Ongoing HIV-1 evolution and reservoir reseeding in two elite controllers with genetically diverse peripheral proviral quasispecies

BACKGROUND Elite controllers (EC) are human immunodeficiency virus (HIV)-positive individuals who can maintain low viral loads for extended periods without antiretroviral therapy due to multifactorial and individual characteristics. Most have a small HIV-1 reservoir composed of identical proviral sequences maintained by clonal expansion of infected CD4+ T cells. However, some have a more diverse peripheral blood mononuclear cell (PBMC)-associated HIV-1 reservoir with unique sequences. OBJECTIVES To understand the turnover dynamics of the PBMC-associated viral quasispecies in ECs with relatively diverse circulating proviral reservoirs. METHODS We performed single genome amplification of the env gene at three time points during six years in two EC with high intra-host HIV DNA diversity. FINDINGS Both EC displayed quite diverse PBMCs-associated viral quasispecies (mean env diversity = 1.9-4.1%) across all time-points comprising both identical proviruses that are probably clonally expanded and unique proviruses with evidence of ongoing evolution. HIV-1 env glycosylation pattern suggests that ancestral and evolving proviruses may display different phenotypes of resistance to broadly neutralising antibodies consistent with persistent immune pressure. Evolving viruses may progressively replace the ancestral ones or may remain as minor variants in the circulating proviral population. MAIN CONCLUSIONS These findings support that the high intra-host HIV-1 diversity of some EC resulted from long-term persistence of archival proviruses combined with the continuous reservoir's reseeding and low, but measurable, viral evolution despite undetectable viremia.

Genome-wide analyses of HTLV-1aD strains from Cape Verde, Africa

We characterised and reported the first full-length genomes of Human T-cell Lymphotropic Virus Type 1 subgroup HTLV-1aD (CV21 and CV79). This subgroup is one of the major determinants of HTLV-1 infections in North and West Africa, and recombinant strains involving this subgroup have been recently demonstrated. The CV21 and CV79 strains from Cape Verde/Africa were characterised as pure HTLV-1aD genomes, comparative analyses including HTLV-1 subtypes and subgroups revealed HTLV-1aD signatures in the envelope, pol, and pX regions. These genomes provide original information that will contribute to further studies on HTLV-1a epidemiology and evolution.

Estimates of HIV-1 incidence based on serological methods: a brief methodological review / Estimativas de incidência da infecção pelo HIV-1 baseadas em métodos sorológicos: uma sumária revisão metodológica

The paper reviews the serological methods employed in the estimation of HIV incidence based on cross-sectional studies, as well as the main findings from studies carried out in Brazil that have used such methods. Each method is briefly described, as well as their advantages and limitations. The different methods are also analyzed as a set of complementary but sometimes contradictory strategies under permanent criticism and review, still far from a gold standard. Finally, an additional question percent central to the accurate monitoring of the AIDS epidemic using such methods percent is discussed: whether the different methods should or should not be adjusted. The debate is open and controversy should be viewed as an unavoidable consequence of a very dynamic research field, informed by the progress in sciences as diverse as epidemiology, biostatistics, mathematical modeling and different branches of basic science, such as immunology, virology, and molecular biology.

O artigo revisa os métodos sorológicos utilizados na estimação da incidência da infecção pelo HIV baseada em estudos seccionais, assim como os principais achados de estudos conduzidos no Brasil que utilizaram estes métodos. Cada um dos métodos foi descrito sucintamente, assim como suas vantagens e limitações. Os diferentes métodos foram ainda analisados enquanto um conjunto de estratégias complementares, por vezes, contraditórias, sob permanente crítica e revisão, ainda longe de um padrão-ouro. Finalmente, uma questão adicional por cento essencial a um monitoramento acurado da epidemia por meio desses métodos por cento é discutida: devem tais métodos ser ajustados ou não? O debate segue em aberto e deve ser visto como um desdobramento inevitável de um campo de pesquisa particularmente dinâmico, informado pelos avanços de ciências as mais diversas, como a epidemiologia, a estatística e a modelagem matemática, além das várias áreas da ciência básica, como imunologia, virologia e biologia molecular.

