Siobhan O'Shea

Human herpesvirus 8: Seroepidemiology among women and detection in the genital tract of seropositive women

An indirect IFA to detect antibodies against latent nuclear antigens of human herpesvirus 8 (HHV-8) was used to determine the prevalence of HHV-8 antibodies in 169 women attending a sexually transmitted diseases clinic and a human immunodeficiency virus (HIV) clinic at a London hospital. Nested polymerase chain reaction was used to detect HHV-8 DNA in 93 blood samples and 89 cervical brush scrapes (CBS). Another 96 CBS from women attending a colposcopy clinic were also analyzed. The overall seroprevalence of HHV-8 was 18.3%. The seroprevalence was higher among women born in Africa (24.7%) than among women born elsewhere (11.5%; P=.06) and was independent of HIV serostatus. HHV-8 DNA was detected in 3 CBS and 6 peripheral blood samples from 11 HHV-8-seropositive women but not in CBS from 78 seronegative women, 96 women from the colposcopy clinic, or in blood samples from 82 seronegative women.

Maternal viral load, CD4 cell count and vertical transmission of HIV‐1

HIV load and CD4 cell numbers were measured among 95 HIV infected women during pregnancy in order to determine their value as prognostic markers for transmission of virus from mother to infant. Among the 94 live births, 13 children were infected with HIV, 69 were uninfected and 12 were of unknown infection status. HIV RNA levels, as measured by nucleic acid sequence based amplification, were significantly higher (P < 0.001) in women who transmitted virus than among those who did not transmit and maternal viral load was a stronger predictor of transmission than CD4 cell number. The predicted rate of transmission relative to maternal HIV RNA was 2% at 1,000 copies, 11% at 10,000 copies and 40% at 100,000 copies/ml. Little variation in viral load occurred during pregnancy and there was an association between viral load and prematurity, the mean gestation at delivery decreasing by 1.3 weeks for every 10‐fold increase in maternal HIV RNA (P = 0.007). This study demonstrates that a high level of maternal HIV RNA is a risk factor for transmission of virus to the infant and maternal viral load is of more value as a prognostic marker for transmission risk than CD4 cell number. High viral load is also associated with premature delivery. Maternal viral load is therefore a useful marker on which to base management decisions during pregnancy. J. Med. Virol. 54:113–117, 1998.

Ethnic differences in stage of presentation of adults newly diagnosed with HIV‐1 infection in south London

To establish whether there were ethnic differences in demographic characteristics, the stage at HIV diagnosis and reasons for and location of HIV testing between 1998 and 2000 in a large ethnically diverse HIV‐1‐infected clinic population in south London in the era of highly active antiretroviral therapy.

Comparison of human immunodeficiency virus type 1-specific inhibitory activities in saliva and other human mucosal fluids.

ABSTRACT Several human mucosal fluids are known to possess an innate ability to inhibit human immunodeficiency virus type 1 (HIV-1) infection and replication in vitro. This study compared the HIV-1 inhibitory activities of several mucosal fluids, whole, submandibular/sublingual (sm/sl), and parotid saliva, breast milk, colostrum, seminal plasma, and cervicovaginal secretions, from HIV-1-seronegative donors by using a 3-day microtiter infection assay. A wide range of HIV-1 inhibitory activity was exhibited in all mucosal fluids tested, with some donors exhibiting high levels of activity while others showed significantly lower levels. Colostrum, whole milk, and whole saliva possessed the highest levels of anti-HIV-1 activity, seminal fluid, cervicovaginal secretions, and sm/sl exhibited moderate levels, and parotid saliva consistently demonstrated the lowest levels of HIV-1 inhibition. Fast protein liquid chromatography gel filtration studies revealed the presence of at least three distinct peaks of inhibitory activity against HIV-1 in saliva and breast milk. Incubation of unfractionated and fractionated whole saliva with antibodies raised against human lactoferrin (hLf), secretory leukocyte protease inhibitor (SLPI), and, to a lesser extent, MG2 (high-molecular-weight mucinous glycoprotein) reduced the HIV-1 inhibitory activity significantly. The results suggest that hLf and SLPI are two key components responsible for HIV-1 inhibitory activity in different mucosal secretions. The variation in HIV inhibitory activity between the fluids and between individuals suggests that there may be major differences in susceptibility to HIV infection depending both on the individual and on the mucosal fluid involved.

