RESUMO
INTRODUCTION: There is a risk of mother-to-child transmission of HIV (MTCT) during pregnancy and breastfeeding. The aim of this study was to assess vertical transmission of HIV among pregnant women who initially had false-negative rapid HIV tests in South African antenatal care (ANC) clinics. METHODS: Pregnant participants were enrolled in a diagnostic study that used nucleic acid amplification testing (NAAT) to screen for early HIV infection among individuals who tested negative on rapid HIV tests used at the point-of-care (POC) facilities. Participants were enrolled from four ANC clinics in the Tshwane district of South Africa. All NAAT-positive participants were recalled to the clinics for further management. Vertical transmission was assessed among exposed infants whose HIV polymerase chain reaction (PCR) results were available. RESULTS: This study enrolled 8208 pregnant participants who tested negative on rapid HIV tests between 2013 and 2016. Their median age was 26 years (interquartile range [IQR]: 23-30). NAAT detected HIV infections in 0.6% (n = 49; 95% confidence interval {CI}: 0.5-0.8) of all study participants. The distribution of these infections among the four clinics ranged from 0.3%- 1.1%, but this was not statistically significant (p = 0.07). Forty-seven participants (95.9%) were successfully recalled and referred for antiretroviral treatment initiation as part of prevention of MTCT (PMTCT). Most women with newly diagnosed HIV infection presented for the first ANC visit in the second (61.9%, n = 26) and third (31.0%, n = 13) trimesters. HIV PCR results were available for thirty-two infants, three of whom tested positive (9.4%; 95% CI: 1.98-25.02). CONCLUSIONS: This study showed that supplemental HIV testing for pregnant women led to earlier linkage to the PMTCT programme. Inaccurate diagnosis of HIV infection at ANC clinics is likely to undermine the efforts of eliminating MTCT particularly in HIV-endemic settings.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/diagnóstico , HIV/genética , Transmissão Vertical de Doenças Infecciosas/estatística & dados numéricos , Complicações Infecciosas na Gravidez/virologia , Adulto , Reações Falso-Negativas , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/transmissão , Humanos , Lactente , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Programas de Rastreamento , Idade Materna , Técnicas de Amplificação de Ácido Nucleico , Sistemas Automatizados de Assistência Junto ao Leito , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Cuidado Pré-Natal/métodos , África do Sul , Adulto JovemRESUMO
This was a prospective study that assessed field performance of the INSTI HIV-1/-2 antibody test (INSTI test) in two antenatal clinics in South Africa (SA). INSTI test was evaluated against rapid tests used at these clinics, and pooled nucleic acid amplification testing (NAAT) performed for individuals with negative rapid tests. Three hundred and eighty-six pregnant women were enrolled; 334 (86.5%) with negative results on the screening rapid test, and 52 (13.5%; 95% confidence interval [CI]: 10.2-17.3%) with positive results on screening and confirmatory rapid tests. INSTI test yielded the same results as other rapid tests in all participants, thus showing a 100% sensitivity (95% CI: 93.2-100.0%) and specificity (95% CI: 98.9-100.0%). Pooled NAAT was performed for 290 participants who had negative rapid tests, and yielded negative results in all pools. These data show excellent field performance of the INSTI test, and highlight that this test can be implementedat SA clinics.
Assuntos
Anticorpos Anti-HIV/sangue , Infecções por HIV/diagnóstico , Técnicas de Amplificação de Ácido Nucleico/normas , Kit de Reagentes para Diagnóstico/normas , Feminino , HIV-1 , HIV-2 , Humanos , Técnicas de Amplificação de Ácido Nucleico/economia , Gravidez , Estudos Prospectivos , Kit de Reagentes para Diagnóstico/economia , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: To assess the prevalence of HIV risk behaviour among sexually active HIV sero-negative individuals in the Tshwane district of South Africa (SA). METHODS: Demographic and HIV risk behaviour data were collected on a questionnaire from participants of a cross-sectional study that screened for early HIV infection using pooled nucleic acid amplification testing (NAAT). The study enrolled individuals who tested negative on rapid HIV tests performed at five HIV counseling and testing (HCT) clinics, which included four antenatal clinics and one general HCT clinic. RESULTS: The study enrolled 9547 predominantly black participants (96.6%) with a median age of 27 years (interquartile range [IQR]: 23-31). There were 1661 non-pregnant and 7886 pregnant participants largely enrolled from the general and antenatal HCT clinics, respectively. NAAT detected HIV infection in 61 participants (0.6%; 95% confidence interval [CI]: 0.4-0.8) in the whole study. A high proportion of study participants, 62.8% and 63.0%, were unaware of their partner's HIV status; and also had high prevalence, 88.5% and 99.5%, of recent unprotected sex in the general and pregnant population, respectively. Consistent use of condoms was associated with protection against HIV infection in the general population. Trends of higher odds for HIV infection were observed with most demographic and HIV risk factors at univariate analysis, however, multivariate analysis did not show statistical significance for almost all these factors. A significantly lower risk of HIV infection was observed in circumcised men (p <0.001). CONCLUSIONS: These data show that a large segment of sexually active people in the Tshwane district of SA have high risk exposure to HIV. The detection of newly diagnosed HIV infections in all study clinics reflects a wide distribution of individuals who are capable of sustaining HIV transmission in the setting where HIV risk behaviour is highly prevalent. A questionnaire that captures HIV risk behaviour would be useful during HIV counselling and testing to ensure that there is a systematic way of identifying HIV risk factors and that counselling is optimised for each individual. HIV risk behaviour surveillance could be used to inform relevant HIV prevention interventions that could be implemented at a community or population level.
