AIDS Cofactor Definition
A cofactor for AIDS refers to an infectious agent or condition that facilitates HIV transmission, accelerates disease progression, or worsens outcomes in HIV-infected individuals by enhancing viral replication, increasing infectiousness, or compromising immune function. 1
Mechanism of STD Cofactors in HIV/AIDS
The term "cofactor" in the AIDS context primarily describes sexually transmitted diseases (STDs) that create a synergistic relationship with HIV, termed "epidemiological synergy." 1
How STD Cofactors Facilitate HIV Transmission
Ulcerative STDs (syphilis, chancroid, herpes):
- HIV is routinely detected in genital ulcer exudate from HIV-infected individuals 1
- Ulcers bleed easily and provide direct mucosal contact during sexual activity, creating entry points for HIV 1
- These infections increase HIV transmission risk by 2-5 fold 1
Non-ulcerative STDs (gonorrhea, chlamydia, trichomoniasis):
- Inflammatory STDs increase both the prevalence of HIV shedding and viral load in genital secretions 1
- Gonococcal infection increases HIV RNA shedding in semen tenfold, though effective treatment rapidly reduces this to baseline 1
- Both ulcerative and non-ulcerative STDs attract CD4+ lymphocytes to infection sites, providing target cells for HIV 1
Specific Examples of AIDS Cofactors
Bacterial STDs as Cofactors
The major treatable STDs with strong cofactor evidence include: 1
- Chlamydia trachomatis
- Neisseria gonorrhoeae
- Treponema pallidum (syphilis)
- Haemophilus ducreyi (chancroid)
- Trichomonas vaginalis
Ureaplasma as a Potential Cofactor
Ureaplasma species have been proposed as AIDS cofactors, though evidence remains limited. 2, 3
- Genital Ureaplasma infections occur with increasing frequency in HIV-infected patients 2
- Ureaplasma may act as a candidate cofactor in AIDS pathogenesis through immune system activation or oxidative stress mechanisms 3
- However, studies show Ureaplasma prevalence in HIV-positive asymptomatic women is similar to HIV-negative populations, making a direct pathogenic role uncertain 4
Mycoplasma Species as Cofactors
Three mycoplasmas have been specifically implicated: 3
- Mycoplasma fermentans
- Mycoplasma penetrans (serological studies suggest association with HIV infection)
- Mycoplasma pirum
These organisms share the capacity to invade eukaryotic cells and may influence HIV pathogenesis through immune activation, superantigen production, or contribution to oxidative stress. 3
Clinical Significance of the Cofactor Concept
The population-attributable risk of non-ulcerative STDs (especially chlamydia and gonorrhea) for HIV transmission may exceed that of ulcerative STDs due to their higher incidence and prevalence, despite lower individual transmission risk. 1
Important Caveats
- While cytomegalovirus and mycoplasmas have been studied as cofactors, most evidence comes from in vitro data requiring clinical confirmation 5
- The responsibility of cofactors in accelerating disease progression versus HIV alone remains incompletely understood 5
- Not all organisms isolated from HIV-infected individuals necessarily function as true cofactors—some may be commensals or markers of sexual behavior rather than causative agents 6, 4