HIV-1 drug mutations in children from northern Tanzania.

OBJECTIVES: In resource-limited settings, it is a challenge to get quality clinical specimens due to poor infrastructure for their collection, transportation, processing and storage. Using dried blood spots (DBS) might be an alternative to plasma for HIV-1 drug resistance testing in this setting. The objectives of this study were to determine mutations associated with antiretroviral resistance among children <18 months old born to HIV-1-infected mothers enrolled in prevention of mother-to-child transmission services in northern Tanzania. PATIENTS AND METHODS: Kilimanjaro Christian Medical Center (KCMC) Clinical Laboratory is the zonal centre for early infant diagnosis using DBS in northern Tanzania. DBS were collected from January 2011 to December 2012. Mothers were kept on triple therapy and single-dose nevirapine before pregnancy and during labour, respectively. Infants were given single-dose nevirapine and most of them were breastfed. Genotypic resistance was determined in those with a viral load of >400 copies/mL. RESULTS: Genotypic resistance mutations were detected in 13 of 46 children (28%). HIV-1 genotypes were A1 (n = 27), C (n = 10), A/D (n = 4), D (n = 3) and CRF10_CD (n = 2). The median age was 12 weeks (IQR 6-28). The mean log10 viral load was 3.87 copies/mL (SD 0.995). All major mutations were detected in the reverse transcriptase gene and none in the protease gene region. The most frequent mutations were Y181C (n = 8) and K103N (n = 4), conferring resistance to non-nucleoside reverse transcriptase inhibitors. CONCLUSIONS: One-third of infants newly diagnosed with HIV in northern Tanzania harboured major drug resistance mutations to currently used antiretroviral regimens. These mutations were detected from DBS collected from the field and stored at room temperature. Surveillance of drug resistance among this population in resource-limited settings is warranted.

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

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.

Epidemiological study of Rift Valley fever virus in Kigoma, Tanzania.

Rift Valley fever virus (RVFV) is an acute, zoonotic viral disease caused by a Phlebovirus, which belongs to the Bunyaviridae family. Among livestock, outbreaks of the disease are economically devastating. They are often characterised by large, sweeping abortion storms and have significant mortality in adult livestock. The aim of the current study was to investigate RVFV infection in the Kigoma region, which is nestled under the hills of the western arm of the Great Rift Valley on the edge of Lake Tanganyika, Tanzania. A region-wide serosurvey was conducted on non-vaccinated small ruminants (sheep and goats, n = 411). Sera samples were tested for the presence of anti-RVFV antibodies and viral antigen, using commercial enzyme-linked immunosorbent assay and reverse transcriptase polymerase chain reaction, respectively. The overall past infections were detected in 22 of the 411 animals, 5.4% (Confidence Interval (CI) 95% = 3.5% - 8.1%). The Kigoma rural area recorded the higher seroprevalence of 12.0% (CI 95% = 7.3% - 18.3%; p < 0.0001), followed by Kibondo at 2.3% (CI 95% = 0.5% - 6.5%; p > 0.05) and the Kasulu district at 0.8% (CI 95% = 0.0% - 4.2%; p > 0.05). The prevalence was 12.5% and 4.7% for sheep and goats, respectively. Reverse transcriptase polymerase chain reaction results indicated that only eight samples were found to be positive (n = 63). This study has confirmed, for the first time, the presence of the RVFV in the Kigoma region four years after the 2007 epizootic in Tanzania. The study further suggests that the virus activity exists during the inter-epizootic period, even in regions with no history of RVFV.