Assuntos
Sorodiagnóstico da AIDS , Infecções por HIV/prevenção & controle , Comportamento Sexual , Adulto , Feminino , Infecções por HIV/transmissão , Humanos , Masculino , Assunção de Riscos , África do Sul , Adulto JovemRESUMO
BACKGROUND: Two thirds of the world's new HIV infections are in sub-Saharan Africa. Acute HIV infection (AHI) is the time of virus acquisition until the appearance of HIV antibodies. Early HIV infection, which includes AHI, is the interval between virus acquisition and establishment of viral load set-point. This study aimed to detect acute and early HIV infections in a hyper-endemic setting. METHODS: This was a cross-sectional diagnostic study that enrolled individuals who had negative rapid HIV results in five clinics in South Africa. Pooled nucleic acid amplification testing (NAAT) was performed, followed by individual sample testing in positive pools. NAAT-positive participants were recalled to the clinics for confirmatory testing and appropriate management. HIV antibody, p24 antigen, Western Blot and avidity tests were performed for characterization of NAAT-positive samples. RESULTS: The study enrolled 6910 individuals with negative rapid HIV results. Median age was 27 years (interquartile range {IQR}: 23-31). NAAT was positive in 55 samples, resulting in 0.8% newly diagnosed HIV-infected individuals (95% confidence interval {CI}: 0.6-1.0). The negative predictive value for rapid HIV testing was 99.2% (95% CI: 99.0-99.4). Characterization of NAAT-positive samples revealed that 0.04% (95% CI: 0.000-0.001) had AHI, 0.3% (95% CI: 0.1-0.4) had early HIV infection, and 0.5% (95% CI: 0.5-0.7) had chronic HIV infection. Forty-seven (86%) of NAAT-positive participants returned for follow-up at a median of 4 weeks (IQR: 2-8). Follow-up rapid tests were positive in 96% of these participants. CONCLUSIONS: NAAT demonstrated that a substantial number of HIV-infected individuals are misdiagnosed at South African points-of-care. Follow-up rapid tests done within a 4 week interval detected early and chronic HIV infections initially missed by rapid HIV testing. This may be a practical and affordable strategy for earlier detection of these infections in resource-constrained settings. Newer molecular tests that can be used at the points-of-care should be evaluated for routine diagnosis of HIV in hyper-endemic settings.
Assuntos
Doenças Endêmicas , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , HIV-1/fisiologia , Doença Aguda/epidemiologia , Adulto , Contagem de Linfócito CD4 , Estudos Transversais , Diagnóstico Precoce , Feminino , Infecções por HIV/imunologia , Humanos , Masculino , Carga ViralRESUMO
Hepatitis B virus (HBV) is a serious global health problem, and HBV genotype is an important determinant of disease progression and treatment outcome. The aim of this study was to assess variations of the precore/core (preC/C) region in HBV genotype A. Sequencing of the preC/C and surface (S) genes of HBV was performed on plasma samples from 20 HBV/HIV co-infected and 5 HBV mono-infected individuals. All preC/C study sequences clustered with subgenotype A1, except for two which clustered with subgenotype D4 reference strains. The nucleotide and amino acid variability was far higher in the preC/C region than in the S region. Mutations associated with reduction or failure of HBV e-antigen (HBeAg) production were observed, with a preC start codon mutation being common (24%). Other mutations (e.g., P5H/L and I97L) associated with severe liver disease were also noticed, some of which were located in the major histocompatibility restricted sites. PreC/C intergenotype nucleotide divergence was >7%, while subgenotypes differed by 2.5-7%. Several study sequences were highly divergent from other African subgenotype A1 strains. This study showed that HBeAg-negative chronic hepatitis B is underestimated in subgenotype A1, and also highlighted the variant South African A1 strains. The major advantage of preC/C sequencing is that it informs patient management as HBeAg-negative chronic hepatitis B responds poorly to conventional interferon-α therapy, and some guidelines treat HBeAg-negative chronic hepatitis B differently from HBeAg-positive chronic hepatitis B. These data suggest that subgenotype A1 may be more involved in severe HBV-related diseases.
