21.3 Multisystemic Infections II: HIV/AIDS Virology, the Philippine Epidemic & RA 11166, Diagnosis (rHIVda), ART, Prevention and Opportunistic Infections including Toxoplasmosis

Why this area matters

HIV/AIDS is named in both the reproductive tract and multisystemic areas of the Microbiology TOS. It also appears in Medicine, Pediatrics, OB-Gynecology and Preventive Medicine. The Philippines has had one of the fastest-growing HIV epidemics in the Asia-Pacific region. Most new infections are in young men who have sex with men, and many people are diagnosed late with opportunistic infections. Questions test:

• virology and drug targets;
• the window period and diagnostic tests;
• the legal rules on testing and confidentiality;
• CD4 thresholds for opportunistic infections;
• prophylaxis and post-exposure care.

Virology and natural history

• Structure: HIV is an enveloped retrovirus with two copies of positive-sense single-stranded RNA. The gag gene encodes the core (p24), pol encodes the enzymes and env encodes gp120 and gp41.
• Replication steps and the drugs that block them:
  • attachment of gp120 to CD4 plus CCR5 or CXCR4 (blocked by maraviroc, a CCR5 antagonist);
  • fusion through gp41 (blocked by enfuvirtide);
  • reverse transcription (blocked by NRTIs and NNRTIs);
  • integration (blocked by integrase inhibitors such as dolutegravir);
  • maturation by protease (blocked by protease inhibitors).
• Natural history:
  • Acute retroviral syndrome comes 2 to 4 weeks after infection: fever, pharyngitis, lymphadenopathy, rash and mucosal ulcers. Viral load is very high and antibody tests may still be negative (the window period).
  • Clinical latency follows, with a gradual fall in CD4 cells over years.
  • AIDS is defined by a CD4 count below 200 cells/uL or an AIDS-defining illness.
• Transmission: sexual, blood (shared needles, transfusion) and mother-to-child (pregnancy, delivery, breastfeeding). People on ART with a sustained undetectable viral load do not transmit HIV sexually (U=U).

The Philippine HIV law and testing (RA 11166)

The Philippine HIV and AIDS Policy Act of 2018 (RA 11166) replaced RA 8504. Its main rules:

• Testing: voluntary, with informed consent, and offered by providers as well as on request.
• Minors: adolescents 15 to 17 years old may consent to testing without parental consent. Younger children, and those unable to consent, need consent from a parent or guardian.
• No compulsory testing for employment, school admission, travel or insurance.
• Confidentiality: HIV status and test results are confidential. Disclosure without consent is penalized except in situations the law allows.
• Discrimination in work, school, travel, housing and health care is prohibited.

Diagnostic tests:

• A reactive screening test (a rapid test or fourth-generation antigen-antibody test) is confirmed with the rapid HIV diagnostic algorithm (rHIVda). This uses three different rapid tests in sequence at DOH-certified rHIVda confirmatory laboratories.
• The rHIVda replaced centralized Western blot confirmation in 2019, cutting turnaround to about a day.
• HIV RNA (viral load) detects acute infection during the window period and monitors treatment.
• Infants of HIV-positive mothers need nucleic acid tests, because maternal antibodies persist for up to 18 months.

Retroviridae: HIV/AIDS Staging & CD4-Stratified Opportunistic Infections

Human Immunodeficiency Virus (HIV-1 and HIV-2) is an enveloped, positive-sense diploid RNA retrovirus that infects cells expressing the CD4 receptor alongside chemokine coreceptors CCR5 (macrophage-tropic, transmitted mucosal strains) or CXCR4 (T-cell-tropic, associated with rapid CD4 decline). Viral replication is mediated by reverse transcriptase, integrase, and protease.

