Publications

OBJECTIVE

To conduct a meta-analytic review of HIV interventions for heterosexual African Americans to determine the overall efficacy in reducing HIV-risk sex behaviors and incident sexually transmitted diseases and identify intervention characteristics associated with efficacy.

METHODS

Comprehensive searches included electronic databases from 1988 to 2005, handsearches of journals, reference lists of articles, and contacts with researchers. Thirty-eight randomized controlled trials met the selection criteria. Random-effects models were used to aggregate data.

RESULTS

Interventions significantly reduced unprotected sex (odds ratio = 0.75; 95% confidence interval = 0.67, 0.84; 35 trials; N = 14 682) and marginally significantly decreased incident sexually transmitted diseases (odds ratio = 0.88; 95% confidence interval = 0.72, 1.07; 10 trials; N = 10 944). Intervention characteristics associated with efficacy include cultural tailoring, aiming to influence social norms in promoting safe sex behavior, utilizing peer education, providing skills training on correct use of condoms and communication skills needed for negotiating safer sex, and multiple sessions and opportunities to practice learned skills.

CONCLUSION

Interventions targeting heterosexual African Americans are efficacious in reducing HIV-risk sex behaviors. Efficacious intervention components identified in this study should be incorporated into the development of future interventions and further evaluated for effectiveness.

Despite reports of viral genetic defects in persons who control human immunodeficiency virus type 1 (HIV-1) in the absence of antiviral therapy, the extent to which such defects contribute to the long-term containment of viremia is not known. Most previous studies examining for such defects have involved small numbers of subjects, primarily focused on subjects expressing HLA-B57, or have examined single viral genes, and they have focused on cellular proviral DNA rather than plasma viral RNA sequences. Here, we attempted viral sequencing from 95 HIV-1 elite controllers (EC) who maintained plasma viral loads of <50 RNA copies/ml in the absence of therapy, the majority of whom did not express HLA-B57. HIV-1 gene fragments were obtained from 94% (89/95) of the EC, and plasma viral sequences were obtained from 78% (61/78), the latter indicating the presence of replicating virus in the majority of EC. Of 63 persons for whom nef was sequenced, only three cases of nef deletions were identified, and gross genetic defects were rarely observed in other HIV-1 coding genes. In a codon-by-codon comparison between EC and persons with progressive infection, correcting for HLA bias and coevolving secondary mutations, a significant difference was observed at only three codons in Gag, all three of which represented the historic population consensus amino acid at the time of infection. These results indicate that the spontaneous control of HIV replication is not attributable to shared viral genetic defects or shared viral polymorphisms.

Originally recognized for their role in lipoprotein metabolism and cardiovascular disease, apolipoprotein (apo) E isoforms (apoE2, apoE3, and apoE4) have also been implicated to play a key role in several biological processes not directly related to their lipid transport function. For example, apoE4 contributes significantly to neurodegeneration in Alzheimer's disease. However, the role of apoE in infectious diseases is less well defined. Here, by examining a large cohort of HIV(+) European and African American subjects, we found that the APOE epsilon4/epsilon4 genotype is associated with an accelerated disease course and especially progression to death compared with the APOE epsilon3/epsilon3 genotype. However, an association between the epsilon4/epsilon4 genotype and HIV-associated dementia (HAD), a neurological condition with clinicopathological features similar to Alzheimer's disease, was not detected. Consistent with the genotype-phenotype relationships observed, compared with recombinant apoE3, apoE4 enhanced HIV fusion/cell entry of both R5 and X4 HIV strains in vitro. These findings establish apoE as a determinant of HIV-AIDS pathogenesis and raise the possibility that current efforts to convert apoE4 to an "apoE3-like" molecule to treat Alzheimer's disease might also have clinical applicability in HIV disease.