Publications

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.

To determine operational and analytical characteristics of respondent-driven sampling (RDS) in international settings and to explore factors that may affect recruitment of most-at-risk populations using RDS, we reviewed HIV biological and behavioral surveillance studies that used this method outside of the United States. We identified 123 eligible studies, 59 from Europe, 40 from Asia and the Pacific, 14 from Latin America, seven from Africa and three from Oceania. Studies collectively recruited 32,298 participants between 2003 and 2007; 53% of studies were conducted among injecting drug users, which generally had faster recruitment compared with studies among sex workers. All but 13 studies reached > or = 90% of their intended sample size, and six studies failed to reach equilibrium for key variables. This review has shown that RDS is an effective technique, when designed and implemented appropriately, to sample most-at-risk populations for HIV biological and behavioral surveys.

OBJECTIVE

It is recommended that women with systemic lupus erythematosus carefully time their pregnancies, but little is known about use of contraception and risk of unintended pregnancy in this population. The goal of this study was to estimate the proportion of women with lupus at risk for unintended pregnancy.

METHODS

We surveyed 309 women with lupus, ages 18-50 years, seen at the University of Pittsburgh lupus center between January and May 2007.

RESULTS

Of the women surveyed, 212 (69%) completed the survey. In the past 3 months, 97 (46% of 212) had faced some risk of unintended pregnancy. Of these, 53 (55% of 97) reported >or=1 occasion on which they had unprotected sex and 22 (23% of 97) reported that in the last 3 months they had unprotected sex "most of the time." No women reported having used emergency contraception after unprotected sex. A desire to "discuss birth control with a health care provider at the lupus center" was reported by 22 (10% of 212) respondents and 16 (17% of 94) women

CONCLUSION

Many women cared for by our lupus center are at risk of unintended pregnancy and are interested in discussing birth control with a health care provider.