Predictors and Prognosis of Stroke in Jos, North-Central Nigeria.

BACKGROUND: Stroke is the second leading cause of death worldwide. Stroke mortality has been shown to be higher in blacks in multiracial studies. It is also a very important cause of disability with its attendant deterioration in the quality of life in survivors. OBJECTIVE: The study sought to determine the risk and prognostic factors associated with stroke in Jos, North Central Nigeria. METHODS: A prospective cohort study of stroke patients that were followed up for 90 days to determine outcomes. The stroke patients were admitted into the neurology unit of Jos University Teaching Hospital between September 2016 and August 2018. RESULTS: We recruited a total of 246 subjects comprising 131 (53.3%) males aged 59.5 ± 13.1 years and 115 (46.6%) females aged 56.7 ± 14.2 years. Obesity, hypertension, dyslipidaemia and alcohol consumption were the commonest risk factors identified. The 90-day case fatality rate of stroke was 22%. Elevated glycated haemoglobin (p = 0.001), loss of consciousness at presentation (p <0.001), atrial fibrillation (p= 0.022), cardiac disease (p < 0.001) and HIV infection (p = 0.001) were significantly associated with poor outcome for stroke. Furthermore, subjects with a high NIHSS had three times the risk of death compared with those with low scores (RR = 2.93; 95% CI = 2.38 - 3.61, p <0.001). CONCLUSION: The prognosis of stroke was poor. The predictors of poor stroke outcome were coma, HIV infection, cardiac disease, high NIHSS and total cholesterol.

HISTORIQUE: L'AVC est la deuxième cause de décès dans le monde. La mortalité par accident vasculaire cérébral s'est avérée plus élevée chez les Noirs dans les études multiraciales. C'est également une cause très importante d'invalidité avec la détérioration de la qualité de vie des survivants. OBJECTIF: L'étude visait à déterminer le risque et les facteurs pronostiques associés à un AVC à Jos, au centre-nord du Nigéria. MÉTHODES: Une étude de cohorte prospective de patients victimes d'un AVC qui a été suivie pendant 90 jours pour déterminer les résultats. Les patients victimes d'unAVC ont été admis dans l'unité de neurologie de l'hôpital universitaire de Jos entre septembre 2016 et août 2018. RÉSULTATS: Nous avons recruté un total de 246 sujets comprenant 131 (53,3%) hommes âgés de 59,5 ± 13,1 ans et 115 (46,6%) femmes âgées de 56,7 ± 14,2 ans. L'obésité, l'hypertension, la dyslipidémie et la consommation d'alcool étaient les facteurs de risque les plus courants identifiés. Le taux de mortalité par accident vasculaire cérébral à 90 jours était de 22%. L'hémoglobine glyquée élevée (p = 0,001), la perte de conscience à la présentation (p <0,001), la fibrillation auriculaire (p = 0,022), les maladies cardiaques (p <0,001) et l'infection à VIH (p = 0,001) étaient significativement associées à de mauvais résultats pour coup. En outre, les sujets avec un NIHSS élevé avaient trois fois le risque de décès par rapport à ceux avec desscores faibles (RR = 2,93; IC à 95% = 2,38 - 3,61, p <0,001). CONCLUSION: Le pronostic de l'AVC était mauvais. Les facteurs prédictifs d'un mauvais pronostic d'AVC étaient le coma, l'infection par le VIH, les maladies cardiaques, un NIHSS élevé et le cholestérol total. MOTS CLÉS: Prédicteurs, pronostic, accident vasculaire cérébral.

On semiparametric estimation of a path-specific effect in the presence of mediator-outcome confounding.

Path-specific effects constitute a broad class of mediated effects from an exposure to an outcome via one or more causal pathways along a set of intermediate variables. Most of the literature concerning estimation of mediated effects has focused on parametric models, with stringent assumptions regarding unmeasured confounding. We consider semiparametric inference of a path-specific effect when these assumptions are relaxed. In particular, we develop a suite of semiparametric estimators for the effect along a pathway through a mediator, but not through an exposure-induced confounder of that mediator. These estimators have different robustness properties, as each depends on different parts of the likelihood of the observed data. One estimator is locally semiparametric efficient and multiply robust. The latter property implies that machine learning can be used to estimate nuisance functions. We demonstrate these properties, as well as finite-sample properties of all the estimators, in a simulation study. We apply our method to an HIV study, in which we estimate the effect comparing two drug treatments on a patient's average log CD4 count mediated by the patient's level of adherence, but not by previous experience of toxicity, which is clearly affected by which treatment the patient is assigned to and may confound the effect of the patient's level of adherence on their virologic outcome.