Clinical Staging & CD4 Thresholds for Opportunistic Pathogens

As circulating CD4+ T-cell counts decline, patients become susceptible to specific opportunistic infections (OIs):

Philippine DOH Antiretroviral Therapy (ART) Guidelines

Under Republic Act No. 11166 (The Philippine HIV and AIDS Policy Act), the Philippine DOH promotes the "Treat All" policy: immediate initiation of ART regardless of CD4 count. The preferred first-line fixed-dose combination regimen is TLD: $\text{First-Line Regimen (TLD)} = \text{Tenofovir Disoproxil Fumarate (TDF)} + \text{Lamivudine (3TC)} + \text{Dolutegravir (DTG)}$ Dolutegravir acts as a potent integrase strand transfer inhibitor (INSTI) with a high genetic barrier to resistance, paired with two nucleoside reverse transcriptase inhibitors (NRTIs).

Prevention

• Post-exposure prophylaxis (PEP): start as soon as possible and within 72 hours of a needlestick or sexual exposure, using a 3-drug regimen (such as TLD) for 28 days. Baseline and follow-up HIV testing is done.
• Pre-exposure prophylaxis (PrEP): tenofovir disoproxil fumarate with emtricitabine, taken daily or, for men who have sex with men, on demand. It is offered to people at substantial risk.
• Prevention of mother-to-child transmission:
  • test every pregnant woman for HIV, syphilis and hepatitis B;
  • give lifelong ART to all pregnant women with HIV;
  • give the infant antiretroviral prophylaxis and early nucleic acid testing.
  • With suppressed viral load, transmission falls below 1%.
• Other measures: condoms, harm reduction and treatment of other STIs.

Starting ART and immune reconstitution

• Start ART for everyone with HIV as soon as possible, often on the day of diagnosis. Delay it in TB meningitis and cryptococcal meningitis, because early ART increases deaths from inflammation.
• Immune reconstitution inflammatory syndrome (IRIS) is a paradoxical worsening of a treated or hidden infection (TB, Cryptococcus, MAC, CMV) weeks after ART starts, as immunity recovers.
• Dolutegravir interactions: rifampicin lowers its levels (dolutegravir is given twice daily), and polyvalent cations (antacids, iron, calcium) reduce absorption.

Tissue Protozoan Infections: Toxoplasma gondii

Toxoplasma gondii is an intracellular coccidian parasite with felines (domestic and wild cats) serving as the definitive hosts (within which sexual reproduction occurs, shedding oocysts in feces). Humans and warm-blooded animals serve as intermediate hosts.

Transmission & Clinical Syndromes

Transmission occurs via: (1) ingestion of sporulated oocysts from soil, water, or vegetables contaminated with cat feces; (2) ingestion of tissue cysts (bradyzoites) in undercooked meats (pork, lamb); or (3) transplacental transmission of rapidly replicating tachyzoites during acute primary maternal infection during pregnancy.

• Congenital Toxoplasmosis: Classic Sabin triad of: (1) Chorioretinitis (severe posterior uveitis and retinal scarring); (2) Hydrocephalus; and (3) Intracranial calcifications (scattered diffusely throughout the brain parenchyma, contrasting with the strictly periventricular calcifications characteristic of congenital cytomegalovirus).
• Toxoplasma Encephalitis in Advanced HIV/AIDS (CD4 < 100/uL): Represents reactivation of latent tissue cysts in the brain. Patients present with fever, altered mental status, and focal neurologic deficits. Contrast-enhanced brain MRI or CT demonstrates multiple ring-enhancing lesions with surrounding vasogenic edema, showing marked predilection for the basal ganglia and corticomedullary junction. First-line therapy is Pyrimethamine + Sulfadiazine + Leucovorin (folinic acid) (leucovorin prevents pyrimethamine-induced bone marrow suppression). Primary prophylaxis with Trimethoprim-Sulfamethoxazole (TMP-SMX) is indicated for HIV patients with CD4 counts < 100/uL who test seropositive for anti-Toxoplasma IgG.

Other opportunistic infections to remember:

• Cryptosporidium causes chronic watery diarrhea.
• Oral and esophageal candidiasis are common.
• Progressive multifocal leukoencephalopathy (JC virus) causes non-enhancing white matter lesions.
• Primary CNS lymphoma (EBV) causes a single enhancing lesion.
• Kaposi sarcoma is caused by HHV-8.
• Tuberculosis occurs at any CD4 count and is the leading cause of death in people with HIV.