S. M'Boup

Slower heterosexual spread of HIV-2 than HIV-1

Because of the similar virological properties of HIV types 1 and 2, HIV-2 was assumed to be as infectious and capable of inducing AIDS as HIV-1. Seroepidemiological studies have shown significant rates of HIV-2 infection in West Africa, and surveys from other regions of the world indicate that the spread of HIV-2 infection continues. However the pathogenic potential of HIV-2 is considered to be lower than that of HIV-1. It is therefore important to understand the transmission properties of HIV-2 and its contribution to the AIDS pandemic. Since 1985, we have prospectively studied 1452 registered female prostitutes in Dakar, Senegal, with sequential evaluation of their antibody status to HIV-1 and HIV-2. During the study the overall incidence of HIV-1 and HIV-2 was the same (1.11 per 100 person-years of observation [pyo]). However, the annual incidence of HIV-1 increased substantially: there was a 1.4-fold increased risk per year and thus a 12-fold increase in risk over the entire study period. The incidence of HIV-2 remained stable, despite higher HIV-2 prevalence. In our population the heterosexual spread of HIV-2 is significantly slower than that of HIV-1, which strongly suggests differences in the viruses infectivity potential.

SEROLOGICAL EVIDENCE FOR VIRUS RELATED TO SIMIAN T-LYMPHOTROPIC RETROVIRUS III IN RESIDENTS OF WEST AFRICA

Serological evidence is presented here suggesting that a virus closely related to simian T-lymphotropic virus type III (STLV-III) infects man in Senegal, west Africa, a region where AIDS or AIDS-related diseases have not yet been observed. 25 sera from Senegalese individuals that were positive for antibodies to HTLV-III by enzyme-linked immunosorbent assay were examined for antibodies to HTLV-III and STLV-III by western blotting. Sera from individuals originating from regions where AIDS has been reported, such as the United States and Burundi (central Africa), reacted best with antigens of HTLV-III, although antibodies that cross-reacted with STLV-III p24 were also detected. Conversely, sera originating from Senegalese people reacted better with STLV-III than with HTLV-III. This was exemplified by the absence of reactivity in sera from both monkeys and Senegalese people to p41, an antigen regularly detected by sera from antibody positive individuals originating from central Africa or from the United States. In contrast sera from central Africa or the United States did not react with p32, the putative envelope transmembrane protein of STLV-III that is regularly detected by sera from both monkeys and antibody-positive Senegalese people. These results suggest that certain healthy Senegalese people have been exposed to a virus that is more closely related to STLV-III than to HTLV-III. The existence and study of such virus variants potentially with differential pathogenicity may provide important information for the development of an AIDS virus vaccine.

Temporary expatriation is related to HIV-1 infection in rural Senegal.

Objectives:To assess temporary expatriation as a risk factor for HIV infection in a rural area of Senegal and to examine the transmission of HIV from expatriates to their families. Design:Cross-sectional study in identified expatriates and in a representative cluster sample of the general population from the same geographical area in northern Senegal. Methods:In 1989, a survey (including questionnaire and serological tests for HIV-1 and HIV-2) was conducted in all expatriates currently living in 11 villages in northern Senegal and spouses of all expatriates (present or not) from this area (‘expatriate’ group, n = 258). In parallel, a cluster sample of 600 adults was drawn from eight villages of the same area, of whom 414 were selected as the control group since they and their spouses had not travelled outside Senegal in the last 10 years. Results:In the ‘expatriate’ group, sera from 39 subjects were confirmed as HIV-positive by Western blot [17 out of 63 men (27.0%) and 22 out of 195 women (11.3%)]. Of these subjects, 33 were infected by HIV-1, four by HIV-2 and two had a dual HIV-1/2 profile. In contrast, only two subjects (one man and one woman) from the control group were infected by HIV-2 and none by HIV-1. In men, HIV-1 seroprevalence was associated with age <40 years [odds ratio (OR), 7.4; P = 0.03] and previous sexually transmitted disease (STD) symptoms (OR, 13.5; P = 0.03), whereas the risk factors in women were age <25 years (OR, 3.7; P = 0.04), being a widow (OR, 30.4; P < 0.01) and presence of sexual activity over the last 2 years (OR, 21.3; P < 0.01). Conclusions:Penetration of HIV-1 infection in a country where HIV-2 is endemic shows-that the HIV-1 epidemic is currently spreading to rural West Africa. Migrant workers appear to play a major role in this epidemic.

