Lamivudine-based two-drug regimens with dolutegravir or protease inhibitor: Virological suppression in spite of previous therapy failure or renal dysfunction

Abstract Background Two-Drug Regimens (2DR) have proven effective in clinical trials but real-world data, especially in resource-limited settings, is limited. Objectives To evaluate viral suppression of lamivudine-based 2DR, with dolutegravir or ritonavir-boosted protease inhibitor (lopinavir/r, atazanavir/r or darunavir/r), among all cases regardless of selection criteria. Patients and methods A retrospective study, conducted in an HIV clinic in the metropolitan area of São Paulo, Brazil. Per-protocol failure was defined as viremia above 200 copies/mL at outcome. Intention-To-Treat-Exposed (ITT-E) failure was considered for those who initiated 2DR but subsequently had either (i) Delay over 30 days in Antiretroviral Treatment (ART) dispensation, (ii) ART changed or (iii) Viremia > 200 copies/mL in the last observation using 2DR. Results Out of 278 patients initiating 2DR, 99.6% had viremia below 200 copies/mL at last observation, 97.8% below 50 copies/mL. Lamivudine resistance, either documented (M184V) or presumed (viremia > 200 copies/mL over a month using 3TC) was present in 11% of cases that showed lower suppression rates (97%), but with no significant hazard ratio to fail per ITT-E (1.24, p= 0.78). Decreased kidney function, present in 18 cases, showed of 4.69 hazard ratio (p= 0.02) per ITT-E for failure (3/18). As per protocol analysis, three failures occurred, none with renal dysfunction. Conclusions The 2DR is feasible, with robust suppression rates, even when 3TC resistance or renal dysfunction is present, and close monitoring of these cases may guarantee long-term suppression.

SARS-CoV-2 testing among patients and healthcare professionals in an HIV outpatient clinic in Brazil

ABSTRACT The COVID-19 pandemic in Brazil has been marked by high infection and death rates. The immune response generated by current vaccination might be influenced by previous natural infection, and baseline estimates may help in the evaluation of vaccine-induced serological response. We evaluated previous SARS-CoV-2 testing (RT-PCR), and performed rapid diagnostic tests (RDT) and high throughput electrochemiluminescence immunoassay (ECLIA) before vaccination among people living with HIV (PLWH), users of antiretroviral prophylaxis (PrEP/PEP), and healthcare professionals in an HIV outpatient clinic (HCP-HC). RDT was positive in 25.7% (95% CI: 19-33%) overall, 31.3% (95% CI : 18-45%) among PLWH, 23.7% (95% CI : 14-34%) in PrEP/PEP users and 21.4% (95% CI : 05-28%) in HCP-HC (p=0.548). Diagnostic RT-PCR testing was very limited, even for symptomatic individuals, and whereas all HCP-HC had one test perfomed, only 35% of the patients (PREP/PEP/PLWH) were tested (p<0.0001). Adequate monitoring of post-vaccination humoral response and breakthrough infections including those in asymptomatic cases are warranted, especially in immunologically compromised individuals.

Impact of covid-19 on people living with HIV-1: care and prevention indicators at a local and nationwide level, Santo André, Brazil

ABSTRACT The world has been dealing with Aids for forty years, covid-19 accentuated societal inequalities and promoted a rupture in care and prevention, including for people living with HIV. We compiled official HIV indicators, analyzed the impact of covid-19 in Brazil, at São Paulo State (SP), and compared it to the municipality of Santo André (in the state of São Paulo), which adopted linkage/retention strategies to mitigate the impact of covid-19. From 2019 to 2020, suppression/adhesion rates remained stable. The number of new treatments decreased both in Brazil (-19.75%) and São Paulo (-16.44%), but not in Santo André, where 80% of new patients started treatment within 30 days from their first TCD4 test (70% in São Paulo and 64% in Brazil). However, PrEP dispensing increased during this period. The distribution of 2,820 HIV self-tests in Santo André lead to only one documented new HIV diagnosis linked to care. Synergistic strategies to swiftly diagnose and connect new cases, ensuring retention as well as rescuing missing patients deserve priority in the fight against HIV, especially in times of covid-19.