Assuntos
Variação Genética , Infecções por HIV/complicações , Antígenos do Núcleo do Vírus da Hepatite B/genética , Vírus da Hepatite B/genética , Hepatite B Crônica/complicações , Hepatite B Crônica/virologia , Adulto , Análise por Conglomerados , Estudos de Coortes , DNA Viral/genética , Feminino , Genótipo , Antígenos de Superfície da Hepatite B/genética , Antígenos E da Hepatite B/genética , Vírus da Hepatite B/classificação , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Análise de Sequência de DNA , África do Sul , Adulto JovemRESUMO
OBJECTIVE: As sub-Saharan Africa is highly endemic for hepatitis B virus (HBV) and human immunodeficiency virus (HIV) infections, and their co-infection requires special management, we aimed to assess the serological and molecular characteristics of HBV in patients with AIDS. DESIGN: This was a cross-sectional, case control study, which enrolled 200 patients with AIDS and 200 HIV-negative controls. HBV serology was done in all participants and HCV serology in participants with a hepatitis B core antibody (anti-HBc) only serological pattern. Nested HBV polymerase chain reaction (PCR) and HBV viral load assays were used for HBV molecular detection. RESULTS: Hepatitis B surface antigen (HBsAg) prevalence was 3-fold higher while the 'anti-HBc only' pattern was 6-fold higher in the AIDS group compared with the controls. Mean HBV viral load was significantly higher in HBsAg-positive patients with CD4+ cell counts <100 cells/µl than in patients with CD4+ cell counts of 100-200 cells/µl (p=0.019). There were markedly reduced hepatitis B surface antibody (anti-HBs) titres in the AIDS group compared with the controls (p=0.002). A significant proportion of AIDS patients with an 'anti-HBc only' pattern had CD4+ cell counts <100 cells/µl (p=0.004). Occult HBV prevalence was 3.5% in the AIDS group compared with 1% in the controls (p=0.092). When occult HBV infection was taken into consideration, the overall HBV prevalence became 10% in the AIDS group and 3% in the control group. CONCLUSION: We showed an increased HBV prevalence in patients with AIDS and identified a CD4+ cell count <100 cells/µl as a major risk factor for the 'anti-HBc only' pattern and increased HBV replication. These data have significant public health implications for HBV in developing countries, especially in areas where antiretroviral (ARV) guidelines do not cater for HBV/HIV co-infection.
Assuntos
Síndrome da Imunodeficiência Adquirida , HIV/imunologia , Vírus da Hepatite B , Hepatite B , Síndrome da Imunodeficiência Adquirida/epidemiologia , Síndrome da Imunodeficiência Adquirida/imunologia , Síndrome da Imunodeficiência Adquirida/virologia , Adulto , África Subsaariana/epidemiologia , Idoso , Contagem de Linfócito CD4/métodos , Estudos de Casos e Controles , Coinfecção , Estudos Transversais , DNA Viral/análise , Feminino , Hepatite B/epidemiologia , Hepatite B/imunologia , Hepatite B/virologia , Antígenos do Núcleo do Vírus da Hepatite B/sangue , Antígenos de Superfície da Hepatite B , Vírus da Hepatite B/genética , Vírus da Hepatite B/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase/métodos , Prevalência , Fatores de Risco , Carga Viral/métodosRESUMO
Urinary lipoarabinomannan (LAM) detection is a promising approach for rapid diagnosis of active tuberculosis (TB). In microbiologically confirmed TB patients, quantitative LAM detection results increased progressively with bacillary burden and immunosuppression. Patients with disseminated TB and/or advanced HIV are target populations for whom urine LAM detection may be particularly useful.