HIV rapid testing as a key strategy for prevention of mother-to-child transmission in Brazil / Teste rápido para o HIV como estratégia de prevenção da transmissão vertical no Brasil / Prueba rápida para el HIV como una estrategia para la prevención de la transmisión vertical en Brasil

OBJECTIVE: To assess the feasibility of HIV rapid testing for pregnant women at maternity hospital admission and of subsequent interventions to reduce perinatal HIV transmission. METHODS: Study based on a convenience sample of women unaware of their HIV serostatus when they were admitted to delivery in public maternity hospitals in Rio de Janeiro and Porto Alegre, Brazil, between March 2000 and April 2002. Women were counseled and tested using the Determine HIV1/2 Rapid Test. HIV infection was confirmed using the Brazilian algorithm for HIV infection diagnosis. In utero transmission of HIV was determined using HIV-DNA-PCR. There were performed descriptive analyses of sociodemographic data, number of previous pregnancies and abortions, number of prenatal care visits, timing of HIV testing, HIV rapid test result, neonatal and mother-to-child transmission interventions, by city studied. RESULTS: HIV prevalence in women was 6.5 percent (N=1,439) in Porto Alegre and 1.3 percent (N=3.778) in Rio de Janeiro. In Porto Alegre most of women were tested during labor (88.7 percent), while in Rio de Janeiro most were tested in the postpartum (67.5 percent). One hundred and forty-four infants were born to 143 HIV-infected women. All newborns but one in each city received at least prophylaxis with oral zidovudine. It was possible to completely avoid newborn exposure to breast milk in 96.8 percent and 51.1 percent of the cases in Porto Alegre and Rio de Janeiro, respectively. Injectable intravenous zidovudine was administered during labor to 68.8 percent and 27.7 percent newborns in Porto Alegre and Rio de Janeiro, respectively. Among those from whom blood samples were collected within 48 hours of birth, in utero transmission of HIV was confirmed in 4 cases in Rio de Janeiro (4/47) and 6 cases in Porto Alegre (6/79). CONCLUSIONS: The strategy proved feasible in maternity hospitals in Rio de Janeiro and Porto Alegre. Efforts must be taken to maximize HIV testing during labor. There is a need of strong social support to provide this population access to health care services after hospital discharge.

OBJETIVO: Analisar a viabilidade da testagem rápida para o HIV entre gestantes na admissão à maternidade e de intervenções para reduzir a transmissão perinatal do HIV. MÉTODOS: Amostra de conveniência de mulheres que desconheciam sua situação sorológica para o HIV quando admitidas para o parto em maternidades públicas do Rio de Janeiro, RJ, e de Porto Alegre, RS, entre março de 2000 e abril de 2002. As mulheres foram aconselhadas e testadas com teste rápido Determine HIV1/2 na maternidade. Infecção pelo HIV foi confirmada pelo algoritmo brasileiro para o diagnóstico da infecção pelo HIV. A transmissão intra-útero foi determinada pelo PCR-DNA-HIV. Foram realizadas análises descritivas dos dados sociodemográficos, número de gestações e de abortos prévios, número de visitas de pré-natal, momento da testagem para o HIV, resultado do teste rápido para o HIV, intervenções recebidas pelos recém-natos e de transmissão vertical do HIV, de acordo com cada cidade. RESULTADOS: A prevalência de HIV entre as mulheres foi 6,5 por cento (N=1.439) em Porto Alegre e 1,3 por cento (N=3.778) no Rio de Janeiro. A maioria foi testada durante o trabalho de parto em Porto Alegre e no pós-parto, no Rio de Janeiro. Cento e quarenta e quatro crianças nasceram de 143 mulheres infectadas pelo HIV. Todos os recém-natos receberam ao menos a profilaxia com zidovudina oral, exceto um em cada cidade. Foi possível evitar qualquer exposição ao leite materno em 96,8 por cento e 51,1 por cento dos recém-natos em Porto Alegre e no Rio de Janeiro, respectivamente. A zidovudina injetável foi administrada durante o trabalho de parto para 68,8 por cento dos recém-natos em Porto Alegre e 27,7 por cento no Rio de Janeiro. Entre aqueles com amostras de sangue coletadas até 48 horas do nascimento, a transmissão intra-útero foi confirmada em quatro casos no Rio de Janeiro (4/47) e em seis casos em Porto Alegre (6/79). CONCLUSÕES: A estratégia mostrou-se factível nas maternidades do Rio de Janeiro e de Porto Alegre. Esforços devem ser empreendidos para maximizar a testagem durante o trabalho de parto. Forte suporte social precisa ser acoplado a essa estratégia para garantir o acesso dessa população ao sistema de saúde após a alta da maternidade.

