High levels of cervical HIV-1 RNA during early HIV-1 infection.

Few data are available on genital tract viral replication early after HIV-1 acquisition, when infectivity is high. We compared cervical HIV-1 RNA from 60 women with paired samples from within 90 days after HIV-1 acquisition and at viral setpoint (4-24 months). Cervical HIV-1 was higher in early compared with setpoint samples (mean 3.43 versus 2.85 log10 copies/swab, P < 0.001). After adjusting for HIV-1-plasma RNA, cervical HIV-1 RNA from 30 days or less after infection was increased by 0.45 log10 copies/swab (P = 0.006).

Higher set point plasma viral load and more-severe acute HIV type 1 (HIV-1) illness predict mortality among high-risk HIV-1-infected African women.

BACKGROUND: There is limited information on the natural history of human immunodeficiency virus type 1 (HIV-1) infection in Africa, especially from individuals with well-defined dates of infection. We used data from a prospective cohort study of female sex workers in Mombasa, Kenya, who were followed up monthly from before the date of HIV-1 infection. METHODS: Antiretroviral-naive women who had a well-defined date of HIV-1 infection were included in this analysis. The effects of set point plasma viral load (measured 4-24 months after infection), early CD4+ cell count, and symptoms of acute HIV-1 infection on mortality were assessed using Cox proportional hazards analysis. RESULTS: Among 218 women, the median duration of follow-up after HIV-1 infection was 4.6 years. Forty women died, and at 8.7 years (the time of the last death), the cumulative survival rate was 51% by Kaplan-Meier analysis. Higher set point viral load, lower early CD4+ cell count, and more-symptomatic acute HIV-1 illness each predicted death. In multivariate analysis, set point viral load (hazard ratio [HR], 2.28 per 1 log10 copies/mL increase; P=.001) and acute HIV-1 illness (HR, 1.14 per each additional symptom; P=.05) were independently associated with higher mortality. CONCLUSION: Among this group of African women, the survival rate was similar to that for HIV-1-infected individuals in industrialized nations before the introduction of combination antiretroviral therapy. Higher set point viral load and more-severe acute HIV-1 illness predicted faster progression to death. Early identification of individuals at risk for rapid disease progression may allow closer clinical monitoring, including timely initiation of antiretroviral treatment.

Hormonal contraception and risk of cervical infections among HIV-1-seropositive Kenyan women.

OBJECTIVE: To evaluate the relationship between hormonal contraceptive use and the acquisition of cervical sexually transmitted infections (STI) among HIV-1-infected women. DESIGN: A prospective cohort study of 242 commercial sex workers in Mombasa, Kenya, followed from the time of HIV-1 infection. METHODS: At monthly follow-up visits, sexual behavior and contraceptive use were recorded, and laboratory screening for STI was performed. Multivariate Andersen-Gill proportional hazards models were constructed to examine the association between the use of hormonal contraception and the occurrence of cervical STI. RESULTS: The median duration of follow-up after HIV-1 acquisition was 35 months, and 799 person-years of follow-up were accrued. After adjustment for demographic factors and sexual behavior, women using the injectable contraceptive depot medroxyprogesterone acetate were at increased risk of Chlamydia trachomatis infection [hazard ratio (HR) 3.1, 95% confidence interval (CI) 1.0-9.4, P = 0.05] and cervicitis (HR 1.6, 95% CI 1.0-2.3, P = 0.03) compared with women using no contraception. The use of oral contraceptive pills was associated with an increased risk of cervicitis (HR 2.3, 95% CI 1.4-3.8, P = 0.001). Hormonal contraception was not associated with an increased risk of infection with Neisseria gonorrhoeae. CONCLUSION: The use of hormonal contraception by HIV-1-infected women was associated with an increased risk of cervicitis and cervical chlamydia infection. HIV-1-seropositive women using hormonal contraception should be counseled about the importance of consistent condom use to prevent both STI and HIV-1 transmission.