Recent HIV infections: evaluation of a simple identification score for newly diagnosed patients

ABSTRACT OBJECTIVE Recognize incident infection to better characterize the groups that fuel HIV epidemic. We propose a simple score to identify recent infections among newly diagnosed patients as a HIV surveillance tool. METHODS Newly diagnosed patients were defined as recent infections when a negative serological test in the previous year was available. Laboratory tests, such as the avidity index (Bio-Rad, according to the CEPHIA protocol), chemiluminescent intensity (CMIA, architect, Abbott), and the nucleotide ambiguity index of partial pol sequences were used as proxies of recency. A simple score based on clinical symptoms of acute retroviral syndrome during the previous year, CD4+ T cell count, and viral load at admission was tested to assess the predictive power, using receiver operating characteristic (ROC) curves, to identify recent cases of infection. RESULTS We evaluated 204 recently diagnosed patients who were admitted to the Ambulatório de Referência em Moléstias Infecciosas de Santo André (Santo André Reference Infectious Diseases Outpatient Clinic), in the metropolitan region of São Paulo, Brazil, recruited between 2011 and 2018. An HIV-negative test in the year prior to enrollment was documented in 37% of participants. The proportion of cases classified as recent infections (less than one year), according to the laboratory proxies were: 37% (67/181) for an avidity index < 40%, 22% (30/137) for a CMIA < 200, and 68% (124/181) for an ambiguity index < 0.5%. Using different combinations of recency definitions, our score showed an area under the ROC curve from 0.66 to 0.87 to predict recency. CONCLUSIONS Using data from patients' interviews and routine laboratory tests at admission, a simple score may provide information on HIV recency and thus, a proxy for HIV incidence to guide public policies. This simple for the Brazilian public health system and other low- and middle-income countries.

Field evaluation of COVID­19 antigen tests versus RNA based detection: Potential lower sensitivity compensated by immediate results, technical simplicity, and low cost

One year into the coronavirus disease 2019 (COVID­19) pandemic, diagnosticstrategies, although central for contact tracing and other preventive measures, arestill limited. To meet the global demand, lower cost and faster antigen tests forsevere acute respiratory syndrome coronavirus 2 (SARS­CoV­2) detection are aconvenient alternative to the gold standard reverse transcription­polymerase chainreaction (RT­PCR) assay. We tested laboratory­based RT­PCR RNA detection andtwo rapid antigen detection (RAD) tests, based on the immunochromatography testfor nucleocapsid protein of SARS­CoV­2 (COVID­19 Ag ECO Test, ECO Diagnóstica,and Panbio COVID­19 Ag Rapid Test Abbott). Paired collection and testing weredone in a small prospective open study in three clinical services in São Paulo,constituted of mostly symptomatic volunteers at collection (97%, 109/112) for amedian of 4 days (interquartile range: 3­6), ranging from 1 to 30. Among the108 paired RT­PCR/RAD tests, results were concordant in 96.4% (101/108). Thetest's performance was comparable, with an overall sensitivity of 87% and aspecificity of 96%. These observations add to other data that suggest that antigentests may provide reasonable sensitivity and specificity and deserve a role toimprove testing strategies, especially in resource­limited settings.

Young age and sex work are associated with HIV seroconversion among transgender women in São Paulo, Brazil

Background: Transgender women worldwide have among the highest prevalence of HIV and the lowest access to prevention among groups at risk. However, few longitudinal studies have directly measured HIV incidence and identified predictors of HIV acquisition among transgender women. Setting: São Paulo, Latin America's largest city. Methods: We conducted a longitudinal study among transgender women in São Paulo. Participants were recruited by a long-chain peer referral process from May 2017 to July 2019. Those age 18 years and older and HIV-negative at baseline were retested every 6 months up to 18 months. HIV incidence was calculated by dividing the number of seroconversions by the person-years (py) of follow-up; 95% confidence intervals (CI) were constructed assuming a Poisson distribution. Conditional maximum likelihood ratios assessed differences in HIV incidence by risk factors. Results: A racial/ethnically diverse sample of 545 transgender women were enrolled. In 485.5 py of follow-up, 13 seroconversions were observed yielding an incidence of 2.68 per 100 py (95% CI 1.43­4.58). HIV incidence was significantly higher among transgender women age 18 to 24 years (rate ratio 3.85, 95% CI 1.24­12.93) and among those who engaged in sex work in the preceding month (rate ratio 5.90, 95% CI 1.71­26.62). Conclusion: HIV transmission continues at a high rate among transgender women in Brazil. Factors such as young age, lower level of education, and limited employment opportunities may lead to dependence upon sex work which in turn increase HIV risk. Transgender-friendly prevention services, particularly programs delivering pre-exposure prophylaxis (PrEP) are urgently needed.

