Community-acquired pneumonia in people with Human Immunodeficiency Virus (HIV) during the current era of effective antiretroviral therapy: A multi-center retrospective cohort study.

BACKGROUND: It is unclear if Human Immunodeficiency Virus (HIV) infection affects the prognosis for community acquired pneumonia (CAP) in the current era of effective anti-retroviral therapy. In this multi-center retrospective cohort study of patients admitted for CAP, we compared the in-hospital mortality rate between people with HIV (PWH) and people without HIV. METHODS: The study included consecutive patients admitted with a diagnosis of CAP across 31 hospitals in Ontario, Canada from 2015 to 2022. HIV infection was based on discharge diagnoses and anti-retroviral prescription. The primary outcome was in-hospital mortality. Competing risk models were used to describe time to death in hospital or discharge. Potential confounders were balanced using overlap weighting of propensity scores. RESULTS: Of 82,822 patients admitted with CAP, 1,518 (1.8%) patients had a diagnosis of HIV. PWH were more likely to be younger, be male and have less comorbidities. In hospital, 67 (4.4%) PWH and 6,873 (8.5%) people without HIV died. HIV status had an adjusted sub-distribution hazard ratio (sHR) of 1.02 (95% CI 0.80-1.31 P=0.8440) for dying in hospital. Of 1,518 PWH, 440 (29.0%) patients had a diagnosis of acquired immunodeficiency syndrome (AIDS). AIDS diagnosis had an adjusted sHR of 3.04 (95% CI 1.69-5.45 P=0.0002) for dying in hospital compared to HIV without AIDS. CONCLUSION: People with and without HIV admitted for CAP had a similar in-hospital mortality rate. For PWH, AIDS significantly increased the mortality risk. HIV infection by itself without AIDS should not be considered a poor prognostic factor for CAP.

AC-2020-12-1420.R1 - HIV care providers' familiarity, concerns, and attitudes about HIV PrEP in Colombia: insights from the PrEP-Col-Study.

In 2019, Colombia approved the combination of tenofovir disoproxil fumarate/emtricitabine for HIV Pre-Exposure Prophylaxis (PrEP). Therefore, we conducted a situational analysis in HIV-care providers to identify barriers and facilitators for PrEP implementation. A survey was applied to a non-probabilistic sample of health care workers of HIV-specialized clinics. We examined PrEP awareness and familiarity, comfort with PrEP-related activities, perceived barriers for PrEP implementation, concerns, and attitudes. Poisson regressions assessed the relationship between these factors and the variable "having a plan to offer PrEP". The participation rate was 41% and included physicians (42.6%) and other health professionals (57.4%). Fifty-one percent of the participants reported more than five years of experience caring for people living with HIV. Forty-two percent of non-physician health care workers were nurses. Most reported high familiarity/comfort with PrEP-relevant activities. Concerns about PrEP were prevalent (> 50%) and included causing more harm than good, reducing condom use, medication non-adherence, drug resistance, and healthcare system barriers. Physicians had a plan to offer PrEP (72.2%) more often than other health professionals (52.6). Having a plan to offer PrEP was related to PrEP knowledge and comfort assessing sexual behavior and providing HIV counseling. Overall, about half of HIV-care providers seemed ready to offer PrEP and constitute an asset for PrEP implementation efforts in Colombia. PrEP awareness among non-physicians, PrEP concerns, and negative attitudes need to be addressed to enhance implementation.

Another piece of the Zika puzzle: assessing the associated factors to microcephaly in a systematic review and meta-analysis.

BACKGROUND: Although it is known that Zika virus (ZIKV) infection during pregnancy may lead to microcephaly in the fetus, the prognostic factors associated with this tragic disorder remain unclear. We conducted a systematic review and meta-analysis to assess the prognostic factors associated with the incidence of microcephaly in congenital ZIKV infection. METHODS: We conducted a comprehensive search in Ovid MEDLINE, Ovid MEDLINE (R) Epub ahead of print, Embase, Embase Classic, Web of Science, CINAHL, Cochrane CENTRAL, LILACS, and various thesis databases to identify human studies reporting microcephaly associated with congenital ZIKV infection. We requested primary data from the authors of the included studies to calculate summary estimates and conduct the meta-analysis of the most prevalent factors. RESULTS: We screened 4106 titles and abstracts, and identified 12 studies for inclusion in the systematic review. The assessment of ZIKV infection and the definition of microcephaly varied among studies. A total of 6154 newborns/fetuses were enrolled; of those, 1120 (18.20%) had a diagnostic of ZIKV infection, of which 509 (45.45%) were diagnosed with microcephaly. Nine studies addressed the link between congenital ZIKV infection and neurological findings in newborns/fetuses. Half of the studies provided primary data. Three out of 11 factors of interest seem to be prognostic factors of microcephaly: infant's sex - males compared to females: Relative Risk (RR) 1.30, 95% Confidence Interval (95% CI) 1.14 to 1.49; the stage of pregnancy when infection occurred - infection in the first trimester of pregnancy compared to infection at other stages of pregnancy: RR 1.41, 95% CI 1.09 to 1.82; and asymptomatic infection compared to symptomatic infection during pregnancy: RR 0.68; 95% CI 0.60 to 0.77. CONCLUSION: Our findings support the female-biased resistance hypothesis and reinforce the risk associated with the stage of pregnancy when ZIKV infection occurs. Continued surveillance of ZIKV infection during pregnancy is needed to identify additional factors that could contribute to developing microcephaly in affected fetuses. PROTOCOL REGISTRATION: This systematic review was registered with the International Prospective Register of Systematic Reviews (PROSPERO), registration no. CRD 42018088075.