OBJETIVO: Analizar la viabilidad de evaluación rápida del HIV entre gestantes en la admisión en la maternidad y de intervenciones para reducir la transmisión perinatal del HIV. MÉTODOS: Muestra de conveniencia de mujeres que desconocían su situación serológica para el HIV al ser admitidas para el parto en maternidades públicas de Rio de Janeiro (Sureste) y de Porto alegre (Sur de Brasil), entre marzo de 2000 y abril de 2002. Las mujeres fueron aconsejadas y evaluadas con prueba rápida Determine HIV1/2 en la maternidad. Infección por el HIV fue confirmada por el algoritmo brasilero para el diagnóstico de la infección por el HIV. La transmisión intra- útero fue determinada por el PCR-DNA-HIV. Fueron realizados análisis descriptivos de los datos sociodemográficos, número de gestaciones y de abortos previos, número de visitas de prenatal, momento de la evaluación para el HIV, resultado de la prueba rápida para el HIV, intervenciones recibidas por los recién nacidos y de transmisión vertical del HIV, de acuerdo con cada ciudad. RESULTADOS: La prevalencia de HIV entre las mujeres fue de 6,5 por ciento (N=1.439) en Porto Alegre y 1,3 por ciento (N=3,778) en Rio de Janeiro. La mayoría fue evaluada durante el trabajo de parto en Porto Alegre y en el postparto, en Rio de Janeiro. Ciento y cuarenta y cuatro niños nacieron de 143 mujeres infectadas por el HIV. Todos los recién nacidos recibieron al menos la profilaxia con zidovudina oral, excepto uno en cada ciudad. Fue posible evitar cualquier exposición a la leche materna en 96,8 por ciento y 51,1 por ciento de los recién nacidos en Porto Alegre y en Rio de Janeiro, respectivamente. La zidovudina inyectable fue administrada durante el trabajo de parto a 68,8 por ciento de los recién nacidos en Porto Alegre y 27,7 por ciento en Rio de Janeiro. Entre aquellos con muestras de sangre colectadas hasta 48 horas de nacimiento, la transmisión intra-útero fue confirmada en cuatro casos en Rio de Janeiro (4/47) y en seis casos en Porto Alegre (6/79). CONCLUSIONES: La estrategia se mostró factible en las maternidades de Rio de Janeiro y de Porto Alegre. Esfuerzos deben ser emprendidos para maximizar la evaluación durante el trabajo de parto. Fuerte soporte social precisa ser acoplado a esa estrategia para garantizar el acceso de dicha población al sistema de salud posterior a ser dado de alta de la maternidad.

