HIV Resistance and Prevention of Mother-to-Child Transmission Regimen in HIV-Infected Infants in Northern Tanzania

Abstract

Prevention of mother-to-child transmission (PMTCT) guidelines recommend that all HIV-infected pregnant women receive antiretroviral therapy (Option B) and HIV-infected infants should initiate therapy with a protease inhibitor-based regimen; however, implementation of these guidelines has lagged in many resource-limited settings. Tanzania only recently implemented these guidelines with little country-specific data to inform whether HIV non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance was present among infected infants under the Option A guidelines. This study aimed to identify primary resistance mutations in HIV-infected infants and to identify risk of nevirapine (NVP) resistance based on maternal and infant NVP exposure. Infant dried blood spots (DBSs) were sent to the zonal reference laboratory at Kilimanjaro Christian Medical Centre Clinical Laboratory and underwent DNA polymerase chain reaction testing for HIV as standard of care. Using the clinical laboratory registry, HIV-positive DBS cards, stored at ambient temperature, were identified and sent for further viral load testing, nucleotide sequencing, and analysis. Clinical information was obtained from the PMTCT clinical sites and the National PMTCT registry for information regarding maternal and infant demographics and PMTCT treatment regimen. Results demonstrated that infants exposed to NVP were more likely to have high level resistance mutations (HLRMs) to NVP than those infants not exposed to NVP (p = .002). The most common HLRMs to NVP were K103 N, Y181C, and Y188 L. HIV subtype A was most common, followed by subtype C. Approximately one-third of HIV-infected infants had documented referral to HIV care. This study demonstrated the ongoing need to scale up and strengthen points along the PMTCT continuum and supported the recommendation for all HIV-infected infants to initiate a lopinavir/ritonavir-based antiretroviral therapy regimen.

Achievements and Challenges in the Prevention of Mother-to-Child Transmission of HIV—A Retrospective Cohort Study from a Rural Hospital in Northern Tanzania

“…Only five of nine HIV-infected children (55.6%) in our study were referred to the CTC, and a previous study from Tanzania found that a mere one third of children with an early positive PCR test had documented referral to therapy [ 20 ]. The clinical course of HIV infection is often aggressive in children not offered ART.…”

“…Additionally, HIV resistance may threaten the success of PMTCT activities. Other studies have demonstrated that resistance to non-nucleoside reverse transcriptase inhibitors such as nevirapine is common in HIV -infected infants in Tanzania [ 20 , 21 ]. Therefore, monitoring of resistance to all classes of ARVs is required both on population and individual level in order to prevent MTCT.…”

Evaluation of archived drug resistance mutations in HIV‐1 DNA among vertically infected adolescents under antiretroviral treatment in Cameroon: Findings during the COVID‐19 pandemic

“…The most prevalent archived NNRTI mutation was K103N, predominant among viraemic adolescents. By contrast, Dow et al also found the K103N mutation to be more prevalent among virally suppressed ALHIV in Tanzania, with no distinction between viraemic and non‐viraemic [41]. Nonetheless, the higher presence of this mutation could be explained by the important exposure of these adolescents to nevirapine‐based ART after exposition during delivery [39].…”

Resource and infrastructure challenges on the RESIST-2 Trial: an implementation study of drug resistance genotype-based algorithmic ART switches in HIV-2-infected adults in Senegal

“…Several studies have used DBS-based testing to perform population-level assessments of the frequency of drug resistance in HIV-1 [ 23 – 25 ] or to analyze ART outcomes in HIV-1-infected patients [ 26 – 28 ]. However, to our knowledge, no studies have attempted to use DBS testing to prospectively inform treatment decisions for HIV-1 or HIV-2-infected individuals in a programmatic setting.…”