for differentiating HIV-1 from HIV-2 infection 5
- If HIV-2 is suspected, consult state health departments for assistance in diagnosis, as no serologic tests are FDA-approved for confirmation of HIV-2 infection 5, 6
Post-Diagnosis Evaluation
Immediate Laboratory Assessment
Before starting antiretroviral therapy (ART), patients should undergo comprehensive baseline testing: 1, 7
- HIV RNA (viral load) level to establish baseline viremia 1, 7
- CD4 cell count with percentage to assess immune function 1, 7
- Genotypic resistance testing to guide regimen selection and detect transmitted drug resistance 1, 7
- HLA-B*5701 testing is required before using abacavir to prevent potentially fatal hypersensitivity reactions 7
- Tropism testing when considering CCR5 inhibitors 7
Comprehensive Medical Evaluation
All persons with positive HIV tests must receive comprehensive medical and psychosocial evaluation or be referred for these services. 5, 6, 7
- Complete medical history, physical examination, and review of systems focusing on: 7
- Opportunistic infection symptoms (fever, weight loss, night sweats, chronic diarrhea)
- Tuberculosis screening (history of exposure, symptoms, tuberculin skin test or interferon-gamma release assay)
- Sexually transmitted infection screening
- Hepatitis B and C co-infection testing
- Assessment for other comorbidities (cardiovascular disease, renal disease, bone disease)
Antiretroviral Therapy (ART) Initiation
When to Start Treatment
All persons diagnosed with HIV should be offered ART immediately upon diagnosis, regardless of CD4 count or viral load. 1, 7
- Rapid intervention following HIV diagnosis improves linkage to care and viral suppression 7
- Early treatment reduces risk of AIDS-related events, death, and HIV transmission to uninfected sex partners 2
- Brief, strengths-based case management after HIV diagnosis facilitates linkage to care 1, 7
Recommended Initial ART Regimens
Preferred regimens include an integrase strand transfer inhibitor (INSTI) plus two nucleoside reverse transcriptase inhibitors (NRTIs). 7
FDA-Approved Agents Include:
- Dolutegravir (INSTI): Indicated in combination with other antiretrovirals for treatment-naïve or treatment-experienced adults and pediatric patients ≥4 weeks and weighing ≥3 kg 8
- Efavirenz (NNRTI): Indicated in combination with other antiretrovirals for adults and pediatric patients ≥3 months old and weighing ≥3.5 kg 9
- Darunavir (protease inhibitor): Must be co-administered with ritonavir and other antiretrovirals for adults and pediatric patients ≥3 years of age 10
Regimen Selection Principles:
- Once-daily regimens are recommended for treatment-naïve patients when possible 7
- Fixed-dose combinations are recommended to decrease pill burden and improve adherence 7
- Genotypic resistance testing results should guide initial regimen selection 1, 7
Special Populations
Pregnant Patients
- Pregnant patients should receive darunavir 600 mg with ritonavir 100 mg twice daily with food 10
- ART is associated with an increased risk of preterm birth in pregnant women, but the benefit of preventing mother-to-child transmission substantially outweighs this risk 2
- Treatment of pregnant women living with HIV is of substantial benefit in reducing mother-to-child transmission rates 2
Pediatric Patients
- Dosage is based on body weight and should not exceed the adult dose 10
- Darunavir tablets should be taken with ritonavir and with food 10
Treatment-Experienced Patients
- In treatment-experienced patients, treatment history and genotypic/phenotypic testing is recommended prior to initiation of therapy to assess drug susceptibility 10
- Treatment-experienced patients with at least one darunavir resistance-associated substitution should receive 600 mg twice daily with ritonavir 100 mg 10
Monitoring During Treatment
Viral Load Monitoring
Viral load should be measured 4-6 weeks after starting or changing ART regimen to assess initial response. 1, 7
- After initial suppression, measure viral load every 3 months until suppressed for at least 1 year 1, 7
- Once virologically suppressed for ≥1 year with consistent adherence, viral load can be monitored every 6 months 7
- If viral load has not declined after starting ART, discuss adherence and medication tolerability 7
CD4 Count Monitoring
CD4 counts should be measured every 6 months until counts are >250/μL for at least 1 year with concomitant viral suppression. 1, 7
- Once CD4 counts are consistently >250/μL, monitoring frequency can be reduced 1
- CD4 monitoring helps assess immune reconstitution and risk for opportunistic infections 5
Liver Function Monitoring
- Monitor serum liver chemistry tests before and during therapy, especially in patients with underlying chronic hepatitis, cirrhosis, or pre-treatment elevations of transaminases 10
- Drug-induced hepatitis (acute hepatitis, cytolytic hepatitis) has been reported with darunavir/ritonavir 10