Placental malaria and perinatal transmission of human immunodeficiency virus type 1.

Prevalence of placental malaria in human immunodeficiency virus (HIV) type 1-infected and -uninfected women and the effect of placental malaria on genital shedding and perinatal transmission of HIV-1 were examined. Genital samples for HIV-1 DNA RNA were collected during labor. Infants were tested for HIV-1 at 1 day and 6 weeks postpartum. Placental malaria was diagnosed by histopathological examination: 372 placentas of HIV-1-infected women and 277 of HIV-1-uninfected women were processed. A higher prevalence of placental malaria was seen in HIV-1-infected women. No association was found between placental malaria and either maternal virus load, genital HIV-1 DNA, or HIV-1 RNA. Placental malaria did not correlate with in utero or peripartal transmission of HIV-1.

Diversity of the human immunodeficiency virus type 1 (HIV-1) env sequence after vertical transmission in mother-child pairs infected with HIV-1 subtype A.

Although several virologic and immunologic factors associated with an increased risk of perinatal human immunodeficiency virus type 1 (HIV-1) transmission have been described, the mechanism of mother-to-child transmission is still unclear. More specifically, the question of whether selective pressures influence the transmission remains unanswered. The aim of this study was to assess the genetic diversity of the transmitted virus after in utero transmission and after peripartum transmission and to compare the viral heterogeneity in the child with the viral heterogeneity in the mother. To allow a very accurate characterization of the viral heterogeneity in a single sample, limiting-dilution sequencing of a 1016-bp fragment of the env gene was performed. Thirteen children were tested, including 6 with in utero infections and 7 with peripartum infections. Samples were taken the day after birth and at the ages of 6 and 14 weeks. A homogeneous virus population was seen in six (46.2%) infants, of whom two were infected in utero and four were infected peripartum. A more heterogeneous virus population was detected in seven infants (53.8%), four infected in utero and three infected peripartum. The phylogenetic trees of the mother-child pairs presented a whole range of different tree topologies and showed infection of the child by one or more maternal variants. In conclusion, after HIV-1 transmission from mother to child a heterogeneous virus population was detected in approximately one-half of the children examined. Heterogeneous virus populations were found after peripartum infection as well as after in utero infection. Phylogenetic tree topologies argue against selection processes as the major mechanism driving mother-to-child transmission but support the hypothesis that virus variability is mainly driven by the inoculum level and/or exposure time.

Placental inflammation and perinatal transmission of HIV-1.

The effect of placental membrane inflammation on mother-to-child transmission (MTCT) of HIV-1 is reported. Placentas from HIV-1-infected women were examined as part of a perinatal HIV-1 project in Mombasa, Kenya. Polymerase chain reaction analysis was used to test for HIV-1 in the infants at birth and at 6 weeks. The maternal HIV-1 seroprevalence was 13.3% (298 of 2,235). The overall rate of MTCT of HIV-1 was 25.4%; polymerase chain reaction analysis revealed that of the 201 infants 6.0% (12) were already HIV-1-positive at birth (intrauterine transmission) and 19.4% (39) were infected during the peripartum period or in early neonatal life (perinatal transmission). The prevalence of acute chorioamnionitis was 8.8%, that of deciduitis was 10.8%, and that of villitis was 1.6%. Acute chorioamnionitis was independently associated with peripartum HIV-1 transmission but not with in utero MTCT (17.9% vs. 6.7%, respectively; adjusted odds ratio, 3.9; 95% confidence interval, 1.2-12.5; p =.025). Other correlates of perinatal MTCT were presence of HIV in the genital tract and in the baby's oral cavity and a high maternal viral load in peripheral blood. The adjusted population attributable fraction of 12.8% (95% confidence interval, 1.5%-22.8%) indicated that approximately 3% of MTCT could be prevented if acute chorioamnionitis was eliminated. We suggest that further research on the role of antimicrobial treatment in the prevention of chorioamnionitis and the reduction of peripartum MTCT needs to be performed.