Pregnancy in HIV‐infected teenagers in London

Objective

The aim of the study was to describe pregnancies in HIV‐infected teenagers.

Methods

A review of the case notes of HIV‐infected pregnant teenagers aged 13–19 years from 12 London hospitals was carried out for the period 2000–2007.

Results

There were 67 pregnancies in 58 young women, of whom one was known to have acquired HIV vertically. The overall mother‐to‐child transmission (MTCT) rate of HIV was 1.5% (one of 66). There were 66 live births. Median ages at HIV diagnosis and conception were 17 and 18 years, respectively. Sixty‐three per cent of women were diagnosed with HIV infection through routine antenatal screening. Eighty‐two per cent of pregnancies (41 of 50) were unplanned, with 65% of women (26 of 40) using no contraception. Forty‐three per cent of the women (20 of 46) had a past history of a sexually transmitted infection (STI). In 63 pregnancies, antiretroviral therapy was started post‐conception, with prevention of HIV MTCT the only indication in 81% of cases. Fifty‐eight per cent of those on highly active antiretroviral therapy (HAART) had an undetectable HIV viral load by delivery. Eighty‐seven per cent were uncomplicated pregnancies. Seventy‐one per cent delivered by Caesarean section and 21% (14 of 64) had a preterm delivery (<37 weeks). In the 12 months after delivery, 45% of women received contraceptive advice and 25% of women became pregnant again.

Conclusion

Obstetric and virological outcomes were favourable in this group of HIV‐infected young women. However, the majority of pregnancies were unplanned with poor documentation of contraception use and advice and low rates of STI screening. A quarter of women conceived again within 12 months of delivery. Effective measures to reduce STIs, unplanned pregnancies and onward HIV transmission in HIV‐infected teenagers are needed.     

Evolution of glomerular filtration rate in HIV‐infected,HIV–HBV‐coinfected and HBV‐infected patients receiving tenofovir disoproxil fumarate

We aimed to compare the evolution of estimated glomerular filtration rate (eGFR) in HIV‐, HIV–HBV‐ and HBV‐infected patients treated with tenofovir disoproxil fumarate (TDF). Three groups of patients receiving TDF > 12 months were recruited: 194 HIV‐infected patients, 85 HIV–HBV‐coinfected patients and 50 HBV‐infected patients. eGFR was estimated using the Modification of the Diet in Renal Disease (MDRD) equation. Multivariate regression models were constructed to estimate factors associated with eGFR decrease from baseline. A total of 329 patients were studied. Median follow‐up was 2.7 years. Median eGFR decrease was ?4.9 (?16.6 to +7.2) mL/min/1.73 m². After multivariate stepwise regression analysis, age (P = 0.0002), non‐African origin (P < 0.0001), baseline eGFR (P < 0.0001) and TDF duration (P = 0.02) were associated with eGFR decrease in the whole population, while hypertension, diabetes and type of infection were not. Age (P < 0.0001), non‐African origin (P = 0.0004), baseline eGFR (P < 0.0001) and TDF duration (P = 0.007) remained associated with eGFR decline in HIV and HIV–HBV‐infected patients, while other variables including HIV risk factor, CDC stage, CD4 and HIV‐RNA levels were not. Age (P = 0.03), non‐African origin (P = 0.004), baseline eGFR (P < 0.0001) and baseline HBV–DNA > 2000 IU/mL (P = 0.04) were associated with eGFR decline in HBV and HIV–HBV‐infected patients, while other variables including HBV risk factor and fibrosis stage were not. Estimated glomerular filtration rate decline under TDF therapy appears mainly associated with older age, non‐African origin, higher baseline eGFR and longer TDF administration but not with the type of viral infection. Regular follow‐up of renal function, especially tubular function is recommended during TDF therapy.     

Diagnosis of treponemal co‐infection in HIV‐infected West Africans

Objectives To evaluate the performance of two enzyme immunoassays (EIA), Murex and ICE, and the Determine TP point‐of‐care test (POCT) in diagnosing treponemal infection (syphilis or yaws) in patients attending a large HIV clinic in Ghana; to determine the prevalence of treponemal co‐infections; and to characterise demographic and clinical features of patients with infection. Methods Samples were tested with EIAs and rapid plasma reagin (RPR), then POCT and reference assays for Treponema pallidum to determine prevalence of active and past infection. Sensitivity and specificity of each assay were calculated and demographic and clinical characteristics of patients compared. Data were collected from case notes of patients retrospectively. Results Overall, 45/284 patient samples (14.8%, 95% CI, 11.1–19.4%) were Treponema pallidum particle agglutination (TPPA) positive, and of these, 27 (64.3%) were RPR positive and 4 (8.9%) were treponemal IgM positive. Both EIAs and Determine TP POCT showed high sensitivities and specificities for identifying infection although RPR was less reliable. Clinical features of syphilis or yaws were rarely identified in TPPA‐positive patients suggesting most had previous or late latent infection. Treatment of various intercurrent infections using short courses of antibiotics active against T. pallidum was common in the clinic. Conclusions A high proportion of this HIV‐infected cohort showed evidence of treponemal infection. Both EIAs as well as the POCT were practical and effective at diagnosing treponemal co‐infection in this setting. RPR alone was unreliable at identifying active treponemal co‐infection, however might be useful in some settings where treponemal‐specific assays are unaffordable.     

Lopinavir protein binding in HIV‐1‐infected pregnant women

Background

Pregnancy may alter protein binding (PB) of highly bound protease inhibitors due to changes in plasma concentrations of albumin and α‐1 acid glycoprotein (AAG). Small changes in PB can greatly impact the fraction of drug unbound (FU) exerting pharmacological effect. We report lopinavir (LPV) PB during third trimester (antepartum, AP) compared to ≥1.7 weeks postpartum (PP) to determine if FU changes compensate for reduced total concentrations reported previously.

