Anne-Grethe Poulsen

Declining Hiv-2 prevalence and incidence among men in a community study from Guinea-bissau

Objective:To assess the present level of HIV-2 infection in an adult population in Bissau and to evaluate sex and age-specific changes in HIV-2 prevalence and incidence between 1987 and 1996. Design and methods:Sex and age-specific changes in HIV-2 prevalence were evaluated comparing a survey from 1987 in a sample of 100 houses with a survey performed in 1996 in an independent sample of 212 houses from the same study area. HIV-2 incidence rates were examined in an adult population (age ≥ 15 years) from 100 randomly selected houses followed with four consecutive HIV serosurveys from 1987 to 1996. Results:The HIV-2 prevalence in 1996 was 6.8% (men, 4.7%; women, 8.4%). Compared with the 1987 survey there was a significant decrease in prevalence among men [age-adjusted relative risk (RR), 0.50; 95% confidence interval (CI), 0.31–0.83], whereas it remained unchanged in women (RR, 1.00; 95% CI, 0.67–1.48). The male-to-female RR decreased from 0.99 (95% CI, 0.61–1.61) in 1987 to 0.51 (95% CI, 0.34–0.76) in 1996. The overall annual incidence rate was 0.54 per 100 person-years of observation (PYO), being higher in women (0.72 per 100 PYO) than in men (0.31 per 100 PYO). With the observation time divided into an early and a late period, there was a decrease in incidence with time among men (0.66 to 0.00 per 100 PYO), but no major change among women (0.59 to 0.85 per 100 PYO). The two trends differed significantly (P = 0.03). We observed a higher annual incidence rate amongst older women aged > 44 years (1.77 per 100 PYO) than among younger women (0.55 per 100 PYO; P = 0.05). Conclusion:There are no signs of an epidemic spread of HIV-2 in Bissau even though the HIV-1 prevalence is increasing rapidly. A significant reduction in the male HIV-2 prevalence and incidence rates has resulted in a major shift in the pattern of spread of HIV-2, from being equally distributed to being predominantly a female infection. Currently, older women in particular seem to have a high risk of getting infected.

Risk Factors for HIV-2 Seropositivity Among Older People in Guinea-Bissau. A Search for the Early History of HIV-2 Infection

