Risk factors for HIV-2 infection in The Gambia

A serosurvey was carried out to assess the prevalence of HIV infection in The Gambia and the importance of possible risk factors. The overall prevalence of HIV-2 infection among the 4228 adults studied was 1.7% while that of HIV-1 was 0.1%. The prevalence of HIV-2 was similar in both sexes but higher among those greater than 25 years of age and those who lived in two small towns along a main transport route. Among men, multivariate analysis showed prevalence of HIV-2 infection was significantly greater among those in the more affluent occupations, those without a secondary education and those with a history of urethral discharge. Among women, infection was more frequent in divorcees and widows and those who had been married several times. The prevalence was also higher in individuals born in Guinea-Bissau and in an ethnic group which originated there.     

The impact of HIV-1 infection on child survival in the developing world

In this study we have used a mathematical projections model and HIV-1 seroprevalence data from samples of pregnant women to estimate infant HIV-1-infection prevalence and HIV-1-attributable mortality among children. This paper presents the results of samples from six developing country capitals and Martinique. The estimated impact of HIV-1 infection on overall infant mortality is low in regions where maternal HIV-1 seroprevalence is low and overall infant mortality is high, but substantial in locations where either maternal HIV-1 seroprevalence is high, or where maternal HIV-1 seroprevalence is moderate and overall infant mortality is low. The estimates for child (ages 1-4 years) and under-5 mortality suggest that the impact of HIV-1 infection on overall mortality in children may exceed the impact on infant mortality. The recent gains made in ensuring child survival are likely to be increasingly reversed in regions where HIV-1 infection is being transmitted in a substantial proportion of pregnancies and births.     

Survival of HIV-1 and HIV-2 perinatally infected children in The Gambia

BACKGROUND: The risk of mother-to-child transmission (MTCT) of HIV-2 is much lower than that of HIV-1, but the long-term prognosis of perinatally infected HIV-2 children is unknown. We re-visited children who were part of a large MTCT study in The Gambia (conducted during 1993-1997), in order to compare the long-term survival of children perinatally infected with HIV-2 with that of seronegative and of HIV-1 infected children. METHODS: Five to eight years' follow-up of a cohort of children born to HIV-negative, HIV-1 positive, and HIV-2 positive mothers. RESULTS: Seven hundred and seventy-four children were followed up for a median of 6.6 years. Of 17 perinatally HIV-1 infected children, three were still alive on 1 July 2001, two had been lost to follow-up, and 12 had died. The median survival was 2.5 years. Of eight HIV-2 infected children five were still alive, none were lost to follow-up and three had died. The mortality hazards ratio of both HIV-1 [9.9; 95% confidence interval (CI), 5.2-19], and of HIV-2 infected children (3.9; CI, 1.2-12) was significantly increased compared with children of seronegative mothers. The mortality hazards ratio of HIV uninfected children of HIV-1 or HIV-2 infected mothers was not significantly increased compared to that of children of seronegative mothers (P = 0.17 and P = 0.5 respectively). CONCLUSIONS: Children with perinatally acquired HIV-2 infection have a higher mortality than children of seronegative mothers. Guidelines for treatment of HIV-1 infected children should be used for treatment of HIV-2 infected children.     

Mortality of HIV-1, HIV-2 and HIV-1/HIV-2 dually infected patients in a clinic-based cohort in The Gambia