- Post-marketing cases of liver injury, including some fatalities, have been reported 10
Management of Treatment Failure
Virologic Failure Assessment
If adherence appears sufficient but viral suppression is not achieved, genotypic resistance testing is recommended. 7
- For patients with persistent quantifiable HIV RNA between 50-200 copies/mL, reassess for causes of virologic failure and implement close monitoring 7
- Review medication interactions, absorption issues, and pharmacokinetic factors 7
Multidrug-Resistant HIV
For patients with extremely limited treatment options due to multidrug resistance, ibalizumab and fostemsavir may be considered as salvage therapy options. 1
Adherence Support and Monitoring
Systematic Adherence Monitoring
Systematic monitoring of ART adherence is essential for successful treatment. 7
- Self-reported adherence should be obtained routinely from all patients 7
- Pharmacy refill data are recommended for objective adherence monitoring 7
- Personal telephone and interactive text reminders improve adherence 7
Barriers to Adherence
Screen for and address factors that impair adherence: 7
- Housing instability and food insecurity
- Psychiatric disorders (depression, anxiety, substance use)
- Medication adverse effects
- Lack of social support
Risk Reduction and Prevention Counseling
Ongoing Risk Assessment
Each visit of an HIV-infected person should include screening for high-risk behavior to assess transmission risk to others. 5
- Patients should be asked about symptoms related to sexually transmitted diseases at each visit 5
- The presence of STDs indicates recent high-risk behavior and increases risk of HIV transmission 5
Pre-Exposure Prophylaxis (PrEP)
PrEP should be offered to HIV-negative persons with ongoing high risk for HIV infection. 1, 7
- Daily tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) is the recommended PrEP regimen 7
- TDF-based PrEP is not recommended for individuals with osteopenia, osteoporosis, or creatinine clearance <60 mL/min 7
Post-Exposure Prophylaxis (PEP)
PEP should be offered to persons with high-risk exposure within the previous 72 hours. 1
Psychosocial Support and Comprehensive Care
Behavioral and Psychosocial Services
Behavioral and psychosocial services are integral to HIV care and should be available on-site or through referral. 1, 6
- Routine screening and treatment for depression is recommended for all HIV-infected patients 1
- Patients should receive assistance with: 6
- Accepting potential life implications of HIV diagnosis
- Coping with stigma and discrimination
- Developing strategies for maintaining physical and emotional health
- Initiating behavioral changes to prevent HIV transmission
Linkage to Care
Brief, strengths-based case management after HIV diagnosis facilitates linkage to care. 1, 7
- Systematic monitoring of time to care linkage, retention, and viral suppression is recommended in all care settings 1
- Early diagnosis allows patients and families to become linked with support networks and care systems effective in maintaining health 5
Prevention of Opportunistic Infections
Prophylaxis Indications
Persons with HIV and altered immune function are at increased risk for infections requiring preventive measures: 5
- Tuberculosis: Screen all patients and provide prophylaxis for latent TB infection 5
- Pneumocystis jirovecii pneumonia (PCP): Prophylaxis indicated when CD4 count <200 cells/μL 5
- Bacterial pneumonia: Consider vaccination (pneumococcal, influenza) 5
Important Safety Considerations
Skin Reactions
Skin reactions ranging from mild to severe, including Stevens-Johnson Syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms, and acute generalized exanthematous pustulosis have been reported with darunavir. 10
- Discontinue treatment if severe reaction develops 10
- Use with caution in patients with known sulfonamide allergy 10
Metabolic Complications
Patients may develop new-onset diabetes mellitus or hyperglycemia during ART. 10
- Initiation or dose adjustments of insulin or oral hypoglycemic agents may be required 10
- Patients may develop redistribution/accumulation of body fat (lipodystrophy) 10
Immune Reconstitution Syndrome
Patients may develop immune reconstitution inflammatory syndrome (IRIS) as immune function improves with ART. 10
- Monitor for inflammatory responses to previously subclinical opportunistic infections 10
Bleeding in Hemophilia
Patients with hemophilia may develop increased bleeding events during protease inhibitor therapy. 10
Drug Interactions
Co-administration of darunavir/ritonavir with other drugs can significantly alter drug concentrations. 10
- Co-administration is contraindicated with drugs highly dependent on CYP3A for clearance and with narrow therapeutic index 10
- Review all potential drug-drug interactions before and during therapy 10
Hepatic Impairment
Darunavir/ritonavir is not recommended for use in patients with severe hepatic impairment. 10