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.     

Vaccine protection against HIV-2 infection in cynomolgus monkeys

The aim of this study was to determine if protection against an infectious human immunodeficiency virus type 2 (HIV-2) challenge could be obtained in cynomolgus macaques by active immunization using whole killed virus vaccine. Four monkeys were immunized with killed HIV-2SBL-6669, two of them with five intramuscular (im) injections of viral preparation containing 100 or 300 micrograms protein emulsified in incomplete Freund's adjuvant (IFA) and the two remaining received four im injections of 25-50 micrograms viral protein in iscoms. Each of the four vaccinated cynomolgus monkeys, along with four unvaccinated controls, were challenged intravenously two weeks after the last booster with approximately 100 animal infectious doses (ID50) of live HIV-2SBL-6669. All four immunized monkeys developed antibodies to HIV-2 envelope and core proteins before challenge exposure to HIV-2, but only the two animals vaccinated with virus in IFA developed detectable neutralizing antibodies. The two monkeys immunized with killed virus in IFA have shown no evidence of infection nine months after challenge with live virus. When blood and lymph node cells from these animals were transfused into naive cynomolgus monkeys, the recipients remained free of infection. In contrast, virus was recovered repeatedly in all nonimmunized animals and in the two animals immunized with iscom-associated viral antigens, which had a low content of envelope gp125 antigen. The demonstration of vaccine-induced protection against HIV-2 in a nonhuman primate raises hope for effective immunization against HIV infections in humans as well.     

HIV-2 does not protect against HIV-1 infection in a rural community in Guinea-Bissau.

OBJECTIVE: To examine the putative protective effect of HIV-2 infection against subsequent HIV-1 infection. DESIGN: Retrospective analysis of data from two cross-sectional surveys in the same community. METHODS: Two surveys between 1989 and 1998 in a rural area in northwestern Guinea-Bissau provided data from residents aged 15-59 years. HIV testing was done in the first survey. In the second survey, tests were made for both HIV and syphilis, and data on sociodemographic factors and sexual behaviour, including commercial sex work, were gathered. Qualitative polymerase chain reaction amplification of HIV-1 and HIV-2 viral DNA was performed on serologically dually reactive samples. RESULTS: Of the 2276 eligible adult villagers initially tested, 60% (1360) provided a second sample. Of 110 HIV-2-infected subjects, 17 became additionally infected with HIV-1 [incidence rate (IR), 26.3/1000 person-years observation]. Of the 1250 HIV-seronegative subjects, 24 became infected with HIV-1 (IR, 2.8/1000 person-years observation). The incidence rate ratio (IRR), comparing the incidence rate in HIV-2-infected people with the rate in HIV-seronegative subjects, was > 1 in all three "risk groups": men, female commercial sex workers, and other women. The overall estimate of the IRR, adjusted for age group and risk group, was 3.24 (confidence interval, 1.5-7.1). CONCLUSIONS: There was no protective effect of HIV-2 in this population. HIV-2 cannot be regarded as a vaccine, but, instead, may be a risk factor for HIV-1 infection.     

Association of human papillomavirus infection and disease with magnitude of human immunodeficiency virus type 1 (HIV-1) RNA plasma level among women with HIV-1 infection

Ninety-three women with human immunodeficiency virus type 1 (HIV-1) infection were enrolled in a cross-sectional study to evaluate the relationship between plasma HIV-1 RNA levels and coincident cervical infection and disease caused by human papillomaviruses (HPVs). HIV-1 RNA plasma levels of >10,000 copies/mL were highly associated with the presence in cervical specimens of HPV DNA of oncogenic (high risk) virus genotypes (P=.006; relative risk, 2.57). In addition, similar HIV-1 RNA plasma levels were associated with abnormal Pap smears (P=.01; relative risk, 2.11). In this study, 81% of women with high-risk HPV cervical infection had abnormal Pap smears. Measurement of HIV-1 RNA plasma levels may help to identify a subgroup of HIV-1-infected women at increased risk for cervical HPV infection and disease.     

Rapid increase of both HIV-1 infection and syphilis among pregnant women in Nairobi, Kenya.