Simple protocol for population (Sanger) sequencing for Zika virus genomic regions

BACKGROUND A number of Zika virus (ZIKV) sequences were obtained using Next-generation sequencing (NGS), a methodology widely applied in genetic diversity studies and virome discovery. However Sanger method is still a robust, affordable, rapid and specific tool to obtain valuable sequences. OBJECTIVE The aim of this study was to develop a simple and robust Sanger sequencing protocol targeting ZIKV relevant genetic regions, as envelope protein and nonstructural protein 5 (NS5). In addition, phylogenetic analysis of the ZIKV strains obtained using the present protocol and their comparison with previously published NGS sequences were also carried out. METHODS Six Vero cells isolates from serum and one urine sample were available to develop the procedure. Primer sets were designed in order to conduct a nested RT-PCR and a Sanger sequencing protocols. Bayesian analysis was used to infer phylogenetic relationships. FINDINGS Seven complete ZIKV envelope protein (1,571 kb) and six partial NS5 (0,798 Kb) were obtained using the protocol, with no amplification of NS5 gene from urine sample. Two NS5 sequences presented ambiguities at positions 495 and 196. Nucleotide analysis of a Sanger sequence and consensus sequence of previously NGS study revealed 100% identity. ZIKV strains described here clustered within the Asian lineage. MAIN CONCLUSIONS The present study provided a simple and low-cost Sanger protocol to sequence relevant genes of the ZIKV genome. The identity of Sanger generated sequences with published consensus NGS support the use of Sanger method for ZIKV population studies. The regions evaluated were able to provide robust phylogenetic signals and may be used to conduct molecular epidemiological studies and monitor viral evolution.

Undiagnosed acute HIV infection identified through RNA testing of pooled serum samples obtained during a dengue outbreak in São Paulo, Brazil

Abstract INTRODUCTION: Improving HIV diagnostics and treatment is necessary to end the AIDS epidemic. Pooled plasma can be used to identify patients with acute HIV disease, even before serological tests. During dengue outbreaks, patients having symptoms common to other acute viral diseases might seek medical care. METHODS: We evaluated HIV RNA in pooled seronegative dengue samples. RESULTS: After excluding individuals with a known HIV diagnosis, an HIV-1 prevalence of 0.73% [95% confidence interval (CI) 0.23-1.76; 4/546 samples] was found. CONCLUSIONS: Promoting strategies to diagnose these individuals and provide them with medical treatment might be instrumental for controlling the HIV epidemic.

High degree of concordance between flow cytometry and geno2pheno methods for HIV-1 tropism determination in proviral DNA

Use of CCR5 antagonists requires previous viral tropism determination. The available methods have high cost, are time-consuming, or require highly trained personnel, and sophisticated equipment. We compared a flow cytometry-based tropism assay with geno2pheno method to determine HIV-1 tropism in AIDS patients, in Bahia, Brazil. We tested peripheral blood mononuclear cells of 102 AIDS patients under antiretroviral therapy by using a cytometry-based tropism assay and geno2pheno assay. Cellular membrane receptors were identified by using CXCR4, CCR5 and CD4 monoclonal antibodies, while detection of cytoplasmic mRNAs for gag and pol HIV regions was achieved by using a labeled probe. Genotypic identification of X4 and R5 tropic viruses was attempted by geno2pheno algorithm. There was a high degree of concordance between cytometry-based tropism assay and geno2pheno algorithm in determination of HIV-1 tropism. Cytometry-based tropism assay demonstrated higher sensitivity and specificity in comparison to geno2pheno, which was used as a gold-standard. One sample could not be amplified by geno2pheno method, but was classified as duotropic by cytometry-based tropism assay. We did not find any association between CD4+ count or plasma HIV-1 RNA viral load and tropism results. The overall performances of cytometry-based tropism assay and geno2pheno assay were almost identical in determination of HIV-1 tropism.

