Dolutegravir resistance in sub-Saharan Africa: should resource-limited settings be concerned for future treatment?

In sub-Saharan Africa (SSA) the burden of non-nucleoside reverse transcriptase inhibitor (NNRTI) HIV drug resistance (HIVDR) has been high over the years. Therefore, in 2018 the World Health Organization (WHO) recommended a regimen based on a integrase strand transfer inhibitor (INSTI), dolutegravir, as the default first-line antiretroviral therapy (ART) in countries in SSA. The scale-up of DTG-based regimens in SSA has gained significant momentum since 2018 and has continued to expand across multiple countries in recent years. However, whether or not the DTG robustness experienced in the developed world will also be achieved in SSA settings is still an important question. Evidence generated from in vitro and in vivo studies suggests that the emergence of DTG HIVDR is HIV-1 subtype dependent. These findings demonstrate that the extensive HIV-1 diversity in SSA can influence DTG effectiveness and the emergence of drug resistance. In addition, the programmatic approach to the transition to DTG adopted by many countries in the SSA region potentially exposes individuals to DTG functional monotherapy, which is associated with the emergence of DTG resistance. In this mini review, we describe the current trends of the effectiveness of DTG as reflected by viral suppression and DTG resistance. Furthermore, we explore how HIV-1 diversity and the programmatic approach in SSA could shape DTG effectiveness and DTG HIVDR in the region

タンザニアで流行する薬剤耐性HIV-1変異に関する研究

熊本大

Hypertension and traditional risk factors for cardiovascular diseases among treatment naïve HIV- infected adults initiating antiretroviral therapy in Urban Tanzania

Abstract Background Cardiovascular diseases (CVDs) have become an important cause of ill health and death among people living with HIV and/or AIDS (PLHIV) in the antiretroviral therapy (ART) era. There is scarce data on the burden of hypertension (HTN) and risk factors for CVDs among PLHIV in developing countries, including Tanzania during the ART era. Objective(s) To determine the prevalence of HTN and risk factors for CVDs among ART naïve PLHIV initiating ART. Methods We analysed baseline data of 430 clinical trial participants on the effect of low-dose aspirin on HIV disease progression among HIV-infected individuals initiating ART. HTN was the outcome CVD. Traditional risk factors for CVDs studied were age, alcohol consumption, cigarette smoking, individual and family history of CVDs, diabetes mellitus (DM), obesity/overweight, and dyslipidaemia. A generalized linear model (robust Poisson regression) was used to determine the predictors for HTN. Results The median (IQR) age was 37 (28, 45) years. Females were the majority contributing 64.9% of all participants. The prevalence of HTN was 24.8%. The most prevalent risk factors for CVDs were dyslipidaemia (88.3%), alcohol consumption (49.3%), and overweight or obesity (29.1%). Being overweight or obese predicted the occurrence of HTN, aPR 1.60 (95% CI 1.16–2.21) while WHO HIV clinical stage 3 was protective against HTN, aPR 0.42(95% CI 0.18–0.97). Conclusion The prevalence of HTN and traditional risk factors for CVDs in the treatment naïve PLHIV initiating ART are significant. Identifying these risk factors and managing them at the time of ART initiation may lower future CVDs among PLHIV

Seroprevalence of Human Herpesvirus Infections in Newly Diagnosed HIV-Infected Key Populations in Dar es Salaam, Tanzania

Background. Human herpesvirus (HHV) infections can significantly increase the risk of human immunodeficiency virus (HIV) transmission and accelerate disease progression. In the population at high risk of HIV infection, also termed as key populations (female sex workers (FSW), men who have sex with men (MSM), and people who inject drugs (PWID)), and their sexual partners, HHV infections can potentially compromise the efforts to prevent and control HIV infection. Here, we investigated the seroprevalence of HHV infections among HIV-infected key populations in Dar es Salaam, Tanzania. Methodology. We analyzed 262 archived serum samples of HIV-infected key populations from the integrated biobehavioral surveillance (IBBS) study conducted in Dar es Salaam, Tanzania. The enzyme-linked immunosorbent assay was used to determine IgG and IgM titers for cytomegalovirus (CMV) and herpes simplex virus (HSV) types 1 and 2. Results. The overall seropositivity of HHV IgG was 92% (95% CI: 87.7–95.3%). HHV IgM was not detected in any of the samples. The most seroprevalent coinfection was CMV at 69.1% (181/262), followed by HSV-2 33.2% (87/262) and HSV-1 32.1% (84/262). HSV-2 infection differed by key population groups; it accounted for FSW (46.3%) () compared to PWID (21.6%) and MSM (22.7%). In contrast, seroprevalence for CMV and HSV-1 was comparable across the key population groups; whereby, CMV was 62%, 75.3%, and 75% and HSV-1 was 26.4%, 39.2%, and 31.8% for FSW, MSM, and PWID, respectively. We also observed that multiple coinfections with CMV-HSV-2 () and CMV-HSV-1-HSV-2 () were significantly associated with key population aged above 40 years. Conclusion. The IgG seroprevalence of CMV, HSV-1, and HSV-2 was high among HIV-positive key populations. These findings indicate that these individuals are prone to recurrence of HHV infections and may harbor replicating viruses that subsequently may affect HIV disease progression. Therefore, this warrants concerted efforts for integrated HIV and sexually transmitted infection prevention programs targeting key populations

HIV virologic response, patterns of drug resistance mutations and correlates among adolescents and young adults: A cross-sectional study in Tanzania

Background The emergence of HIV drug resistance mutations (DRMs) is of significant threat to achieving viral suppression (VS) in the quest to achieve global elimination targets. We hereby report virologic outcomes and patterns of acquired DRMs and its associated factors among adolescents and young adults (AYA) from a broader HIV drug resistance surveillance conducted in Tanzania. Methods Data of AYA was extracted from a cross-sectional study conducted in 36 selected facilities using a two-stage cluster sampling design. Dried blood spot (DBS) samples were collected and samples with a viral load (VL) ≥1000 copies/mL underwent genotyping for the HIV-1 pol gene. Stanford HIV database algorithm predicted acquired DRMs, Fisher’s exact test and multivariable logistic regression assessed factors associated with DRMs and VS, respectively. Findings We analyzed data of 578 AYA on antiretroviral therapy (ART) for 9–15 and ≥ 36 months; among them, 91.5% and 88.2% had VS (VLConclusions VS amongst AYA is lower than the third UNAIDs target. Additionally, a high prevalence of ADR and high levels of circulating clinically relevant DRMs may compromise the long-term VS in AYA. Furthermore, the first VL result of ≥1000copies/ml after ART initiation is a significant risk factor for developing DRMs. Thus, strict VL monitoring for early identification of treatment failure and genotypic testing during any ART switch is recommended to improve treatment outcomes for AYA