Challenges in HIV Viral Suppression in Low- and Middle-Income Countries

Viral suppression rates of pediatric patients with HIV in low- and middle-income countries are well below target when compared with adult patients in low- and middle-income countries and pediatric patients in high-income countries, according to a systematic review published in Clinical Infectious Diseases.

Researchers from Amsterdam and the HIV Department of the World Health Organization (WHO) conducted a meta-analysis of randomized controlled trials, cohort studies, and cross-sectional studies focusing pediatric patients who started antiretroviral therapy (ART) from 2000-2005, 2006-2009, and 2010-present.

The meta-analysis search identified 72 studies reporting on a total of 51,347 children, focused on viral outcomes in children and adolescents age <18 years who were infected with HIV and began ART treatment while living in low- and middle-income countries. Study inclusion was determined by numerous variables, including country, study design, study period, percentage of female participants, and patients’ median age at first-line ART initiation, among others.

The researchers assessed viral suppression rates over 3 distinct time periods, corresponding to when discrete changes were made in WHO recommendations for pediatric HIV treatment and vertical transmission prophylaxis. During the early time period (2000-2005, n=30 studies), the WHO recommended treatment with a single drug to prevent mother-to-child transmission and a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based ART for all children.

In the intermediate time period (2006-2009, n=35 studies), patients were treated using an extended regiment of prophylactic antiretroviral drugs for mother and child, with no change in first-line ART recommendations. The current time period (2010-present, n=7 studies) was defined by the introduction of maternal triple therapy to prevent mother-to-child transmission, and protease inhibitor (PI)-based treatment for children <3 years of age.

Primary patient analysis was conducted by calculating the proportion of children with viral suppression; researchers divided the number of children with viral load (VL)<1000 cps/ml by the number of children who were undergoing treatment who had VL results at that time point. Additional intention-to-treat analyses to determine the viral suppression rate were conducted by dividing the number of children with VL<1000 cps/ml at 12 months by the number of children who had started first-line ART.

The investigators found that after 6 months of therapy with first-line ART, a pooled proportion of 62% of patients in the early group (95% confidence interval [CI], 55-69.3, total n=5448), 74.3% in the intermediate group (95% CI, 69.7-78.9, total n=12,665), and 80.3% of patients in the current group (95% CI, 70-90.6, total n=627) had viral suppression (P =.03).

After 12 months of therapy, viral suppression in the early group increased (64.7% [95% CI, 57.5-71.8, total n=5929), while rates in the intermediate and current group stayed the same and decreased, respectively (74.2% [95% CI, 70.2-78.2, total n=14,150] and 72.7% [95% CI, 62.6-82.8, total n=543], respectively; P =.187).

At 24 months, viral suppression rates were 75.7% (95% CI, 70.1-81.4, total n=2935) in the early group, 81.1% (95% CI, 95.8-86.5, total n=2831) in the intermediate group, and 76.6% (95% CI, 67.9-85.20, total n=496) in the current group (P =.759).

In intention-to-treat analyses, the researchers found a pooled proportion of 42.7% (95% CI, 33.7-51.7) in the early group, 45.7% (95% CI, 33.2-58.3) in the intermediate group, and 62.5% (95% CI, 53.3-72.6) in the current group had viral suppression after 12 months of first-line ART therapy (P =.114).

Using a threshold of VL<400 cps/ml to conduct a sensitivity analysis, the researchers found that 63.8% (95% CI, 56.3-71.3), 73.2% (95% CI, 69-77.3), and 72.7% (95% CI, 62.6-82.8) in the early, intermediate, and current groups, respectively, had viral suppression (P =.192).Rates were lower across all groups using a threshold of VL<50 cps/ml (P =.568).

“[In low- and middle-income countries], viral suppression rates were 60%-75% in most analyses and have only marginally improved since the beginning of the millennium,” the researchers wrote.

Additionally, the researchers note that pediatric outcomes are considerably poorer than those found in a meta-analysis of adults in similar low- and middle-income countries, and are considerably poorer than the ≥90% suppression rates in pediatric patients with HIV in high-income countries.

“To achieve the 90-90-90 targets by 2020, accelerated efforts are fundamental to improve HIV treatment in this vulnerable population,” the researchers concluded. “Research into long-term treatment outcomes is essential in this population of children who will need adequate treatment for the rest of their lives.”

Limitations

• Studies included in each time period may not reflect the guidelines of that time period, due to delayed implementation.
• Few studies reported separate viral suppression rates for PI and NNRTI treatment children.
• It was not possible for researchers to correct for relevant characteristics like age, clinical or immunological status, or level of treatment adherence.
• Because the researchers used a strict definition of viral suppression, all children with missing VL results were considered having viral failure; therefore, intention-to-treat analysis may underestimate the actual viral suppression rate.

Disclosures: The authors declare no competing interests.

Reference

Boerma RS, Boender TS, BussinkAP, et al. Suboptimal viral suppression rates among HIV-infected children in low- and middle-income countries: a meta-analysis. Clin Infect Dis. 2016. doi: 10.1093/cid/ciw645