Immunological and Virological Outcomes of Patients Switched from LPV/r to ATV/r-Containing Second- Line Regimens.

BACKGROUND: Atazanavir/ritonavir (ATV/r) recently became the preferred protease inhibitor (PI) for use in Nigeria since it is dosed once daily, which may improve treatment adherence and has fewer side effects than lopinavir/ritonavir (LPV/r)--the most widely available PI in resource-limited settings. We, therefore, aimed to evaluate the immunologic and virologic effects of switching patients to an ATV/r-containing regimen. METHODS: In a large antiretroviral treatment programme at the Lagos University Teaching Hospital in Nigeria, 400 patients were switched to ATV/r-based second-line ART. We conducted a retrospective evaluation of immunologic and virologic outcomes following 24 months on the ATV/r regimens. RESULTS: Of the 400 patients switched to an ATV/r containing regimen, 255 were virologically suppressed on LPV/r prior to switch, 107 were switched due to failure on a first-line regimen, 28 were on saquinavir/ritonavir (SQV/r)-based regimen, while 10 were unintentionally switched while non-suppressed on a LPV/r-based regimen. Demonstrable and sustained immunological responses were documented as the median (IQR) CD4+ cell count increased steadily from 466 (323) cells/mm3 at the time of switch to 490 (346) cells/mm3 at 6 months, and 504 (360) cells/mm3 at 24 months. Of 99 patients evaluated 12 months after ATV/r switch, 2 (2%) had detectable viral load (VL). None of the 26 (0%) in this group evaluated at 24 months had detectable viral load. In a comparison group of 576 patients who were maintained on LPV/r-based second line regimens, 359 (62.3%) had undetectable viral loads. Of 318 patients with VL data 24 months later, 25 (7.9%) had detectable VL. There was no significant difference between the proportion of patients maintained on LPV/r (7.9%) and those switched to ATV/r (0%) in the development of virologic failure after 24 months of follow-up. CONCLUSION: Among patients that were switched to ATV/r-containing regimens, we found improvements in immunological responses and no increase in risk of virologic failure.

Patients who present late to HIV care and associated risk factors in Nigeria.

OBJECTIVES: Our objectives were to assess trends in late presentation and advanced HIV disease (AHD) and determine associated risk factors. METHODS: We conducted a retrospective cohort analysis of patients who had received care and treatment at the AIDS Prevention Initiative Nigeria Plus (APIN)/Harvard School of Public Health-President's Emergency Plan for AIDS Relief (PEPFAR) programme at the Jos University Teaching Hospital, Jos, Nigeria from 2005 to 2010. We used the European Consensus Definition to assess trends in late presentation (CD4 count < 350 cells/µL or AIDS-defining illness) and AHD (CD4 count < 200 cells/µL or AIDS-defining illness) and evaluated associated risk factors using logistic regression methods. RESULTS: Among 14,487 eligible patients, 12,401 (85.6%) were late presenters and 9127 (63.0%) presented with AHD. Late presentation decreased from 88.9% in 2005 to 80.1% in 2010 (P < 0.001). Similarly, AHD decreased from 67.8% in 2005 to 53.6% in 2010 (P < 0.001). In logistic regression models adjusting for sociodemographic and biological variables, male sex [adjusted odds ratio (aOR) = 1.80; 95% confidence interval (CI) 1.60-2.04], older age (aOR = 1.37; 95% CI 1.22-1.54), civil service employment (aOR = 1.48; 95% CI 1.00-2.21), referral from out-patient (aOR = 2.18; 95% CI 1.53-3.08) and in-patient (aOR = 1.55; 95% CI 1.11-2.17) services, and hepatitis B virus (aOR = 1.43; 95% CI 1.26-1.63) and hepatitis C virus (aOR = 1.18; 95% CI 1.02-1.37) coinfections were associated with late presentation. Predictors of AHD were male sex (aOR = 1.67; 95% CI 1.54-1.82), older age (aOR = 1.26; 95% CI 1.16-1.36), unemployment (aOR = 1.34; 95% CI 1.00-1.79), referral from out-patient (aOR = 2.40; 95% CI 1.84-3.14) and in-patient (aOR = 1.97; 95% CI 1.51-2.57) services and hepatitis B virus coinfection (aOR = 1.30; 95% CI 1.19-1.42). CONCLUSIONS: Efforts to reduce the proportion of patients who first seek care at late stages of disease are needed. The identified risk factors should be utilized in formulating targeted public health interventions to improve early diagnosis and presentation for HIV care.