OBJECTIVE: To assess and compare the mortality rates of patients with HIV-1, HIV-2 or both infections (HIV-D) in the same population. DESIGN: Clinic-based cohort study. METHODS: HIV-seropositive patients aged 15 years and older who attended the Medical Research Council clinics in Fajara between May 1986 and September 1997 were recruited. Clinical assessment using the Karnofsky score, CDC cell staging, WHO staging, and CD4 cell counts was performed at baseline. Patients attended clinic every 3 months; if they did not attend, they were visited at home by field workers to ascertain survival status. No patient was on antiretroviral therapy during the study period. RESULTS: Data from 1519 HIV-positive adult patients were analysed. A total of 746 patients had HIV-1, 666 HIV-2, and 107 patients had HIV-D. A total of 828 patients (55%) died, and 161 (11%) were lost to follow-up. The median follow-up was 12 months (range 0-128). CD4 cell counts were available for 894 patients. Compared with HIV-1, the adjusted hazards ratio for mortality in the CD4 cell count category 500 cells/microl or greater was 0.50 for HIV-2 (95% CI 0.28-0.88) and 1.27 (95% CI 0.51-3.7) for HIV-D. Among those with CD4 cell counts less than 500 cells/microl the mortality rates in HIV-2 and HIV-D were similar to those in HIV-1. DISCUSSION: HIV-2-infected patients with CD4 cell counts of 500 cells/microl and greater had a significantly lower mortality rate than HIV-1-infected patients. HIV-2-infected patients with advanced disease had the same poor prognosis as patients with HIV-1. Dually infected patients had mortality rates similar to HIV-1.     

Retinal manifestations of HIV-1 and HIV-2 infections among hospital patients in The Gambia, West Africa

BACKGROUND: In developed countries, 50-75% of AIDS patients develop retinal complications and about 20-40% acquire cytomegalavirus (CMV) retinitis. We conducted a cross-sectional survey to determine prevalence of these in The Gambia where both HIV-1 and HIV-2 infection are present and the prevalence of HIV-1 is rising. METHOD: All patients attending hospital whose percentage CD4+ cells (CD4%) was below 14, the level associated typically with an AIDS diagnosis, and one half of those whose CD4% was 14 or above were asked to join the study. Fifty-six HIV-1, 52 HIV-2 and 12 dually infected patients were recruited. Photographs of the fundi were taken and interpreted independently. The findings were related to the patients' percentage CD4+ cells. RESULTS: The CD4% was < 14 in 40 patients and < 7 in 17 patients. Thirty-six patients were male. No cases of CMV retinitis were found. Four patients whose CD4% were 4, 5, 11 and 23 had cotton wool spots ranging in number from 1 to 14 for any one patient. The prevalence of cotton wool spots was 8% (95% CI, 0-16%) among patients with CD4% below 14 and 12% (95% CI, 0-27) among patients with CD4% below 7. One of the 4 patients had associated microaneurysm and blot haemorrhages typical of more advanced HIV microvasculopathy. CONCLUSION: CMV retinitis is less common in The Gambia than in developed countries. Non-infectious retinopathy may also be less common.     

Clinical and laboratory predictors of survival in Gambian patients with symptomatic HIV-1 or HIV-2 infection.

OBJECTIVES: To determine which clinical and immunological features of patients with symptomatic HIV-1 and HIV-2 infection best predict survival in The Gambia. METHODS: All patients presenting to two hospitals in The Gambia between January 1987 and June 1990 with symptoms or signs suggesting chronic HIV infection were tested for HIV-1 and HIV-2 antibodies. Eighteen HIV-1 and 31 HIV-2-infected patients were recruited to the study, investigated intensively on admission and followed up until the end of 1990. Presenting clinical features, such as Karnofsky score, diagnosis of AIDS according to World Health Organization Bangui or Centers for Disease Control criteria and number of associated infections, together with five immunological measurements, as well as type of HIV infection, were related to length of survival using proportional hazard models fitted to Kaplan-Meier plots of survival times. RESULTS: Karnofsky score and diagnosis of AIDS were the best clinical predictors of survival. Type of HIV infection or number of associated infections did not predict outcome. The most powerful laboratory predictors were log(e) serum neopterin level, CD4 cell count and log(e) serum beta 2-microglobulin (beta 2M) level. The estimated median survival times (90% confidence interval) of the HIV-1 and HIV-2-infected were six (4-11) and 13 (9-20) months, respectively. These survival times do not differ significantly. CONCLUSIONS: The Karnofsky score and measurements of serum neopterin or beta 2M, which are easier and cheaper to perform than CD4 counts, may prove to be useful guides to prognosis for HIV infection in Africa.     