Effectiveness of highly active antiretroviral therapy (HAART) used concomitantly with rifampicin in patients with tuberculosis and AIDS

This study evaluated the effectiveness of two HAART regimens concomitant to rifampicin based tuberculosis (TB) treatment. Patients with TB/HIV diagnosis followed at the TB program between June 2000 and March 2005 were prospectively evaluated. The different HAART regimens in antiretrovirals (ARV) treatment naïve and ARV experienced patients were compared. The effectiveness of HAART was defined as a VL <80 copies/mL from month 4 to month 10 after TB treatment. One hundred and forty-two patients were included. Among these, 68 (47 percent) were treatment naïve and 76 (53 percent) previously exposed. Odds ratio (OR) in naïve patients treated with efavirenz (EFV) based regimen (n=42) compared to ritonavir/saquinavir (RTV/SQV) based regimen (n=26) was 8.0 (CI=1.67-38.35, p=0.008). OR from ARV experienced patients treated with RTV/SQV based regimen compared to EFV was 3.08 (CI=0.65-14.6, p=0.15), although with no statistical significance. Better effectiveness and tolerability were observed in antiretrovirals treatment naïve patients using EFV based regimens. Although not statistically significant, a favorable virologic response and a better tolerability were observed in the ARV experienced patients group who received a RTV/SQV based regimen.

Prevalence of HIV type 1 drug resistance mutations in treatment-naïve and experienced patients from resource-limited settings with universal access to antiretroviral therapy: a survey in two small Brazilian cities

Concerns have been raised that universal availability of antiretroviral agents in resource-limited settings might lead to the emergence and spread of resistant strains. We present the largest survey on human immunodeficiency virus type 1 (HIV-1) resistance among treatment-naïve and experienced patients followed in small, relatively underprivileged cities in Brazil with universal availability to standard of care antiretroviral combinations. Samples were collected between 2004 and 2006 from 95 patients followed in the cities of Saquarema and Santo Antonio de Pádua, state of Rio de Janeiro. A proviral fragment encompassing protease and reverse transcriptase (RT) regions was generated and drug susceptibility level was inferred. Among 50 strains from drug-naïve subjects, one (2 percent) had intermediate-level resistance to RT inhibitors. Among 38 patients on therapy as of sampling, 28 (73.7 percent) had plasma viral load (PVL) below detection limit (26 of whom without evidence of resistance mutations) and 11 (28.9 percent) harbored strains with reduced susceptibility. Only two strains harbored both protease and RT inhibitor mutations. Among seven patients who were off-treatment as of sampling, two (28.5 percent) harbored strains with reduced susceptibility to RT inhibitors. The relatively high frequency of undetectable PVL among patients on treatment and the overall low prevalence of resistance-associated mutations are reassuring. Continued surveillance, however, is necessary.

Autochthonous horizontal transmission of a CRF02_AG strain revealed by a human immunodeficiency virus type 1 diversity survey in a small city in inner state of Rio de Janeiro, Southeast Brazil

As part of an ongoing study on the features of AIDS spread towards small cities and rural areas, we present a molecular survey of human immunodeficiency virus type 1 (HIV-1) polymerase sequences recovered between 2004 and 2006 from 71 patients receiving care in the city of Saquarema, inner state of Rio de Janeiro. Phylogenetic reconstructions found the two prevalent lineages in the state (subtypes B [59 strains, 83.1 percent], F1 [6 strains; 8.4 percent], and BF1 recombinants [four strains; 5.6 percent]), as well as two (2.8 percent) CRF02_AG strains, which seems to be an emerging lineage in the capital. These CRF02_AG sequences were recovered from a married heterosexual couple who never traveled abroad, thus providing the first molecular evidence of autochthonous horizontal transmission of this lineage of major global importance. Also, three phylogenetic clusters of strains recovered from a total of 18.3 percent of the cohort were uncovered. Their close genetic relatedness suggests they were recovered from patients who probably took part in the same chain of viral spread. In conjunction with our previous surveys from inner Rio de Janeiro, these results suggest that although small cities harbor unique molecular features of HIV-1 infection, they also clearly reflect and may rapidly absorb the diversity recorded in large urban centers.