Evaluation of Paracheck-Pf(TM) rapid malaria diagnostic test for the diagnosis of malaria among HIV-positive patients in Ibadan, south-western Nigeria.

Febrile illnesses occur frequently among HIV positive patients and these are often treated presumptively as malaria in endemic areas. Parasite-based diagnosis of malaria will eliminate unnecessary treatment, reduce drug-drug interactions and the chances for the emergence of drug resistant Plasmodium. We evaluated finger prick blood samples from 387 people living with HIV (PLWHIV) and suspected of having malaria by expert microscopy and Paracheck-Pf(TM) - a histidine-rich protein-II based malaria rapid diagnostic test. The study was conducted at the PEPFAR supported AIDS Prevention Initiative in Nigeria (APIN) Clinic of the University College Hospital Ibadan, southwest Nigeria. Outcome parameters were prevalence of malaria parasitemia, sensitivity and specificity of Paracheck-Pf as well as the positive and negative predictive values for Paracheck-Pf using microscopy of Giemsa-stained blood film as gold standard. Malaria parasites were detected in 19·1% (74/387) of enrollees by microscopy and 19·3% (74/383) by Paracheck-Pf. Geometric mean parasite density was 501/µl (range 39-749 202/µl). Sensitivity and specificity of Paracheck-Pf at all parasite densities were 55·4% and 89·3% while corresponding figures at parasite densities ≥200/µl were 90·9% and 90·3%. Sensitivity and specificity at parasite densities ≥500/µl was 97·6% and 90·3%. Positive and negative predictive values for parasite density ≥200/µl were 55·4% and 98·7%, respectively. Paracheck-Pf was found to be a useful malaria diagnostic tool at parasite densities ≥200/µl facilitating appropriate clinical management.

Temporal changes in renal glomerular function associated with the use of Tenofovir Disoproxil Fumarate in HIV-infected Nigerians.

BACKGROUND: Reports of renal dysfunction in Tenofovir Disoproxil Fumarate (TDF)-treated HIV-1 infected patients have raised concerns about potential nephrotoxicity. OBJECTIVE: To compare the effects on renal function of TDF-containing highly active anti-retroviral therapy (HAART) with a non-TDF-containing HAART. METHODS: This was an observational study.Clinical and laboratory data of 186 HIV-1 infected adult Nigerians on first-line HAART for at least 48 weeks were reviewed. Eighty-four patients whose nucleos(t)ide reverse transcriptase inhibitor (NRTI) backbone included TDF were compared to 102 patients on other NRTI backbones. Creatinine clearance (CLcr) was estimated using the Cockcroft-Gault equation. Changes in serum creatinine and CLcr from the baseline for each patient were compared between the TDF-treated and the TDF-free patients. We also assessed the associations of other variables with change in CLcr... RESULTS: Baseline median serum creatinine (mmol/L) was 77 and 84 in the TDF-treated and TDF-free groups, respectively (p=0.59). Baseline median CLcr (mls/min) was 83 in the TDF-treated patients vs 78 in the TDF-free group. At 48 weeks, serum creatinine increased by 18.1% and 1.2% in the TDF-treated and TDF-free arms, respectively. There was a decrease of 4.8% in GFR in the TDF arm compared to a gain 5.1% in the TDF-free arm. CONCLUSION: Tenofovir Disoproxil Fumarate-containing HAART is associated with a slight decline in the medium term in CLcr compared with HAART regimens containing alternative Nucleosid(t) Reverse Transcriptase Inhibitors.

Impact of HIV type 1 subtype on drug resistance mutations in Nigerian patients failing first-line therapy.

