Effects of HIV-related stigma among an early sample of patients receiving antiretroviral therapy in Botswana.

Botswana, with its estimated HIV prevalence of 37%, instituted a policy of universal access to antiretroviral therapy (ART) in 2002. Initial enrolment lagged behind expectations, with a shortfall in voluntary testing that observers have attributed to HIV-related stigma - although there are no published data on stigma among HIV-positive individuals in Botswana. We interviewed 112 patients receiving ART in 2000, finding evidence of pervasive stigma in patterns of disclosure, social sequelae, and delays in HIV testing. Ninety-four percent of patients reported keeping their HIV status secret from their community, while 69% withheld this information even from their family. Twenty-seven percent of patients said that they feared loss of employment as a result of their HIV status. Forty percent of patients reported that they delayed getting tested for HIV; of these, 51% cited fear of a positive test result as the primary reason for delay in seeking treatment, which was often due to HIV-related stigma. These findings suggest that success of large-scale national ART programmes will require initiatives targeting stigma and its social, economic and political correlates.

Antibodies to the HIV type 2 core protein p26 and Vpx: association with disease progression.

A longitudinal cohort study was conducted to define the prevalence and temporal pattern of antibody response to the HIV-2 virion-associated proteins p26gag and Vpx. One hundred and forty-one asymptomatic HIV-2-infected women were enrolled, and followed for up to 11 years. Eighty-one percent of the subjects had antibodies to p26, and 51% to Vpx; response to these two antigens was not correlated. The response to both proteins was determined early in infection, and remained stable over time. The absence of antibodies to p26 was a highly significant predictor of CDC category IV HIV-related disease (p < 0.01) in both univariate and multivariate analysis. Antibody response to Vpx alone was not associated with disease progression. However, those individuals lacking anti-p26 antibodies, and with anti-Vpx antibodies, were six times more likely to be classified as CDC category IV by the end of the study (p < 0.01). This represents the first identification of virus-specific serological markers for HIV-2-related disease progression.

HIV-1 and HIV-2 dual infection: lack of HIV-2 provirus correlates with low CD4+ lymphocyte counts.

OBJECTIVE: We conducted this study to genetically characterize dual infection in individuals demonstrating a dual serological profile. METHODS: All subjects were first evaluated by immunoblot for antibody reactivity to the major viral antigens for HIV-1 and HIV-2. Sera were judged to be dual-seropositive if they reacted with strong and equal intensity with the envelope antigens of both HIV-1 and HIV-2 and were confirmed with type-specific recombinant env peptides. We used nested polymerase chain reaction (PCR) to amplify proviral gag and env sequence from peripheral blood mononuclear cell (PBMC) DNA from HIV-1- and HIV-2-infected individuals. Positive amplification was detected after Southern blot hybridization. RESULTS: Plasmid dilution and mixing showed equivalent sensitivity of HIV-1 and HIV-2 primers that was not altered by heterologous target sequences. The DNA PCR showed 100% sensitivity and specificity for detection of monotypic HIV infection. Serologically defined HIV-dual reactives were evaluated by this assay, with 100% detection in female sex workers (21 out of 21), but only 38.5% detection (five out of 13) in hospitalized patients; all being HIV-1 positive only. The lack of HIV-2 proviral signal was significantly correlated with low CD4+ lymphocyte counts (Pvalue = 0.04). CONCLUSION: The results suggest that HIV dual infection may not be a static condition. Levels of HIV-2 may decrease with disease progression or sequester in tissue reservoirs; our results may also suggest that HIV-1 effectively overgrows HIV-2 in the dually exposed host individual.

Distinct quasi-species in the blood and the brain of an HIV-2-infected individual.

Sequences of the HIV-2 envelope C2-C3 region were obtained after direct PCR amplification of proviral DNA from the brain and peripheral blood mononuclear cells of an HIV-2-infected AIDS patient. Tissue-specific sequences confirmed previous observations that HIV-2 is indeed present in the central nervous system of infected individuals. Distinct but related quasi-species were present in these two different tissues of the same individual. Residues at position 18 and 19 of the V3 loop and overall charge of the loop suggest that the brain virus was NSI/macrophage tropic; whereas the sequences from the two blood samples were indicative of a SI/T-cell tropic virus. This is the first description of these two genotypes in the same HIV-2-infected individual. Analysis of more samples from different compartments would help to better understand tissue-specific factors in quasi-species evolution in vivo.

Intrapatient variability of the human immunodeficiency virus type 2 envelope V3 loop.

Studies of HIV-2 infection have shown lower rates of sexual and perinatal transmission and a prolonged incubation period to AIDS as compared to HIV-1. To evaluate the role of genetic variation in HIV pathogenesis, we studied intrapatient variability in the V3 loop of the HIV-2 envelope gene over time in five seropositive individuals. Proviral sequences derived from uncultured PBMC DNA (n = 102) demonstrated an average sequence heterogeneity within a sample of 1.4% (0-4.1%). This was significantly lower than the V3 sequence heterogeneity observed in HIV-1, which can be as high as 6.1%. In HIV-2-seropositive healthy patients the average intrapatient nucleotide variability rate was 0.6% compared to 2.0% in patients with clinical AIDS. The lower rate of variability between HIV-2 and HIV-1 is compatible with differences in transmission and pathogenesis of these two related viruses.