OBJECTIVE: To determine the prevalence of HIV-1 and syphilis antibodies in a population of pregnant women in Nairobi, Kenya, between 1989 and 1991. METHODS: As part of an ongoing prospective study on the effect of HIV-1 infection and sexually transmitted diseases, 4883 pregnant women were screened for HIV-1 and syphilis antibodies in one health-centre in Nairobi. RESULTS: HIV-1 seroprevalence increased from 6.5 to 13.0% (P < 0.001) and syphilis seroreactivity from 2.9 to 5.3% (P = 0.002), while there was no change in gonococcal infection rates. The most rapid increase in HIV-1 prevalence was observed in women aged less than 25 years. There was no evidence of demographic fluctuations in the population during this time, or of changes in sexual behaviour, except that fewer women enrolled in 1991 reported having more than one sex partner, compared with women enrolled in 1989 (39.1 versus 20.0%; P = 0.0001). HIV-1-seropositive women were more likely to be seroreactive for syphilis than HIV-1-seronegative mothers (7.7 versus 3.2%; odds ratio = 2.5; 95% confidence interval, 1.7-3.8; P < 0.001), but there was no difference between the two groups in terms of gonorrhoea prevalence. CONCLUSION: These data confirm an association between HIV-1 and syphilis infection, and indicate that both are spreading rapidly among women in Nairobi outside high-risk groups. Increased efforts to control both infections are urgently required.     

In vitro correlates of HIV-2-mediated HIV-1 protection

A prospective study of high-risk commercial sex workers in Senegal has shown that HIV-2 infection may reduce the risk of subsequent HIV-1 infection; these findings have been confirmed and extended, now with 13 years of observation. While exploring the biological mechanisms behind this natural protection, we found that a significant proportion of peripheral blood mononuclear cells obtained from HIV-2-infected subjects resisted in vitro challenge with CCR5-dependent HIV-1 viruses but not CXCR4-dependent viruses. High levels of beta-chemokines, the natural ligands of the CCR5 coreceptor, were correlated with low levels of viral replication, and resistance was abrogated by antibodies to beta-chemokines. Our results suggest that beta-chemokine-mediated resistance may be an important correlate of HIV protection against HIV-1 infection and relevant to HIV vaccine design.     

Predictors of incident tuberculosis among HIV-1-infected women in Tanzania.

SETTING: The development of tuberculosis (TB) in HIV-1-infected individuals is associated with accelerated HIV-1 disease progression. OBJECTIVE: To examine the predictors of incident TB in HIV-1-infected Tanzanian women. DESIGN: A prospective cohort of 1078 HIV-1-infected pregnant women was enrolled in a randomized clinical trial to examine the role of vitamin supplements in HIV-1 disease progression and fetal outcomes. RESULTS: Of 1008 women evaluated for TB, 88 (8.7%) developed TB. After controlling for age, education and hemoglobin concentration, in multivariate analysis, low CD4 cell count, elevated erythrocyte sedimentation rate (ESR), decreased mid-upper arm circumference, and high viremia were associated with an increased risk of TB. CD4 <200 vs. > or = 500 cells/mm3 was associated with a 4.44-fold increase in risk of TB (95%CI 2.10-9.40). Individuals with high viremia (> or = 50,000 copies/ml) had a 2.43-fold increase in risk of TB (95%CI 1.24-4.76). Elevated malarial parasite density was slightly associated with a 65% (95%CI 19-85) decreased risk of TB. CONCLUSIONS: The risk of developing TB was elevated among women with low CD4 cell counts, elevated ESR, coinfections with other pathogens, poor nutrition and high viremia. There is a slight inverse association between malarial infection and TB, possibly because treating malaria may reduce the risk of TB.     

HIV-1 infection among New York City inmates

A blinded seroprevalence survey for HIV-1 infection was conducted among individuals entering New York City (NYC) prisons in 1989. Data collected included age group, race/ethnicity, syphilis serologic results and self-admitted drug use. Remnant serum specimens were tested for HIV-1 antibody by enzyme-linked immunosorbent assay and confirmed by Western blot. Of 2236 inmates surveyed, 413 (18.5%) were HIV-1 positive. Rates varied by subgroup, and were higher for women than men (25.8 versus 16.1%; odds ratio 1.8; P less than 0.01), for drug users than inmates who denied drug use (25 versus 14%; odds ratio 2.3; P less than 0.01), for intravenous heroin users (43 versus 15% in drug users not using heroin), and for inmates with positive rapid plasma reagin test (RPR) results (34.5 versus 16.1% in RPR-negative inmates). Use of intravenous heroin was most strongly related, by logistic regression, to HIV-1 seropositivity. The results are among the highest found in US inmates, and suggest that there were 12,500 seropositive individuals incarcerated in 1989. This represents approximately 10% of the estimated number of seropositive individuals in NYC. The NYC Correctional System should be viewed as a front-line institution in the fight against AIDS through provision of HIV-related prevention services and clinical care, and drug treatment.     