Maternal plasma viral RNA levels determine marked differences in mother-to-child transmission rates of HIV-1 and HIV-2 in The Gambia. MRC/Gambia Government/University College London Medical School working group on mother-child transmission of HIV

OBJECTIVES: To determine the rates of, and risk factors for, mother-to-child transmission (MCT) of HIV-1 and HIV-2 infection in The Gambia. DESIGN: A blinded, prospective, community-based cohort study of 29.549 pregnant women attending the eight largest antenatal clinics in The Gambia. METHODS: Women were tested for HIV-1 and HIV-2 infection. Infected subjects and a group of HIV-seronegative women were followed with their babies until 18 months after delivery. Maternal CD4 cell count percentages were measured before and 18 months after delivery, and the antenatal plasma viral load was determined. Babies were tested for HIV by the polymerase chain reaction and/or serology at 2, 9 and 18 months of age. RESULTS: The study enrolled 144 women positive for HIV-1 and 294 for HIV-2 plus 565 seronegative pregnant women: the mean antenatal percentage CD4 cell counts of 96 HIV-1-positive, 223 HIV-2-positive and 125 HIV-seronegative mothers were 31% [95% confidence interval (CI) 28-33], 41% (95% CI 39-42) and 47% (95% CI 45-49), respectively. The geometric mean antenatal plasma viral load of 94 HIV-1-infected women was 15,100 copies x 10(3) ml (95% CI 10,400-19,000) which was much higher than that of 60 randomly selected HIV-2-infected women, which was 410 copies x 10(3) ml (95% CI 150-910) (P < 0.001). The estimated transmission rate of HIV-1 was 24.4% (95% CI 14.6-33.9) and that of HIV-2 was 4.0% (95% CI 1.9-7.4). Five of 17 HIV-1-positive and three of eight HIV-2-positive babies were infected after 2 months of age. Birth in the rainy season [odds ratio (OR) 2.9; 95% CI 1.2-7.2], a low postnatal CD4 cell percentage (OR for a 10% fall 2.4; 95% CI 1.1-5.1) and a high maternal plasma viral load (OR for a 10-fold increase 2.9; 95% CI 1.1-7.8) were risk factors for transmission that applied equally to both viruses. CONCLUSION: Low maternal HIV-2 RNA levels, which on average are 37-fold less than in HIV-1 infection, relate to the low MCT rate of HIV-2.     

Association between HIV-2 infection and genital ulcer diseases among male sexually transmitted disease patients in The Gambia.

OBJECTIVE: To investigate whether genital ulcer diseases are cofactors which enhance the transmission of HIV-2 in West Africa. DESIGN: A cross-sectional study of 435 men presenting with a sexually transmitted disease (STD). SETTING: The outpatient clinic of the Medical Research Council Laboratories, a primary care facility in Fajara, a suburb of Banjul, the capital city of The Gambia (West Africa). PATIENTS, PARTICIPANTS: Six hundred and twenty-four men presenting with a genital complaint, of whom 443 had an STD. Eight of the men with an STD were excluded from further analysis because they were HIV-1-infected (five patients) or had indeterminate Western blot patterns (three patients). The remaining 21 HIV-2-infected and 414 seronegative men constituted our study-group. MAIN OUTCOME MEASURES: Participants were questioned about previous STD and behavioural and demographic characteristics. A physical examination was performed and serum collected for measurement of antibodies against Haemophilus ducreyi and Treponema pallidum. RESULTS: HIV-2-infected men were more likely than HIV-seronegative participants to have previously had a genital ulcer [odds ratio (OR), 3.00; 95% confidence interval (Cl), 1.18-7.60] and to have antibodies against T. pallidum (OR, 5.95; 95% Cl, 2.10-16.91), or H. ducreyi (OR, 4.59; 95% Cl, 1.71-12.33). Circumcised patients with residual foreskin were more likely to be HIV-2 infected than patients with complete circumcision. HIV-2-seropositive patients were six times more likely to have generalized lymphadenopathy than their seronegative counterparts. CONCLUSIONS: Our data suggest that genital ulcerative diseases, such as syphilis and chancroid, are probably cofactors that increase the transmission of HIV-2 in West Africa, and that HIV-2 infection frequently results in generalized lymphadenopathy.     