The natural history and clinical significance of intermittent viraemia in patients with initial viral suppression to < 400 copies/ml.

ObjectivesTo determine the prevalence and prognostic significance of intermittent viraemia (IV) in patients who attained an undetectable viral load (VL) < 400 copies/ml within 6 months on highly active antiretroviral therapy (HAART). MethodsRetrospective analysis of viral load rebound ⩾ 400 copies/ml and CD4 cell counts rise for 765 patients followed for ⩾ 12 months following initial VL undetectability, comparing the 226 (29.5%) who maintained an undetectable VL for > 1 year from initiation of HAART and 122 (15.9%) who had one or more episodes of IV. Genotypic resistance was evaluated at the time of the first episode of IV ⩾ 2000 copies/ml. ResultsPatients with IV had a threefold higher rate of sustained virological rebound [hazards ratio (HR), 3.15; 95% confidence interval (CI), 1.72–5.77;P < 0.001). For patients with and without IV, the Kaplan–Meier estimates at 24 and 36 months after initiation of HAART were 19.3% (95% CI, 8.9–21.5) versus 7.7% (95% CI, 4.5–13.0) and 31.6% (95% CI, 21.8–44.2) versus 12.9% (95% CI, 7.5–21.5), respectively (P < 0.001). The median CD4 cell count rise at 18 and 24 months was significantly lower in those with IV than in those without: 138 [interquartile range (IQR), 58–221] versus 224 × 106 cells/l (IQR, 119–357) (P = 0.0001) and 200 (IQR, 89–294) versus 260 × 106 cells/l (IQR, 125–384) (P = 0.003), respectively. In a subgroup of 16 patients, genotypic resistance mutations were found in the reverse transcriptase gene for five (31%) and in the protease gene in one. A probable contributing factor/event was identified for most patients with IV, such as poor adherence (42.6%), intercurrent infection (26.2%) or drug interaction (6.8%). ConclusionsPatients with IV > 400 copies/ml are three times more likely to experience sustained viral rebound and to have an impaired CD4 cell rise relative to those who maintain undetectable VL. This supports the adoption of a more pro-active approach to treatment intensification and the need for caution with structured treatment interruptions.

Interpretation of rubella serology in pregnancy—pitfalls and problems

Clinical and laboratory expertise is essenrial for evaluating rubella specific IgM test results in pregnancy

Guidelines for the management of HIV infection in pregnant women and the prevention of mother-to-child transmission. British HIV Association

Aims of the guidelines These guidelines, drawn up by a multidisciplinary group of clinicians and lay workers active in the management of pregnant women infected with HIV, aim to give up‐to‐date information on interventions to reduce the risk of mother to child transmission of the virus. The evidence on the use of interventions to prevent mother to child transmission of HIV has been graded according to the strength of the data as per the definitions of the US Agency for Health Care Policy and Research [ 1 ]. Weighted evidence on the use of combination antiretroviral therapy (ART) for the treatment of HIV infection per se is presented in the BHIVA guidelines for adults [ 2,3 ]. The highest level evidence (i.e. randomised controlled trials (RCTs) or large, well conducted meta‐analyses) is only available for formula feeding, prelabour caesarean section and zidovudine monotherapy. The need to treat mothers for HIV infection has led to the widespread use of ART in pregnancy which in turn results in new questions such as how to deliver when the mother, on therapy, has no detectable plasma viraemia with the most sensitive assays. In addressing many common and/or difficult clinical scenarios in the absence of ‘best evidence’ the guidelines rely heavily on ‘expert opinion’.

