Prevalence of drug resistant HIV-Infections in nontreated Patients at the Lighthouse Hospital in Lilongwe, Malawi

Im Jahr 2015 wurde Plasmaproben von 161 HIV-positive Menschen auf HIV-Drug-Resistance untersucht. Die Patienten waren therapienaiv und wurde am Lighthouse-Hospital in Lilongwe, die Hauptstadt Malawis behandelt. Es zeigte sich eine HIVDR von insgesamt 17% welche aus mehreren Gesichtspunkte dargestellt worden sind, um zu zeigen ob 20105 in Malawi eingesetzte first-line Therapieregime eine gute Wirksamkeit zeigte.The thesis investigates the prevalence of drug resistant HIV-Infections in non-treated patients in 2015 at the Lighthouse Hospital in Lilongwe, the capital city of Malawi. 161 plasma samples have been collected and analyzed to look into the rates of HIVDR in the collective and examine how this can be related to national HIVDR levels, the WHO guidelines and put in perspective how the results may have had an impact in the evolution of ART in Africa, but also worldwide. Firstly HIV-RNA was isolated from the plasma samples. The HIV-RNA was then transcribed in DNA and afterwards amplified to collect multiple copies of the gag-pol area of the genome, which contains the genetic information for the HIV Reverse Transcriptase (RT) and Protease (P). The experiments concluded with sequencing the gag-pol area of the HIV-DNA and entering the sequences in the Databank of the Stanford University to establish the HIV-Subtype and detect HIVDR and its severity in the drug classes of Protease Inhibitors (PI) as well as Nucleoside Reverse Transcriptase Inhibitors (NRTI) and Non-nucleoside Reverse Transcriptase Inhibitors (NNRTI). HIV RNA was isolated in 100 samples and were successfully sequenced. An overall rate of 17% mutations associated with HIVDR was found. Some samples showed multiple mutations, 13 % in the class of NNRTI, 8 in the class of PI and 1% in the class of NRTI. A further examination showed the severity of the HIVDR mutations in these drug classes and some particular substances that were recommended as first-line therapy regime by national guidelines in Malawi. In 2015 TLE (ART consisting of Tenofovir and Lamivudine, two NRTIs as well as Efavirenz, an NNRTI) was recommended as first-line regime by nationals guidelines. 13% high- and intermediate-level HIVDR was found for Efavirenz. There was a significant higher probability for a Patient in the group to show an HIVDR for Efavirenz in comparison to other substances of the first-line drug regime. The TLE Regime which has been used in 2015 at the Lighthouse Hospital in Lilongwe had an overall good effect in the therapy of HIV-Infections. Still the results show that 12% of the patients may suffer from poor response due to HIVDR. In these cases a transmitted HIVDR maybe assumed in these non treated patients. These may seem alarming, but it is not sure if the patients were forward about their therapy, or if maybe drug sharing or self therapy with drugs from black market could have been an issue. In conclusion these high rates of HIVDR in the drug class of NNRTI was also seen world wide in other examinations. As a response, the WHO updated Guidelines recommend since 2018 other ART regimes consisting of a combination with Integrase Inhibitors (INI) when available. Studies show that INI are less susceptible to develop an HIVDR due to a high resistance barrier. Still this medication is expensive an not always available in poor countries. The annual reports of UNAIDS give a positive development in the fight to contain HIV world-wide