In vitro and structural evaluation of PL-100 as a potential second-generation HIV-1 protease inhibitor.

OBJECTIVES: HIV-1 protease inhibitors (PIs) are key components of HIV therapy. PL-100 is a novel lysine sulphonamide that demonstrates potent antiviral activity against multiresistant HIV-1 strains as well as a higher genetic barrier for development of resistance mutations compared with first-generation PIs. In the present study, we compared the antiviral activity of PL-100 against HIV-1 subtype B with that of darunavir. METHODS: We used tissue culture experiments to evaluate the in vitro development of resistance to PL-100 and tested the antiviral activity of several clinically approved PIs against PL-100-selected resistant variants. Structural modelling was also used to compare the binding of PL-100 and darunavir to the HIV-1 protease (PR) enzyme. RESULTS: PL-100-resistant variants that emerged within 8-48 weeks showed low- to high-level resistance (3.5- to 21.6-fold) to PL-100, but commonly retained susceptibility to darunavir, which, in contrast, did not select for resistance mutations over a period of 40 weeks. Structural modelling demonstrated that binding of PL-100 was predominantly based on polar interactions and delocalized hydrophobic interactions through its diphenyl groups, while darunavir has numerous interactions with PR that include hydrogen bonding to PR backbone oxygens at amino acid positions A28, D29 and D30 via di-tetrahydrofuran (di-THF) groups. CONCLUSIONS: Hydrogen-bonding contacts and the di-THF group in darunavir, as well as the hydrophobic nature of PL-100, contribute to PI binding and a high genetic barrier for resistance. Redesigning the structure of PL-100 to include a di-THF group might improve it.

Evaluation and comparison of four quantitative SARS-CoV-2 serological assays in COVID-19 patients and immunized healthy individuals, cancer patients, and patients with immunosuppressive therapy.

BACKGROUND: Semi-quantitative and quantitative immunoassays are the most commonly used methodology to evaluate immunity post immunization. OBJECTIVES: To compare four quantitative SARS-CoV-2 serological assays in COVID-19 patients and immunized healthy individuals, cancer patients, and patients with immunosuppressive therapy. STUDY DESIGN: 210 serological samples from COVID-19 infection and vaccination cohorts were used to create a serological sample repository. Serological methods from four manufacturers, namely Euroimmun, Roche, Abbott, and DiaSorin, were evaluated for quantitative, semi-quantitative, and qualitative antibody measurements. All four methods measure IgG antibodies against the SARS-CoV-2 spike receptor-binding domain and report the results in Binding Antibody Unit/mL (BAU/mL). A Total Error Allowable (TEa) of ±25% was chosen as the criteria to determine whether two methods are clinically equivalent quantitatively. Semi-quantitative results (titers) were derived using numeric antibody concentration divided by the cut-off value for each method. RESULTS: All paired quantitative comparisons demonstrated unacceptable performance. With ±25% as TEa, the best agreement was 74 (35.2% out of 210 samples) between Euroimmun and DiaSorin, whereas the lowest agreement was 11 (5.2% out of 210 samples) between Euroimmun and Roche. Antibody titers amongst all four methods were significantly different (p < 0.001). The highest titer difference from the same sample is between Roche and DiaSorin with a 1392-fold difference. On qualitative comparison, none of the paired comparison showed acceptable comparison (p < 0.001). CONCLUSIONS: Poor correlation exists between four evaluated assays, quantitatively, semi-quantitatively, and qualitatively. Further harmonization of assays is required to achieve comparable measurements.

Barriers and facilitators to HIV pre-exposure prophylaxis uptake among transgender women in Colombia: A qualitative analysis using the COM-B model.

Transgender women [TGW] in Colombia are disproportionately affected by HIV due to their low sociodemographic conditions, varied risk behaviours, difficulty accessing health services, and discrimination. Offering pre-exposure prophylaxis [PrEP] as part of a combination of prevention strategies is an appropriate option for this population to reduce their risk of HIV infection. However, little is known about how to implement a PrEP program for TGW in Colombia. Between June and October 2020, we conducted individual interviews with 16 TGW from four different cities in Colombia. The interviews assessed contextual influences, knowledge, skills, perceptions, and beliefs. We used qualitative thematic analysis to identify themes and the Capability, Opportunity, Motivation, and Behavior framework to further delineate barriers and possible interventions. After delineating the main themes across the three subdomains of the model, nine barriers were identified: one related to capability, knowledge, and perception of PrEP; six related to opportunity, which includes, family relations, sexual work environment, stable partner relations, interactions with healthcare workers, health service provision, and community interactions and opportunities; and two related to motivation, mental health, and concerns about medication side effects. Mapping barriers with interventions generated the following intervention functions: education, training, enablement, and environmental structure; and the following policy functions: communication/marketing, legislation, and changes in service provision. Examples of possible interventions are presented and discussed.

