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1.
J Viral Hepat ; 23(7): 522-34, 2016 07.
Article in English | MEDLINE | ID: mdl-26924428

ABSTRACT

The introduction of direct-acting antiviral agents (DAAs) has made hepatitis C infection curable in the vast majority of cases and the elimination of the infection possible. Although initially too costly for large-scale use, recent reductions in DAA prices in some low- and middle-income countries (LaMICs) has improved the prospect of many people having access to these drugs/medications in the future. This article assesses the pricing and financing conditions under which the uptake of DAAs can increase to the point where the elimination of the disease in LaMICs is feasible. A Markov simulation model is used to study the dynamics of the infection with the introduction of treatment over a 10-year period. The impact on HCV-related mortality and HCV incidence is assessed under different financing scenarios assuming that the cost of the drugs is completely paid for out-of-pocket or reduced through either subsidy or drug price decreases. It is also assessed under different diagnostic and service delivery capacity scenarios separately for low-income (LIC), lower-middle-income (LMIC) and upper-middle-income countries (UMIC). Monte Carlo simulations are used for sensitivity analyses. At a price of US$ 1680 per 12-week treatment duration (based on negotiated Egyptian prices for an all oral two-DAA regimen), most of the people infected in LICs and LMICs would have limited access to treatment without subsidy or significant drug price decreases. However, people in UMICs would be able to access it even in the absence of a subsidy. For HCV treatment to have a significant impact on mortality and incidence, a significant scaling-up of diagnostic and service delivery capacity for HCV infection is needed.


Subject(s)
Antiviral Agents/therapeutic use , Hepatitis C, Chronic/drug therapy , Marketing , Developing Countries , Humans , Microbial Sensitivity Tests
2.
Clin Infect Dis ; 54 Suppl 4: S245-9, 2012 May.
Article in English | MEDLINE | ID: mdl-22544182

ABSTRACT

The HIV drug resistance (HIVDR) prevention and assessment strategy, developed by the World Health Organization (WHO) in partnership with HIVResNet, includes monitoring of HIVDR early warning indicators, surveys to assess acquired and transmitted HIVDR, and development of an accredited HIVDR genotyping laboratory network to support survey implementation in resource-limited settings. As of June 2011, 52 countries had implemented at least 1 element of the strategy, and 27 laboratories had been accredited. As access to antiretrovirals expands under the WHO/Joint United Nations Programme on HIV/AIDS Treatment 2.0 initiative, it is essential to strengthen HIVDR surveillance efforts in the face of increasing concern about HIVDR emergence and transmission.


Subject(s)
Anti-Retroviral Agents/pharmacology , HIV Infections/drug therapy , Health Policy , Developing Countries , Drug Resistance, Viral , Global Health , Health Surveys , Humans , World Health Organization
3.
AIDS ; 14(1): 85-8, 2000 Jan 07.
Article in English | MEDLINE | ID: mdl-10714571

ABSTRACT

RATIONALE: COL-1492 is a nonoxynol-9 (N-9)-containing vaginal gel and may be a potential microbicide. As part of an effectiveness trial, an initial toxicity study was conducted. OBJECTIVES: The main objective of the reported study was the assessment of the toxicity of a 52.5 mg N-9 gel, COL-1492, when used a number of times each day by female sex workers. METHODS: This was a randomized, placebo-controlled triple-blinded trial among female sex workers. The participants were asked to use the product for each vaginal sexual act. At each monthly visit a gynaecological examination with sexually transmitted disease sampling and colposcopy was performed. Venous blood was drawn for syphilis and HIV serology. All women received intensive counselling on condom use. Male condoms and sexually transmitted disease treatment were given free of charge. RESULTS: Only blinded results on the colposcopic examinations are reported. The incidence of lesions with or without an epithelial disruption was low: 0.06 and 0.29, respectively, per 100 woman-days in group A; 0.09 and 0.26 respectively per 100 woman-days in group B. There was no significant difference between the two arms. CONCLUSION: The multiple daily use of COL-1492 by female sex workers did not show an increase of local toxicity over that of a placebo. Colposcopy was discontinued in the autumn of 1997 in accordance with a Data Safety Monitoring Board decision. In the currently ongoing effectiveness trial the assessment of the product's toxicity continues to be monitored by simple visual examination.


