HIV This Week

Briand N, Mandelbrot L, Le Chenadec J, Tubiana R, Teglas JP, Faye A, Dollfus C, Rouzioux C, Blanche S, Warszawski J; for the ANRS French Perinatal Cohort. No relation between in-utero exposure to HAART and intrauterine growth retardation. AIDS . 2009;23(10):1235-43 

The use of highly active antiretroviral treatment during pregnancy is now standard care to prevent mother-to-child HIV transmission in developed countries. There is controversy about its impact on low birth weight. Briand and colleagues set out to evaluate the impact of antiretroviral therapy during the pregnancy on birth weight, length, and head circumference. The study was performed in uninfected infants born to HIV-1-infected mothers, enrolled from 1990 to 2006 in the Agence Nationale de Recherches sur le SIDA French Perinatal Cohort CO1. The authors excluded mothers who used illicit drugs during pregnancy or had no prenatal care before the third trimester, twins and stillbirths. They used Z-scores adjusted for gestational age and sex. In 8192 mother-infant pairs, the mean birth weight Z-scores increased between 1990 and 1997 and then remained stable until 2006. There was no significant relation between the type of antiretroviral therapy and the proportion of small for gestational age (birth weight Z-score </= -2SD), which was 4% overall. Infants exposed to highly active antiretroviral treatment compared with mono antiretroviral therapy had a lower mean birth weight Z-scores (difference -0.09, 95% confidence interval -0.15 to -0.02); however, there was no difference between highly active antiretroviral treatment exposure in 2005-2006 and monotherapy in 1999-2004, which corresponded to standard care during each period, respectively. Length or head circumference Z-scores were not associated with antiretroviral therapy exposure. Among pregnancies with highly active antiretroviral treatment, there was no relation between the duration and type of therapy and the anthropometric parameters. Those findings in a large cohort suggest that highly active antiretroviral treatment during pregnancy does not increase the incidence of infants who are small for gestational age.

Editors’ note: Z-scores are standard scores based on the normal distribution and in this case are French standards. In this study, uninfected infants were judged small for gestational age if their birth weight Z-score was lower than 2 standard deviations, corresponding to the third percentile adjusted for gestational age and sex. Since 2004, combination antiretroviral treatment has been recommended for all HIV-positive pregnant women in France and, in 2005-2006, 93% of women in the 90 centres of the cohort received it to prevent mother-to-child transmission. Encouragingly, increasing use of antiretroviral drugs during pregnancy in France over the past 15 years has not increased the incidence of small for gestational age infants, nor affected length or head circumference.

Smith K, Kuhn L, Coovadia A, Meyers T, Hu CC, Reitz C, Barry G, Strehlau R, Sherman G, Abrams EJ. Immune reconstitution inflammatory syndrome among HIV-infected South African infants initiating antiretroviral therapy. AIDS. 2009;23(9):1097-107.

Smith and colleagues set out to determine the incidence, clinical manifestations, and risk factors for immune reconstitution inflammatory syndrome (IRIS) in young children initiating highly active antiretroviral therapy. Using data from a prospective cohort of antiretroviral-naïve HIV-infected children less than 24 months of age enrolled in a treatment strategies trial in Johannesburg, South Africa. Among 169 HIV-infected children initiating antiretroviral therapy, April 2005 to November 2006, the records of 83 children suspected to have IRIS within 6 months of starting treatment were reviewed to determine whether they met criteria for IRIS. Seven were excluded due to incomplete follow-up. Pretreatment and post-treatment characteristics of children with and without IRIS were compared. Overall, 34/162 (21%) children developed IRIS at a median of 16 days (range 7-115 days) post-antiretroviral therapy initiation. Bacille Calmette-Guérin reaction was most common occurring in 24/34 (71%) children, primarily injection site lesions and/or ipsilateral axillary lymphadenitis with abscess. Other IRIS conditions (not mutually exclusive) included Mycobacterium tuberculosis (n = 12), cytomegalovirus pneumonia (n = 1), Streptococcus pneumonia sepsis (n = 1), and severe seborrheic dermatitis (n = 1). Children with IRIS were younger (median age 7 vs. 10 months, P = 0.007) with a lower CD4 cell percentage (median 13.9 vs. 19.2, P = 0.009) at antiretroviral treatment initiation than controls. After 24 weeks on antiretroviral treatment, 62% of IRIS cases vs. 28% of controls had HIV RNA more than 400 copies/ml (P = 0.001), odds ratio = 2.88 (95% confidence interval = 1.14-7.29) after adjusting for baseline factors. Infants and young children with advanced HIV disease initiating antiretroviral treatment are at high risk for developing IRIS, leading to additional morbidity and possibly impairing virologic response to antiretroviral treatment.

Editors’ note: All the children in this study had advanced HIV disease at the time of antiretroviral treatment initiation so it is possible that the incidence of immune reconstitution inflammatory syndrome (IRIS) would be much lower when infants are started on treatment as soon as they are diagnosed, as is currently recommended. The fact that the most common IRIS manifestation in this study (71% of children) was reaction to the tuberculosis vaccine BCG lends support to the WHO guidelines discouraging BCG for HIV-infected infants.

Hesseling AC, Johnson LF, Jaspan H, Cotton MF, Whitelaw A, Schaaf HS, Fine PEM, Eley BS, Marais BJ, Nuttall J, Beyersa N, Godfrey-Faussettg P. Disseminated bacille Calmette–Guérin disease in HIV-infected South African infants. Bull World Health Organ. 2009;87:505–511.

The authors set out to determine the population-based incidence of disseminated bacille Calmette–Guérin (BCG) disease in HIV-infected infants (aged less than 1 year) in a setting with a high burden of tuberculosis and HIV infection coupled with a well-functioning programme for the prevention of HIV infection in infants. The numerator, or number of new cases of disseminated BCG disease, was derived from multicentre surveillance data collected prospectively on infants with a confirmed HIV infection during 2004–2006. The denominator, or total number of HIV-infected infants who were BCG-vaccinated, was derived from population-based estimates of the number of live infants and from reported maternal HIV infection prevalence, vertical HIV transmission rates and BCG vaccination rates. The estimated incidences of disseminated BCG disease per 100 000 BCG-vaccinated, HIV-infected infants were as follows: 778 (95% confidence interval, CI: 361–1319) in 2004 (vertical HIV transmission rate: 10.4%); 1300 (95% CI: 587–2290) in 2005 (transmission rate: 6.1%); and 1013 (95% CI: 377–1895) in 2006 (transmission rate: 5.4%). The pooled incidence over the study period was 992 (95% CI: 567–1495) per 100 000. Multicentre surveillance data showed that the risk of disseminated BCG disease in HIV-infected infants is considerably higher than previously estimated, although likely to be under-estimated. There is an urgent need for data on the risk–benefit ratio of BCG vaccination in HIV-infected infants to inform decision-making in settings where HIV infection and tuberculosis burdens are high. Safe and effective tuberculosis prevention strategies are needed for HIV-infected infants.

Editors’ note: In light of the results of this three-year multicentre surveillance study in South Africa, WHO now recommends that BCG vaccination be delayed for all babies born to mothers with HIV infection until they are determined to not have HIV infection, even in high TB burden settings. This gives added impetus to UNAIDS’ call at the 2009 World Health Assembly for the elimination of mother-to-child transmission by 2015. Strengthened antenatal services, increased HIV testing uptake, contraceptive services for women living with HIV who are not planning a pregnancy, timely provision of antiretroviral prophylaxis, and infant feeding counselling are among the building blocks to achieve this goal.