Late postnatal transmission of HIV-1 and associated factors

BACKGROUND: The present study was undertaken to determine the risk and timing of late postnatal transmission (LPT) of human immunodeficiency virus type 1 (HIV-1). METHODS: Breast-fed infants previously enrolled in 2 trials of antiretroviral prophylaxis were monitored in Malawi. Kaplan-Meier and proportional hazard models assessed cumulative incidence and association of factors with LPT. RESULTS: Overall, 98 infants were HIV infected, and 1158 were uninfected. The cumulative risk of LPT at age 24 months was 9.68% (95% confidence interval, 7.80%-11.56%). The interval hazards at 1.5-6, 6-12, 12-18, and 18-24 months were 1.22%, 4.05%, 3.48%, and 1.27%, respectively. CONCLUSIONS: The risk of LPT beyond 6 months is substantial. Weaning at 6 months could prevent >85% of LPT.     

Trypanosoma cruzi transmission in a captive primate unit, Rio de Janeiro, Brazil

A breeding in captivity program of neotropical primates for subsequent reintroduction in nature is in progress at the Primatology Center of Rio de Janeiro (CPRJ). Almost 200 animals of 20 species that include both wild captured animals and specimens born in captivity are maintained in CPRJ. Here, we examined 198 primates of CPRJ for infection with the protozoan parasite Trypanosoma cruzi. The animals included 18 species of eight genera. We also performed an "ad lib" search for triatomines that could be incriminated as putative transmitters of the protozoan in this scenario. Anti-T. cruzi antibodies were observed (by indirect immunofluorescence assay-IFA) in 40 monkeys (26.5%). Four Panstrongylus megistus were collected in the monkey's food storage room near the cages and in human dwellings in the proximity to CPRJ. T. cruzi were isolated from nine primates of two genera (Leontopithecus and Saguinus) and from two individuals of the vector P. megistus. The transmission inside the cages could be attested by the isolation of the T. cruzi from primates born in captivity. Multi-locus enzyme electrophoresis (MLEE) demonstrated that the two isolates from Saguinus bicolor bicolor displayed a zymodeme 1 profile in four out of five tested enzymes, while all isolates derived from Leontopithecus showed zymodeme 2 for four out of the five tested enzymes. Mini-exon gene analysis genotyped all isolates as T. cruzi II, which is associated with human disease in Brazil. A wild primate unit such as CPRJ, located inside the forest and near to human dwellings and with T. cruzi II infected animals, deserves a careful surveillance in order to prevent expansion of the infection.     

Users' and providers' perspectives on technological procedures for 'normal' childbirth in a public maternity hospital in Salvador, Brazil

OBJECTIVE: To reveal the effect of cultural practices on the way in which normal birth is conducted in a public hospital in Brazil. MATERIAL AND METHODS: This article about a public maternity hospital in Salvador, Brazil, compares the points of view of providers and users on four technological normal childbirth procedures: trichotomy, episiotomy, oxytocin infusion, and epidural analgesia. Fieldwork carried out from 2002 to 2003 combined qualitative and quantitative methods. RESULTS: Institutional practices make childbirth unnecessarily difficult for women. Nonetheless, most women accept the conditions because the medical procedures make sense according to their cultural understandings. Service providers support the use of such procedures, although doctors are aware that they contradict recommendations found in scientific medical literature. This article argues that from the perspective of both providers and users, the technological procedures are infused with a culturally specific set of meanings and values. CONCLUSIONS: Policymakers must address the cultural understandings of both users and health care professionals in order to improve maternal healthcare in public hospitals in Brazil.     

Co-infection with HTLV-1 is associated with a shorter survival time for HIV-1-infected patients in Bahia, Brazil

Co-infection with HTLV-1 reaches 20% among patients infected by HIV-1 in Bahia, Brazil. To evaluate its impact on survival, we conducted a retrospective, case-control study involving 198 patients (63 cases). Co-infection was associated with parenteral exposure (P = 0.0001) and female sex (P = 0.02). Co-infected patients had a shorter mean survival (1849 days) than controls (2430 days, P = 0.001), regardless of sex or baseline CD4 cell count. In Bahia, Brazil, co-infection with HIV-1 and HTLV-1 is associated with a shorter survival time.     

CC and CXC chemokines in breastmilk are associated with mother-to-child HIV-1 transmission