Subject(s)
Anti-HIV Agents/adverse effects , Nonoxynol/adverse effects , Administration, Intravaginal , Adult , Anti-HIV Agents/therapeutic use , Colposcopy , Condoms , Female , HIV Infections/prevention & control , Humans , Male , Nonoxynol/therapeutic use , Placebos , Sex Work , Sexually Transmitted Diseases/prevention & control , Vaginal Creams, Foams, and Jellies
4.
J Infect Dis ; 180(6): 1886-93, 1999 Dec.
Article in English | MEDLINE | ID: mdl-10558945

ABSTRACT

A randomized, double-blind, placebo-controlled clinical trial was conducted in Nairobi, Kenya, to compare single-dose ciprofloxacin with a 7-day course of erythromycin for the treatment of chancroid. In all, 208 men and 37 women presenting with genital ulcers clinically compatible with chancroid were enrolled. Ulcer etiology was determined using culture techniques for chancroid, serology for syphilis, and a multiplex polymerase chain reaction for chancroid, syphilis, and herpes simplex virus (HSV). Ulcer etiology was 31% unmixed chancroid, 23% unmixed syphilis, 16% unmixed HSV, 15% mixed etiology, and 15% unknown. For 111 participants with chancroid, cure rates were 92% with ciprofloxacin and 91% with erythromycin. For all study participants, the treatment failure rate was 15%, mostly related to ulcer etiologies of HSV infection or syphilis, and treatment failure was 3 times more frequent in human immunodeficiency virus-infected subjects than in others, mostly owing to HSV infection. Ciprofloxacin is an effective single-dose treatment for chancroid, but current recommendations for empiric therapy of genital ulcers may result in high treatment failure due to HSV infection.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Anti-Infective Agents/therapeutic use , Chancroid/drug therapy , Ciprofloxacin/therapeutic use , Erythromycin/therapeutic use , Adolescent , Adult , Aged , Anti-Bacterial Agents/administration & dosage , Anti-Infective Agents/administration & dosage , Chancroid/microbiology , Chancroid/virology , Ciprofloxacin/administration & dosage , Double-Blind Method , Erythromycin/administration & dosage , Female , HIV Infections/complications , HIV-1 , Haemophilus ducreyi/genetics , Haemophilus ducreyi/isolation & purification , Herpes Genitalis/virology , Humans , Kenya , Male , Middle Aged , Polymerase Chain Reaction , Simplexvirus/genetics , Simplexvirus/isolation & purification , Syphilis/complications , Syphilis/microbiology , Treatment Outcome , Treponema pallidum/genetics , Treponema pallidum/isolation & purification
5.
N Engl J Med ; 339(24): 1739-43, 1998 Dec 10.
Article in English | MEDLINE | ID: mdl-9845708

ABSTRACT

BACKGROUND: In Southeast Asia, disseminated infection with Penicillium marneffei is common among patients with human immunodeficiency virus (HIV) infection. Even after successful primary treatment, the relapse rate for this potentially fatal systemic fungal infection is about 50 percent. METHODS: We conducted a double-blind trial in Thailand to evaluate itraconazole as secondary prophylaxis against P. marneffei infection in patients with the acquired immunodeficiency syndrome (AIDS) who were in complete remission after treatment for culture-proved P. marneffei infection. The patients were randomly assigned to receive either oral itraconazole (200 mg daily) or placebo as maintenance therapy. RESULTS: Of the 72 HIV-infected patients who completed initial treatment for P. marneffei infection, 71 were enrolled in the maintenance study. None of the 36 patients assigned to itraconazole had a relapse of P. marneffei infection within one year, whereas 20 of the 35 patients assigned to placebo (57 percent) had relapses (P<0.001). Among the 20 patients who had relapses, P. marneffei was cultured from blood (15 patients), lymph-node tissue (3 patients), skin (3 patients), and sputum (1 patient). The median time to relapse was 24 weeks after the completion of the initial treatment (95 percent confidence interval, 19.0 to 36.1). Survival and toxic effects were similar in the two groups. CONCLUSIONS: In patients infected with HIV who have completed successful primary treatment of P. marneffei infection, secondary prophylaxis with oral itraconazole is well tolerated and prevents relapses of this opportunistic infection.


Subject(s)
AIDS-Related Opportunistic Infections/prevention & control , Antifungal Agents/therapeutic use , Itraconazole/therapeutic use , Mycoses/prevention & control , Penicillium , AIDS-Related Opportunistic Infections/mortality , Acquired Immunodeficiency Syndrome/mortality , Adult , Antifungal Agents/adverse effects , Disease-Free Survival , Double-Blind Method , Female , Humans , Itraconazole/adverse effects , Male , Middle Aged , Mycoses/mortality , Secondary Prevention , Survival Rate
6.
Clin Infect Dis ; 26(5): 1107-10, 1998 May.
Article in English | MEDLINE | ID: mdl-9597237

ABSTRACT

Disseminated infection with Penicillium marneffei is common in patients infected with human immunodeficiency virus (HIV) in Southeast Asia. Treatment with amphotericin B alone is effective but requires a prolonged hospital stay. We conducted an open-label nonrandomized study to evaluate the efficacy and safety of treatment with amphotericin B at a dosage of 0.6 mg/(kg.d) intraveneously for 2 weeks, followed by a 400-mg/d dosage of oral itraconazole for 10 weeks. Of the 74 HIV-infected patients we studied who had disseminated P. marneffei infection, diagnosed by positive fungal culture and clinical evidence of infection, 72 (97.3%) responded to the treatment. There were no serious adverse drug effects. It was concluded that the regimen was effective and safe for treatment of disseminated P. marneffei infection in HIV-infected patients.