A diverse array of non-subtype B HIV-1 viruses circulates in Africa and dominates the global pandemic. It is important to understand how drug resistance mutations in non-B subtypes may develop differently from the patterns described in subtype B. HIV-1 reverse transcriptase and protease sequences from 338 patients with treatment failure to first-line ART regimens were evaluated. Multivariate logistic regression was used to examine the effect of subtype on each mutation controlling for regimen, time on therapy, and total mutations. The distribution of HIV-1 subtypes included CRF02_AG (45.0%), G (37.9%), CRF06_cpx (4.4%), A (3.6%), and other subtypes or recombinant sequences (9.2%). The most common NRTI mutations were M184V (89.1%) and thymidine analog mutations (TAMs). The most common NNRTI mutations were Y181C (49.7%), K103N (36.4%), G190A (26.3%), and A98G (19.5%). Multivariate analysis showed that CRF02_AG was less likely to have the M41L mutation compared to other subtypes [adjusted odds ratio (AOR) = 0.35; p = 0.022]. Subtype A patients showed a 42.5-fold increased risk (AOR = 42.5, p = 0.001) for the L210W mutation. Among NNRTI mutations, subtype G patients had an increased risk for A98G (AOR = 2.40, p = 0.036) and V106I (AOR = 6.15, p = 0.010), whereas subtype CRF02_AG patients had an increased risk for V90I (AOR = 3.16; p = 0.003) and a decreased risk for A98G (AOR = 0.48, p = 0.019). Five RT mutations were found to vary significantly between different non-B West African subtypes. Further study to understand the clinical impact of subtype-specific diversity on drug resistance will be critically important to the continued success of ART scale-up in resource-limited settings.

Service uptake and performance of the prevention of mother-to-child transmission (PMTCT) programme in Ibadan, Nigeria.

The Prevention of Mother to Child Transmission (PMTCT) programme in the University College Hospital (UCH), Ibadan has been in existence for more than five years and has scaled up to other sites. The study evaluated the service uptake and performance of the programme using national key indicators. Antenatal and delivery records of women enrolled between July 2002 and June 2007 were reviewed. A total of 51952 women attended first antenatal visits and received HIV pre-test counselling. Of these, 51614 (99.5%) accepted HIV test and 49134 (95.2%) returned for their results. Out of the tested patients, 2152 (4.2%) were identified to be HIV positive. Partners of positive patients accepting HIV testing were 361 (16.7%) with 87 (18.6%) testing positive. There were a total of 942 deliveries out of which 39.2% of the mothers and 95.2% of the babies respectively received ARV prophylaxis. In all, 85.8% (788/918) of the mothers opted for formula as the method of infant feeding. Out of the 303 babies eligible for ELISA testing, 68.3% reported for the test and 17 (8.7%) tested positive. There has been progress in the programme, reflected in the increase in the number of new clients accessing the PMTCT service. However, partner testing and follow up of mother-infant pairs remain formidable challenges that deserve special attention.

Presentation and survival of patients with AIDS-related Kaposi's sarcoma in Jos, Nigeria.

AIDS-related Kaposi's sarcoma (AIDS-KS) remains a significant cause of morbidity and mortality. We describe the pattern of presentation and survival in Jos, Nigeria. We identified 48 HIV-positive patients with AIDS-KS and matched them for age and sex with an equal number of HIV-positive patients without AIDS-KS. We compared their clinical, immunological, virological characteristics and survival. They were similar in age and body mass index profile but patients with AIDS-KS had more tuberculosis co-infection (P, 0.02), lower median CD4 count (P, 0.003) and higher mortality (P, 0.002). Surprisingly, patients with AIDS-KS had lower levels of median viral load (29,347 copies/mL) compared with controls (80,533 copies/mL). We recommend specific AIDS-KS therapy in addition to highly active antiretroviral therapy in order to improve survival.

Does immunological status affect the prevalence of Hepatitis C virus infection among HIV/AIDS patients?