INTRODUCTION: CC and CXC chemokines may play a role in mother-to-child HIV-1 transmission by blocking HIV-1 binding to chemokine receptors and impeding viral entry into cells. METHODS: To define correlates of breastmilk chemokines and associations with infant HIV-1 acquisition, chemokines in breastmilk and infant HIV-1 infection risk were assessed in an observational, longitudinal cohort study. We measured MIP-1alpha, MIP-1beta, RANTES, and SDF-1 in month 1 breastmilk specimens from HIV-1-infected women in Nairobi and HIV-1 viral load was calculated in maternal plasma and breastmilk at delivery and 1 month postpartum. Infant infection status was determined at birth and months 1, 3, 6, 9, and 12. RESULTS: Among 281 breastfeeding women, 60 (21%) of their infants acquired HIV-1 during follow-up, 39 (65%) of whom became infected intrapartum or after birth. MIP-1alpha, MIP-1beta, RANTES, and SDF-1 were all positively correlated with breastmilk HIV-1 RNA (P<0.0005). Women with clinical mastitis had 50% higher MIP-1alpha and MIP-1beta levels (P<0.001 and P=0.006, respectively) and women with subclinical mastitis (breastmilk Na(+)/K(+)>1) had approximately 70% higher MIP-1alpha, MIP-1beta and RANTES (P<0.002 for all) compared to women without mastitis. Independent of breastmilk HIV-1, increased MIP-1beta and SDF-1 were associated with reduced risk of infant HIV-1 (RR=0.4; 95% CI 0.2-0.9; P=0.03 and RR=0.5; 95% CI=0.3-0.9; P=0.02, respectively) and increased RANTES was associated with higher transmission risk (RR=2.3; 95% CI 1.1- 5.3; P=0.04). CONCLUSIONS: These observations suggest a complex interplay between virus levels, breastmilk chemokines, and mother-to-child HIV-1 transmission and may provide insight into developing novel strategies to reduce infection across mucosal surfaces.     

HIV-1 coreceptor usage, transmission, and disease progression

HIV-1 coreceptor usage is believed to play a critical role in pathogenesis. To initiate infection, HIV-1 interacts with two cell surface receptors; CD4 is the primary receptor and the beta-chemokine receptors CCR5 and CXCR4 usually serve as secondary receptors. HIV-1 strains transmitted in vivo generally use CCR5. Viruses that use CCR5 (R5 viruses) appear to be associated with relatively stable infection. Years after chronic infection is established, CXCR4 utilizing strains emerge in approximately 50% of infected individuals. Viruses that use the coreceptor CXCR4 (X4 viruses) are associated with rapid CD4+ cell decline and disease progression. However, the mechanism by which X4 viruses are associated with accelerated disease progression has never been properly elucidated. For example, the association between X4 virus and acceleration of HIV-1 disease progression has been ascribed to the expanded spectrum of CXCR4+ precursor cells susceptible to infection by X4 strains. It has also been postulated that the decline of the host immune system associated with clinical AIDS may allow X4 viruses to evolve and replicate freely in late-stage infection. Discriminating between these and other alternatives is central to increasing our understanding of the fundamental pathogenic processes involved in HIV-1 infection. In this article, we critically review those studies published over the last few years that purport to examine the relationship between HIV-1 coreceptor usage, transmission, CD4+ T-cell depletion, and disease progression.     

Maternal-fetal DNA admixture is associated with intrapartum mother-to-child transmission of HIV-1 in Blantyre, Malawi

BACKGROUND: The mechanism of mother-to-child transmission (MTCT) of HIV-1 is not well described. METHODS: Of 328 HIV-infected mother-infant pairs, we identified 91 that had discordant angiotensin I-converting enzyme and glutathione S-transferase M1 alleles. Maternal alleles in cord blood were quantified with real-time polymerase chain reaction, as indicators of microtransfusions. RESULTS: HIV-1 infected infants had more maternal DNA in cord blood than their uninfected counterparts. Increased maternal DNA in cord blood was associated with preterm delivery, low birth weight, and maternal immunosuppression. CONCLUSION: Intrapartum MTCT was associated with placental microtransfusions. The associations among placental microtransfusion, in-utero MTCT, maternal immunosuppression, and poor birth outcome should be further investigated.     

HIV-1 transmission, by stage of infection

BACKGROUND: The epidemiological impact of public health interventions targeted at reducing transmission of human immunodeficiency virus type 1 (HIV-1) during early or late-stage infection depends on the contribution of these disease stages to transmission within a particular epidemic. METHODS: Transmission hazards and durations of periods of high infectivity during primary, asymptomatic, and late-stage infection were estimated for HIV-1-serodiscordant heterosexual couples in Rakai, Uganda, by use of a robust probabilistic framework. RESULTS: Primary infection and late-stage infection were estimated to be 26 and 7 times, respectively, more infectious than asymptomatic infection. High infectiousness during primary infection was estimated to last for approximately 3 months after seroconversion, whereas high infectiousness during late-stage infection was estimated to be concentrated between 19 months and 10 months before death. CONCLUSIONS: Primary and late-stage HIV-1 infection are more infectious than previously estimated, but for shorter periods. In a homogeneous population, the asymptomatic stage of infection will typically contribute more to the net transmission of HIV-1 over the lifetime of an infected individual, because of its longer duration. The dependence of the relative contribution of infectious stages on patterns of sexual behavior and the phase of epidemics is discussed.     

