Infants in southern Africa start antiretroviral therapy late with advanced disease

Three quarters of infants starting antiretroviral therapy (ART) across eleven clinics in southern Africa had severe HIV disease and 87.2% met the 2006 World Health Organization (WHO) definition of severe immunosuppression, according to a study presented at the 2014 Southern African HIV Clinicians Society conference in Cape Town, South Africa, last month.

There was a modest improvement in the proportion of infants who started treatment before the onset of severe immunosuppression or severe HIV-related illnesses after 2009, but the majority of infants starting treatment in 2012 had stage 3 or 4 HIV disease.

The study described the outcomes of infants starting ART at eleven clinics in Malawi, South Africa, Zambia and Zimbabwe. The study included data on 4945 infants who had not previously taken ART (treatment naive), aged less than 12 months, who started more than three antiretroviral drugs after 2003. Infants were followed up for a median time of 11.2 months (IQR: 2.8-20 months). The data were collected by sites contributing to the International Epidemiologic Database to Evaluate AIDS in Southern African (IeDEA-SA).

There is limited evidence regarding the outcomes for infants starting ART in routine care settings of southern Africa. Infants with HIV are a high-risk population as it is estimated that without ART provision, up to 30% of HIV-positive infants will die before reaching one year of age and 50% by two years of age. In 2010, WHO introduced infant ART guidelines which recommended that all children under the age of 24 months should be initiated on ART immediately after diagnosis with HIV.

The overall median age at ART initiation was 5.9 months with a median CD4 percentage of 18.5%. More than half (57.9%) of the infants had been exposed to prevention of mother-to-child transmission (PMTCT) measures.

Initiation of treatment after 2009 was associated with lower mortality, with an adjusted hazard ratio of 0.75 (95% CI: 0.59-0.94) and was the only predictor of virological suppression. There was a notable improvement from the start of 2010 both in baseline characteristics at ART initiation and the associated outcomes. The median age at ART initiation declined from 6.1 months to 5.4 months (p = 0.00), when comparing the 2004 to 2009 and the 2010 to 2012 cohorts. This correlated with an improvement in other baseline characteristics of the two cohorts, namely the proportion of those with WHO stage 3 or 4 disease was 81.2% compared to 63.4% (p = 0.00) and 89.2% of participants had severe immune suppression between 2004 and 2009 compared to 81.3% (p = 0.00) in the 2010 to 2012 cohort. The median CD4 percentage also rose from 18 to 20.7% (p = 0.00) between the two groups.

“This suggests that the introduction of the WHO 2010 guidelines for initiating pediatrics did lead to prompter ART initiation with improved outcomes 
beyond an improvement in baseline disease characteristics,” said Dr Mireille Porter, the presenter of the study.

Overall, the probability of virological suppression at six and twelve months was 21% and 41% respectively. Loss to follow-up (LTFU), defined as no visit for more than nine months prior to site database closure, was 29%.

Mortality was twice as high in infants with severe immunosuppression (aHR: 2.19; 95% CI: 1.44-3.35), 1.36 times higher in those with WHO stage 3 or 4 disease (aHR: 1.36; 95% CI: 1.04 -1.78) and anaemia and lower weight-for-age z-score were also associated with higher mortality.

According to the survival analysis, 39.4% of infants would be alive and in care at 36 months, 13.01% would have died, 24.48% transferred out, with a loss to follow-up of 23.23%.

“The proportion of infants initiating ART with baseline disease severity, the high probability of mortality and the high loss to follow-up is a concern. However, the majority of those remaining in care had good virological responses on ART,” said Dr Porter.

Gender differences and the effect of pregnancy on adolescent ART outcomes in South Africa

Pregnant adolescents initiated ART earlier and experienced reduced mortality on ART, but were at high risk of virological failure and loss to follow-up after starting ART, according to another study presented at the conference.

A total of 3175 treatment-naive adolescents, aged between 9 and 21, were included in a multicentre cohort study from across four South African provinces. Routine data were collected and analysed from 82 public ART facilities for adolescents who initiated ART between 2004 and 2011.

Adolescents have a high rate of HIV acquisition and adolescents receiving ART are at an increased risk for poor adherence, reduced virological suppression and virological failure. However, relatively few data comparing gender differences and the effects of pregnancy in adolescent ART outcomes in low-income settings are available.

Of the 3175 participants included in the study, 2127 (67%) were female, of whom 10.7% (n = 227) were pregnant. The median age at ART initiation was 11.6 years in boys, 15.5 years in non-pregnant girls and 18.9 years in pregnant girls (p = 0.0001).   

Baseline HIV disease characteristics were better in pregnant girls compared to non-pregnant girls and boys. The median CD4 was 147 cells/mm³ in boys and 143 cells/mm³ in non-pregnant girls compared to 205 cells/mm³ in pregnant girls (p = 0.0001). 60.1% of boys and 62.4% of non-pregnant girls had a WHO stage 3 or 4 illness compared to only 44.8% in pregnant girls (p = 0.0001).

There was no significant difference in the cumulative incidence of mortality after starting ART among the three groups, with an adjusted sub-hazard ratio of 1.03 (95%CI: 0.23-4.51, p = 0.96) for pregnant girls. However, pregnant girls had worse outcomes regarding virological failure and virological suppression than in other groups.

Pregnant girls were half as likely to achieve virological suppression at 24 months than non-pregnant girls and boys (aOR:0.58; 95%CI:0.39-0.86, p = 0.006). There was no significant difference in the likelihood of virological suppression at 24 months between non-pregnant girls and boys (aOR:0.92; 95%CI:0.57-1.48, p = 0.73).

Pregnant girls were almost five times as likely to reach confirmed virological failure (aHR:4.85; 95%CI:1.78-13.1, p = 0.002) compared to non-pregnant girls and boys. There was no significant difference in the cumulative probability of confirmed virological failure after starting ART of non-pregnant girls compared to boys (aHR:1.12; 95%CI:0.57-1.48, p = 0.73).

Pregnant adolescent girls were almost twice as likely to be lost to follow-up compared to boys and non-pregnant girls (aSHR:1.94; 95%CI: 1.03-3.65, p = 0.04).

“Programmes targeting a reduction in adolescent pregnancy, transformation of reproductive services to be more adolescent friendly, and increased ART adherence-support for pregnant adolescents in particular, may be important interventions to improve outcomes of adolescents on ART, as well as to potentially reduce vertical HIV transmission”, said Dr Geoffrey Fatti, who was presenting the study.