Intrafamilial transmission of HIV-1 infection from individuals with unrecognized HIV-1 infection

OBJECTIVE: To describe the clinical, epidemiological and molecular evidence for transmission of HIV-1 infection from a person with unrecognized HIV infection to a family member in two unconnected families where the route of transmission could not be conclusively determined. DESIGN: Case studies, molecular analysis of viral strains and a clinical and laboratory investigation of risk factors for transmission. SETTING: State referral centres for HIV/AIDS in two Australian teaching hospitals. RESULTS: Previously unrecognized HIV-1 infection was diagnosed in two unconnected females following blood donation in different Australian cities. Initially, no source of infection was identified but subsequently HIV-1 infection was diagnosed in the sister of one case and the adult son of the other. Using nucleic acid-based methods, it was demonstrated that one index case and her sister were infected with highly homologous 'Russian-type' HIV-1 subtype A, and the other index case and her son were infected with highly homologous HIV-1 subtype E (CRF01_AE). Sexual history taking from the sister and the son of the respective index cases revealed prior sexual partners from geographical areas in which the corresponding subtypes are known to be prevalent. Extensive history taking, cross-validated by independent reviewers, found no evidence whatsoever that any form of sexual contact or known blood contact could explain the HIV-1 infection in the two index cases. However, there was evidence that some form of domestic contact involving unperceived blood transfer may have occurred. CONCLUSION: Intra-familial transmission of HIV-1 infection should be considered when a source of HIV-1 infection cannot be determined.     

Predictors of intrauterine and intrapartum transmission of HIV-1 among Tanzanian women.

OBJECTIVE: To examine predictors of vertical transmission of HIV-1 in Dar-es-Salaam, Tanzania. DESIGN: Observational design. METHODS: Consenting HIV-1-infected pregnant women (n = 1078) were enrolled in a trial to examine the role of vitamin supplements. Intrauterine HIV-1 infection (HIV-positive at birth); intrapartum and early breastfeeding transmission (HIV-positive at 6 weeks among those uninfected at birth) were defined using the PCR. RESULTS: Of 734 infants who had a specimen taken at birth, 62 were HIV positive [8.4%; 95% confidence interval (CI),6.4--10.5%], whereas 59 infants were positive among 367 infants who were uninfected at birth and were retested at 6 weeks (16.1%; 95%CI, 12.3--19.8%). In multivariate analyses, maternal CD4 cell count, viral load, and clinical stage were significant predictors of both definitions of transmission. Viral load of 50 000 copies/ml or more at delivery was associated with a 4.21-fold increase in risk of intrapartum and early breastfeeding transmission (95%CI, 1.59--11.13;P = 0.004). Babies who were HIV negative at birth and born before 34 weeks of gestation were 2.19 times more likely to become infected during intrapartum and early breastfeeding periods compared with those born after 37 weeks (95%CI, 1.19--4.04; P = 0.01). Gonorrhea at baseline was related to intrauterine transmission [multivariate risk ratio (RR), 5.50; 95%CI, 2.04--14.81; P < 0.001] but not intrapartum and early breastfeeding transmission. Signs of lower genital infections at or after enrollment were also associated with transmission. CONCLUSIONS: Reducing prematurity, rate of HIV disease progression, and maternal viral load at or after delivery could help to reduce vertical transmission. Treatment of sexually transmitted infections at onset of prenatal care, about 20 weeks on average, was inadequate for prevention of transmission. Whether sustained clearance of lower genital tract infections result in reduced transmission remains to be determined.     