The role of polymorphisms at position 89 in the HIV-1 protease gene in the development of drug resistance to HIV-1 protease inhibitors.

OBJECTIVES: Relatively little is known about the development of resistance to protease inhibitors (PIs) in non-B subtypes. In subtype B viruses, L89 is commonly found at position 89 in the HIV protease (PR) gene, whereas M89 is commonly observed as a polymorphism in other subtypes. We compared the frequencies of substitutions at position 89 in PR in tissue culture selections and in clinical databases of PI-naive and PI-experienced populations. METHODS: Representative subtype A/CRF01_AE (n = 2 and 3) and subtype C (n = 5) isolates were cultured in MT-2 cells and cord blood mononuclear cells (CBMCs), respectively, under increasing drug pressure with PIs, and drug resistance mutations were identified. RESULTS: The M89 natural polymorphism in non-B subtypes commonly led to the appearance of an M89T mutation in selections with atazanavir in subtypes A/AE and C, and was accompanied by other previously recognized atazanavir mutations. The M89T mutation contributed to phenotypic resistance to atazanavir and cross-resistance to lopinavir and nelfinavir, but not to other PIs. A shift from a L89 natural polymorphism to L89I/M arose in two of five subtype C selections with PIs. M89I/V/T mutations were acquired by 10%-11% of individuals harbouring non-B subtypes who were failing PI-based regimens, but were rarely observed in drug-naive persons and in patients failing non-PI-based regimens. CONCLUSIONS: The M/L89 natural polymorphism present in non-B subtypes may lead to the M89T mutational pathway conferring resistance to atazanavir, lopinavir and nelfinavir.

Quantitative Analysis of SARS-CoV-2 Antibody Levels in Cancer Patients Post Three Doses of Immunization and Prior to Breakthrough COVID-19 Infections.

(1) Background: COVID-19 vaccine effectiveness should be carefully evaluated and explicitly defined. To our knowledge, this is the first report to quantitatively evaluate humoral responses post 3 doses of SARS-CoV-2 immunization and prior to breakthrough COVID-19 infection in Canadian cancer patients. (2) Methods: In a prospective cohort study, we enrolled 185 cancer participants post COVID-19 vaccination in Kingston, Ontario, Canada. IgG antibodies against the SARS-CoV-2 spike receptor-binding domain were quantified by immunoassay post three doses of immunization. With the COVID-19 rapid antigen test and polymerase chain reaction (PCR), 16 breakthrough infections were identified. Results: Following SARS-CoV-2 vaccination (including BNT162b2, AZD1222, and mRNA-1273), the mean serum anti-spike protein antibody level was 197.2 BAU/mL (binding antibody unit, SD ± 393.9), 1335.9 BAU/mL (±3337.8), and 3164.8 BAU/mL (±6500.9) post the first, second, and third dose of vaccination. Observed differences were significant (p ≤ 0.001). The average antibody level of 3164.8 BAU/mL post the third dose was 89.9 times that of the seroconversion level (35.2 BAU/mL). This indicates that most vaccines approved are effective in producing robust antibody responses. In 11 breakthrough cases confirmed by PCR, prior to infection, the average antibody concentration was 3675.6 BAU/mL with the highest concentration being 9107.4 BAU/mL. Compared with this average antibody concentration of 3675.6 BAU/mL (104.4 times that of the seroconversion concentration), 0% of single dosed, 9.6% of double vaccinated, and 29.5% of triple vaccinated cancer patients had higher SARS-CoV-2 antibody levels. When patients were split into hematological and solid cancer, the hematological cancer group demonstrated lower serological responses than the solid cancer group in the first and second doses (first dose, average concentration 11.1 vs. 201.4 BAU/mL, respectively, p < 0.05; second dose, average concentration 441.5 vs. 1725.9 BAU/mL, respectively, p < 0.05). There was no difference in the third dose level (1756.3 vs. 2548.0 BAU/mL, p = 0.21). (4) Conclusions: Most vaccines were effective in producing robust antibody responses when more than one dose was given, and the more doses the higher the serological response. Likely due to the highly contagious nature of SARS-CoV-2 variants, a significant number of participants had SARS-CoV-2 antibody responses lower than the average antibody concentration prior to the known breakthrough infections. Additional vaccination is likely required to ensure immunity against infection by SARS-CoV-2.

Quantitative Analysis of SARS-CoV-2 Serological Responses Post Three Doses of Immunization and Prior to Breakthrough COVID-19 Infections.