Severe and Norwegian scabies are strongly associated with retroviral (HIV-1/HTLV-1) infection in Bahia,Brazil

Severe scabies has been associated with HTLV infection. To evaluate the impact of HTLV-I/HIV-1 co-infection on the clinical presentation of scabies, we reviewed 91 cases of scabies in Bahia, Brazil, during a 3 year period. Infections by HIV-1 (50%), HTLV-I (32%), and both (20%) were highly prevalent. Crusted or severe scabies were strongly associated with HTLV-I and, to a lesser degree, with HIV-1 infection. Co-infected patients had a higher risk of death (P = 0.01). Severe forms of scabies were highly predictive of double retroviral infection.     

HIV-1 in placentas of untreated HIV-1-infected women in relation to viral transmission, infectious HIV-1 and RNA load in plasma

The presence of HIV in the placenta was analysed in relation to virological and immunological factors and vertical transmission of HIV in 39 pregnancies between 1989 and 1993 among 37 HIV-1-infected women without zidovudine prophylaxis. HIV-1 was detected in 12 of 37 (31%) placentas by immunohistochemistry and in 3 of 18 by PCR. Altogether 14/39 (36%) placentas bore evidence of HIV-1 infection, although there was no relation with the outcome of HIV infection in the child. Neither was there a relation between placental infection and either CD4 cell counts or HIV-1 RNA levels. However, HIV-1 was isolated from plasma in 20 of 39 (50%) pregnancies, which was inversely related to the presence of HIV in the placenta. When HIV-1 was identified in the placenta, HIV-1 was isolated from plasma in 3/14 (21%) pregnancies, vs 17/25 (68%) when it was not (p = 0.01), with a relative risk of having a placenta positive for HIV of 3.9 in pregnancies with a negative plasma HIV isolation. This inverse relation may point to differences in tropism between HIV-1 in placenta and plasma. The results show that the placental barrier prevents HIV transmission, irrespective of whether HIV enters the placenta or not.     

A polymorphism in PRF1 gene is associated with HIV-1 vertical transmission in Brazilian children

We investigated the possible association between PRF1 gene polymorphisms and HIV-1 vertical transmission in Brazilian children by analyzing PRF1 gene coding and untranslated regions in 173 perinatally infected children (HIV+), 51 exposed uninfected (HIV-), and 171 HIV-unexposed uninfected children. Seven single nucleotide polymorphisms were identified in our samples. The rs885822 C allele and CC genotype were significantly more frequent in HIV-negative than in HIV-positive patients and associated with a protective effect toward HIV vertical transmission.     

Socio-demographic and epidemiological characteristics associated with human immunodeficiency virus type I (HIV-1) infection in HIV-1-exposed but uninfected individuals, and in HIV-1-infected patients from a southern Brazilian population

The ability to control human immunodeficiency virus type 1 (HIV-1) infection and progression of the disease is regulated by host and viral factors. This cross-sectional study describes the socio-demographic and epidemiological characteristics associated with HIV-1 infection in 1,061 subjects attended in Londrina and region, south of Brazil: 136 healthy individuals (Group 1), 147 HIV-1-exposed but uninfected individuals (Group 2), 161 HIV-1-infected asymptomatic patients (Group 3), and 617 patients with AIDS (Group 4). Data were obtained by a standardized questionnaire and serological tests. The age of the individuals ranged from 15.1 to 79.5 years, 54.0% and 56.1% of the Groups 3 and 4 patients, respectively, were men. The major features of groups 2, 3, and 4 were a predominance of education level up to secondary school (55.8%, 60.2% and 62.4%, respectively), sexual route of exposure (88.4%, 87.0% and 82.0%, respectively), heterosexual behavior (91.8%, 75.2% and 83.7%, respectively), and previous sexually transmitted diseases (20.4%, 32.5%, and 38.1%, respectively). The patients with AIDS showed the highest rates of seropositivity for syphilis (25.6%), of anti-HCV (22.3%), and anti-HTLV I/II obtained by two serological screening tests (6.2% and 6.8%, respectively). The results documenting the predominant characteristics for HIV-1 infection among residents of Londrina and region, could be useful for the improvement of current HIV-1 prevention, monitoring and therapeutic programs targeted at this population.     

HIV-1 and hepatitis B transmission in Sudan

A seroepidemiologic survey was conducted among 773 male soldiers living in five urban locations in Sudan to study the prevalence of and risk factors for HIV-1 and hepatitis B transmission. Twenty-eight per cent of the study population were born and raised in southern Sudan, an area bordering Kenya, Zaire and Uganda, whilst 72% of the study subjects were from northern Sudan. Seventy-eight per cent of the study population had serologic evidence of past hepatitis B infection, and 13 soldiers were confirmed positive for HIV-1 antibody. All 13 HIV-positive soldiers had recently been deployed in southern Sudan. Multivariate analysis indicated an association between living in southern Sudan and both hepatitis B (odds ratio 8.2) and HIV-1 infection (odds ratio 14). Additionally, sexual relations with prostitutes (odds ratio 1.5) and medical injections for schistosomiasis (odds ratio 2.72) were independent predictors of hepatitis B markers in this military population. The findings of this study suggest that sexual promiscuity is a risk factor for hepatitis B transmission in Sudan. They also indicate one possible route for the spread of HIV-1 from central to northern Africa.