BACKGROUND: Even though HIV-HCV co-infection rates vary widely according to western reports, not so much has been documented about the situation in our environment. We determined the prevalence of HCV among our HIV cohort as well as described the relationship between the immune and virological status of the patients in this report. METHODS: Data of 1044 consenting HIV infected patients (confirmed by Western blot assay) receiving treatment at our centre between Sep 2002 and Feb 2005 were analyzed using EpiInfo 2004 retrospectively. The sera of the patients were used to determine their anti-HCVstatus by third generation ELISA (DIA.PRO Diagnostic, Bioprobes srl, Italy). HIV RNA levels and CD4 cell counts were also determined at recruitment by Roche Amplicor 1.5 and Flow Cytometry (Partec, Germany). RESULTS: Ninety out of 1044 patients (8.6%) were positive for anti-HCV The rate of co-infection was highest among the divorced (10.3%), followed by widows (9.9%) though this did not reach statistical significance. The odds of finding anti-HCV was more than twice with CD4 cell counts >600 cells/microlitre compared to below 200 cells/microlitre (p=0.026). The median HIV RNA levels of HCV co-infected individuals was 514 copies/ml, while it was 200 copies/ml for HIV monoinfected persons (p>0.05). CONCLUSION: The prevalence of HCV among this HIV cohort is high. There is also an associated higher chance of detecting anti-HCV in sera of the HIV patients whose immunological status is better than severely immunocompromised individuals.

Rapid HIV testing and counselling in labour in a northern Nigerian setting.

Between April and August 2004, all pregnant women in labour at JUTH, were offered rapid HIV testing and counselling with opportunity to decline testing. HIV positive women were offered the standard nevirapine mono-therapy prophylaxis regimen (HIVNET 012). Four hundred and thirty (99.8%) of the 431 pregnant women who were offered rapid HIV testing and counselling, agreed to test. A sero-conversion rate of 2.1% (5 of 235) was found among women who had previously tested negative for HIV during the index pregnancy. A seroprevalence rate of 9.6% (16 of 166) was found among women with unknown HIV status. One patient who had an indeterminate HIV status prior to labour tested positive in labour. Rapid HIV testing and counselling in labour is a useful practice in high prevalence settings since it detects a substantial number of HIV-infected women and HIV-exposed babies that would otherwise have missed interventions to prevent MTCT.

Regulation of adiponectin in adipocytes upon exposure to HIV-1.

OBJECTIVES: Adipose dysregulation, dyslipidemia, and insulin resistance are hallmarks of HIV-related lipodystrophy. The precise mechanisms behind these disturbances are unknown. In HIV-infected patients, we previously demonstrated a strong relationship between lipodystrophy and levels of adiponectin, an adipose peptide implicated in regulation of glucose and lipid metabolisms. In this study we investigated the effect of HIV on adipocytes, to determine whether HIV can directly infect adipocytes and/or alter the regulation and secretion of the adipocyte-derived hormone adiponectin. METHODS: Human subcutaneous preadipocytes and adipocytes were exposed to HIV-1 under various conditions. Adiponectin was measured in supernatants and cell lysates. RESULTS: Although adipocytes expressed CD4, the major HIV receptor, they could not be infected in vitro. However, exposure to HIV dramatically increased the secretion of adiponectin from human adipocytes, in the absence of infection. This was exacerbated with sustained exposure to HIV in a transwell assay. Further, human peripheral mononuclear cells also produced adiponectin, but this was largely dependent upon T-cell activation. CONCLUSIONS: We propose that the stimulation of adiponectin production by HIV can perturb adiponectin regulation, leading to substantially decreased levels upon viral suppression by antiretroviral therapy. These data suggest a potential molecular mechanism of adiponectin regulation in HIV-infected patients.

Partner disclosure of HIV status among HIV positive mothers in Northern Nigeria.

Partner consent and support can substantially enhance adherence to PMTCT interventions. This study explores the issues concerning disclosure of HIV status to partners of HIV sero-positive mothers in a PMTCT programme in Jos, Northern Nigeria. Previously field-tested questionnaires were administered by trained counsellors to 570 consenting HIV positive mothers who were participating in the PMTCT programme at Jos University Teaching Hospital (JUTH), Jos. The findings were entered into Epi Info and analysed using frequencies. The median age of respondents was 29 years while that of their partners was 37 years. Five hundred and fifty-five (99.5%) of respondents were married. Majority of the women were Christians (82.9%) while 16.9% were Moslems. Seventy four percent (419/563) of the mothers were aware of their husband's HIV sero-status. Of these, 65.4% (274/419) of the partners were HIV positive while 34.6% were sero-negative. Eighty nine percent (500/560) of the women have disclosed their HIV status to their partners. Of these, 39.6% (199/502) required the assistance of health workers while 59.4% (298/502) did it by themselves. Following disclosure of HIV status, 86.9% (430/495) of the partners were supportive, 5.7% were indifferent, 6.7% were quarrelsome and abusive while 1.0% was violent. The reactions of partners of HIV positive mothers to disclosure of their wives' HIV status are predominantly supportive. This should strengthen strategies to promote partner disclosure.

