Sophie Le Cœur

Human immunodeficiency virus–hepatitis C virus co-infection in pregnant women and perinatal transmission to infants in Thailand

OBJECTIVES The objectives of this study were to assess the prevalence and factors associated with hepatitis C virus (HCV) infection in human immunodeficiency virus (HIV)-infected and -uninfected Thai pregnant women and the rate of HCV transmission to their infants. PATIENTS AND METHODS Study subjects included 1435 HIV-infected pregnant women and their infants, enrolled in a perinatal HIV prevention trial, and a control group of 448 HIV-uninfected pregnant women. Women were screened for HCV antibodies with an enzyme immunoassay. Positive results were confirmed by recombinant immunoblot and HCV RNA quantification. Infants were tested for HCV antibodies at 18 months or for HCV RNA at between 6 weeks and 6 months. RESULTS Of the HIV-infected women, 2.9% were HCV-infected compared to 0.5% of HIV-uninfected women (p=0.001). Only history of intravenous drug use was associated with HCV infection in HIV-infected women. Ten percent of infants born to co-infected mothers acquired HCV. The risk of transmission was associated with a high maternal HCV RNA (p=0.012), but not with HIV-1 load or CD4 count. CONCLUSIONS Acquisition of HCV through intravenous drug use partially explains the higher rate of HCV infection in HIV-infected Thai women than in HIV-uninfected controls. Perinatal transmission occurred in 10% of infants of HIV-HCV-co-infected mothers and was associated with high maternal HCV RNA.

Laboratory and clinical predictors of disease progression following initiation of combination therapy in HIV-infected adults in Thailand

Background Data on determinants of long-term disease progression in HIV-infected patients on antiretroviral therapy (ART) are limited in low and middle-income settings. Methods Effects of current CD4 count, viral load and haemoglobin and diagnosis of AIDS-defining events (ADEs) after start of combination ART (cART) on death and new ADEs were assessed using Poisson regression, in patient aged ≥18 years within a multi-centre cohort in Thailand. Results Among 1,572 patients, median follow-up from cART initiation was 4.4 (IQR 3.6–6.3) years. The analysis of death was based on 60 events during 6,573 person-years; 30/50 (60%) deaths with underlying cause ascertained were attributable to infections. Analysis of new ADE included 192 events during 5,865 person-years; TB and Pneumocystis jiroveci pneumonia were the most commonly presented first new ADE (35% and 20% of cases, respectively). In multivariable analyses, low current CD4 count after starting cART was the strongest predictor of death and of new ADE. Even at CD4 above 200 cells/mm3, survival improved steadily with CD4, with mortality rare at ≥500 cells/mm3 (rate 1.1 per 1,000 person-years). Haemoglobin had a strong independent effect, while viral load was weakly predictive with poorer prognosis only observed at ≥100,000 copies/ml. Mortality risk increased following diagnosis of ADEs during cART. The decline in mortality rate with duration on cART (from 21.3 per 1,000 person-years within first 6 months to 4.7 per 1,000 person-years at ≥36 months) was accounted for by current CD4 count. Conclusions Patients with low CD4 count or haemoglobin require more intensive diagnostic and treatment of underlying causes. Maintaining CD4≥500 cells/mm3 minimizes mortality. However, patient monitoring could potentially be relaxed at high CD4 count if resources are limited. Optimal ART monitoring strategies in low-income settings remain a research priority. Better understanding of the aetiology of anaemia in patients on ART could guide prevention and treatment.

New-Onset Diabetes and Antiretroviral Treatments in HIV-Infected Adults in Thailand.

Background:Use of several antiretrovirals (ARVs) has been shown to be associated with a higher risk of diabetes in HIV-infected adults. We estimated the incidence of new-onset diabetes and assessed the association between individual ARVs and ARV combinations, and diabetes in a large cohort in Thailand. Methods:We selected all HIV-1–infected, nondiabetic, antiretroviral-naive adults enrolled in the Program for HIV Prevention and Treatment cohort (NCT00433030) between January 2000 and December 2011. Diabetes was defined as confirmed fasting plasma glucose ≥126 mg/dL or random plasma glucose ≥200 mg/dL. Incidence was the number of cases divided by the total number of person-years of follow-up. Association between ARVs and ARV combinations, and new-onset diabetes was assessed using Cox proportional hazards models. Results:Overall, 1594 HIV-infected patients (76% female) were included. Median age at antiretroviral therapy initiation was 32.5 years. The incidence rate of diabetes was 5.0 per 1000 person-years of follow-up (95% confidence interval: 3.8 to 6.6) (53 cases). In analyses adjusted for potential confounders, exposure to stavudine + didanosine [adjusted hazard ratio (aHR) = 3.9; P = 0.001] and cumulative exposure ≥1 year to zidovudine (aHR = 2.3 vs. no exposure; P = 0.009) were associated with a higher risk of diabetes. Conversely, cumulative exposure ≥1 year to tenofovir (aHR = 0.4 vs. no exposure; P = 0.02) and emtricitabine (aHR = 0.4 vs. no exposure; P = 0.03) were associated with a lower risk. Conclusions:The incidence of diabetes in this predominantly female, young, lean population was relatively low. Although stavudine and didanosine have now been phased out in most antiretroviral therapy programs, our analysis suggests a higher risk of diabetes with zidovudine, frequently prescribed today in resource-limited settings.