Association of X4 tropism with disease progression in antiretroviral-treated children and adolescents living with HIV/AIDS in São Paulo, Brazil

Management of children with HIV/AIDS is specially challenging. Age-related issues do not allow for direct transposition of adult observations to this population. CXCR4 tropism has been associated with disease progression in adults. The geno2pheno web-base is a friendly tool to predict viral tropism on envelope V3 sequences, generating a false positive rate for a CXCR4 prediction. We evaluated the association of HIV-1 tropism prediction with clinical and laboratory outcome of 73 children with HIV/AIDS in São Paulo, Brazil. The CXCR4 tropism was strongly associated with a lower (nadir) CD4 documented during follow-up (p < 0.0001) and with disease severity (clinical event and/or CD4 below 200 cells/mm3) at the last observation, using commonly applied clinical cutoffs, such as10%FPRclonal (p = 0.001). When variables obtained during follow-up are included, both treatment adherence and viral tropism show a significant association with disease severity. As for viremia suppression, 30% (22/73) were undetectable at the last observation, with only adherence strongly associated with suppression after adjustment. The study brings further support to the notion that antiretroviral treatment adherence is pivotal to management of HIV disease, but suggests that tropism prediction may provide an additional prognostic marker to monitor HIV disease in children.

Genetic diversity and primary resistance among HIV-1-positive patients from Maringá, Paraná, Brazil / Diversidade genética e resistência primária entre pacientes HIV-1-positivos de Maringá, Paraná, Brasil

The objective of this study is to identify subtypes of Human Immunodeficiency Virus type 1 (HIV-1) and to analyze the presence of mutations associated to antiretroviral resistance in the protease (PR) and reverse transcriptase (RT) regions from 48 HIV-1 positive treatment naïve patients from an outpatient clinic in Maringá, Paraná, Brazil. Sequencing was conducted using PR, partial RT and group-specific antigen gene (gag) nested PCR products from retrotranscribed RNA. Transmitted resistance was determined according to the Surveillance Drug Resistance Mutation List (SDRM) algorithm. Phylogenetic and SimPlot analysis of concatenated genetic segments classified sequences as subtype B 19/48 (39.6%), subtype C 12/48 (25%), subtype F 4/48 (8.3%), with 13/48 (27.1%) recombinant forms. Most recombinant forms were B mosaics (B/F 12.5%, B/C 10.4%), with one C/F (2.1%) and one complex B/C/F mosaic (2.1%). Low levels of transmitted resistance were found in this study, 2/48 (2.1% to NRTIs and 2.1% for PI). This preliminary data may subsidize the monitoring of the HIV evolution in the region.

O objetivo foi identificar subtipos do Vírus da Imunodeficiência Humana tipo-1 (HIV-1) e analisar a presença de mutações/polimorfismos nas regiões da protease (PR) e transcriptase reversa (TR) de 48 pacientes virgens de tratamento atendidos no município de Maringá, Paraná, Brasil. O sequenciamento foi conduzido usando produtos de nested PCR dos genes da PR, TR parcial e group-specific antigen gene (gag) de RNA retrotranscrito. A interpretação da resistência transmitida foi realizada segundo o algoritmo Surveillance Drug Resistance Mutation List (SDRM). As análises filogenética e SimPlot dos segmentos concatenados classificaram as sequências como subtipo B 19/48 (39,6%), subtipo C 12/48 (25%), subtipo F 4/48 (8,3%), com 13/48 (27,1%) formas recombinantes. A maioria das formas recombinantes era mosaicos B (B/F 12,5%, B/C 10,4%), com um C/F (2,1%) e um mosaico complexo B/C/F (2,1%). A prevalência de resistência transmitida foi de 4,2% (2,1% para ITRN e 2,1% para IP). Baixos níveis de resistência transmitida foram encontrados nesse estudo, 2/48 (2,1% para INTR e 2,1% para IP). Esses achados, embora preliminares, podem contribuir no monitoramento da epidemia de HIV na região.