Intrapatient Diversity and Its Correlation with Viral Setpoint in Human Immunodeficiency Virus Type 1 CRF02_A/G-IbNG Infection

ABSTRACT The human immunodeficiency virus type 1 (HIV-1) viral setpoint during the disease-free interval has been strongly associated with future risk of disease progression. An awareness of the correlation between viral setpoint and HIV-1 genetic evolution over time is important in the understanding of viral dynamics and infection. We examined genetic diversity in HIV-1 CRF02_A/G-IbNG-infected seroincident women in Dakar, Senegal; determined whether a viral setpoint kinetic pattern existed for CRF02_A/G-IbNG during the disease-free interval; and correlated viral load level and diversity. Samples were drawn during the disease-free interval from consenting CRF02_A/G-IbNG-infected, antiretroviral therapy-naïve female commercial sex workers in Dakar, Senegal. Based on sequential plasma RNA values, low and high viral setpoint groups were established. Intrapatient diversity and divergence over time was determined from earlier and later time point DNA samples from each person. Most individuals followed the viral setpoint paradigm. For each 1|−|log10 copy/ml of plasma increase in viral load, intrapatient diversity increased by 1.4% (P = 0.028). A greater diversification rate was observed in the high viral setpoint group than in the low viral setpoint group (P = 0.01). Greater nucleotide (P = 0.015) and amino acid (P = 0.048) divergences and a greater nucleotide divergence rate (P = 0.03) were found in the high viral setpoint group. There was no difference between the groups in the ratio of the number of nonsynonymous substitutions per nonsynonymous site to the number of synonymous substitutions per synonymous site. The greater intrapatient diversity, divergence, and diversification rates observed in the high viral setpoint group supports the notion that diversity is driven by cycles of viral replication resulting in accumulated mutations. Recognizing diversity potential based on viral load levels in individuals may inform the design of vaccines and therapies.

Cost-effective diagnosis of HIV-1 and HIV-2 by recombinant-expressed env peptide (566/996) dot-blot analysis.

OBJECTIVEnTo characterize the recombinant env peptides, 566 (HIV-1) and 996 (HIV-2), for their ability to serodiagnose HIV-1 and HIV-2 infection. To develop a cost-effective dot-blot format for these peptides, and to evaluate its performance in a developing country laboratory.nnnDESIGNnThe recombinant env peptides were evaluated using a select panel of sera (n = 327) with known serostatus from geographically diverse areas. A dot-blot assay was developed and tested on a second set of immunoblotted sera (n = 331) and further evaluated in the field on a third set of sera (n = 2718) from study populations.nnnMETHODSnAll sera were evaluated by immunoblot with both HIV-1 and HIV-2 viral lysates. The recombinant env peptides were characterized in immunoblot assay before development of the dot-blot assay.nnnRESULTSnThe 566 (HIV-1) peptide showed 100% sensitivity and specificity. The 996 (HIV-2) peptide performed similarly, but showed the presence of HIV-1 cross-reactive epitopes. When the two env peptides were used together, there was high specificity and sensitivity for detecting HIV-positive sera in both immunoblot and dot-blot formats. The dot-blot assay performed in the field showed slightly lower specificity and sensitivity for HIV diagnosis. The relative cost of this assay combined with non-commercial immunoblot confirmation was 10-fold lower than conventional commercial assays.nnnCONCLUSIONSnThe 566 and 996 env peptides are appropriate antigens for HIV serotype diagnosis. A dot-blot assay using these peptides may be a useful cost-effective method for HIV diagnosis applicable in developing country laboratories.

A STLV-III related human retrovirus, HTLV-IV: analysis of cross-reactivity with the human immunodeficiency virus (HIV).

A category of viruses has been identified which is related to human immunodeficiency virus (HIV) but is more closely related to a group of simian retroviruses (STLV-III). These viruses named HTLV-IV, LAV-II, or SBL-6669, are prevalent in West-Africa. In this study, we analysed the cross-reactivity at the protein level between HTLV-IV and HIV (HTLV-IIIB). The results indicate that most people infected with HTLV-IV have antibodies that react to the major gag protein of HIV p 24. There is also a high degree of immunologic cross-reactivity between the pol gene products of HIV and HTLV-IV. Among these the endonuclease/integrase is more conserved than the reverse transcriptase. In contrast, the envelope glycoproteins that are the most frequently detected antigens by antibodies from exposed individuals are serotype specific. These data make the env gene products the most interesting antigens for serotype specific diagnosis of human retroviruses infections.

Relationship of simian T-lymphotropic virus type III to human retroviruses in Africa.

HTLV-I has common characteristics of a simian retrovirus (STLV-I) such as extremely cross reactive major viral antigens. Further the major proteins of HTLV-III/HIV are similar to and cross react with those of STLV-III which causes an immunodeficiency syndrome similar to AIDS in macaque monkeys. It appears however that even though STLV-III has been found in green monkeys it does not adversely affect them. These similarities suggest that these viruses have a common ancestry. In their quest for more information on commonality between simian lymphotropic viruses and human retroviruses researchers found that antibodies of healthy prostitutes in West Africa reacted with related antigens of STLV-III e.g. the p24 p55 and gp 120/160 antigens. Researchers then isolated this human retrovirus and called it HTLV-IV. The prostitutes were healthy at the time of examination and 15 months later continued to show no symptoms of AIDS. This differs from global seroepidemiologic data of individuals with HTLV-III/HIV who upon exposure eventually develops AIDS related complex or AIDS. Present evidence shows that a number of related T-lymphotropic viruses affect their respective hosts pathogenically different. Further research may lead to the identification of distinctive structural and mechanistic differences responsible for the pathogenicity of the AIDS virus (HTLV- III/HIV). Research has shown that env-related antigens of HTLV-III/HIV STLV-III and HTLV-IV all cross react which means that common conserved regions of these viruses are immunogenic. Additional research marking these cross-reactive epitopes can provide the basis for the development of an AIDS vaccine.