BACKGROUND: Vaccine mediated SARS-CoV-2 antibody responses should be carefully evaluated. With regular follow-up in healthy individuals, we aimed to determine SARS-CoV-2 serological responses post three doses of immunization and prior to breakthrough infections in the Canadian population. METHODS: In a prospective cohort study, we enrolled 140 healthy participants post COVID-19 vaccination in Kingston, Ontario, Canada. IgG antibodies against the SARS-CoV-2 spike receptor-binding domain were quantified by immunoassay post three doses of immunization. With COVID-19 rapid antigen test, polymerase chain reaction, and whole genome sequencing, 27 breakthrough infections were identified. RESULTS: Following SARS-CoV-2 vaccine (including BNT162b2, AZD1222, and mRNA-1273), the median serum anti-spike protein antibody level was 143.6 BAU/mL (binding antibody unit, interquartile range 79.0-266.6) post the first dose of immunization, 1046.4 BAU/mL (423.9-1738.2) post the second dose, and 1604.7 BAU/mL (700.1-3764.0) post the third dose. Observed differences were significant (p ≤ 0.001). The median antibody level of 1604.7 BAU/mL post third dose is 45.6 times that of the seroconversion level (35.2 BAU/mL). This indicates that most vaccines approved are effective in producing robust antibody responses. In seven breakthrough cases characterized by whole genome sequencing, prior to infection, antibody concentrations of breakthrough cases were at 3249.4 (Delta), 2748.4 (Delta), 4893.9 (Omicron), 209.1 (Omicron), and 231.5 (Omicron), 725.7 (Omicron), and 2346.6 (Omicron) BAU/mL. Compared with the average antibody concentration of 2057.7 BAU/mL (58 times that of the seroconversion concentration) from above seven cases, 37.2% of triple vaccinated, 19.0% of double vaccinated, and 1.5% single dosed individuals have higher SARS-CoV-2 antibody levels. CONCLUSIONS: Most vaccines are effective in producing robust antibody responses when more than one dose is given, and the more doses the higher the serological response. Likely due to the highly contagious nature of SARS-CoV-2 variants, a significant number of participants have SARS-CoV-2 antibody responses lower than the average antibody concentration prior to the known breakthrough infections. Additional vaccination is likely required to ensure immunity against infection by SARS-CoV-2.

Applying implementation science frameworks to identify factors that influence the intention of healthcare providers to offer PrEP care and advocate for PrEP in HIV clinics in Colombia: a cross-sectional study.

BACKGROUND: Few studies have used implementation science frameworks to identify determinants of PrEP prescription by healthcare providers. In this work, we developed and psychometrically examined a questionnaire using the theoretical domains framework (TDF) and the consolidated framework for implementation research (CFIR). We used this questionnaire to investigate what factors influence the intention of healthcare providers to offer PrEP care and advocate for PrEP. METHODS: We conducted a cross-sectional study in 16 HIV healthcare organizations in Colombia. A 98-item questionnaire was administered online to 129 healthcare professionals. One hundred had complete data for this analysis. We used exploratory factor analysis to assess the psychometric properties of both frameworks, and multinomial regression analysis to evaluate the associations of the frameworks' domains with two outcomes: (1) intention to offer PrEP care and (2) intention to advocate for PrEP impmentation. RESULTS: We found support for nine indices with good internal consistency, reflecting PrEP characteristics, attitudes towards population needs, concerns about the use of PrEP, concerns about the role of the healthcare systems, knowledge, beliefs about capabilities, professional role, social influence, and beliefs about consequences. Notably, only 57% of the participants were likely to have a plan to care for people in PrEP and 66.7% were likely to advocate for PrEP. The perception of the need for PrEP in populations, the value of PrEP as a practice, the influence of colleagues, and seeing PrEP care as a priority was related to being less likely to be unwilling to provide or advocate for PrEP care. CONCLUSION: Our findings suggested the importance of multilevel strategies to increase the provision of PrEP care by healthcare providers including adquisition of new skills, training of PrEP champions, and strength the capacity of the health system.

Adaptation and Pilot Evaluation of an Intervention Addressing the Sexual Health Needs of Gay Men Living with HIV Infection in Colombia.

Interventions addressing the sexual health need of HIV-positive men who have sex with men (MSM) in Latin America are scarce. We adapted and evaluated GPS, a group-based intervention led by peers, developed using the Information-Motivation-Behavioral (IMB) model and motivational interviewing (MI). We used McKleroy et al framework to culturally adapt GPS to MSM living with HIV infection in Colombia. Then, a one-armed pilot trial examined changes in depressive symptoms, loneliness, self-efficacy for engaging in sexual risk reduction behaviors, sexual sensation seeking and sexual compulsivity at pre-intervention, post-intervention, and 3-month follow-up. These results were complemented with semistructured interviews with participants 3 months after the intervention. GPS was identified to be culturally acceptable with few changes in materials and exercises. Facilitators showed high levels of adherence and fidelity to MI principles. Seven of 11 eligible participants finished the intervention; GPS positively influenced self-efficacy for condom negotiation, depressive symptoms, and condomless anal sex with partners of unknown HIV status. Exit interviews revealed that GPS was well-designed, relevant, facilitated discussion of sex in a nonjudgmental manner, and helped make positive changes in participants' sexual lives. These results provided preliminary evidence of an intervention to address sexual and mental health of MSM living with HIV in Latin America.