Treatment Failure in HIV-Infected Children on Second-line Protease Inhibitor–Based Antiretroviral Therapy

BACKGROUND Human immunodeficiency virus (HIV)-infected children failing second-line antiretroviral therapy (ART) have no access to third-line antiretroviral drugs in many resource-limited settings. It is important to identify risk factors for second-line regimen failure. METHODS HIV-infected children initiating protease inhibitor (PI)-containing second-line ART within the Program for HIV Prevention and Treatment observational cohort study in Thailand between 2002 and 2010 were included. Treatment failure was defined as confirmed HIV type 1 RNA load >400 copies/mL after at least 6 months on second-line regimen or death. Adherence was assessed by drug plasma levels and patient self-report. Cox proportional hazards regression analyses were used to identify risk factors for failure. RESULTS A total of 111 children started a PI-based second-line regimen, including 59 girls (53%). Median first-line ART duration was 1.9 years (interquartile range [IQR], 1.4-3.3 years), and median age at second-line initiation was 10.7 years (IQR, 6.3-13.4 years). Fifty-four children (49%) experienced virologic failure, and 2 (2%) died. The risk of treatment failure 24 months after second-line initiation was 41%. In multivariate analyses, failure was independently associated with exposure to first-line ART for >2 years (adjusted hazard ratio [aHR], 1.8; P = .03), age >13 years (aHR, 2.9; P < .001), body mass index-for-age z score < -2 standard deviations at second-line initiation (aHR, 2.8; P = .03), and undetectable drug levels within 6 months following second-line initiation (aHR, 4.5; P < .001). CONCLUSIONS Children with longer exposure to first-line ART, entry to adolescence, underweight, and/or undetectable drug levels were at higher risk of failing second-line ART and thus should be closely monitored.

Risk factors of preterm delivery in HIV-infected pregnant women receiving zidovudine for the prevention of perinatal HIV

Aim:  Several studies have shown that preterm delivery, a primary cause of perinatal mortality and morbidity, is more frequent in HIV‐positive women. This study aimed to determine factors associated with prematurity in HIV‐infected women and identify risks for which specific interventions could be targeted.

Incidence of Tuberculosis and Associated Mortality in a Cohort of Human Immunodeficiency Virus-Infected Children Initiating Antiretroviral Therapy

Abstract Background. We assessed the incidence of tuberculosis, risk factors for tuberculosis, and the contribution of tuberculosis on mortality in a large cohort of human immunodeficiency virus (HIV)-infected children <15 years of age initiating first-line antiretroviral therapy (ART) between 1999 and 2012 in Thailand, one of the 22 high tuberculosis burden countries. Methods. A physician reviewed and classified tuberculosis cases. Incidence was the number of children with incident tuberculosis, defined as a first or recurrent tuberculosis diagnosis >30 days after ART initiation, divided by the total person-years of follow-up (PYFU). Risk factors for incident tuberculosis were identified using Fine and Gray’s competing risks models, with death from other causes treated as a competing event, and risk factors for death were identified using Cox models. Results. At ART initiation, 670 children (55% female) had a median age of 6.4 years (interquartile range, 2.0–9.6), body mass index-for-age z-score −0.8 (−1.9 to 0.0), HIV ribonucleic acid viral load 5.1 log10 copies/mL (4.6–5.6), and CD4 9% (3–17). Median duration of follow-up was 7.7 years. Tuberculosis incidence was 7 per 1000 PYFU (95% confidence interval [CI], 5–11) and decreased with ART duration. Lower age-adjusted hemoglobin, hematocrit, and CD4 at ART initiation were associated with a higher risk of incident tuberculosis. Of the 30 incident tuberculosis cases, 9 died. Diagnosis of incident tuberculosis was associated with mortality (unadjusted hazard ratio = 10.2, 95% CI = 4.8–21.5, P < .001 and adjusted hazard ratio = 5.4, 95% CI = 2.5–11.7, P < .001). Conclusions. Incident tuberculosis was strongly associated with mortality. CD4 counts or hemoglobin or hematocrit levels may prompt clinicians to consider a possible tuberculosis infection.

Intergenerational relationships within families of HIV-infected adults under antiretroviral treatment in Northern Thailand.

ABSTRACT Thailand has been severely affected by AIDS/HIV. The epidemic has undermined the health of the population of working age, placing stress on intergenerational relations and threatening the social fabric. Older people in families affected by the disease, although not the main victims, have experienced major changes in relationships with their adult children and grandchildren. However, the availability of antiretrovirals has transformed HIV infection from a lethal to a chronic disease. Intergenerational relationships are analysed with data from a quantitative survey of HIV-infected adults currently receiving antiretroviral treatment in Northern Thailand. The introduction of antiretroviral treatment has eased the pressure on families. Where HIV-infected adults are more dependent on their older parents, it is because they are single and childless or single parents. While ageing parents remain a source of support for their adult children, the introduction of antiretroviral treatment has radically changed the prospects for HIV-infected adults and their regained health allows them to work, take care of their family and fulfil their filial duties as expected in Thai society. If Thailands original aim in introducing health policies in this area was to curtail the HIV epidemic, its positive impact on intergenerational relations is an additional benefit.