HIV-1 tropism and CD4 T lymphocyte recovery in a prospective cohort of patients initiating HAART in Ribeirão Preto, Brazil

While human immunodeficiency virus (HIV)-1 chemokine co-receptors 5 tropism and the GWGR motif in the envelope third variable region (V3 loop) have been associated with a slower disease progression, their influence on antiretroviral response remains unclear. The impact of baseline V3 characteristics on treatment response was evaluated in a randomised, double blind, prospective cohort study with patients initiating highly active antiretroviral therapy with lopinavir or efavirenz plus azithothymidine/3TC (1:1) over 48 weeks. Similar virological and immunological responses were observed for both treatment regimens. The 43 individuals had a mean baseline CD4 T cell count of 119 cells/mm³ [standard deviation (SD) = 99] and a mean viral load of 5.09 log10 copies/mL (SD = 0.49). The GWGR motif was not associated with a CD4 T cell response, but predicted R5 tropism by the geno2pheno[clinical20 percent] algorithm correlated with higher CD4 T cell levels at all monitoring points (p < 0.05). Moreover, higher false-positive rates (FPR) values from this analysis revealed a strong correlation with CD4 T cell recovery (p < 0.0001). Transmitted drug resistance mutations, documented in 3/41 (7.3 percent) cases, were unrelated to the assigned antiretroviral regimen and had no impact on patient outcomes. In conclusion, naÏve HIV-1 R5 infected patients exhibited higher CD4 T cell counts at baseline; this difference was sustained throughout therapy. The geno2pheno[clinical] option FPR positively correlated with CD4 T cell gain and may be useful in predicting CD4 T cell recovery.

Epidemiologic and clinical characteristics of pregnant women living with HIV/AIDS in a region of Southern Brazil where the subtype C of HIV-1 infection predominates

Southern Brazil has the highest prevalence rate of AIDS in the country and is the only region in the Americas where HIV-1 subtype C prevails. OBJECTIVE: We evaluated the epidemiologic and clinical characteristics of pregnant women living with HIV/AIDS in the South region of Santa Catarina, Brazil. METHODS: All pregnant women with HIV infection attending the obstetric outpatient clinic of Criciúma, State of Santa Catarina, in 2007 (n = 46) were invited to participate. Data of 36 eligible participants were obtained through a standardized questionnaire. RESULTS: The great majority were young, with a steady partner, low family income, low education level and referring early first sexual intercourse. Many reported use of illicit non-injecting drugs (55.5 percent) and unprotected sex with partners that were HIV-positive (57.7 percent), injecting drug user (22.2 percent), male inmate (19.4 percent), truck driver (13.8 percent), with history of sexually transmitted disease (11.1 percent) or men who have sex with men (MSM) (2.8 percent). Most (66.7 percent) of the participants had their HIV diagnosis done during the pregnancy, 7 (19.4 percent) had a previous history of HIV mother-to-child transmission. Therapy based on highly active antiretroviral therapy (94 percent) was initiated at 19.3 weeks on average and 33 percent showed irregular antiretroviral adherence. CONCLUSION: These results confirm previous data on HIV epidemiology in Brazil and suggest that the women partners' sexual behavior and unprotected sexual intercourse are important aspects of HIV epidemic. Additional efforts in education, prophylaxis and medication adherence are needed.

Sequence analysis of the 2009 pandemic influenza A H1N1 virus haemagglutinin gene from 2009-2010 Brazilian clinical samples

In this paper, we analysed the haemagglutinin (HA) gene identified by polymerase chain reaction from 90 influenza A H1N1 virus strains that circulated in Brazil from April 2009-June 2010. A World Health Organization sequencing protocol allowed us to identify amino acid mutations in the HA protein at positions S220T (71 percent), D239G/N/S (20 percent), Y247H (4.5 percent), E252K (3.3 percent), M274V (2.2 percent), Q310H (26.7 percent) and E391K (12 percent). A fatal outcome was associated with the D239G mutation (p < 0.0001). Brazilian HA genetic diversity, in comparison to a reference strain from California, highlights the role of influenza virus surveillance for study of viral evolution, in addition to monitoring the spread of the virus worldwide.

Molecular characterisation of newly identified HIV-1 infections in Curitiba, Brazil: preponderance of clade C among males with recent infections