Subject(s)
AIDS-Related Opportunistic Infections/drug therapy , Amphotericin B/therapeutic use , Antifungal Agents/therapeutic use , Itraconazole/therapeutic use , Mycoses/drug therapy , Penicillium , Adult , Amphotericin B/administration & dosage , Female , Humans , Itraconazole/administration & dosage , Male , Middle Aged , Thailand , Treatment Outcome
7.
AIDS ; 12(4): 433-7, 1998 Mar 05.
Article in English | MEDLINE | ID: mdl-9520174

ABSTRACT

OBJECTIVE: To determine the safety of a vaginal microbicide, COL-1492, containing 52.5 mg nonoxynol-9, applied once daily for 14 days among healthy volunteers. METHODS: A randomized, double-blind controlled trial with three arms, COL-1492 gel versus placebo gel versus no-treatment controls, was conducted. Outcomes of interest were reported genital symptoms, incidence of gynaecological signs, and incidence of genital lesions revealed by colposcopy. Participants were enrolled in four centres (Belgium, The Netherlands, and two in Thailand). RESULTS: A total of 534 women participated in the study: 179 used COL-1492, 178 used placebo, and 177 were no-treatment controls. Study visits were scheduled 1 week prior to enrollment (day -7), day 0 (enrollment), day 8 and day 14. The most frequently reported genital symptom was vaginal discharge in both the COL-1492 and placebo groups. This appeared to be related to leakage of the product out of the vagina. The incidence of lesions associated with epithelial disruption (ulcers and abrasions) was very low (< 2%) and there was no statistically significant difference between the three groups. Of the lesions observed by colposcopy that did not involve epithelial disruption, petechial haemorrhage was the most frequently detected, with an incidence of 20.1, 9.0 and 7.3% in the COL-1492, placebo and control groups, respectively. COL-1492 users had a higher incidence of erythema (8.4 versus 2% in the other groups). CONCLUSION: COL-1492 showed minimal toxicity when applied once daily. A Phase III trial to assess the product's effectiveness in HIV prevention is currently ongoing.


Subject(s)
Anti-HIV Agents/adverse effects , HIV Infections/prevention & control , Nonoxynol/adverse effects , Spermatocidal Agents/adverse effects , Adult , Anti-HIV Agents/therapeutic use , Colposcopy , Double-Blind Method , Female , HIV/drug effects , Humans , Middle Aged , Nonoxynol/therapeutic use , Spermatocidal Agents/therapeutic use , Treatment Outcome , Vaginal Discharge/chemically induced , Vaginal Diseases/chemically induced
8.
Sex Transm Infect ; 74(4): 265-70, 1998 Aug.
Article in English | MEDLINE | ID: mdl-9924466

ABSTRACT

BACKGROUND: Interferon alfa (IFN-alpha) exhibits dose related in vitro activity against human immunodeficiency virus (HIV), with complete inhibition of HIV replication at IFN-alpha concentrations > or = 256 IU/ml. In mid-1990, Kenyan investigators reported that oral administration of an extremely low dose (150 IU/day) of natural human (nHu) IFN-alpha resulted in complete alleviation of AIDS related complex and AIDS symptoms and resolution of opportunistic infections without additional treatment. Moreover, loss of HIV antibody seropositivity was reported in approximately 10% of treated patients. Subsequent small studies failed to substantiate these spectacular claims, but controversy on the efficacy of this treatment persisted. METHODS: We studied 559 adult Ugandan patients with WHO stage 2-4 HIV infection and a Karnofsky performance score of more than 50, who had not received any drugs with antiretroviral activity in the previous 3 months. The patients were randomly assigned in a double blind fashion either to 150 IU oral nHuIFN-alpha/day or placebo. The duration of treatment was extended from 28 weeks to 60 weeks 9 months after enrollment had started. At that time 112 subjects had already received 28 weeks of treatment and been discontinued from the study. RESULTS: Both study groups were comparable with respect to all baseline characteristics studied, except that the nHuIFN-alpha group had slightly lower absolute CD4+ lymphocyte counts (median 60.7 x 10(6)/l) than the placebo group (median 85.3 x 10(6)/l) (p = 0.033). Therefore, all analyses were adjusted for CD4+ lymphocyte counts at entry. In both treatment groups there was relentless progression of HIV disease. Subjects treated with nHuIFN-alpha and placebo had similar mortality, disease progression rates, decline of CD4+ lymphocyte counts and Karnofsky performance scores, and prevalence of symptoms. No patient reverted to HIV-1 seronegative antibody status. Serious adverse events were not seen. Quality control of the study medication documented that the active drug indeed contained IFN-alpha activity. CONCLUSIONS: The current large, randomised, double blind, placebo controlled study did not show any benefit from oral treatment with 150 IU nHuIFN-alpha/day in a population of African patients with symptomatic HIV infection.