Assuntos
Lipopolissacarídeos/urina , Tuberculose/diagnóstico , Urina/química , Adulto , Feminino , Humanos , Masculino , Sensibilidade e Especificidade , Tuberculose/patologiaRESUMO
BACKGROUND: Effective tuberculosis (TB) control in HIV-prevalent settings is hindered by absence of accurate, rapid TB diagnostic tests. We evaluated the accuracy of a urine lipoarabinomannan (LAM) test for TB diagnosis in South Africa. METHODS: Hospitalized adults with signs and/or symptoms of active TB were enrolled. Sputum smear microscopy and mycobacterial culture, mycobacterial blood culture, and HIV testing were performed. A spot urine specimen was tested for LAM. RESULTS: Four hundred ninety nine participants were enrolled; 422 (84.6%) were HIV infected. In microbiologically confirmed TB patients, the LAM test was positive in 114 of 193 [sensitivity 59%, (95% confidence interval: 52 to 66)], including 112 of 167 [67% (59 to 74)] who were HIV infected. Among individuals classified as "not TB", the LAM test was negative in 117 of 122 [specificity 96% (91 to 99)], including 83 of 88 [94% (87 to 98)] who were HIV infected. In confirmed TB patients, the LAM test was more sensitive than sputum smear microscopy (42%, 82 of 193, P < 0.001) and detected 56% (62 of 111) of those who were sputum smear negative. HIV infection [adjusted odds ratio (AOR 13.4)], mycobacteremia (AOR 3.21), and positive sputum smear (AOR 2.42) were risk factors for a positive LAM test. CONCLUSIONS: The urine LAM test detected a subset of HIV-infected patients with severe TB in whom sputum smear microscopy had suboptimal sensitivity. The combination of urine LAM testing and sputum smear microscopy is attractive for use in settings with high HIV burden.
Assuntos
Infecções por HIV/complicações , Lipopolissacarídeos/urina , Tuberculose/diagnóstico , Urina/química , Adolescente , Adulto , Idoso , Técnicas Bacteriológicas/métodos , Sangue/microbiologia , Feminino , Hospitais , Humanos , Pacientes Internados , Masculino , Microscopia/métodos , Pessoa de Meia-Idade , Sensibilidade e Especificidade , África do Sul , Escarro/microbiologia , Adulto JovemRESUMO
BACKGROUND: Coinfection with hepatitis B virus (HBV) and human immunodeficiency virus (HIV) is common in Africa; however, the impact of HBV infection on the outcomes of antiretroviral therapy programs is unclear. We evaluated the impact of chronic hepatitis B on HIV virologic response, changes in CD4 cell count, hepatotoxicity, and mortality among Africans receiving highly active antiretroviral therapy (HAART). METHODS: We conducted a retrospective cohort study involving a workplace HAART program in South Africa. Participants received HAART according to a protocol and were followed up for up to 72 weeks. On the basis of pre-HAART serum assays, patients were classified as being hepatitis B surface antigen (HBsAg) negative, HBsAg positive with a low HBV DNA level (= 1 x 10(4) copies/mL), and HBsAg positive with a high HBV DNA level (> 1 x 10(4) copies/mL). The relationships between HBV status and HIV RNA suppression, change in CD4 cell count, mortality, and hepatotoxicity were assessed with use of regression techniques. RESULTS: Five hundred thirty-seven individuals fulfilled the inclusion criteria; 431 (80.3%) of these patients were HBsAg negative, 60 (11.2%) were HBsAg positive with a low HBV DNA level, and 46 (8.6%) were HBsAg positive with a high HBV DNA level. All groups had similar rates of HIV RNA suppression (P = .61), CD4 cell count increases (P =.75), and mortality (17 total deaths; P=.11) for up to 72 weeks after the initiation of HAART. Baseline transaminase levels were highest in the group with high HBV DNA levels (P=.004). Hepatotoxicity was similar between the HBsAg-negative group and the group with low HBV DNA levels but was higher in the group with high HBV DNA levels (incidence rate ratio, 4.4). CONCLUSIONS: We revealed that HBV status does not affect HIV RNA suppression, CD4 cell count response, or mortality during the first 72 weeks of HAART in an African setting. The risk of HBV-associated hepatotoxicity, however, is associated with the baseline HBV DNA level.