As in many areas of Brazil, the AIDS epidemic in Curitiba is relatively stable, but surveillance is important to support public policy. The molecular characteristics of HIV may be instrumental for monitoring epidemic trends. We evaluated plasma HIV-1 RNA (n = 37) from 38 cases presenting with positive serology, who were among 820 consenting volunteers visiting the downtown counselling and serology testing centre. Seroprevalence was 4.6 percent (CI 95 percent 3.2-6.3) and the estimated HIV incidence, as defined by the BED assay, was 2.86 persons/years (CI 95 percent 1.04-4.68). An additional set of contemporaneous, anonymous samples from a local laboratory was also analysed (n = 20). Regions of the HIV-1 polymerase (n = 57) and envelope (n = 34) were evaluated for subtyping, determination of mosaic structure, primary drug resistance mutations (pDRM), envelope V3 loop motifs and amino acid signatures related to viral tropism. HIV-1 clade B was observed in 53 percent of cases; HIV-1C in 30 percent and BC mosaics in 14 percent, with one F genome and one CF mosaic. Clade C infection was associated with recent infections among males (p < 0.03). Stanford surveillance pDRM was observed in 8.8 percent of sequences, with 7 percent showing high level resistance to at least one antiretroviral drug. Tropism for CXCR4 co-receptor was predicted in 18 percent of envelope sequences, which were exclusively among clade B genomes and cases with serological reactivity to chronic infection.

Antiretroviral resistance mutations in human immunodeficiency virus type 1 infected patients enrolled in genotype testing at the Central Public Health Laboratory, São Paulo, Brazil: preliminary results

Antiretroviral resistance mutations (ARM) are one of the major obstacles for pharmacological human immunodeficiency virus (HIV) suppression. Plasma HIV-1 RNA from 306 patients on antiretroviral therapy with virological failure was analyzed, most of them (60 percent) exposed to three or more regimens, and 28 percent of them have started therapy before 1997. The most common regimens in use at the time of genotype testing were AZT/3TC/nelfinavir, 3TC/D4T/nelfinavir and AZT/3TC/efavirenz. The majority of ARM occurred at protease (PR) gene at residue L90 (41 percent) and V82 (25 percent); at reverse transcriptase (RT) gene, mutations at residue M184 (V/I) were observed in 64 percent. One or more thymidine analogue mutations were detected in 73 percent. The number of ARM at PR gene increased from a mean of four mutations per patient who showed virological failure at the first ARV regimens to six mutations per patient exposed to six or more regimens; similar trend in RT was also observed. No differences in ARM at principal codon to the three drug classes for HIV-1 clades B or F were observed, but some polymorphisms in secondary codons showed significant differences. Strategies to improve the cost effectiveness of drug therapy and to optimize the sequencing and the rescue therapy are the major health priorities.

Produçäo de um antígeno de sarampo por multiplicidade de infecçäo, com rendimento e reprodutibilidade / The role of m.o.i. in standardization of measles antigen preparation

Sarampo é uma doença potencialmente grave e comum, cuja vacinaçäo previne ou atenua as manifestaçöes clínicas. Métodos sorológicos utilizados na detecçäo de anticorpos para o vírus do sarampo têm sido empregados, como o teste de inibiçäo da hemaglutinaçäo e ELISA. Para produçäo de antígeno do sarampo com maior rendimento, e melhor reprodutibilidade, realizamos estudos com diferentes multiplicidades de infecçäo (M.I). Nossos resultados levam-nos a sugerir que a produçäo de antígenos de sarampo é mais eficiente com a utilizaçäo de multiplicidade de infecçäo (M.I) de 0,01 com boa reprodutibilidade, tanto na preparaçäo de ensaios de HA como de ELISA, devendo servir de parâmetro na preparaçäo de antígenos em larga escala para uso em ensaios diagnósticos

Alteraçöes imunológicas associadas ao vírus da imunodeficiência humana (HIV) / Immunological changes associated with human immunodeficiency virus (HIV)

A infecçäo pelo vírus da imunodeficiência humana, HIV, pode geral imunodisfunçäo que propicia o desenvolvimento de processos oportunistas, neoplásicos ou infecciosos, quase sempre fatais. O processo patológico associado a infecçäo envolve, caracteristicamente, a destruiçäo ou mau funcionamento dos linfócitos T auxiliares (CD4+). Isto decorre, entre outros fatores, do parasitismo direto do vírus ou da resposta imune estabelecida secundariamente, que pode incluir mecanismos auto-imunes. Essa alteraçäo, associada a açäo direta do HIV sobre outras células do organismo, pertuba a produçäo de fatores tróficos, a proliferaçäo, diferenciaçäo e capacidade efetora de diferentes células do sistema imune. O longo período de latência, no qual uma maioria de indivíduos permanece assintomática ou com alteraçöes discretas, sugere a importância de cofatores ainda mal delineados, talves inerentes ao hospedeiro ou de outros agentes ambientais, que parecem modular a progressäo para a síndrome (AIDS/SIDA)