Annemiek de Ruiter

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.

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.

Steady-state lopinavir levels in third trimester of pregnancy

Stek and colleagues reported low lopinavir levels in the third trimester of pregnancy at standard dosing. Since their initial report in 2003, we have taken steady-state trough lopinavir levels in all pregnant women in the third trimester; the results of 26 women on a lopinavir/ritonavir regimen are reported. The median trough level was 3.66 μg/ml, range 0.25–9.97; the median HIV viral load was 49 copies/ml at delivery. All infants were HIV polymerase chain reaction negative at 3 months.

Pregnant women with HIV infection can expect healthy survival: three-year follow-up.

Objectives:To document postpartum disease-free survival of HIV-infected women taking antiretroviral therapy (ART) during pregnancy. Methods:Laboratory and clinical data were collected on all HIV-infected pregnant women delivering from 1998 to 2002 and followed up until September 2004 at 6 hospitals in London. Mothers were grouped according to receipt of zidovudine monotherapy (ZDVm), highly active antiretroviral therapy (HAART) given during and continued after pregnancy (cHAART), and short-term HAART given during pregnancy and discontinued on delivery (START). Results:Eight-five women took ZDVm, 155 took cHAART, and 71 took START. The mean follow-up for all mothers was 33 months, with a total of 847 person-years. At the first antenatal clinic (ANC) visit, 72% of women were in Centers for Disease Control and Prevention (CDC) stage A, 85% were treatment naive, and the ZDVm group had a median HIV viral load (VL) 10-fold less than those mothers who started HAART during pregnancy. At last follow-up, 1 patient had died and 6 (1.9%) had progressed to CDC stage C; 62% of all women, including a quarter of the ZDVm group, were receiving HAART for their own health; and 83% of all mothers had a VL <50 HIV RNA copies/mL of plasma regardless of whether they were on treatment or not. Conclusions:The median-term postpartum prognosis of HIV-infected pregnant women with access to HAART is good. Exposure to short-course ZDVm or START during pregnancy did not jeopardize their response to subsequent therapy.

Problems in the interpretation of HIV-1 viral load assays using commercial reagents.

During routine monitoring of human immunodeficiency virus (HIV) viral load, two problems arose. First, a number of patients, the majority being African, were found to have low viral loads by the Chiron branched‐chain DNA assay in conjunction with low CD4+ cell numbers. In order to determine whether this was due to failure of the branched‐chain DNA assay to detect non‐B subtypes of HIV, selected samples were subtyped and HIV RNA quantified by branched‐chain DNA, NASBA, and the Roche Monitor RT‐PCR assay. Twenty‐eight (97%) of 29 Africans were infected with a non‐B subtype of HIV and 15 (93.7%) of 16 non‐Africans with subtype B. Twenty‐three samples had a low viral load by branched‐chain DNA, which was confirmed by the NASBA and RT‐PCR assays. All three assays detected B and non‐B subtypes with similar efficiency; NASBA failed to detect HIV RNA in a small number of non‐B samples. Discrepancies between viral load and CD4+ cell numbers did not appear therefore to be related to subtype. Second, while quantification of HIV RNA was being conducted using version 2 of the branched‐chain DNA assay (lower detection limit 500 HIV RNA copies/ml) the manufacturers had developed a more sensitive assay and a comparative evaluation was therefore conducted. In approximately 30% of samples the viral load was up to 10 times higher with the more sensitive assay. These experiences emphasise the importance of close collaboration between the clinic and the laboratory. J. Med. Virol. 61:187–194, 2000.

Antenatal Atazanavir: A Retrospective Analysis of Pregnancies Exposed to Atazanavir

Introduction. There are few data regarding the tolerability, safety, or efficacy of antenatal atazanavir. We report our clinical experience of atazanavir use in pregnancy. Methods. A retrospective medical records review of atazanavir-exposed pregnancies in 12 London centres between 2004 and 2010. Results. There were 145 pregnancies in 135 women: 89 conceived whilst taking atazanavir-based combination antiretroviral therapy (cART), “preconception” atazanavir exposure; 27 started atazanavir-based cART as “first-line” during the pregnancy; and 29 “switched” to an atazanavir-based regimen from another cART regimen during pregnancy. Gastrointestinal intolerance requiring atazanavir cessation occurred in five pregnancies. Self-limiting, new-onset transaminitis was most common in first-line use, occurring in 11.0%. Atazanavir was commenced in five switch pregnancies in the presence of transaminitis, two of which discontinued atazanavir with persistent transaminitis. HIV-VL < 50 copies/mL was achieved in 89.3% preconception, 56.5% first-line, and 72.0% switch exposures. Singleton preterm delivery (<37 weeks) occurred in 11.7% preconception, 9.1% first-line, and 7.7% switch exposures. Four infants required phototherapy. There was one mother-to-child transmission in a poorly adherent woman. Conclusions. These data suggest that atazanavir is well tolerated and can be safely prescribed as a component of combination antiretroviral therapy in pregnancy.