Assuntos
Antirretrovirais/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Hepatite B Crônica/epidemiologia , Adulto , Antirretrovirais/efeitos adversos , Contagem de Linfócito CD4 , Estudos de Coortes , DNA Viral/sangue , Feminino , Seguimentos , Infecções por HIV/imunologia , Infecções por HIV/mortalidade , Antígenos de Superfície da Hepatite B/sangue , Humanos , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , Estudos Retrospectivos , África do Sul/epidemiologia , Transaminases/sangue , Resultado do Tratamento , Carga ViralRESUMO
OBJECTIVE: Hepatotoxicity is a significant complication of antiretroviral therapy (ART). We assessed the incidence of and risk factors for hepatotoxicity among HIV-infected individuals on ART in South Africa. DESIGN: We conducted a retrospective cohort study in a workplace HIV care program in South Africa which uses a first-line regimen of efavirenz, zidovudine, and lamivudine and provides routine clinical and laboratory monitoring. METHODS: We included subjects with baseline and follow-up alanine transaminase and aspartate aminotransferase tests. Severe hepatotoxicity cases were identified during the first 12 months of ART. Potential risk factors, including concomitant medication use, tuberculosis, and hepatitis B and C, were determined from clinical records, database queries, and serological testing. Associations with hepatotoxicity were investigated using Cox proportional hazards modeling. RESULTS: Of the 868 subjects (94% male, median age 41 years), the median nadir CD4 cell count was 136/microl, 25% received concomitant tuberculosis treatment during ART, and 17% of a randomly selected subset were positive for hepatitis B surface antigen (HBsAg). We identified 7.7 episodes of severe hepatotoxicity per 100 person-years. Tuberculosis treatment increased risk 8.5 fold, positive HBsAg 3.0 fold, and nadir CD4 cells count < 100/microl 1.9 fold. Importantly, the fraction of patients with severe hepatotoxicity on ART (4.6%) was similar to the fraction with liver enzyme elevations > 5 times the upper limit of normal before starting ART (4%). CONCLUSIONS: In this African ART cohort, we found a low incidence of and minimal morbidity due to hepatotoxicity. HBsAg and concomitant tuberculosis therapy significantly increased the risk of hepatotoxicity.
Assuntos
Fármacos Anti-HIV/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas , Infecções por HIV/tratamento farmacológico , Tuberculose/tratamento farmacológico , Adulto , Alanina Transaminase/análise , Fármacos Anti-HIV/administração & dosagem , Antituberculosos/uso terapêutico , Aspartato Aminotransferases/análise , Quimioterapia Combinada , Feminino , Infecções por HIV/complicações , Infecções por HIV/imunologia , Hepatite B/imunologia , Antígenos de Superfície da Hepatite B/sangue , Humanos , Incidência , Fígado/efeitos dos fármacos , Fígado/enzimologia , Masculino , Pessoa de Meia-Idade , Doenças Profissionais/tratamento farmacológico , Doenças Profissionais/epidemiologia , Doenças Profissionais/imunologia , Estudos Retrospectivos , África do Sul/epidemiologia , Resultado do Tratamento , Tuberculose/complicações , Tuberculose/epidemiologiaRESUMO
During 6 months of treatment, we measured human immunodeficiency virus (HIV)-1 virus loads, CD4 T cell counts, and immune activation markers, in 111 HIV-1-infected patients with active tuberculosis (TB). The median virus load (baseline, 5.58 log(10) copies/mL) significantly increased at 1 month (5.71 log(10) copies/mL), then returned to near-baseline levels at 3 months (5.40 log(10) copies/mL) and at 6 months (5.36 log(10) copies/mL). In contrast, the median CD4 counts increased at 1 month (186/mm(3)), at 3 months (238/mm(3)), and at 6 months (239/mm(3)). CD4 counts and virus loads did not change during therapy. Expression of CD38 and HLA-DR remained high throughout treatment, whereas plasma levels of interleukin-6 decreased over time.
Assuntos
Antituberculosos/uso terapêutico , Linfócitos T CD4-Positivos/imunologia , Infecções por HIV/complicações , HIV-1/genética , HIV-1/isolamento & purificação , RNA Viral/análise , Tuberculose/tratamento farmacológico , Tuberculose/imunologia , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/imunologia , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Antituberculosos/farmacologia , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos/efeitos dos fármacos , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , Humanos , Mycobacterium tuberculosis , África do Sul , Tuberculose/complicações , Tuberculose/virologia , Carga ViralRESUMO
HIV-1 subtype C accounts for the vast majority of infections in South Africa. However, increasingly non-C subtypes are being detected. Here we report 10 viruses that contain sequences that group with subtypes A, D, and G as well as CRF02_AG and 1 that could not be classified. Most of these individuals were from other countries in Africa. Some of these sequences were in combination with subtype C, possibly indicating local recombination events. Although there is no indication of endemic spread of these viruses, continued monitoring is warranted to track genetic changes, which may impact on diagnostic testing, therapeutic responses to antiretroviral therapies, and vaccine design.