Subject(s)
Acquired Immunodeficiency Syndrome/drug therapy , Antiviral Agents/administration & dosage , Interferon-alpha/administration & dosage , Acquired Immunodeficiency Syndrome/immunology , Administration, Oral , Adolescent , Adult , Aged , Antiviral Agents/adverse effects , CD4 Lymphocyte Count , Disease Progression , Double-Blind Method , Female , Follow-Up Studies , Humans , Interferon-alpha/adverse effects , Male , Middle Aged , Survival Analysis , Treatment Failure
10.
BMJ ; 313(7055): 440, 1996 Aug 24.
Article in English | MEDLINE | ID: mdl-8776303

ABSTRACT

PIP: Increased access, in middle-income countries, to innovative but costly medical technologies for the treatment of human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) raises important policy considerations about how to optimize their use. Realizing the full potential of antiretroviral therapy, for example, requires widespread availability of HIV tests to identify those in the early stage of HIV infection, counseling services to inform people of their test results and explain the therapeutic options, available and affordable drugs, monitoring of drug efficacy and toxicity, mechanisms to ensure long-term compliance, and well functioning psychosocial support systems. In Thailand, a cost-effectiveness study modelling the use of different antiretroviral treatment options demonstrated that investments in antiretroviral therapy and formula feeding to prevent maternal-child HIV transmission were more effective and affordable than providing antiretroviral agents to those with established HIV infection. The cost of preventing vertical HIV transmission amounted to 16% of Thailand's national AIDS budget. The cost of extending access to and compliance with treatment and preventing opportunistic infections would be 129% of the budget, while that of providing antiretroviral drugs to all those with symptomatic HIV infection would be 235-630% of the budget (depending on the complexity of the regimen). More such studies are needed to develop a conceptual framework for policy development.^ieng


Subject(s)
Developing Countries , HIV Infections , Acquired Immunodeficiency Syndrome/economics , Acquired Immunodeficiency Syndrome/prevention & control , Acquired Immunodeficiency Syndrome/transmission , Antiviral Agents/therapeutic use , Cost-Benefit Analysis , HIV Infections/economics , HIV Infections/prevention & control , HIV Infections/transmission , Humans , Infectious Disease Transmission, Vertical , Thailand
11.
J Int Assoc Physicians AIDS Care ; 2(3): 25-32, 38, 1996 Mar.
Article in English | MEDLINE | ID: mdl-11363344

ABSTRACT

AIDS: The Ninth International Conference on AIDS and STD in Africa (ICASA) discussed the devastating effect AIDS is having on African countries. Most African nations experience AIDS caseloads that are 100-fold higher than those in industrialized nations, with much lower funding. HIV problems can be managed, even in the African environment where fiscal resources are scarce. Twelve million Africans are currently living with HIV, and the epidemic continues to spread. Statistics are presented on the prevalence of HIV by nation. Current studies show that there will be benefits from linking HIV prevention information to STD treatment programs. Strengthening STD services is proven to decrease risk behavior and syphilis prevalence in some areas; these findings suggest that future programs for HIV prevention may work. Most African countries have staggering numbers of AIDS patients, leading to a corresponding problem of dealing with orphaned children. These children frequently lack the finances for schooling or adequate nutrition. There is an urgent need to develop effective means to reduce the transfer of HIV from mothers to infants, and several studies were highlighted showing that genital HIV shedding and the appearance of HIV-infected cells in breast milk may be contributing to the high rate of HIV-antibodies in infants.^ieng


Subject(s)
Acquired Immunodeficiency Syndrome , Sexually Transmitted Diseases , Acquired Immunodeficiency Syndrome/epidemiology , Acquired Immunodeficiency Syndrome/prevention & control , Acquired Immunodeficiency Syndrome/therapy , Africa/epidemiology , Child , Female , Humans , Male , Sexually Transmitted Diseases/epidemiology , Sexually Transmitted Diseases/prevention & control
12.
AIDS ; 9(7): 665-73, 1995 Jul.
Article in English | MEDLINE | ID: mdl-7546409