Because the seroprevalence of HIV-2 has been shown to be high in older age groups, we conducted a survey of all persons aged 50 years or over in two districts in Bissau, investigating the presence of HIV antibodies and possible risk factors for HIV infection with a particular emphasis on age, the impact of the war of independence (1963-74), traditional marital and extramarital sex patterns, blood contact and contact with monkeys. In 670 participants, the HIV-2 prevalence was 14.3%; 16.1% in women and 12.3% in men. The HIV-1 prevalence was only 0.5% (3/670). The HIV-2 prevalence peaked for men in the 60-69 years age group, and for women in the 50-59 years age group, declining markedly in the following age group for both men and women (OR=0.09 (0.01-0.51), OR=0.37 (0.15-0.82), respectively). This pattern could be due to differential mortality for HIV-2 infected individuals or to a cohort effect for a generation who were sexually active at the time of the war of independence in the 1960s and early 1970s in Bissau. Supporting the link with the colonial army, women who had had sex with a white man had a higher seroprevalence (OR=3.63 (1.12-11.24)). The ethnic group indigenous to Bissau city had a much lower prevalence, but demographic and cultural risk factors such as marital status, religion, education and having lived outside Bissau were not associated with HIV-2. In the multivariate analyses for women, variables related to extramarital sex or prostitution (having sex with a white man, having lived in Senegal, not living with husband, and not marrying first sexual partner) were associated with higher risk. For men, previous spouses who had died or had divorced were associated with higher prevalence. Having married the first sexual partner was protective against HIV-2 infection for both men (OR=0.29 (0.09-0.76)) and women (OR=0.19 (0.04-1.00)). Hospitalizations, possibly due to transfusions, tended to be associated with higher risk, but only for women (OR=1.83 (0.97-3.48)). The focus of the HIV-2 epidemic in Guinea-Bissau is likely to be endogenous, and the war of independence and the colonial army with its associated prostitution may have played an important part in propagating the virus.Because the seroprevalence of HIV-2 has been shown to be high in older age groups, we conducted a survey of all persons aged 50 years or over in two districts in Bissau, investigating the presence of HIV antibodies and possible risk factors for HIV infection with a particular emphasis on age, the impact of the war of independence (1963-74), traditional marital and extramarital sex patterns, blood contact and contact with monkeys. In 670 participants, the HIV-2 prevalence was 14.3%; 16.1% in women and 12.3% in men. The HIV-1 prevalence was only 0.5% (3/670). The HIV-2 prevalence peaked for men in the 60-69 years age group, and for women in the 50-59 years age group, declining markedly in the following age group for both men and women (OR = 0.09 (0.01-0.51), OR = 0.37 (0.15-0.82), respectively). This pattern could be due to differential mortality for HIV-2 infected individuals or to a cohort effect for a generation who were sexually active at the time of the war of independence in the 1960s and early 1970s in Bissau. Supporting the link with the colonial army, women who had had sex with a white man had a higher seroprevalence (OR = 3.63 (1.12-11.24)). The ethnic group indigenous to Bissau city had a much lower prevalence, but demographic and cultural risk factors such as marital status, religion, education and having lived outside Bissau were not associated with HIV-2. In the multivariate analyses for women, variables related to extramarital sex or prostitution (having sex with a white man, having lived in Senegal, not living with husband, and not marrying first sexual partner) were associated with higher risk. For men, previous spouses who had died or had divorced were associated with higher prevalence. Having married the first sexual partner was protective against HIV-2 infection for both men (OR = 0.29 (0.09-0.76)) and women (OR = 0.19 (0.04-1.00)). Hospitalizations, possibly due to transfusions, tended to be associated with higher risk, but only for women (OR = 1.83 (0.97-3.48)). The focus of the HIV-2 epidemic in Guinea-Bissau is likely to be endogenous, and the war of independence and the colonial army with its associated prostitution may have played an important part in propagating the virus.

HIV-2 genetic variation and DNA load in asymptomatic carriers and AIDS cases in Guinea-Bissau.

The purpose of this study was to document which genetic subtypes of HIV-2 are present in Guinea-Bissau and to investigate whether asymptomatic HIV-2 carriers and AIDS patients carry distinct genetic variants. A secondary aim was to correlate proviral DNA load to clinical and immunologic status of the patients. Thirty-eight asymptomatic HIV-2 carriers and 11 AIDS patients from Bissau, Guinea-Bissau were included in a cross-sectional study in which HIV-2 env V3 sequences, HIV-2 DNA load, and CD4-positive (CD4+) lymphocyte counts were determined. Phylogenetic analyses showed that all investigated subjects carried subtype A HIV-2 variants and that the sequences from AIDS patients and asymptomatic carriers did not form distinct subclusters in the tree. As expected, patients with AIDS had significantly higher median HIV-2 DNA load than did asymptomatic carriers (4.6 vs. 2.0 log10 HIV-2 DNA copies/10(6) CD4+ lymphocytes). Our study indicates that the HIV-2 epidemic in Guinea-Bissau is almost exclusively caused by subtype A HIV-2 variants and that the HIV-2 infections among the asymptomatic carriers and AIDS cases included in the study do not have distinct epidemiologic histories.

HTLV-1 infection in a population-based cohort of older persons in Guinea-Bissau West Africa: risk factors and impact on survival.