HIV infection among pregnant women in Nigeria.

OBJECTIVES: To determine risk factors for HIV among pregnant women (N = 2657) receiving antenatal services in Jos, Plateau state, Nigeria. METHODS: Information about potential risk factors was obtained at interview. Biological samples were collected for detection of HIV and other sexually transmitted infections (STIs). RESULTS: The prevalence of HIV was 8.2%. Women aged 20-29 years had more than 4-fold increased risk of HIV. Women of Catholic (adjusted odds ratio (AOR) = 1.72, 95% CI = 1.01-2.95) and Pentecostal (AOR = 2.57, 95% CI = 1.46-4.52) denominations were more likely to be HIV-infected when compared to Moslem women. The risk of HIV was also increased among women with multiple marriages and in women married to a banker/accountant. Other predictors of HIV were having a husband with other partners, perceived risk of HIV, STIs, candidiasis and bacterial vaginosis. CONCLUSIONS: Development of effective interventions, including behavioral change, expansion of perinatal HIV prevention services and STI control, should be given the highest priority.

CCR5 receptor expression is down-regulated in HIV type 2 infection: implication for viral control and protection.

HIV-2 is known to display an attenuated phenotype in vivo with prolonged time to disease and decreased rate of transmission. Observational studies in Senegal have demonstrated protection from HIV-1 infection, although the putative mechanism for immunoprotection remains undefined. We evaluated HIV-2-seropositive women from a cohort of commercial sex workers in Dakar, Senegal and identified individuals with very low surface CCR5 receptor expression on CD4+ T cells. In vitro up-regulation of the CCR5 receptor was readily achieved. Down-regulation of the CCR5 was not correlated with activation markers (HLA-DR), beta-chemokine levels, or plasma viral loads. A correlation was observed with HIV-2-specific CD8+ T cell activity as measured by intracellular cytokine production. We postulate that down-regulation of the CCR5 receptor in HIV-2 infection contributes to slower disease course and to the protective mechanism against HIV-1 superinfection, mediated in part by HIV-2-specific cellular immune responses.

Immunologic and virologic response after tetanus toxoid booster among HIV-1- and HIV-2-infected Senegalese individuals.

Twelve HIV-1-infected, nine HIV-2-infected patients and eight HIV-negative subjects were given a 40IU booster dose of tetanus toxoid (TT). Blood was collected on days 0, 7 and 30 after immunization. Changes in HIV-1 or HIV-2 RNA load were evaluated by nested PCR. TT-IgG antibody levels were quantified by ELISA. CD4 cell counts as well as activation, memory and maturation markers of T lymphocyte subsets were determined by flow cytometry. The induction of apoptosis was investigated using 7-aminoactinomycin D (AAD) and propidium iodide (PI) staining. Proliferative responses to TT and pokeweed mitogen (PWM) were determined by the level of [(3)H] thymidine incorporation. Seven and 30 days after immunization, there was no detectable increase in HIV-1 or HIV-2 plasma load. There were also no changes in CD4 cell counts, CD69, HLA-DR and memory CD45RO or naive CD45RA antigens. Immunization did not increase the spontaneous apoptosis of peripheral blood mononuclear cells (PBMCs), CD4+ and CD8+ T cells subsets neither in controls nor in HIV-infected patients. Similarly, apoptosis induced in vitro by PWM or by the specific TT recall antigen did not vary during the study period. The proliferative response to PWM and to the TT recall antigen was decreased both in HIV-1- and HIV-2-infected patients compared to HIV-negative controls. Immunization significantly increased the TT-IgG levels in healthy controls and in HIV-infected patients. However, the anti-TT-IgG response, as measured by the fold-increase index between days 0 and 30, was significantly higher in healthy controls than in HIV-1- (P=0.036) and HIV-2-infected patients (P=0.003). In conclusion, we found no deleterious immunologic or virologic effect was detected in healthy HIV-1- and HIV-2-infected individuals after antigenic challenge with a TT booster. However, the response to TT vaccination was lower in HIV-1- and in HIV-2-infected individuals than in healthy HIV-negative controls.