HIV-1 Env蛋白与HIV-1感染

人免疫缺陷病毒Ⅰ型(HIV-1)是艾滋病的主要病原体,HIV-1 Env蛋白在病毒的感染、侵入和干扰机体免疫机能等方面发挥着重要作用,它可以干扰细胞正常的信号转导途径、导致合胞体的形成、引发细胞病变。HIV-1感染的细胞类型包括 CD_4~+辅助T细胞、单核巨噬细胞、树突状细胞、朗罕氏细胞、胎盘滋养层细胞、神经元细胞等。HIV-1感染引发的病理变化与免疫系统的变化密切相关,免疫系统的     

Discrimination of HIV-2 infection from HIV-1 infection by western blot and radioimmunoprecipitation analysis

Serum and plasma samples were collected from blood donors who were confirmed positive for antibodies to HIV-1 in the United States, and from blood donors and individuals in West Africa and Portugal who were positive for antibodies to HIV-1, HIV-2, or both. Western blots and sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) radioimmunoprecipitation assays (RIPA) utilizing native HIV-1 and HIV-2 proteins were performed on these specimens to determine the ability of these procedures to discriminate between HIV-1 and HIV-2 infections. Extensive serologic cross reactivity between HIV-1 and HIV-2 p24 was found in both populations. Antibody reactivity to the envelope protein gp120 was able to discriminate 20 of 20 (100%) U.S. specimens as HIV-1 infections. In specimens from West Africa and Portugal, Western blot and RIPA were in complete agreement on 33 of 42 samples (78.6%). Among these 33 specimens, 10 were found to be reactive for antibodies to HIV-1 only, 10 were reactive to HIV-2 only, and 13 were considered to be dually reactive, having antibodies reactive with both HIV-1 gp120 and HIV-2 gp120. Nine of the 42 specimens were discordant by Western blot and RIPA classification, being dually reactive by one procedure and reactive with only one viral gp120 by the other technique. Because of the serological cross reactivities between HIV-1 and HIV-2, in certain populations it is difficult to ascertain whether an individual is infected with HIV-1, HIV-2, a new viral type, or whether the individual is infected simultaneously with multiple viruses. More specific tests such as viral isolation or molecular probes may be necessary to distinguish between infections with these viruses in certain populations.     

Trends and interaction of HIV-1 and HIV-2 in Guinea-Bissau, west Africa: no protection of HIV-2 against HIV-1 infection.

OBJECTIVES: To study trends in the prevalence and incidence of HIV-1 and HIV-2 infections in Guinea-Bissau over the last 7 years, and to evaluate the protective effect of HIV-2 against HIV-1 infection. DESIGN: Prospective follow-up of a cohort of police officers in Guinea-Bissau, and sentinel surveillance of pregnant women in Bissau. METHODS: Participants in the police cohort were tested regularly for antibodies to HIV and Treponema pallidum, and information about sexual risk behaviour and a history of sexually transmitted diseases was obtained. Simultaneously, pregnant women at the maternity wards at the National Hospital in Bissau were screened annually for HIV antibodies. To evaluate changes in prevalence and incidence of HIV in the police cohort, the study period was divided into three time strata with 2-3 years in each stratum. For the evaluation of a protective effect of HIV-2 on subsequent HIV-1 infection, two multivariate Poisson regression models were constructed, adjusting for different selected confounding variables. RESULTS: Between 1990 and 1997, 2637 police officers were included in the cohort study, 90.7% of whom were male. The overall prevalence of HIV-1 was 0.9%, of HIV-2 it was 9.7% and of HIV-1 and HIV-2 dual reactivity it was 0.5%. For pregnant women the prevalence rates were 0.9, 5.5 and 0.2% for HIV-1, HIV-2 and dual reactivity respectively. The prevalence of HIV-1 increased significantly whereas the prevalence of HIV-2 declined significantly during the study period, among both police officers and pregnant women. The total incidence of HIV-1 and HIV-2 was 0.74 and 0.83 per 100 person-years respectively in the police cohort. The incidence of HIV-1 increased slightly from 0.62 to 0.78 per 100 person-years (not significant), whereas the incidence of HIV-2 declined significantly from 0.90 to 0.35 per 100 person-years over the study period. Seven police officers seroconverted from HIV-2 to dual reactivity (1.22 per 100 person-years). The adjusted incidence ratio of acquiring HIV-1 infection among HIV-2-positive subjects compared with HIV-negative subjects was 1.65 [95% confidence interval (CI), 0.73-3.74] and 1.98 (95% CI, 0.80-4.87), depending on the confounding variables included. CONCLUSIONS: Our study shows an increasing prevalence of HIV-1 and a decreasing prevalence of HIV-2 in Guinea-Bissau. The incidence of HIV-2 declined significantly whereas the incidence of HIV-1 was relatively stable over the study period. No protective effect of HIV-2 against subsequent HIV-1 infection was observed, instead HIV-2-positive subjects had a tendency towards higher risk of acquiring HIV-1 infection compared with seronegative subjects.     