Scales to Assess Knowledge, Motivation, and Self-Efficacy for HIV PrEP in Colombian MSM: PrEP-COL Study.

OBJECTIVE: We evaluated the construct validity Spanish version of knowledge, stigma, norms, and self-efficacy scales regarding PrEP in MSM. METHODS: Sample of 287 MSM. Exploratory confirmatory factor analysis and item response theory were used to validate the constructs. Correlations and confidence interval-based estimation of relevance analyses were conducted to correlate the scales with willingness and intention to use PrEP. RESULTS: Attitude, stigma, and descriptive and subjective norms scales showed good construct validity and were related to intention and willingness to use PrEP. However, the knowledge scale and self-efficacy scales require further refinement. CONCLUSIONS: The study provides useful information for assessing information, motivation, and self-efficacy related to PrEP use. Our results could be used to test the scales and the theoretical model in other contexts to confirm their usefulness.

HIV-1 protease codon 36 polymorphisms and differential development of resistance to nelfinavir, lopinavir, and atazanavir in different HIV-1 subtypes.

The amino acid at position 36 of the HIV-1 protease differs among various viral subtypes, in that methionine is usually found in subtype B viruses but isoleucine is common in other subtypes. This polymorphism is associated with higher rates of treatment failure involving protease inhibitors (PIs) in non-subtype B-infected patients. To investigate this, we generated genetically homogeneous wild-type viruses from subtype B, subtype C, and CRF02_AG full-length molecular clones and showed that subtype C and CRF02_AG I36 viruses exhibited higher levels of resistance to various PIs than their respective M36 counterparts, while the opposite was observed for subtype B viruses. Selections for resistance with each variant were performed with nelfinavir (NFV), lopinavir (LPV), and atazanavir (ATV). Sequence analysis of the protease gene at week 35 revealed that the major NFV resistance mutation D30N emerged in NFV-selected subtype B viruses and in I36 subtype C viruses, despite polymorphic variation. A unique mutational pattern developed in subtype C M36 viruses selected with NFV or ATV. The presence of I47A in LPV-selected I36 CRF02_AG virus conferred higher-level resistance than L76V in LPV-selected M36 CRF02_AG virus. Phenotypic analysis revealed a >1,000-fold increase in NFV resistance in I36 subtype C NFV-selected virus with no apparent impact on viral replication capacity. Thus, the position 36 polymorphism in the HIV-1 protease appears to have a differential effect on both drug susceptibility and the viral replication capacity, depending on both the viral subtype and the drug being evaluated.

Application of the "syndemics" theory to explain unprotected sex and transactional sex: A crosssectional study in men who have sex with men (MSM), transgender women, and non-MSM in Colombia. / Aplicación de la teoría de la "sindemia" para entender el sexo sin protección y el sexo comercial: un estudio transversal en hombres que tienen sexo con hombres (HSH), mujeres transexuales y hombres que no tienen sexo con hombres en Colombia

INTRODUCTION: Men who have sex with men (MSM) and transgender women (TW) in Colombia are highly affected by HIV. To improve understanding of the role of HIV risk behaviors in HIV acquisition, we used the syndemic framework, a useful concept to inform prevention efforts. OBJECTIVE: To examine the effect of four psychosocial conditions, namely, forced sex, history of childhood sexual abuse, frequent alcohol use, and illicit drug use on unprotected sex and the synergistic effects ("syndemic" effects) of these conditions on HIV risk behavior. MATERIALS AND METHODS: We enrolled a total of 812 males (54.7% men who have sex with men, MSM; 7.3% transgender women, and 38% non-MSM). The participants were recruited from neighborhoods of low socioeconomic status through free HIV-counseling and -testing campaigns. We performed Poisson regression analysis to test the associations and interactions between the four psychosocial conditions and unprotected sex with regular, occasional, and transactional partners. To test the "syndemic" model, we assessed additive and multiplicative interactions. RESULTS: The prevalence of any psychosocial condition was 94.9% in transgender women, 60.1% in MSM, and 72.2% in non-MSM. A higher likelihood of transactional sex was associated in MSM (prevalence ratio (PR)=7.41, p<0.001) and non-MSM (PR=2.18, p< 0.001) with three or all four conditions compared to those with one condition. Additive interactions were present for all combinations of psychosocial problems on transactional sex n MSM. No cumulative effect or additive interaction was observed in transgender women. CONCLUSIONS: Our study highlights the need for bundled mental health programs addressing childhood sexual abuse, illicit drug use, and frequent alcohol use with other HIV prevention programs.