ABSTRACT

PIP: An increasing incidence of tuberculosis has been recorded in areas where both human immunodeficiency virus (HIV) and Mycobacterium tuberculosis are prevalent. 98% of HIV-associated tuberculosis cases occur in developing countries, most notably sub-Saharan Africa. This trend has led to the consideration of tuberculosis prevention therapy for HIV-infected patients. The efficacy of isoniazid for this purpose has been demonstrated in numerous clinical trials, but its application has been limited by concerns about hepatotoxicity, non-adherence, drug resistance, and costs. Recommended is the approach adopted in the US of providing a six-month course of isoniazid to those with a positive tuberculin skin test reaction and epidemiologic risk factors; for those already infected with HIV, 12 months of treatment is suggested. Rifampicin preventive therapy is recommended for those infected by isoniazid-resistant bacilli. Needed are studies to assess operational feasibility, cost-benefits, the use of life-long isoniazid preventive therapy in areas of high tuberculosis transmission, and alternative regimens such as short-course multidrug treatment.^ieng


Subject(s)
AIDS-Related Opportunistic Infections/prevention & control , Antitubercular Agents/therapeutic use , Isoniazid/therapeutic use , Tuberculosis, Pulmonary/prevention & control , Adult , Antitubercular Agents/administration & dosage , Chemical and Drug Induced Liver Injury/etiology , Cost-Benefit Analysis , Humans , Isoniazid/administration & dosage , Patient Compliance , Randomized Controlled Trials as Topic , Risk Factors , Tuberculosis, Multidrug-Resistant/etiology , Tuberculosis, Multidrug-Resistant/prevention & control , Tuberculosis, Pulmonary/etiology
13.
J Infect Dis ; 171(6): 1611-4, 1995 Jun.
Article in English | MEDLINE | ID: mdl-7769301

ABSTRACT

Menfegol is a spermicide with in vitro activity against human immunodeficiency virus (HIV). A randomized placebo-controlled safety study covered the use of menfegol foaming tablets for 14 days at increasing frequencies of insertion by 125 prostitutes in Dakar, Senegal. The frequencies of colposcopically diagnosed genital lesions were 5.0%, 11.8%, 27.8%, 49.7%, and 29.4% among menfegol recipients when tablets were used once every other day or 1, 2, 4, or 8 times a day, respectively (P < .05). Among placebo recipients, frequencies were 11.1% and 23.5% when tablets were used < 8 times daily and 8 times daily, respectively. There was no association between subjective genital symptoms and the incidence of colposcopically detected lesions. The high incidence of genital lesions when menfegol foaming tablets were used more than once daily suggests that their frequent use should not be recommended to prevent HIV transmission. In use at low frequency, the tablets' toxicity might be balanced by anti-HIV properties. Safety studies on vaginal microbicides should use objective methods, such as colposcopy, to assess the incidence of lesions.


Subject(s)
Contraceptive Agents, Female/adverse effects , Polyethylene Glycols/adverse effects , Uterine Cervical Diseases/chemically induced , Vaginal Diseases/chemically induced , Adult , Double-Blind Method , Female , Humans , Mucous Membrane/drug effects , Research Design , Sex Work
14.
N Engl J Med ; 332(12): 779-84, 1995 Mar 23.
Article in English | MEDLINE | ID: mdl-7862181

ABSTRACT

BACKGROUND: We studied the efficacy of a short-course regimen of chemotherapy for pulmonary tuberculosis in Kinshasa, Zaire. We also assessed whether, among patients with human immunodeficiency virus (HIV) infection, treatment should be extended from 6 to 12 months. METHODS: HIV-seropositive and HIV-seronegative outpatients with pulmonary tuberculosis were treated with rifampin, isoniazid, pyrazinamide, and ethambutol daily for two months, followed by rifampin plus isoniazid twice weekly for four months. The HIV-positive patients who had no evidence of tuberculosis were then randomly assigned to receive either rifampin plus isoniazid or placebo twice weekly for a further six months. We also followed a comparison group of HIV-seronegative patients who received no further treatment for tuberculosis after six months. RESULTS: After six months, 260 of 335 HIV-seropositive and 186 of 188 HIV-seronegative participants could be evaluated, and their rates of treatment failure were similar: 3.8 and 2.7 percent, respectively. At 24 months, the HIV-seropositive patients who received extended treatment had a relapse rate of 1.9 percent, as compared with 9 percent among the HIV-seropositive patients who received placebo for the second 6 months (P < 0.01). Extended treatment did not improve survival, however. Among the HIV-seronegative patients, 5.3 percent relapsed. CONCLUSIONS: Among HIV-seropositive patients with pulmonary tuberculosis, extending treatment from 6 to 12 months reduces the rate of relapse but does not improve survival. The six-month program of partly intermittent antituberculous treatment may be an acceptable alternative when resources are limited.


