Virologic outcome among patients receiving antiretroviral therapy at five hospitals in Haiti.

Viral load (VL) assessment is the preferred method for diagnosing and confirming virologic failure for patients on antiretroviral therapy (ART). We conducted a retrospective cross-sectional study to evaluate the virologic suppression rate among patients on ART for ≥6 months in five hospitals around Port-au-Prince, Haiti.Plasma VL was measured and patients with VL <1,000 copies/mL were defined as virologically suppressed. A second VL test was performed within at least six months of the first test. Factors associated with virologic suppression were analyzed using logistic regression models accounting for site-level clustering using complex survey procedures.Data were analyzed for 2,313 patients on ART for six months or longer between July 2013 and February 2015. Among them, 1,563 (67.6%) achieved virologic suppression at the first VL test. A second VL test was performed within at least six months for 718 (31.0%) of the patients. Of the 459 patients with an initial HIV-1 RNA <1,000 copies/mL who had a second VL performed, 394 (85.8%) maintained virologic suppression. Virologic suppression was negatively associated with male gender (adjusted odds ratio [aOR]: 0.80, 95% CI: 0.74-0.0.86), 23 to 35 months on ART (aOR:0.72[0.54-0.96]), baseline CD4 counts of 201-500 cells/mm3 and 200 cells/mm3 or lower (aORs: 0.77 [0.62-0.95] and 0.80 [0.66-0.98], respectively), poor adherence (aOR: 0.69 [0.59-0.81]), and TB co-infection (aOR: 0.73 [0.55-0.97]).This study showed that over two-thirds of the patients in this evaluation achieved virologic suppression after ≥ six months on ART and the majority of them remained suppressed. These results reinforce the importance of expanding access to HIV-1 viral load testing in Haiti for monitoring ART outcomes

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

Flowchart describing the number of patients with first and second VL test and percent of virologic suppression among them.

<p>Flowchart describing the number of patients with first and second VL test and percent of virologic suppression among them.</p

Factors associated with viral suppression using univariable and multivariable logistic regression models.

<p>Factors associated with viral suppression using univariable and multivariable logistic regression models.</p

Demographic, clinical, virologic, and immunological characteristics of study participants at the time of the first viral load testing (n = 2,313).

<p>Demographic, clinical, virologic, and immunological characteristics of study participants at the time of the first viral load testing (n = 2,313).</p

A TLR7-nanoparticle adjuvant promotes a broad immune response against heterologous strains of influenza and SARS-CoV-2

The ideal vaccine against viruses such as influenza and SARS-CoV-2 must provide a robust, durable and broad immune protection against multiple viral variants. However, antibody responses to current vaccines often lack robust cross-reactivity. Here we describe a polymeric Toll-like receptor 7 agonist nanoparticle (TLR7-NP) adjuvant, which enhances lymph node targeting, and leads to persistent activation of immune cells and broad immune responses. When mixed with alum-adsorbed antigens, this TLR7-NP adjuvant elicits cross-reactive antibodies for both dominant and subdominant epitopes and antigen-specific CD8+ T-cell responses in mice. This TLR7-NP-adjuvanted influenza subunit vaccine successfully protects mice against viral challenge of a different strain. This strategy also enhances the antibody response to a SARS-CoV-2 subunit vaccine against multiple viral variants that have emerged. Moreover, this TLR7-NP augments antigen-specific responses in human tonsil organoids. Overall, we describe a nanoparticle adjuvant to improve immune responses to viral antigens, with promising implications for developing broadly protective vaccines