Introducción. Los hombres que tienen sexo con hombres (HSH), y las mujeres transgenero (MT) en Colombia continuan estando a mayor riesgo de VIH. Para entender como los comportamientos se asocian al VIH, se uso la teoria de la sindemia, la cual se ha considerado muy útil en el desarrollo de estrategias de prevención. Objetivo. Examinar el efecto de cuatro afecciones psicosociales, a saber: historia de sexo forzado, historia de abuso sexual infantil, consumo frecuente de alcohol y consumo de drogas ilícitas en las relaciones sexuales sin protección, así como los efectos sinérgicos (efectos "sindémicos") de estas afecciones sobre el comportamiento de riesgo para HIV. Materiales y métodos. Se hizo un estudio transversal que incluyó 812 participantes (hombres que tienen sexo con hombres, HSH: 54,7 %; mujeres transgénero: 7,3 % y hombres que no tenían sexo con otros hombres: 38 %). Los participantes se reclutaron en barrios de estratos socioeconómicos bajos a través de campañas gratuitas de asesoramiento y pruebas de HIV. Se hizo un análisis de regresión de Poisson para probar las asociaciones e interacciones entre las cuatro condiciones psicosociales y las relaciones sexuales sin protección con parejas regulares, ocasionales y comerciales. Para probar el modelo "sindémico" se evaluaron las interacciones aditivas y multiplicativas. Resultados. La prevalencia de cualquiera de las condiciones psicosociales fue de 94,9 % en mujeres transexuales, de 60,1 % en HSH y de 72,2 % en hombres que no tienen sexo con hombres. Se encontró una mayor probabilidad de tener sexo comercial en los HSH (razón de prevalencia (RP)=7,41, p<0,001) y en los que no tienen sexo con otros hombres (RP=2.18, p<0,001) con tres de las condiciones psicosociales, o con las cuatro, en comparación con aquellos con una sola condición. Las interacciones aditivas se registraron entre todas las combinaciones de problemas psicosociales con el sexo comercial en los HSH. No se observó un efecto acumulativo ni interacciones en mujeres transexuales. Conclusiones. El estudio resalta la necesidad de combinar programas de salud mental que aborden el abuso sexual infantil, el abuso de drogas y el consumo frecuente de alcohol con otros programas de prevención del HIV.

Effects of the K65R and K65R/M184V reverse transcriptase mutations in subtype C HIV on enzyme function and drug resistance.

BACKGROUND: We investigated the effects of mutations K65R and K65R plus M184V on enzymatic function and mechanisms of drug resistance in subtype C reverse transcriptase (RT). METHODS: Recombinant subtype C HIV-1 RTs containing K65R or K65R+M184V were purified from Escherichia coli. Enzyme activities and tenofovir (TFV) incorporation efficiency by wild-type (WT) and mutant RTs of both subtypes were determined in cell-free assays. Efficiency of (-) ssDNA synthesis and initiation by subtype C RTs was measured using gel-based assays with HIV-1 PBS RNA template and tRNA3Lys as primer. Single-cycle processivity was assayed under variable dNTP concentrations. Steady-state analysis was performed to measure the relative inhibitory capacity (ki/km) of TFV-disphosphate (TFV-DP). ATP-dependent excision and rescue of TFV-or ZDV-terminated DNA synthesis was monitored in time-course experiments. RESULTS: The efficiency of tRNA-primed (-)ssDNA synthesis by subtype C RTs was: WT > K65R > K65R+M184V RT. At low dNTP concentration, K65R RT exhibited lower activity in single-cycle processivity assays while the K65R+M184V mutant showed diminished processivity independent of dNTP concentration. ATP-mediated excision of TFV-or ZDV-terminated primer was decreased for K65R and for K65R+M184V RT compared to WT RT. K65R and K65R+M184V displayed 9.8-and 5-fold increases in IC50 for TFV-DP compared to WT RT. The Ki/Km of TFV was increased by 4.1-and 7.2-fold, respectively, for K65R and K65R+M184V compared to WT RT. CONCLUSION: The diminished initiation efficiency of K65R-containing RTs at low dNTP concentrations have been confirmed for subtype C as well as subtype B. Despite decreased excision, this decreased binding/incorporation results in diminished susceptibility of K65R and K65R+M184 RT to TFV-DP.

Role of genetic diversity amongst HIV-1 non-B subtypes in drug resistance: a systematic review of virologic and biochemical evidence.