Subject(s)
AIDS-Related Opportunistic Infections/drug therapy , Antibiotics, Antitubercular/therapeutic use , Tuberculosis, Pulmonary/drug therapy , AIDS-Related Opportunistic Infections/mortality , Adult , Female , HIV Seropositivity , Humans , Male , Prospective Studies , Single-Blind Method , Time Factors , Treatment Outcome , Tuberculosis, Multidrug-Resistant , Tuberculosis, Pulmonary/mortality
15.
AIDS ; 8(9): 1277-80, 1994 Sep.
Article in English | MEDLINE | ID: mdl-7802980

ABSTRACT

OBJECTIVE: A60 is a high molecular weight mycobacterial antigen complex. The detection of immunoglobulin (Ig) G antibodies to A60 has been advocated as a reasonably sensitive and specific test for active tuberculosis (TB). We aimed to compare the sensitivity of this test among HIV-seropositive and HIV-seronegative patients with pulmonary TB. METHODS: The presence and concentration of anti-A60 IgG antibodies was assessed by enzyme-linked immunosorbent assay in 208 HIV-seropositive and 91 HIV-seronegative Zaïrian patients with smear-positive pulmonary TB. The relationship between anti-A60 IgG levels and HIV serostatus, CD4+ lymphocyte counts, presence of clinical AIDS, and tuberculin skin test results was verified. RESULTS: Only 36.5% of the HIV-seropositive, compared with 69.2% of the HIV-seronegative patients had a positive anti-A60 IgG test (P < 0.00001). Among HIV-seropositive patients, anti-A60 IgG levels did not differ according to CD4+ lymphocyte counts, presence of clinical AIDS, or tuberculin skin test results. CONCLUSIONS: Among patients with pulmonary TB, the sensitivity of testing for anti-A60 IgG was much lower among HIV-seropositive than among HIV-seronegative patients, even from the early stages of HIV-related immunodeficiency. This limits the utility of anti-A60 IgG-antibody testing in the diagnosis of TB among HIV-infected patients.


Subject(s)
AIDS-Related Opportunistic Infections/diagnosis , Antibodies, Bacterial/blood , Antigens, Bacterial , Immunoglobulin G/blood , Tuberculosis, Pulmonary/diagnosis , AIDS-Related Opportunistic Infections/complications , AIDS-Related Opportunistic Infections/immunology , Adult , Enzyme-Linked Immunosorbent Assay/statistics & numerical data , Female , HIV Seronegativity/immunology , HIV Seropositivity/immunology , Humans , Male , Sensitivity and Specificity , Serologic Tests/statistics & numerical data , Tuberculosis, Pulmonary/complications , Tuberculosis, Pulmonary/immunology
16.
AIDS ; 7(9): 1241-5, 1993 Sep.
Article in English | MEDLINE | ID: mdl-8216982

ABSTRACT

OBJECTIVES: To compare the specificity of the World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) case definitions for AIDS in autopsy cases from Zaïre. SETTING: Mama Yemo Hospital and University Hospital morgues in Kinshasa, and Karawa Hospital in Equateur Region, Zaïre. METHODS: Autopsy cases with a clinical diagnosis of AIDS on the death certificate or chart were studied. Evaluation included post-mortem HIV-1 serology, chart review for specific AIDS-related symptoms and signs, and application of WHO and CDC case criteria to the clinical and autopsy diagnoses. RESULTS: Of the 68 diagnosed AIDS cases, 98% fulfilled WHO criteria for AIDS and 93% fulfilled both WHO and CDC criteria. All cases fulfilling both criteria were HIV-1-seropositive. Opportunistic infections accounted for 84% of CDC AIDS-defining conditions. Disseminated tuberculosis was the most frequent (41%) specific diagnosis; Pneumocystis carinii pneumonia was rare (< 2%). CONCLUSIONS: There was good concordance between WHO and CDC case definitions. A diagnosis of AIDS on the chart or death certificate is adequate for surveillance purposes in this population.