In 1989, a population‐based cohort of persons aged ≥50 years was established in an urban area of Guinea‐Bissau, West Africa. Overall, 346 persons were interviewed in detail about risk behaviors and had capillary blood drawn. Among women, 12.4% were HTLV‐1 seropositive, compared with 4.6% in men. No HTLV‐2 was found. Seropositivity varied considerably according to place of birth and ethnic group. In women, but not in men, HTLV‐1 seropositivity was strongly associated with early sexual debut (10–14 yrs, 33.3%; 15–17 yrs, 26.0%; 18–20 yrs, 6.5%; 21+ yrs, 0%; ptrend = 0.001), lifetime number of male partners (ptrend = 0.006), and the male partners number of co‐wives (ptrend = 0.006). There was also a 3.1‐fold increased risk of being HTLV‐1 seropositive if the woman was also HIV‐2 seropositive. In a multivariate‐risk‐factor analysis, the strongest association with HTLV‐1 was a history of having been bitten by a monkey (n = 11; combined ORadjusted = 10.1; 95% CI 2.3–44.4). Ornamental scarification was associated with a 3.3‐fold increased risk. Ethnic affiliation also significantly influenced the risk of being HTLV‐1 seropositive. Follow‐up performed in January 1996 revealed no difference in survival between HTLV‐1‐seropositive and ‐seronegative individuals over 6 years (rate ratio = 1.4, 95% CI 0.7–2.8). In conclusion, this population, which has very high HIV‐2 seroprevalence, is also highly endemic for HTLV‐1. Whereas sexual behaviors are clearly important for HTLV‐1 spread in women, non‐sexual risk factors were the only ones of potential importance in men. HTLV‐1 had no impact on survival in this older population. Int. J. Cancer 76:293–298, 1998.© 1998 Wiley‐Liss, Inc.

Immunodeficiency in HIV-2 infection: a community study from Guinea-Bissau.

In a community study in Guinea-Bissau, West Africa, 47 HIV-2-seropositive cases and 87 matched controls were evaluated immunologically using immuno-alkaline phosphatase linked to avidin-biotin complex for the assessment of CD4 and CD8 status. HIV-2-seropositive individuals had significantly lower total numbers of CD4 cells and CD4/CD8 ratios, 38% having a total number of CD4 cells less than or equal to 0.5 x 10(9)/l and 36% having a CD4/CD8 ratio less than or equal to 0.8. Total numbers of CD4 cells less than or equal to 0.5 x 10(9)/l or CD4/CD8 ratio less than or equal to 0.8 were found in 53% of the HIV-2 seropositives compared with 11% among controls [odds ratio (OR) = 7.3; 95% confidence interval (CI): 3.1-17.1]. Lymphadenopathy was significantly more frequent among HIV-2 seropositives than among controls (OR = 3.4; 95% Cl: 1.5-7.6). HIV-2 seropositives with lymphadenopathy had significantly fewer lymphocytes (P = 0.008) and lower total CD4 (P = 0.029) and total CD8 number (P = 0.011) than HIV-2 seropositives without lymphadenopathy. This study indicates that HIV-2 has a significant immunosuppressive effect.

Humoral and Cellular Responses to Pneumocystis carinii, CMV, and Herpes simplex in Patients with AIDS and in Controls

The titers of IgG and IgA to Pneumocystis carinii in 36 AIDS patients did not differ significantly from those in 31 controls. Only 2/15 patients (13%) with P. carinii pneumonia (PCP) had titers of IgM antibodies greater than or equal to 5, which is significantly less frequent than in 32 controls (62%) and in 21 AIDS patients without PCP (43%). The risk of PCP was 5 times higher in patients without IgM antibodies to P. carinii than in patients who had these antibodies. A significantly higher percentage of those without PCP (57%) showed increasing titers of IgM antibodies to P. carinii in the second of paired samples taken about 6 months apart, compared with whose with PCP (9%; p = 0.05). All patients had high titers of antibodies to CMV and HSV and normal total concentrations of immunoglobulins. None of the patients responded in lymphocyte transformation to P. carinii, CMV, or HSV antigens. There is no obvious explanation to the selective lack of IgM antibodies to P. carinii in patients with PCP. Lack of IgM antibodies may be a marker for an immunodeficiency to P. carinii.

