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 (VL<1000copies/mL) at early and late time points, respectively. Genotyping of 64 participants (11.2%) who had VL ≥1000 copies/ml detected 71.9% of any DRM. Clinically relevant DRMs were K103N, M184V, M41L, T215Y/F, L210W/L, K70R, D67N, L89V/T, G118R, E138K, T66A, T97A and unexpectedly absent K65R. Participants on a protease inhibitor (PI) based regimen were twice as likely to not achieve VS compared to those on integrase strand transfer inhibitors (INSTI). The initial VL done 6 months after ART initiation of ≥1000copies/mL was the primary factor associated with detecting DRMs (p = .019). CONCLUSIONS: 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.

Utilization of dried blood spot specimens can expedite nationwide surveillance of HIV drug resistance in resource-limited settings.

INTRODUCTION: Surveillance of HIV drug resistance (HIVDR) is crucial to ensuring the continued success of antiretroviral therapy (ART) programs. With the concern of reduced genotyping sensitivity of HIV on dried blood spots (DBS), DBS for HIVDR surveillance have been limited to ART-naïve populations. To investigate if DBS under certain conditions may also be a feasible sample type for HIVDR testing in ART patients, we piloted nationwide surveys for HIVDR among ART patients using DBS in two African countries with rapid scale-up of ART. METHODS: EDTA-venous blood was collected to prepare DBS from adult and pediatric ART patients receiving treatment during the previous 12-36 months. DBS were stored at ambient temperature for two weeks and then at -80°C until shipment at ambient temperature to the WHO-designated Specialized HIVDR Laboratory at CDC in Atlanta. Viral load (VL) was determined using NucliSENS EasyQ® HIV-1 v2.0 kits; HIVDR genotyping was performed using the ATCC HIV-1 Drug Resistance Genotyping kits. RESULTS: DBS were collected from 1,368 and 1,202 ART patients; 244 and 255 these specimens had VL ≥1,000 copies/mL in Kenya and Tanzania, respectively. The overall genotyping rate of those DBS with VL ≥1,000 copies/mL was 93.0% (95% CI: 89.1%-95.6%) in Kenya and 91.8% (87.7%-94.6%) in Tanzania. The turnaround times for the HIVDR surveys from the time of collecting DBS to completing laboratory testing were 6.5 months and 9.3 months for the Kenya and Tanzania surveys, respectively. CONCLUSIONS: The study demonstrates a favorable outcome of using DBS for nationwide surveillance of HIVDR in ART patients. Our results confirm that DBS collected and stored at ambient temperature for two weeks, and shipped with routine courier services are a reliable sample type for large-scale surveillance of acquired HIVDR.

Uptake of guidelines on prevention of mother-to-child transmission of HIV in rural Tanzania: time for change.

Guidelines on prevention of mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV) are inconsistently implemented in low-income countries. Strategies are needed to improve the uptake of these guidelines to prevent avoidable new HIV infections of infants. In 2010 the World Health Organisation presented its new PMTCT guidelines, offering two options for short courses of antiretroviral prophylaxis: Option A and Option B. Option A consists of antenatal prophylaxis with zidovudine followed by intrapartum and postpartum prophylaxis with single-dose nevirapine and zidovudine plus lamivudine. Option B recommends triple antiretroviral prophylaxis until after finishing breastfeeding. Tanzania has adopted Option A, and it is currently implementing it. A new option termed Option B+ has emerged recently, which recommends providing lifelong antiretroviral treatment to all HIV-positive pregnant women. In this article, we discuss the likely impact of this last PMTCT strategy in rural Africa with an example of an observational cross-sectional analysis in a rural referral hospital in Tanzania aiming to assess the uptake of PMTCT recommendations. Gaps were identified at all steps of the PMTCT pathway. Effective uptake of PMTCT guidelines has been shown to be extremely challenging in this setting. The continuously changing recommendations on PMTCT stress the need for a much simpler and effective approach. We argue in favour of implementing Option B+ in Tanzania. Financial challenges need to be faced, but Option B+ would help to overcome many barriers that prevent guidelines to be implemented in order to increase coverage and ultimately achieve the goal of 'virtual elimination' of mother-to-child transmission in sub-Saharan Africa.

HIV and parasitic co-infections among patients seeking care at health facilities in Tanzania.

Untreated tropical parasitic co-infections appear to speed the progression of HIV-1 disease. However, to date, there have been few studies conducted in resource limited settings to ascertain the interaction of parasitic co-infection where HIV/AIDS management largely depends on CD4+ T lymphocyte cells counts and WHO clinical staging. This study aimed to determine the prevalence of parasites, their association with CD4+ T lymphocyte cells changes and clinical manifestation of HIV-infection in patients attending HIV/AIDS management clinics in Tanzania. Adult HIV-infected patients registering for the first time at HIV/AIDS management clinics were recruited; with physical examination and laboratory tests performed at baseline and after 6 months. Patients were assigned a clinical stage and scr.eened for helminths and Plasmodium sp. co-infection, CD4+ T lymphocyte cells, haemoglobin and HIV-1 p24 antigen. Of the 421 HIV-1 infected patients studied, 198 (47.0%) were co-infected with one or more parasites. Of those studied, 93/421(22.1%) had helminth only co-infection, and 50/421 (12.9%) had Plasmodium sp only co-infection. Mixed Plasmodium sp and helminth co-inf6ction was diagnosed in 55/421 (13.0%) patients. Helminths frequently diagnosed included: hookworm 65/421(15.4%), Schistosomiasis 49/421(11.6%), Strongyloides stercoralis 57/421(13.5%), and Ascaris lumbricoides 54/421(12.8%). No statistical association was found between CD4+ T lymphocyte cells < 200/ 1, or WHO clinical stage III/ IV with parasite co-infections (AOR 1.2, 95%CI 0.8-1.8). Anaemia was common in parasite co-infected patients (32.8% vs. 18.8%). Parasite co-infection was associated with risk of anaemia (AOR 2.1, 95%CI 1.3-3.2). In multivariable logistic regression analysis, baseline CD4+ T lymphocyte cells <200/V1 was significantly associated with CD4+ T lymphocyte cells <20041 (AOR 2.4, 95%CI 1.3-4.7) at six months. HIV-1 P24 antigen mean concentration was higher in parasite co- infected patients (ranges 47.6 to 56.9) as compared to patients without parasite co-infection (5.5). We have looked at one set of parasites and found high prevalence of malaria and helminth co-infection in HIV-infected individuals. Given the available reports on health impacts of helminth co-infection in HIV/AIDS patients and the anecdotal reports of helminths health effects in HIV-uninfected persons, helminths and other prevalent parasites should not be ignored in HIV/AIDS programs. Based on local helminth epidemiology and HIV-infected cohort specific helminths co-infection prevalence data, mass treatment of soil transmitted helminths can be incorporated into HIV/AIDS management programmes.