Item #49: Genetic Immunity to HIV

Some researchers claim that HIV exploits special receptors on human T-cells that, due to a hypothetical genetic mutation, many “Caucasian Europeans” lack, but most Africans have. What's interesting is that many gay men also seem to possess these mysterious receptors, as do intravenous drug users and transfusion recipients.

Farber states in footnote 13 "Some researchers claim that HIV exploits special receptors on human T-cells that, due to a hypothetical genetic mutation, many 'Caucasian Europeans' lack, but many Africans have. What's interesting is that many gay men also seem to possess these mysterious receptors, as do intravenous drug users and transfusion recipients".

Again, these sentences betray Farber's ignorance of a substantial body of scientific information. As we explain in a detailed endnote76 , a fraction of Caucasians have genetic predispositions which render them less likely to contract HIV (not immune) or more likely to progress slowly. However, the vast majority of Caucasians have no known genetic predisposition that makes them less likely to contract HIV or progress to AIDS. Many Caucasians do contract HIV and do progress to AIDS.

Genetic explanations are often used to try to explain why some people are resistant to HIV infection or resistant to progression to AIDS, without using AIDS drugs. This is much less dangerous than questioning the underlying paradigm: HIV=AIDS=Death, which is threatened every time someone who is clearly exposed to HIV-positive people remains stubbornly HIV-negative or when people live for decades while HIV-positive without illness developing.

These genetic explanations are not convincing, however:

1. “Each group of men [AIDS; ARC; HIV-positive without symptoms; HIV-negative] had frequencies of Gc genotypes and alleles similar to those of the other groups and the control group.” [1]
2. “We have been following a 78-year-old man who, as a result of a test performed before cataract surgery in 1985, was found to be seropositive for HIV-1...He has never had any symptoms or signs of HIV infection, and repeated clinical examinations and laboratory tests performed since 1985 have revealed no opportunistic infections or abnormalities other than HIV-1 seropositivity and glucose-6-phosphate dehydrogenase deficiency…No evidence of CCR5 mutations [that are believed to confer immunity] was found.” [2]
3. “Env peptide-stimulated PBMCs of ESNs produced more IL-2 and less IL-10 compared with those of HIV-infected individuals; no differences were observed in chemokine production or in CCR5 expression.” [3]
4. “CEM15 (or APOBEC3G) has recently been identified as an inhibitor of human immunodeficiency virus type 1 (HIV-1) replication in vitro. To evaluate the impact of its genetic variations on the progression of acquired immunodeficiency syndrome (AIDS), we have performed an extensive genetic analysis of CEM15. We have sequenced CEM15 in a cohort of 327 HIV-1-seropositive patients with extreme disease progression phenotypes--either slow progression or rapid progression--and in 446 healthy control subjects, all of white descent. We have identified 29 polymorphisms with allele frequencies >1%, 14 of which were newly characterized. There were no significant associations between the polymorphisms or haplotypes of CEM15 and a disease progression phenotype in our cohort.” [4]
5. “we identified four therapy naive individuals who are strongly seropositive for HIV-1 but who lack evidence of detectable HIV p24 antigen, plasma RNA, and proviral DNA in routine diagnostic testing…One individual was heterozygous for CCR5 Delta32, but CCR5 expression on CD4(+) T cells was normal to high in all four individuals.” [5]
6. “Among hemophiliacs from the Multicenter Hemophilia Cohort Study who remained HIV-1 seronegative despite a high (94%) risk for acquisition of HIV-1 infection, only 7/43 were homozygous for the protective CCR5 Delta32 polymorphism. Among the remainder, neither CCR5 density nor beta-chemokine production, nor in vitro susceptibility to infection with the HIV-1 isolate JR-FL could distinguish HRSN hemophiliacs from healthy controls.” [6]
7. “It has been hypothesized that protection against human immunodeficiency virus (HIV)-1 infection may result from either acquired host immunity, inheritance of a dysfunctional CCR5 HIV-1 coreceptor, or a low or attenuated virus inoculum. 37 HIV-1-uninfected persons engaging in repeated high-risk sexual activity with an HIV-1-infected partner were prospectively studied to determine the contribution of these factors in protecting against HIV-1 transmission. More than one-third (13/36) demonstrated HIV-1-specific cytotoxicity, and this activity significantly correlated with the wild type CCR5 genotype. Only 1 subject (3%) demonstrated the homozygous CCR5 32-bp deletion (Delta32/Delta32). Median plasma HIV-1 RNA levels from 18 HIV-1-infected sex partners were not statistically different from those of matched infected control patients. These results indicate that inheritance of the Delta32 CCR5 mutation does not account for the majority of persistently HIV-1-resistant cases.” [7]
8. “A cohort of 19 LTNP [Long-Term Non-Progressors] was established in 1997. Plasma viraemia and CD4 cell counts were measured two to three times each year until 2003. Analyses of nef and vpr viral genes, CCR5 genotypes, co-receptor tropism, viral replication capacity, and immunological parameters were performed…None of the patients was homozygous for the delta-32 CCR5 genotype, which was found in heterozygosis in three.” [8]

1. Gilles K et al. Genetic Susceptibility to AIDS: Absence of an Association with Group-Specific Component (Gc). N Engl J Med. 1987 Sep 3; 317(10): 631.
2. Sulis E et al. Prolonged Asymptomatic HIV-1 Infection. N Engl J Med. 2000 Apr 20; 342(16): 1221-2.
3. Mazzoli S et al. HIV-specific mucosal and cellular immunity in HIV-seronegative partners of HIV-seropositive individuals. Nat Med. 1997 Nov; 3(11): 1250-7.
4. Do H et al. Exhaustive Genotyping of the CEM15 (APOBEC3G) Gene and Absence of Association with AIDS Progression in a French Cohort. J Infect Dis. 2004 Dec 15; 188.
5. Kloosterboer N et al. Natural controlled HIV infection: Preserved HIV-specific immunity despite undetectable replication competent virus. Virology. 2005 Jun 27.
6. Salkowitz JR et al. Characterization of High-Risk HIV-1 Seronegative Hemophiliacs. Clin Immunol. 2001 Feb; 98(2): 200-211.
7. Goh WC et al. Protection against human immunodeficiency virus type 1 infection in persons with repeated exposure: evidence for T cell immunity in the absence of inherited CCR5 coreceptor defects. J Infect Dis. 1999 Mar; 179(3): 548-57.
8. Rodes B et al. Differences in disease progression in a cohort of long-term non-progressors after more than 16 years of HIV-1 infection. AIDS. 2004 May 21; 18(8): 1109-16.