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Antibodies from the serum of patients with the acquired immune deficiency syndrome (AIDS) or with the AIDS-related complex and from the serum of seropositive healthy homosexuals, recognize two major glycoproteins in cells infected with human T-cell lymphotropic virus type III (HTLV III). These glycoproteins, gp160 and gp120, are encoded by the 2.5-kilobase open reading frame located in the 3' end of the HTLV-III genome, as determined by amino terminus sequence analysis of the radiolabeled forms of these proteins. It is hypothesized that gp160 and gp120 represent the major species of virus-encoded envelope gene products for HTLV-III.

At least 10 different genetic human immunodeficiency virus type 1 (HIV-1) subtypes (A-J) are responsible for the AIDS pandemic. Much of the understanding of HIV-1 disease progression derives from studies in the developed world where HIV infection is almost exclusively subtype B. This has led many to question whether the properties and consequences of HIV-1 infection can be generalized across subtypes that afflict the majority of infected persons in the developing world. From 1985 to 1997, a prospective study of registered female sex workers in Senegal tracked the introduction and spread of HIV-1 subtypes A, C, D, and G. In clinical follow-up, the AIDS-free survival curves differed by HIV-1 subtype. Women infected with a non-A subtype were 8 times more likely to develop AIDS than were those infected with subtype A (hazard ratio=8.23; P=. 009), the predominant subtype in the study. These data suggest that HIV-1 subtypes may differ in rates of progression to AIDS.

The objective was to develop and to validate an immunossay to identify recent human immunodeficiency virus type 1 (HIV-1) infections that can be used on dried serum spots (DSS). A single, indirect enzyme-linked immunosorbent assay was developed to quantify antibodies toward four HIV-1 antigens: consensus peptides of the immunodominant epitope of gp41 (IDE), consensus V3 peptides, recombinant integrase, and recombinant p24. The parameters of the logistic regression used to classify the samples were estimated on a training sample (210 serum samples) using resampling techniques to get stable estimates and then applied to a validation sample (761 serum samples). The IDE and V3 peptides were the best able to discriminate between the antibodies present in serum from recently (<6 months) infected individuals and those with long-lasting infection. Combined quantification of antibody binding to these two synthetic antigens allowed us to identify recent infections with an area under the receiver operating characteristic curve of 0.949 and a sensitivity of 88.3%, with a specificity of 97.6% in patients with long-term infection (but not AIDS) and 86.0% in patients suffering from AIDS with a threshold of 0.50 in the validation sample. This simple immunoassay can be used to identify recently HIV-1-infected patients. Its performance is compatible with its use in population-based studies including DSS.The human immunodeficiency virus (HIV) epidemic is generally assessed by monitoring seroprevalence i.e., the proportion of persons with HIV antibodies (including recently infected people and people who were infected several years previously). To understand recent changes in the HIV epidemic, it is necessary to estimate the incidence, i.e., the number of newly infected subjects in a defined period. A strategy based on a sensitive/less sensitive testing algorithm was recently used to identify serum samples from recently infected individuals (16). This strategy that uses both a sensitive and a less-sensitive enzyme immunoassay (S/LS EIA), also called a detuned assay, was applied to various situations, providing estimates of HIV incidence (12,14,16,18,24,33,35). One of the major drawbacks of this strategy is that the test is an adaptation of a commercial EIA, which poses problems for long-term availability. It is therefore necessary to develop and to validate simple immunoassays that can continuously be used independent of any commercial source. The knowledge of the anti-HIV type 1 (anti-HIV-1) antibody response (5,8,20,38) and recent studies aimed at identifying antigens to distinguish recent infections (27, 30) allowed us to design a candidate assay to assess persons with recent infection. We report the development and the validation of this assay for the identification of recent HIV-1 infections (EIA-RI) and its application to dried blood spots.

We compared the neutralization sensitivity of early/transmitted HIV-1 variants from patients infected by subtype B viruses at 3 periods of the epidemic (1987–1991, 1996–2000, 2006–2010). Infectious pseudotyped viruses expressing envelope glycoproteins representative of the viral quasi-species infecting each patient were tested for sensitivity to neutralization by pools of sera from HIV-1 chronically infected patients and by an updated panel of 13 human monoclonal neutralizing antibodies (HuMoNAbs). A progressive significantly enhanced resistance to neutralization was observed over calendar time, by both human sera and most of the HuMoNAbs tested (b12, VRC01, VRC03, NIH45-46G54W, PG9, PG16, PGT121, PGT128, PGT145). Despite this evolution, a combination of two HuMoNAbs (NIH45-46G54W and PGT128) still would efficiently neutralize the most contemporary transmitted variants. In addition, we observed a significant reduction of the heterologous neutralizing activity of sera from individuals infected most recently (2003–2007) compared to patients infected earlier (1987–1991), suggesting that the increasing resistance of the HIV species to neutralization over time coincided with a decreased immunogenicity. These data provide evidence for an ongoing adaptation of the HIV-1 species to the humoral immunity of the human population, which may add an additional obstacle to the design of an efficient HIV-1 vaccine.

TOC summary line: This new virus may be another cause of encephalitis.

This report describes serologic evidence for a virus similar to that known as simian T-lymphotropic virus type III of African Green monkeys (STLV-IIIAGM) infecting apparently healthy people in Senegal, West Africa, and the isolation of virus from these individuals. Serum samples from selected healthy West African people showed unusual serologic profiles when tested with antigens of HTLV-III/LAV, the etiologic agent of AIDS, and of STLV-IIIAGM. The samples reacted strongly with all of the major viral antigens of STLV-IIIAGM but showed variable or no reactivity with the major viral antigens of HTLV-III/LAV by radioimmunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A new human T-lymphotropic virus (HTLV-IV) isolated from these people was grown in vitro and shown to have retroviral type particles, growth characteristics, and major viral proteins similar to those of the STLV-III and HTLV-III/LAV group of retroviruses. The gp120/160, gp32, p64, p55, p53, p24, and p15 proteins precipitated were the same size as and reactive with STLV-IIIAGM proteins. The serologic data suggest that this virus shares more common epitopes with STLV-IIIAGM than with the prototype HTLV-III/LAV that infects people in the United States and Europe. Further study of this virus and of the origin of the HTLV-III/LAV group of viruses may expand our understanding of the human AIDS virus.

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