Omnibus tests for comparison of competing risks with adjustment for covariate effects.

This article develops omnibus tests for comparing cause-specific hazard rates and cumulative incidence functions at specified covariate levels. Confidence bands for the difference and the ratio of two conditional cumulative incidence functions are also constructed. The omnibus test is formulated in terms of a test process given by a weighted difference of estimates of cumulative cause-specific hazard rates under Cox proportional hazards models. A simulation procedure is devised for sampling from the null distribution of the test process, leading to graphical and numerical technques for detecting significant differences in the risks. The approach is applied to a cohort study of type-specific HIV infection rates.

Robust HIV type 2 cellular immune response measured by a modified anthrax toxin-based enzyme-linked immunospot assay.

Evaluation of immune mechanisms responsible for control of viral replication is critical to understanding HIV-2 attenuated biological characteristics in pathogenesis and transmission. Evaluation of the cellular immune response is often based on labor-intensive techniques that limit the scope of most studies performed. A simple and rapid anthrax toxin-based ELISPOT method to assess HIV-2 cellular immune response was developed. The modified anthrax toxin-based antigen presentation process performed better than a recombinant vaccinia system and the ELISPOT method significantly enhanced the ease and simplicity of the assay. Using this method, a robust HIV-2 cellular immune response directed toward the p26 core protein was exhibited in 21 of 24 (87.5%) infected women, and all 8 seronegative subjects were negative in both assays. Cellular immune responses were associated with low HIV-2 viral load. This simple and rapid modified anthrax toxin-based ELISPOT method allowed us to demonstrate, strong cellular immune responses that may be critical determinants in the HIV-2 attenuated phenotype.

Cellular immunity to human immunodeficiency virus type 1 (HIV-1) clades: relevance to HIV-1 vaccine trials in Uganda.

The first prophylactic human immunodeficiency virus type 1 (HIV-1) vaccine trial in Africa, with a clade B immunogen, is currently under way in Uganda, in a region where clades A and D are endemic. The use of a B clade vaccine is based on anticipated cross-recognition of endemic strains of HIV-1 in Uganda, but, in fact, little is known about the cytotoxic T lymphocyte (CTL) responses in that region. Seventeen HIV-1-infected volunteers from Kampala, Uganda, were studied to determine the immune responses elicited by natural infection with local HIV-1 strains. Despite the presence of broad cross-clade recognition, the CTL responses to the infecting viral clade were highest in most people. Recognition of nonendemic clade B antigens was similar to that of the coendemic local clade, and, in some instances, cross-recognition of clade B was greater. Nevertheless, the degree of cross-clade cellular responses we observed lends justification to the use of clade B-based immunogens in the current phase 1 vaccine trial in Uganda.

Molecular evolution of human immunodeficiency virus type 1 subtype A in Senegal: 1988-1997.

OBJECTIVE: Few studies have been able to track the genetic diversity of HIV-1 viruses in human populations over time. We analyzed the molecular evolution of subtype A over a 10-year period, in a cohort of female sex workers with a known time of infection. STUDY DESIGN/METHODS: We amplified and sequenced the C2-V3 region of the surface envelope glycoprotein from 73 HIV-1-infected women, infected between 1987-1997. RESULTS: Fifty-one patients were infected by subtype A viruses. The viruses demonstrated significant diversification (p < 0.001) with mean genetic distance increasing from 8.6% in 1989 to 15.9% in 1997. The slope of the fitted curve suggested a rate of diversification of 0.7% per year. The majority of subtype A viruses clustered with HIV-1 subtype A/G recombinant form (IbNG). CONCLUSION: The genetic diversity of HIV-1 subtype A infections doubled over the first 10 years of this high risk population's epidemic, suggesting that implementation of vaccines early in the epidemic may have a higher likelihood of success based on levels of genetic diversity. The A/G recombinant form (IbNG) has taken epidemic proportions in West Africa. This is of particular importance in understanding the epidemiology of HIV-1 subtypes in Africa and to further dissect the potential phenotypic and biological characteristics of these viruses.