Anti-human immunodeficiency virus type 1 humoral immune response and highly active antiretroviral treatment

Highly active antiretroviral treatment (HAART) of human immunodeficiency type 1 (HIV-1) infection is very effective in controlling infection, but elimination of viral infection has not been achieved as yet, and upon treatment interruption an immediate rebound of viremia is observed. A combination of HAART with an immune stimulation might allow treatment interruption without this rebounding viremia, as the very low viremias observed with successful HAART may be insufficient to permit maintenance of a specific anti-HIV-1 immune response. The objective of this study was to compare the humoral immune response of individuals undergoing successful HAART (NF=no failure) with that of individuals with evidence of failure of therapy (FT) and to verify if the viremia peaks observed in individuals with therapy failure would act as a specific stimulus for the humoral anti-HIV-1 immune response. Antibodies binding to gp120 V3 genotype consensus peptides were more frequently observed for FT, mainly against peptides corresponding to sequences of genotypes prevalent in the Rio de Janeiro city area, B and F. HIV-1 neutralization of HIV-1 IIIB and of four primary isolates from Rio de Janeiro was less frequently observed for plasma from the NF than the FT group, but this difference was more expressive when plasma from individuals with detectable viremia were compared to that of individuals with undetectable viral loads in the year before sample collection. Although statistically significant differences were observed only in some specific comparisons, the study indicates that presence of detectable viremia may contribute to the maintenance of a specific anti-HIV-1 humoral immune response.

Immune reconstitution syndrome in patients treated for HIV and tuberculosis in Rio de Janeiro

We made a retrospective longitudinal study from January 2000 to January 2003 to examine cases of immune reconstitution syndrome (IRS) and its incidence rate in tuberculosis (TB)-human immunodeficiency virus (HIV) co-infected patients. The incidence rate (IR) was calculated using a Poisson regression. The confidence interval (CI) that was stipulated was 95 percent. IRS occurred in 10/84 HIV and TB-positive patients; nine of them were on highly active anti-retroviral therapy (HAART) during a mean of 61.7 (±59) days following the introduction of antiretrovirals. Lymph-node enlargement was the sole clinical manifestation. CD4 counts were <100 cells/mm³in 50 percent of the patients, at the time of TB diagnosis. All but two patients were treated with prednisone, and recovered from TB within a mean of 91 days (±30 days). One relapse of TB was observed, but there were no IRS-related deaths. The incidence rate was higher (IR=11.18; CI, 1.41-88.76) in patients that had superficial lymph node enlargement at the moment of TB diagnosis (not associated with TB), extrapulmonary TB (IR=1.97; CI, 0.44-8.79), were antiretroviral naive (IR=1.85; CI, 0.48-7.16), and CD4 counts <100 cells/mm³ (IR=1.50; CI, 0.40-5.59), although with a wide CI. IRS was frequent in our sample, occurred more frequently in HIV-naive patients with lymph-node enlargement and extrapulmonary TB. No cases of new pulmonary lesions or worsening of pulmonary infiltrates were observed.

Epidemiologic features of HIV infection in three municipalities of inner Rio de Janeiro State, Brazil

In Brazil relatively little attention is being paid to the study of the features of the spread of the AIDS epidemic towards small cities and rural areas. We report a descriptive study on the epidemiological features of HIV infection among 208 adult patients seen between July 1999 and May 2006 in the municipal HIV/AIDS Programs of three cities of inner Rio de Janeiro State: Saquarema, Santo Antonio de Pádua and Miracema. A portrait of a heterosexual epidemic emerged, with an overall male to female ratio of 1.1. More than 90 percent were residents of the studied cities, demonstrating a local demand for HIV-related assistance and the importance of municipal HIV/AIDS Programs. Past or current use of snorted cocaine was reported by a quarter of the patients. Older age and male gender were independent predictors of having a diagnosis of AIDS at presentation. The latter is in accordance with a more recent wave of epidemic spread towards female gender. A low frequency of male circumcision, an important determinant of heterosexual HIV transmission, was recorded. Almost 60 percent of the patients first presented in advanced stages of HIV infection, suggesting the existence of a large pool of undiagnosed cases in the community.