The genetic diversity of HIV-1 has required its classification into types and subtypes. There is controversy as to how and to what extent genetic diversity may affect the emergence of antiretroviral drug resistance in HIV-1 subtypes other than B. To better understand the impact of genetic diversity (represented by different HIV-1 subtypes) on resistance to reverse transcriptase and protease inhibitor drugs, a systematic review was conducted on virologic and biochemical evidence obtained from work with non-B HIV-1 subtypes. We searched 11 databases and retrieved 3,486 citations on all aspects of non-B subtype-related resistance research. Twenty-seven studies with virologic and/or biochemical data met the eligibility criteria for our systematic review. Nineteen studies were found that reported phenotypes in non-B subtypes (304 from naive isolates and 242 from drug-exposed isolates) and 11 studies that used molecular biology techniques to study non-B resistance to antiretroviral drugs. Compared to the NL4-3 laboratory strain, lower baseline susceptibilities of recombinant A/G subtype virus to protease inhibitors were observed and a substantial proportion of subtype C isolates displayed higher IC50 at baseline for atazanavir. Some A/G isolates were found to have reduced susceptibility to abacavir. Mutations not typical of B subtypes include the reverse transcriptase mutation V106M and the protease mutations M89I/V and N83T. Virologic and biochemical data suggest that K65R is more likely to emerge in subtype C HIV-1. There is evidence to suggest differential effects of other mutations according to subtype, e.g. the protease inhibitor mutations I93L and M89I/V. Importantly, the most widely used commercial phenotyping systems do not take into account gag variations among natural isolates, which could limit the accuracy of measured susceptibility. Enzymatic and virologic data support the concept that naturally occurring polymorphisms in different non-B subtypes can affect the susceptibility of HIV-1 to different antiretroviral drugs, the magnitude of resistance conferred by major mutations, and the propensity to acquire some resistance mutations. Tools may need to be optimized to accurately measure drug susceptibility of non-B subtypes, especially for protease inhibitors.

Psychometric properties and validity of the Center for Epidemiological Studies Depression Scale (CES-D) in a population attending an HIV clinic in Cali, Colombia / Propiedades psicométricas y validez de la escala de depresión del Center for Epidemiological Studies (CES-D) en personas atendidas en una clínica de HIV en Cali, Colombia

INTRODUCTION: Depression in people living with HIV/AIDS is associated with poor health outcomes. Despite this, assessment of depressive symptoms is not a routine clinical practice in the care of people with HIV in Colombia. One reason could be the lack of validated depression screening scales for this population. OBJECTIVE: To test the reliability and construct validity of the 20- and 10-item-Center for Epidemiological Studies Depression Scale in patients attending an HIV clinic in Cali, Colombia. MATERIALS AND METHODS: A non-random sample of 105 adults was enrolled. The 20 item-CES-D (CES-D-20) scale was administered twice: At baseline and 2-4 weeks later. We calculated the Cronbach's alpha coefficient and the intraclass correlation coefficient. In addition, we used an exploratory and confirmatory factorial analysis, as well as the item response theory to assess the validity of the scale. RESULTS: Most participants were men (73%), with a mean age of 40 years, 53% of whom had not completed high school. Cronbach's coefficients were 0.92 and 0.94 at baseline and at the second interview, respectively. The intraclass correlation was 0.81 (95% CI: 0.72-0.88). Although all 20 items loaded distinctly in 4 factors, 5 items did not load as expected. The structure factor of the CES-D-20 was not confirmed, as 4 items had poor goodness of fit. The CES-D-10 appeared to perform better in this population. CONCLUSIONS: These results support the reliability and validity of the CES-D-10 instrument to screen for depressive symptoms in people living with HIV in Colombia.

Introducción. La depresión en personas con HIV/sida se asocia con resultados negativos para la salud. La evaluación de los síntomas depresivos no es una práctica clínica rutinaria en el cuidado de personas con HIV/sida en Colombia, lo cual puede deberse a la carencia de escalas validadas para la tamización de la depresión en esta población. Objetivo. Evaluar la reproducibilidad y validez de constructo de dos versiones de la escala de depresión del Center for Epidemiological Studies (CES-D), la de 20 ítems y la de 10 ítems, en personas con HIV/sida atendidas en una clínica de Cali, Colombia. Materiales y métodos. Se seleccionó una muestra no probabilística de 105 adultos con HIV/sida. La escala CES-D se utilizó dos veces (línea basal y 2 a 4 semanas después). La consistencia interna fue evaluada con el coeficiente alfa de Cronbach. La reproducibilidad se evaluó con el coeficiente de correlación intraclase. Para verificar la validez del constructo se utilizó un análisis factorial exploratorio y la teoría de respuesta al ítem. Resultados. El 73 % de la muestra correspondía a hombres, la edad promedio fue de 40 años y el 53 % tenía baja escolaridad. El coeficiente alfa de Cronbach fue de 0,92 (línea basal) y de 0,94 (segunda entrevista). El coeficiente de correlación intraclase fue de 0,81 (IC95% 0,72-0,88). Aunque en cuatro de los factores en la escala de 20 ítems claramente hubo carga factorial, cinco de los ítems no tuvieron un ajuste adecuado. La CES-D de 10 ítems parece funcionar mejor en esta población. Conclusiones. Los resultados respaldaron la reproducibilidad y la validez de la escala CES-D para la tamización de síntomas depresivos en personas con HIV/sida en Colombia.

Antiretroviral therapy : optimal sequencing of therapy to avoid resistance.