Serial CD4 and CD8 T-lymphocyte counts and associated mortality in an HIV-2-infected population in Guinea-Bissau

In an urban community in Guinea-Bissau, we followed a cohort of human immunodeficiency virus type 2 (HIV-2) seropositive individuals (N = 47) and seronegative controls (N = 82). T-lymphocyte subset determinations were done in 1988, 1990, and 1992. Serial determinations of CD4 percentages, CD8 percentages, and CD4/CD8 ratios for the same individual were stable for 31 seropositive and 51 seronegative individuals with repeated measurements. We found no significant differences in the changes during a 2- or 4-year period in CD4 percentages, CD8 percentages, absolute CD8 T-lymphocyte counts, CD4/CD8 ratio, white blood cell counts, lymphocyte percentages, and absolute lymphocyte counts for HIV-2-seropositive compared with HIV-2-seronegative individuals. Only absolute CD4 T-lymphocyte counts changed more for the HIV-2-seropositive than for HIV-2-seronegative individuals (p = 0.037). HIV-2-infected individuals who lived with an HIV-2-infected spouse had a lower CD4/CD8 ratio and had higher mortality than HIV-2 infected individuals who lived with an uninfected spouse. However, there were no significant differences in immunological and hematological values for the 8 HIV-2 seropositive individuals who died and the 39 who survived in the 8-year follow-up period. In conclusion, progression of immunosuppression in HIV-2 infection seems to be slower than in HIV-1 infection and may not be inevitable in all individuals.

Long-term survival in trial of medium-titre Edmonston-Zagreb measles vaccine in Guinea-Bissau: five-year follow-up.

A trial of protective efficacy which compared medium-titre Edmonston-Zagreb (EZ) measles vaccine (10(4.6) p.f.u.) from the age of 4 months with the standard Schwarz (SW) measles vaccine given from the age of 9 months was started in an urban community in Guinea-Bissau in 1985. Because trials of high-titre measles vaccine have found increased mortality among female recipients, we examined whether EZ medium-titre vaccine was associated with any long-term impact on mortality, suppression of T-cells, or growth. The mortality rate ratio over 5 years of follow-up was 1.12 for EZ children compared with children in the standard group (P = 0.63). Seventy-five percent of the children still residing in the area at 5 years of age took part in an immunological and anthropometric examination. There was no difference in T-cell subsets between the two groups. There was no difference in mid-upper-arm circumference, but EZ children were significantly shorter than the children in the standard group. In conclusion, medium-titre EZ was not associated with reduced survival or persistent immunosuppression.

HIV-2 Infection in Denmark

A collection of 3019 selected serum samples (ss), comprising 329 ss from intravenous drug abusers, 558 ss from homosexual men, 682 samples from persons attending a STD clinic, 100 ss from individuals of African origin, 300 ss from sexual contacts to Africans, 650 ss from Danish blood donors who resided in Africa greater than 2 years prior to donating the ss, and 400 ss with equivocal antibody reactions in an HIV-1 Western blot was tested for antibodies against HIV-2 by in-house HIV-2 ELISA and Western blot. Four ss were positive for antibodies against HIV-2. Three of the ss originated from West African men, the fourth belonged to the spouse of one of these men. Three of the samples presented with an uncharacteristic reaction in a HIV-1 Western blot. The study indicates that HIV-2 infection is not yet widespread in Denmark and that it remains closely related to West Africa.

Transmission of HIV-2 in a west African family household.

HIV-2 has been isolated from AIDS patients in Guinea-Bissau and the Cape Verde Islands. It is closely related to the simian T-lymphotropic virus III and to the human T-lymphotropic virus IV. It is more distantly related to HIV-1 which causes AIDS. HIV-1 is spread by sexual intercourse blood and transplacentally. HIV-2 is presumably spread the same way. The matriarch of a family in Guinea-Bissau died of slim disease and was found to be seropositive for HIV-2. Her husband was also seropositive but her 7 children and 2 grandchildren were negative indicating that sexual intercourse but not other close family contact transmits HIV-2.