Methods

P1026s enrolled women receiving LPV/ritonavir, soft gel capsules 400/100 mg or 533/133 mg twice daily. LPV FU, albumin and AAG were determined AP and PP.

Results

AP/PP samples were available from 29/25 women respectively with all but one woman receiving the same dose AP/PP. LPV FU was increased 18% AP vs. PP (mean 0.96±0.16% AP vs. 0.82±0.21% PP, P=0.001). Mean protein concentrations were reduced AP (AAG=477 mg/L; albumin=3.28 mg/dL) vs. PP (AAG=1007 mg/L; albumin=3.85 mg/dL) (P<0.0001 for each comparison). AAG concentration correlated with LPV binding. Total LPV concentration did not correlate with LPV FU AP or PP. However, higher LPV concentration PP was associated with reduced PB and higher FU after adjustment for AAG.

Conclusions

LPV FU was higher and AAG lower AP vs. PP. The 18% increase in LPV FU AP is smaller than the reduction in total LPV concentration reported previously and is not of sufficient magnitude to eliminate the need for an increased dose during pregnancy.

     

Lung function abnormalities in HIV‐infected adults and children

Despite the advent of antiretroviral therapy (ART), the human immunodeficiency virus (HIV) epidemic remains a global health crisis with a high burden of respiratory disease among infected persons. While the early complications of the epidemic were dominated by opportunistic infections, improved survival has led to the emergence of non‐infectious conditions that are associated with chronic respiratory symptoms and pulmonary disability. Obstructive ventilatory defects and reduced diffusing capacity are common findings in adults, and the association between HIV and chronic obstructive pulmonary disease is increasingly recognized. There is synergism between viral factors, opportunistic infections, conventional influences like tobacco smoke and biomass fuel exposure, and potentially, the immunological effects of ART on the development of HIV‐associated chronic obstructive lung disease. Pulmonary function data for HIV‐infected infants and children are scarce, but shows that bronchiectasis and obliterative bronchiolitis with severe airflow limitation are major problems, particularly in the developing world. However, studies from these regions are sorely lacking. There is thus a major unmet need to understand the influences of chronic HIV infection on the lung in both adults and children, and to devise strategies to manage and prevent these diseases in HIV‐infected individuals. It is important for clinicians working with HIV‐infected individuals to have an appreciation of their effects on measurements of lung function. This review therefore summarizes the lung function abnormalities described in HIV‐positive adults and children, with an emphasis on obstructive lung disease, and examines potential pathogenic links between HIV and the development of chronic pulmonary disability.     

Morbidity and mortality in ageing HIV‐infected haemophilia patients

Over 25 years of follow‐up is now available for HIV‐infected haemophilia patients. The aim of this study was to retrospectively asses the morbidity and mortality of HIV infection and the effects of HAART in these patients. Data on HIV infection, its treatment and all types of comorbidity were collected from medical records of all 60 HIV‐positive haemophilia patients who were treated at the Van Creveldkliniek since 1980 and compared with data from 152 HIV‐negative patients with severe haemophilia and the general age‐matched male population. AIDS developed in 27 patients (45%), while 31 patients died (52%). Death was solely or partially AIDS‐related in 71%. Development of AIDS and AIDS‐related deaths declined strongly after the introduction of HAART. Only one major ischaemic cardiovascular event occurred in our study population. Of the 27 patients who were still treated at our clinic in 2010, 25 (93%) were on HAART. They had more often hypertension and diabetes, but less often overweight and obesity and lower cholesterol levels than the general population. The occurrence of spontaneous intracranial bleeding was higher in HIV‐positive haemophilia patients on HAART than in HIV‐negative patients with severe haemophilia (16.6 vs. 1.2 per 1000 patient years). Since the introduction of HAART, the impact of HIV infection on morbidity and survival has decreased. The increased prevalences of hypertension and diabetes, however, warrant regular screening. HIV‐positive haemophilia patients on HAART appear to have an increased risk of spontaneous intracranial bleeding.     

Impact of gastrointestinal endoscopy on HIV‐infected children

Objective: To evaluate the role of gastrointestinal (GI) endoscopy in human immunodeficiency virus (HIV)‐infected children with GI problems. Methods: From 1998 to 2002, we retrospectively reviewed all cases of HIV‐infected children presenting with GI problems in which an upper or lower GI endoscopy was indicated. The initial diagnostic endoscopic examination and any repeat endoscopic session leading to a new diagnosis were used in the data analysis. Tissue biopsies were obtained from all abnormal lesions and representative sites of normal‐appearancing GI mucosa. Results: Fourteen patients (median age: 22.5 months) underwent 23 sessions of GI endoscopy, including 10 esophagogastroduodenoscopy, nine colonoscopy and four flexible sigmoidoscopy. Chronic diarrhea was the most common indication, followed by lower GI bleeding, abdominal/retrosternal pain, dysphagia/odynophagia, and upper GI bleeding. Gross endoscopic abnormalities were observed in 78.3%; whereas histological inflammation and opportunistic pathogens were identified in 87% and 43.5%, respectively. Cytomegalovirus was the most common identified pathogen. Abnormal gross findings were significantly associated with histological inflammation and identification of pathogens (P = 0.006 and 0.046, respectively). Specific changes in medical management were made in 50% of cases as a result of endoscopic investigation. Conclusion: If non‐invasive investigations for HIV‐infected children with GI symptoms fail to establish a diagnosis, gastrointestinal endoscopy should be performed and often yields a positive result leading to changes in medical management.