Rubella vaccination: persistence of antibodies for up to 16 years.

Sera from 123 volunteers vaccinated six to 16 years previously with one of four rubella vaccines (Cendehill, RA27/3, HPV77-DE5, and To-336) were tested for rubella antibodies by single radial haemolysis and radioimmunoassay. By radioimmunoassay 110 (89.4%) of the vaccinees had antibody concentrations greater than the minimum immune titre (that is, greater than 15,000 IU/1), 11 (8.9%) were seropositive but had concentrations less than or equal to 15,000 IU/1, and two (1.6%) were seronegative. Eight (6.5%) were seronegative by single radial haemolysis, of whom five had received Cendehill vaccine. Six to eight years after vaccination subjects who had received Cendehill vaccine had the lowest geometric mean titre of antibody by radioimmunoassay while the subjects who had received HPV77-DE5 vaccine had the highest. Although antibody concentrations less than or equal to 15,000 IU/1 were not detected among subjects given RA27/3 vaccine six to eight years previously, such low levels were detected in two (15.4%) vaccinated 11-16 years previously. These results emphasise the importance of long-term surveillance programmes so that vaccination policies may be reviewed.

Persistence of specific IgM and low avidity specific IgG1 following primary rubella.

Persistence of specific IgM in sera following primary rubella infection was compared with the maturation of the specific IgG1 response. 206 sera, from 171 patients with primary rubella, taken 1 day to 2.5 years after onset of illness, were tested. Rubella-specific IgM was detected by M-antibody capture radioimmunoassay in 100% of sera taken 15-28 days after onset, but in only 9% taken 3-4 months after onset. However, using the diethylamine (DEA) shift value (DSV) method, low avidity specific IgG1 was detected in 91% sera taken at 3-4 months and at 5-7 months 21% of sera remained positive. Using an avidity index method, with urea in the wash buffer, none of the sera were positive for low avidity specific IgG1 beyond 3 months after onset. With DEA in the wash buffer, the number of sera positive rose to 38% at 3-4 months. Thus, the DSV method for detecting low avidity specific IgG1 is a useful additional test for confirming or refuting a diagnosis of primary rubella and is of particular value for assessing pregnant patients.

Evidence for horizontal and not vertical transmission of human herpesvirus 8 in children born to human immunodeficiency virus-infected mothers.

A survey of antibody responses to human herpesvirus 8 (HHV-8) was undertaken to examine the mode of transmission of this virus to children born to mothers with HIV. Methods. Serum samples from a cohort of 92 mother-infant pairs and a cross-sectional cohort of 100 children (median age, 4 years) were tested. In the cohort of mother-infant pairs, 14 infants were HIV-infected, 72 were not and the HIV status was unknown for 6. In the cohort of children 70 were HIV-infected and 30 were vertically exposed but uninfected. Serologic responses to two HHV-8 antigens, latency-associated nuclear antigen and the structural antigen encoded by open reading frame 65 were detected by immunofluorescent antibody test and enzyme-linked immunoassay. Results were confirmed by Western blot. Results. All HHV-8-seropositive mothers were African (17 of 92, 18.5%). Six of their infants were HHV-8-seronegative and 11 had at least 1 HHV-8-seropositive sample. One of the 11 infants tested only at birth had a lower antibody titer than the mother; the remaining 10 infants had decreasing titers up to 7 months of age and 6 became seronegative. No infants born to HHV-8-seronegative mothers had antibodies to the virus. The seroprevalence to HHV-8 was 6% in the cohort of children. All had African mothers and their median age was greater than that of the cohort (8.4 vs. 4.0 years). Five were coinfected with HIV. Conclusions. HHV-8 was not vertically transmitted by any of the HIV-coinfected mothers. Acquisition of antibody to HHV-8 occurred in older children, implying a horizontal route of transmission.