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.

PIP: Between February 1985 and February 1993 in Dakar, Senegal, the Social Hygiene Clinic screened 1452 registered female prostitutes (5608 samples) for sexually transmitted diseases, including HIV-1 and HIV-2. The overall prevalence rate stood at 11.3% for HIV-2 while it was 6.2% for HIV-1. 12 women (0.8%) tested positive for HIV-1 and HIV-2. Health workers followed the 1277 women who were initially HIV seronegative to determine seroconversion. 46 of these women seroconverted to HIV-2 and another 46 seroconverted to HIV-1. Overall incidence of HIV-2 and HIV-1 was 1.11 per person years of observation (pyo). Eight women (incidence = 0.19 per 100 pyo) seroconverted to both HIV-2 and HIV-1. When the researchers controlled for age, nationality, years of registered prostitution, calendar year, and time in study, the relative risk for HIV-2 infection each year did not change. On the other hand, there was a significant 1.43 annual increase in the risk for HIV-1 infection (p .002), indicating a 12-fold increase in the risk of HIV-1 infection over the study period. These findings suggest that the 2 viruses have a distinctly different in-vivo biology and that HIV-2 has a lower infectivity than does HIV-1.

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

OBJECTIVE: To 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. DESIGN: The 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. METHODS: All 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. RESULTS: The 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. CONCLUSIONS: The 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.

Hepatic arterial embolization for metastatic hormone-secreting tumors. Technique, effectiveness, and complications.

Ten patients with hepatic metastases from islet cell tumors or carcinoid tumors had clinical symptoms from hormonal secretion and/or pain related to the mass effect of neoplastic liver involvement. Hepatic arterial embolization (HAE) using radiographically guided catheters to inject thrombogenic material was applied to the right and/or left hepatic arteries separately 5 to 7 days apart. All ten patients improved within days of the procedure as confirmed by a decrease in measurable hormone levels (gastrin, adrenocorticotropin, and 5-hydroxy indole acetic acid) or by a decrease in tumor size and improved symptoms. Three patients underwent repeated reembolization from two to four times over nine to 50-month intervals for symptom control. Complications of and indications for HAE in these patients are discussed. It appears to be an effective treatment for dealing with the hormonal syndromes and local symptoms related to the hepatic metastases of hormone-secreting tumors.

Clinical, hematologic, and immunologic cross-sectional evaluation of individuals exposed to human immunodeficiency virus type-2 (HIV-2).

We studied the clinical status and certain hematologic and immunologic parameters in healthy prostitutes from Dakar, Senegal who were seropositive for antibodies to human immunodeficiency virus type-2 (HIV-2). Generalized lymphadenopathy and clinical signs or symptoms similar to those which are seen with human immunodeficiency virus type-1 (HIV-1) infection were not present. Comparison to seronegative prostitutes and minor surgery control patients were made and significant elevations were seen in T8 lymphocytes (p = .03), IgG (p = .0001), and beta 2-microglobulin (p = .03). The mean T4 lymphocyte count in seropositive prostitutes was lower than in seronegative prostitutes (757 vs. 1179, p = .15), but this difference was not statistically significant and appeared to be correlated with age. No significant differences were noted between the seronegative and seropositive prostitutes in lymphocyte stimulation studies to certain mitogens. Antilymphocyte antibodies above background were not present in either population. We conclude that HIV-2 is a sexually transmitted agent that produces immunologic alterations consistent with a persistent viral infection. HIV-2 seropositive prostitutes studied to date do not show clinical signs of immune suppression, as has been described with HIV-1 infection. The pathogenic potential of HIV-2 appears to differ from that of HIV-1, the etiologic agent of the AIDS pandemic.

Transfusion-acquired human immunodeficiency virus infection among immunocompromised persons.

Transmission of the human immunodeficiency virus (HIV) was studied in a group of patients with cancer who received transfusion of blood components harvested from a single, asymptomatic, seropositive donor. Of ten living recipients, nine had antibodies to the virus in fresh or cryopreserved sera at a median of 384 days (range, 237 to 686) after transfusion. In three patients, an enzyme-linked immunosorbent assay was negative at the same time that Western blot and radioimmunoprecipitation techniques showed seropositivity. Cultures for HIV obtained at a median of 615 days (range, 322 to 714) after transfusion were positive in seven of nine seropositive recipients. Six seropositive recipients have developed immunologic and clinical sequelae of HIV infection at a median of 286 days (range, 56 to 745) after transfusion. The sera of the two patients without clinical sequelae neutralized HIV in an in-vitro assay, whereas the seven other seropositive patients lacked such neutralizing antibodies. Our study characterizes the clinical, serologic, virologic, and immunologic manifestations of HIV infection in immunocompromised persons.