Subject(s)
Acquired Immunodeficiency Syndrome/diagnosis , Acquired Immunodeficiency Syndrome/epidemiology , Acquired Immunodeficiency Syndrome/pathology , Adolescent , Adult , Autopsy , Centers for Disease Control and Prevention, U.S. , Death Certificates , Democratic Republic of the Congo/epidemiology , Female , Humans , Male , Medical Records , Middle Aged , United States , World Health Organization
17.
J Infect Dis ; 168(1): 106-11, 1993 Jul.
Article in English | MEDLINE | ID: mdl-8515097

ABSTRACT

Rates of infection with Mycobacterium tuberculosis were compared in Kinshasa, Zaire, in 521 household contacts of 74 human immunodeficiency virus type 1 (HIV-1)-seropositive index patients and in 692 household contacts of 95 HIV-1-seronegative [corrected] index patients with sputum smear-positive pulmonary tuberculosis: No difference was noted between contacts of HIV-1-seropositive and -seronegative patients. The increasing prevalence of M. tuberculosis infection with increasing age was similar in household contacts of seropositive and seronegative patients; by age 16 years, 75% were purified protein derivative-positive. The similarly low rates of M. tuberculosis infection in household contacts of HIV-1-seropositive and -seronegative index patients with sputum smear-positive pulmonary tuberculosis indicates that HIV-1-seropositive patients with pulmonary tuberculosis are not more infectious than HIV-1-seronegative patients with pulmonary tuberculosis.


Subject(s)
HIV Seropositivity/complications , Tuberculosis, Pulmonary/transmission , Adolescent , Adult , Aged , Aged, 80 and over , Analysis of Variance , Child , Child, Preschool , Cross-Sectional Studies , Democratic Republic of the Congo/epidemiology , Humans , Infant , Middle Aged , Mycobacterium tuberculosis , Tuberculosis, Pulmonary/complications , Tuberculosis, Pulmonary/epidemiology
18.
Lancet ; 342(8864): 143-6, 1993 Jul 17.
Article in English | MEDLINE | ID: mdl-8101257

ABSTRACT

Tuberculosis (TB) is the most common opportunistic infection in African patients who die from AIDS, yet the stage of immunodeficiency at which TB develops is uncertain. We studied the immune status of HIV-infected outpatients with pulmonary TB in relation to their clinical presentation in a cross-sectional study of 216 HIV-seropositive and 146 HIV-seronegative ambulatory incident cases of smear-positive and culture-positive pulmonary TB in Kinshasa, Zaire. HIV-seropositive and seronegative patients had median CD4 lymphocyte counts of 316.5/microL and 830.5/microL, respectively. Of the HIV-seropositive patients, 32.9% had less than 200 CD4 lymphocytes/microL, 37% between 200 and 499, and 30.1% 500 or more. Clinical AIDS, as defined by the WHO clinical case-definition or a modified version, was of similar limited use as a predictor of immunodeficiency. Among HIV-seropositive patients, oral candidosis, lymphopenia, a negative tuberculin purified protein derivative test, and cutaneous anergy were strongly associated with CD4 counts of less than 200/microL, and seemed to be better markers of immune dysfunction. We conclude that pulmonary TB develops across a broad spectrum of HIV-induced immunodeficiency and that a diagnosis of pulmonary TB is of limited use as a marker of stage of HIV disease in African HIV-infected outpatients.


PIP: Between March 1989 and September 1991, physicians compared CD4 lymphocyte counts of 216 HIV-seropositive patients whose sputum smears tested positive for pulmonary tuberculosis (TB) with those of 146 HIV- negative patients who also tested positive for TB at a TB screening center in Kinshasa, Zaire. The researchers wanted to investigate the immune status of HIV-infected outpatients with pulmonary TB in relation to clinical criteria. HIV seropositive patients had much lower CD4 lymphocyte counts than did HIV seronegative patients (total CD4 count, 316.5/mcl vs. 830.5/mcl; CD4 count, 13% vs. 36%; p .001). 90.4% of HIV-positive patients had CD4 counts 800 compared with 48% of HIV- negative patients. 32.9% of HIV-positive patients had CD4 counts 200 while just 1.4% of HIV-negative patients did. As CD4 counts fell, weight loss, diarrhea during the previous month, past or present herpes zoster, and oral candidosis occurred more frequently (p = .004 for oral candidosis and p = .02 for the rest). Negative purified protein derivative RT23 (PPD) tests and cutaneous anergy occurred more often as immunodeficiency rose (p .001). Increased immunosuppression was also characterized by no detectable cavitation on chest radiography, anemia, and low total lymphocyte counts (p = .02 for absence of cavitation and p .001 for the others). These results suggested that pulmonary TB occurred along the continuum of immunodeficiency as defined by CD4 counts. Thus, it is not likely to be a marker of the severity of HIV infection. Instead weight loss, diarrhea during the previous month, past or present herpes zoster, oral candidosis, negative PPD test and cutaneous anergy, absence of detectable cavitation on chest radiography, anemia, and low total lymphocyte appeared to be better markers of the severity of HIV-related immunodeficiency.