No Brasil, relativamente pouca atenção vem sendo dispensada ao estudo das características do avanço da epidemia de Aids em direção aos pequenos municípios e áreas rurais. Apresentamos um estudo descritivo sobre as características epidemiológicas da infecção pelo HIV entre 208 pacientes adultos atendidos entre julho de 1999 e maio de 2006 pelos Programas Municipais de HIV/Aids de três municípios do interior do Estado do Rio de Janeiro: Saquarema, Santo Antonio de Pádua, e Miracema. Os resultados delineiam uma epidemia de perfil heterossexual, com uma razão de sexos homem-mulher de 1,1. Mais de 90 por cento eram residentes das cidades estudadas, demonstrando uma demanda local por assistência relacionada ao HIV e a importância dos Programas Municipais de HIV/Aids. Um quarto dos pacientes referiu antecedentes de uso de cocaína inalada. Variáveis idade e gênero masculino mostraram-se independentemente associadas a um diagnóstico de Aids quando da apresentação. Esta última mostra-se de acordo com um mais recente avanço da epidemia em direção às mulheres. Registramos uma baixa freqüência de circuncisão masculina, um importante determinante da transmissão heterossexual do HIV. Quase 60 por cento dos pacientes se apresentaram em estágios avançados de infecção HIV, o que sugere a existência de um grande reservatório de casos não diagnosticados na comunidade.

Molecular evidence that human immunodeficiency virus type 1 dissemination in a small Brazilian city was already taking place in the early 1990s

We recently performed a molecular epidemiology survey of human immunodeficiency virus type 1 (HIV-1) infection in Miracema, a small city in Southeast Brazil, and found multiple monophyletic clusters, consistent with independent introductions and spread of different viral lineages in the city. Here we apply Bayesian coalescent-based methods to the two largest subtype B clusters and estimate that the most recent common ancestors that gave rise to these two transmission chains were in circulation around 1991-1992. The finding that HIV-1 spread in this Brazilian small city was already taking place at a time Aids was considered a problem restricted to large urban centers may have important public health implications.

HIV-1 seroprevalence in the general population of Salvador, Bahia State, Northeast Brazil / Soroprevalência do HIV-1 na população geral de Salvador, Bahia, Brasil

To estimate HIV-1 seroprevalence in the general population of Salvador, Bahia, Brazil, we conducted a cross-sectional survey of 3,437 residents from 1998 to 2000. Subjects were drawn from 30 sentinel areas representing a wide range of living conditions. Plasma samples were screened for HIV-1 antibodies by ELISA and confirmed by immunofluorescent assay. Subtype determination by HMA was performed after proviral DNA amplification. Phylogenetic analysis using parsimony was performed with the neighbor-joining method. Overall HIV-1 seroprevalence was 0.55 percent (19/3,446): 0.8 percent for men and 0.36 percent for women. Seroprevalence was higher in the 31-45-year age group (1 percent) and among persons with family income less than twice the minimum wage (0.78 percent) as compared to 0.33 percent for the higher income group. Syphilis was detected in 37 percent of HIV seropositive individuals. Phylogenetic inferences identified 10 samples as subtype B in the env region and 2 samples with Benv/Fgag/Fpol and Fenv/Bgag. Age > 30 years, male gender, and income < 2 times the minimum wage were identified as risk factors for HIV-1 infection. Extrapolating the proportion of seropositive individuals to Salvador, the number of HIV-1 infected individuals was estimated at 13,750.