In the second decade of highly active antiretroviral therapy, drug regimens offer more potent, less toxic and more durable choices. However, strategies addressing convenient sequential use of active antiretroviral combinations are rarely presented in the literature. Studies have seldom directly addressed this issue, despite it being a matter of daily use in clinical practice. This is, in part, because of the complexity of HIV-1 resistance information as well as the complexity of designing these types of studies. Nevertheless, several principles can effectively assist the planning of antiretroviral drug sequencing. The introduction of tenofovir disoproxil fumarate, abacavir and emtricitabine into current nucleoside backbone options, with each of them selecting for an individual pattern of resistance mutations, now permits sequencing in the context of previously popular thymidine analogues (zidovudine and stavudine). Similarly, newer ritonavir-boosted protease inhibitors could potentially be sequenced in a manner that uses the least cross-resistance prone protease inhibitor at the start of therapy, while leaving the most cross-resistance prone drugs for later, as long as there is rationale to employ such a compound because of its utility against commonly observed drug-resistant forms of HIV-1.

Protease inhibitor resistance in HIV-infected patients: molecular and clinical perspectives.

The problem of HIV-1 drug resistance has established a need for new compounds that retain activity against mutated resistant viral isolates. Fortunately, a number of new compounds have recently been developed that possess excellent activity against HIV-1 strains that contain as many as eight relevant drug-resistance mutations in the viral protease (PR) gene. These newer protease inhibitors (PI) are characterized by higher genetic barrier for drug resistance, meaning that higher numbers of mutations are required for resistance to develop in comparison with older members of the PI family of drugs. Thus, different PIs can be used sequentially in HIV therapy in a manner that can overcome previous drug resistance and potentially forestall the development of additional resistance mutations in the viral PR. All currently used PIs, in general, require ritonavir to be used as a pharmacological boosting agent. There is a need to develop novel PIs, that will not require such boosting, and that are also characterized by potent antiviral activity and a high genetic barrier for resistance.

Psychometric properties of a Spanish version of the 10-item Berger's stigma scale in Colombia: a validation study / Propiedades psicométricas de una versión en español de la escala de Berger de diez ítems en Colombia: un estudio de validación

Introduction: HIV-related stigma is detrimental to people living with HIV (PLH), and reducing it is essential for achieving an HIV/AIDS-free generation. Abbreviated stigma scales can improve the feasibility of surveys that broadly explore factors affecting PLH. This study tested the psychometric properties of a Spanish translation of the abbreviated 10-item Berger's HIV stigma scale. Methods:We recruited a sample of 105 PLH regularly attending a specialized clinic in Cali, Colombia. English-to-Spanish and Spanish-to-English back translation was performed of the Berger's 10-item HIV stigma scale.Exploratory and confirmatory factor analyses were carried out to assess its validity. Pre- and post-test reliability (15 days) was estimated with the intra-class correlation coefficient (ICC). Results: The Confirmatory Factor Analysis (CFA) was used to confirm a two-factor solution with three poor items removed, resulting in a 7-item HIV Stigma Scale. The resulting 7-item HIV stigma scale had a Cronbach's alpha of 0.73 with an ICC of 0.83 (CI 95%: 0.75­0.89). One factor loaded three items related to negative self-image (internalised stigma), and the other four items were related to personalized (enacted) HIV stigma. Both factors were related to depression and adherence to antiretroviral therapy. Conclusion: The Spanish translation of the 10-item HIV stigma scale did not perform well due to problems in items 4, 5, and 6. Rather, a modified 7-item version had a good fit with a two-factor loading in which both HIV stigma factors correlated significantly with depression and HIV medication adherence.

Introducción: el estigma asociado al VIH atenta contra la salud de las personas que viven con VIH (PVV), así que reducirlo es esencial para erradicar el VIH/SIDA. Las escalas abreviadas para estigma pueden facilitar la ejecución de encuestas amplias sobre factores que afectan a las PVV. Este estudio examinó las propiedades psicométricas de una traducción al español de la escala de Berger de 10 ítems. Métodos: se reclutaron 105 PVV en una clínica de VIH en Cali, Colombia. La escala de Berger de 10 ítems se tradujo del inglés al español y después del español al inglés. La validez de constructo se evaluó con análisis factoriales (exploratorios/confirmatorios). La confiabilidad pre y postest (15 días) se estimó con el coeficiente de correlación intraclase (CCI). Resultados: el análisis factorial confirmó una solución de dos factores carente de tres ítems de pobre desempeño, resultando en una escala final de siete ítems, la cual tuvo un coeficiente alfa de Cronbach de 0,73 y un CCI de 0,83 (IC 95%: 0,75-0,89). Un factor cargó tres ítems relacionados con autoimagen negativa (estigma internalizado), y otros cuatro ítems relacionados con el estigma personalizado (estigma declarado/ejercido por terceros). Ambos factores estuvieron asociados a depresión y baja adherencia a tratamiento antirretroviral. Conclusión: la escala de 10 ítems en español para estigma asociado al VIH tuvo pobre desempeño por problemas con los ítems 4, 5 y 6. En cambio, una versión modificada de siete ítems tuvo mejor desempeño, cargando dos factores correlacionados significativamente con depresión y adherencia al tratamiento antirretroviral.