Antiretroviral drug resistance, HIV-1 tropism, and HIV-1 subtype among men who have sex with men with recent HIV-1 infection

OBJECTIVE: Antiretroviral drug treatment may be complicated in individuals infected with antiretroviral drug-resistant or non-subtype B HIV-1 strains. HIV-1 tropism may also affect disease progression. We analyzed antiretroviral drug resistance, HIV-1 subtype, and HIV-1 tropism among 195 men who have sex with men from six major cities in the United States, using samples collected within 6 months of HIV-1 seroconversion (1999-2003). METHODS: HIV-1 genotyping was performed using the ViroSeq HIV-1 Genotyping System. HIV-1 tropism was determined using a commercial assay. HIV-1 subtyping was performed by phylogenetic analysis of pol region sequences. RESULTS: Thirty-one (15.9%) of the men had evidence of antiretroviral drug resistance. Seven (3.6%) men had multi-class resistance, including three (1.5%) with resistance to all three antiretroviral drug classes. We found no statistically significant association of antiretroviral drug resistance with demographic factors, sexual practices, self-reported sexually transmitted infections, use of recreational drugs, or use of antiretroviral drug post-exposure prophylaxis. All samples were HIV-1 subtype B. Four men had CXCR4-using HIV-1 strains. One man with a CXCR4-using strain also had antiretroviral drug resistance. CONCLUSIONS: Antiretroviral drug resistance is relatively common among recently infected men who have sex with men in the United States. CXCR4-using strains were detected in a small number of these infections, which were all subtype B HIV-1.     

Risk factors for Kaposi's sarcoma-associated herpesvirus infection among HIV-1-infected pregnant women in the USA

OBJECTIVES: We sought to identify risk factors for infection with the Kaposi's Sarcoma-associated herpesvirus (KSHV) among pregnant women and to examine a reported association of KSHV with injecting drug use (IDU) and hepatitis C virus (HCV) infection. DESIGN: Cross-sectional evaluation of questionnaire data and KSHV and HCV seroprevalence in the Women and Infants Transmission Study. METHODS: In sera collected from HIV-1-infected pregnant women (n = 887) and, at age 12 months, their offspring (n = 900) at six sites in the USA and Puerto Rico, KSHV and HCV antibodies were detected with sensitive and specific enzyme immunoassays. Risk of KSHV was estimated by the unadjusted and adjusted odds ratio (OR(adj)) and 95% confidence interval (CI). The geographic referent sites were Chicago and Boston. RESULTS: Forty-seven (5.3%) of the women and three (0.3%) of the infants were KSHV seropositive. In univariate and multivariate analyses, KSHV in the women was associated with enrollment in Puerto Rico, Houston or Brooklyn (OR(adj), 4.3; 95% CI, 1.8-10.4) or Manhattan (OR(adj), 9.8; 95% CI, 3.7-25.6); non-completion of high school (OR(adj), 1.8; 95% CI, 0.9-3.4); the number of sexually transmitted diseases (OR(adj), 1.4; 95% CI, 1.0-1.9 per disease); and especially with IDU and HCV infection (OR(adj), 3.5; 95% CI, 1.5-7.9). CONCLUSIONS: Transmission of KSHV by blood inoculation may be highly inefficient, but our data support the hypothesis that it does occur. Large formal studies to evaluate whether KSHV transmission occurs via transfusion are needed to inform decisions regarding screening volunteer blood donors to protect the blood supply.     

HIV-1 incidence among women of reproductive age in Malawi

The aim of this study was to determine HIV-1 incidence among women of reproductive age in Malawi. A prospective study design was followed. HIV-1 uninfected women were followed up for nine visits during a period of 12 months. At baseline, women received HIV-1 counselling and testing. At each visit, venous blood was collected for HIV-1 testing. Incidence rate for HIV-1 was estimated using person-years of follow up (PYFU). Risk factors for HIV acquisition were assessed using Cox proportional hazard models. A total of 842 HIV-1 negative women were enrolled in the study. Of these, 787 had subsequent HIV testing and 31 were found HIV-1 infected; an overall incidence rate of 4.51 (95% confidence interval: 2.96-6.06) per 100 PYFU was obtained. Young age, using hormonal injectable contraceptives and bacterial vaginosis were the main predictors of HIV acquisition. The incidence of HIV continues to be high among women in Malawi, and young women appear to be at higher risk.