A seroprevalência do HIV-1 na população geral de Salvador, Bahia, Brasil, foi estimada em estudo de corte transversal com 3.437 indivíduos entre 1998-2000, residentes de 30 áreas sentinelas com ampla va-riedade de condições de vida. Realizou-se uma triagem para anticorpos anti-HIV-1 por ELISA e confirmados por imunofluorescência. A determinação do subtipo foi realizada por HMA, após amplificação do DNA proviral. As análises filogenéticas foram realizadas com PAUP utilizando os algoritmos neighbor-joining. A seroprevalência do HIV-1 foi de 0,55 por cento (19/3.446): 0,8 por cento para os homens e 0,36 por cento para as mulheres. A seroprevalência foi mais alta no grupo de 31-45 anos (1 por cento) e entre as pessoas com renda familiar inferior a dois salários mínimos (0,78 por cento). A sífilis foi diagnosticada em 37 por cento dos participantes HIV soropositivos. A análise filogenética identificou 10 amostras como subtipo B na região env, e duas amostras Benv/Fgag/Fpol e Fenv/Bgag. Idade > 30 anos, sexo masculino, renda < 2 salários mínimos se comportaram como fatores de riscos para a infecção por HIV-1. Se extrapolarmos a proporção de soropositivos para Salvador, o número de infectados pelo HIV seria 13.750.

Human immunodeficiency virus type- 1 subtypes of infected patients in Espírito Santo, Brazil

Genetic variability of human immunodeficiency virus type - 1(HIV-1) is a potential threat for both diagnosis and treatment of HIV/AIDS, as well as the development of effective vaccines. Up to now, HIV subtypes circulating among HIV-positive patients in the state of Espírito Santo were not known. In the present study, blood samples from 100 therapy-naïve HIV-1 infected patients were collected and the HIV subtype was determined through the Heteroduplex Mobility Assay (HMA). Ninety-seven out of 100 studied samples were subtyped by HMA, 73 samples (75.2 percent) were from subtype B, 9 (9.3 percent) from subtype F, 3 (3.1 percent) from subtype C, 6 (6.2 percent) Benv/Fgag, and another 6 (6.2 percent) Fenv/Bgag, what suggests that recombinant viruses were present in the studied samples. Twenty-eight percent of the subtype B samples were represented by the Brazilian B" subtype, which were identified by RFLP with Fok I. Data presented here demonstrate that the epidemiological characteristics of the HIV epidemic in the state of Espírito Santo are similar to those from the other Southeastern states and helped to better understand the genetic polymorphism of HIV in Brazil.

A genotyping study of human immunodeficiency virus type-1 drug resistance in a small Brazilian municipality

In Brazil, surveillance studies on antiretroviral drug resistance among drug-naïve and treatment-experienced patients have focused primarily on patients living in large urban centers. As the epidemic spreads towards small municipalities and the innermost parts of the country, it will be essential to monitor the prevalence of antiretroviral drug resistance in these areas. We report the first survey on the prevalence of antiretroviral drug resistance in a small Brazilian municipality. Between July 1999 and March 2005, 72 adult human immunodeficiency virus type-1(HIV-1)-infected patients received care at the Municipal HIV/AIDS Program of the small, southeastern municipality of Miracema, state of Rio de Janeiro. A genotyping study of antiretroviral drug resistance was performed in 54 patients. Among 27 samples from treatment-experienced patients, 9 (33.3 percent) harbored strains with reduced drug susceptibility. Among these, 6 had reduced susceptibility to reverse transcriptase (RT) inhibitors and 3 to both RT and protease inhibitors. No primary antiretroviral drug resistance was recorded among 27 drug-naïve subjects. The relatively low prevalence of resistance mutations in the Miracema cohort argues against the concern that resource-poor settings should not implement widespread accessibility to standard of care antiretroviral combinations due to the possibility of sub-optimal adherence leading to the emergence and spread of drug-resistant strains.