A simple relationship between viral load and survival time in HIV-1 infection.

Despite important recent insights into the short-term dynamics of HIV-1 infection, our understanding of the long-term pathogenesis of AIDS remains unclear. Using an approach that places rapid progressors, typical progressors, and nonprogressors on a single clinical spectrum of disease progression, we quantitate the previously reported relationship between viral load and survival time. We introduce the concept of viral constant, present evidence that this quantity is conserved across patients, and explore the immunopathological implications of this finding. We conclude with a quantitative approach for assessing the benefits of a given regime of antiviral therapy.     

Lack of protection against HIV-1 infection among women with HIV-2 infection.

OBJECTIVE: To assess whether HIV-2 infection protects against HIV-1 infection by comparing the rate of HIV-1 seroconversion among HIV-negative and HIV-2-seropositive women followed in a cohort study in Abidjan, C?te d'Ivoire. DESIGN: Prospective cohort study METHODS: HIV seroconversion was assessed in 266 HIV-seronegative, 129 HIV-1-seropositive, and 127 HIV-2-seropositive women participating in a closed cohort study of mother-to-child transmission of HIV conducted during 1990-1994. Participants were seen every 6 months, and blood samples were obtained. All blood samples were screened for HIV antibodies by enzyme immunoassay (EIA) and confirmed by line immunoassay (LIA) and Western blot. Among women who were HIV-seronegative at enrolment, seroconversion was defined as new EIA-reactivity confirmed on LIA and Western blot. Among HIV-1- or HIV-2-seropositive women, seroconversion to dual reactivity was defined as new dual reactivity on the LIA that was confirmed by reactivity on both HIV-1- and HIV-2-monospecific EIA. RESULTS: Five HIV-seronegative women became HIV-1-seropositive [seroconversion rate, 1.1 per 100 person-years; 95% confidence interval (CI), 0.3-2.5), and none became HIV-2-seropositive. No HIV-1-seropositive women became HIV-1/2 dually reactive, whereas six HIV-2-seropositive women acquired HIV-1 seroreactivity and thus became HIV-1/2 dually reactive (seroconversion rate 2.9 per 100 person-years; 95% CI, 1.1-6.3). HIV-2-seropositive women were more likely to acquire HIV-1 seroreactivity than were HIV-seronegative women (rate ratio, 2.7; 95% CI, 0.7-11.2), but this difference was not statistically significant (P>0.15). CONCLUSION: HIV-2 infection does not appear to protect against HIV-1 infection.     

HIV-1感染中的白介素-2免疫治疗作用

抗反转录病毒治疗（ART）开始的时机越来越早,但总有免疫重建失败或者Ⅰ型艾滋病病毒（HIV-1）潜伏感染灶无法清除的情况,因此白介素-2（IL-2）目前被广泛研究用于辅助ART治疗、加强免疫重建或者活化潜伏感染的HIV-1。目前比较确定的是：（1）IL-2能延长CD4＋T细胞的半衰期,增加CD4＋T细胞的数量;（2）IL-2合并ART与单独使用ART相比,不能减少HIV-1相关的机会性感染或死亡,临床应用着重于活化HIV-1储存库细胞;（3）IL-2合并ART能有效增加HIV-1储存库细胞的消减速率,外周循环中HIV-1感染的处于静止状态的记忆T细胞数量下降,甚至检测不出来;（4）IL-2的临床应用趋向周期性使用和长期使用。