HIV infection and AIDS in a small municipality in Southeast Brazil

OBJETIVO: Estudos sobre as características da infecção pelo HIV em pequenos municípios brasileiros são de grande importância para o desenho de estratégias de intervenção, para a alocação apropriada de recursos e melhoria da assistência. O objetivo foi investigar as características clínicas e epidemiológicas da infecção pelo HIV em um pequeno município. MÉTODOS: Foi realizado estudo descritivo em Miracema, município do noroeste do Estado do Rio de Janeiro, entre julho de 1999 e dezembro de 2003. Foram analisados todos os pacientes adultos com diagnóstico de infecção pelo HIV atendidos no Programa Municipal de HIV/Aids. Dados clínicos e epidemiológicos foram coletados prospectivamente por meio de questionário padronizado. RESULTADOS: Foram analisados no total 65 pacientes adultos que receberam atendimento no Programa Municipal de HIV/Aids. A maioria (34) eram mulheres (razão de sexos homem-mulher de 0,9). Encontrou-se preponderância absoluta de pacientes que nasceram em Miracema ou municípios vizinhos (94 por cento), moravam em Miracema (90,7 por cento), eram solteiros (70,8 por cento), atribuíam a aquisição da infecção ao contato heterossexual desprotegido (72,3 por cento) e tinham antecedentes de uso de cocaína inalada (27,7 por cento). Desordens do sistema nervoso central (incluindo cinco casos de neurocriptococose) e insuficiência respiratória aguda semelhante à pneumocistose pulmonar foram as principais causas de morbidade. A maioria dos pacientes (56,9 por cento) iniciou acompanhamento em estágios avançados de infecção pelo HIV. CONCLUSÕES: A preponderância de pacientes em estágios avançados de infecção pelo HIV sugere a existência de um grande reservatório de casos não diagnosticados na comunidade. Uma característica marcante da casuística foi a inversão da razão de sexos homem-mulher. Investigações adicionais cobrindo áreas geográficas maiores são urgentemente necessárias para o melhor entendimento do espectro clínico e epidemiológico da infecção pelo HIV em pequenos municípios brasileiros e áreas rurais.

Is human immunodeficiency virus/acquired immunodeficiency syndrome decreasing among Brazilian injection drug users? Recent findings and how to interpret them

We briefly review findings from Brazilian settings where the human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) epidemic among injection drug users (IDUs) seems to be decreasing, highlighting recent findings from Rio de Janeiro and discussing methodological alternatives. Former analyses using serologic testing algorithm for recent HIV seroconversion have shown that HIV incidence has been low in IDUs recruited by two different surveys carried out in Rio, where low injection frequencies and infection rates have been found among new injectors. The proportion of AIDS cases among IDUs in Rio has been fairly modest, compared to São Paulo and especially to the southernmost states. Notwithstanding, the interpretation of findings from serial surveys constitutes a challenge, magnified in the assessment of HIV spread among IDUs due to the dynamic nature of the drug scenes and limitations of sampling strategies targeting hard-to-reach populations. Assessment of epidemic trends may profit from the triangulation of data, but cannot avert biases associated with sampling errors. Efforts should be made to triangulate data from different sources, besides exploring specific studies from different perspectives. In an attempt to further assess the observed trends, we carried out original analyses using data from Brazilian AIDS databank.

Molecular epidemiology of human immunodeficiency virus-1 in the state of Ceará, Northeast, Brazil

We analyzed, by env and gag heteroduplex mobility assay, 149 human immunodeficiency virus (HIV-1) positive samples collected in Ceará during the year 2000. The prevalence of subtype B was 81.2 percent and the prevalence of subtype F and B/F recombinants were both 2.7 percent. Eight (5.4 percent) and 12 (8 percent) out of 149 samples showed indeterminate results in the env and gag analysis respectively. By FokI restriction fragment length polymorphism, 34 percent of the subtype B samples were identified as the typical Brazilian subtype B.In the present study, we identified HIV-1 subtype F and B/F in Ceará for the first time. Our results contribute to the understanding of HIV in Brazil, and may prove useful for the development of vaccine candidates