Subject(s)
AIDS-Related Opportunistic Infections/immunology , CD4-Positive T-Lymphocytes/pathology , HIV Infections/immunology , HIV-1 , Tuberculosis, Pulmonary/immunology , Acquired Immunodeficiency Syndrome/immunology , Adult , Cross-Sectional Studies , Democratic Republic of the Congo , Female , HIV Seropositivity/immunology , Humans , Immunocompromised Host , Leukocyte Count , Lymphocytes/pathology , Male , Sensitivity and Specificity
19.
Trans R Soc Trop Med Hyg ; 87(3): 263-6, 1993.
Article in English | MEDLINE | ID: mdl-8236386

ABSTRACT

Diarrhoea is the most common manifestation of acquired immunodeficiency syndrome (AIDS) in Africa. Numerous parasitic or bacterial agents have been implicated, but a pathogen-specific aetiology has not been found. Enteric viruses (i.e., rotavirus, small round structured viruses, coronavirus, and adenovirus) were detected by enzyme-linked immunosorbent assay or electron microscopy in faecal specimens of 17% of 198 consecutive adult admissions to a general medical ward of an urban hospital in Kinshasa, Zaire. Overall, 57% of patients were seropositive for infection with human immunodeficiency virus (HIV) 1; of these, 50% were classified as World Health Organization AIDS stage IV. The prevalence of enteric viruses in stool specimens did not differ significantly between patients with and without HIV infection, and was not associated with acute or chronic diarrhoea, or constitutional symptoms. However, a trend (P = 0.14) towards greater frequency of virus in stools from patients in the lower 3 quintiles of the CD4/CD8 T cell ratio was seen. This trend approached statistical significance (P = 0.07) with stratification by HIV infection. Although we found no evidence in this population to support a major pathogenic role for these viruses alone in the enteropathy of AIDS, increased viral shedding was weakly associated with immunodeficiency.


PIP: During July-October 1989 in Zaire, a physician examined and took blood and stool samples from 198 adult patients at Mama Yemo Hospital in central Kinshasa to learn the prevalence of enteric viruses and their link to diarrhea, immunosuppression, and wasting among HIV infected and uninfected patients. In Kinshasa, diarrhea is prevalent and heterosexual intercourse is the main mode of HIV transmission. 57.6% of the patients were infected with HIV. 50% of the HIV-positive patients had AIDS. 93% of all HIV-positive patients either had AIDS (stage IV) or advanced stage III disease. 49% of them died while in the hospital. 22% of the HIV-negative patients died while in the hospital. 17% of all adult patients studied were infected with at least 1 enteric virus, especially rotavirus. Enteric viruses were isolated from both HIV infected and uninfected patients (17% and 18%, respectively). State of immunocompromise did not significantly affect viral shedding, but fewer patients in the less immunocompromised stages shed viruses than did those in the advanced stages of immunocompromise (3 vs. 72 patients). When examining the ratio of circulating CD4 and CD8 T cells in HIV-infected patients, however, there was a trend toward greater frequency of enteric viruses (p = .07). Chronic diarrhea was significantly associated with HIV seropositivity (p 0.01), HIV stage (p .001), and CD4/CD8 T cell ratio (p .01). Acute diarrhea was not associated with any of the above, however. These findings suggest that enteric viruses were not a significant cause of diarrhea, but they were isolated somewhat more often in patients of advanced immunosuppression.


Subject(s)
Acquired Immunodeficiency Syndrome/complications , Adenoviruses, Human/isolation & purification , Coronaviridae/isolation & purification , Diarrhea/microbiology , Feces/microbiology , Rotavirus/isolation & purification , Acquired Immunodeficiency Syndrome/epidemiology , Democratic Republic of the Congo/epidemiology , Diarrhea/epidemiology , Enzyme-Linked Immunosorbent Assay , Female , Humans , Male , Prevalence
20.
J Acquir Immune Defic Syndr (1988) ; 6(4): 419-23, 1993 Apr.
Article in English | MEDLINE | ID: mdl-8455147

ABSTRACT

Sentinel serosurveillance for HIV infection has been carried out in Shaba province, Zaire, among consecutive pregnant women attending antenatal clinics from 1989 to 1991. There were four surveillance sites (three urban and one semiurban), at which a total of 13 surveillance studies were made of 4,205 women. Overall, 3.1% were HIV seropositive. There were no significant differences in HIV seroprevalence between surveillance sites, and HIV seroprevalence did not increase at any of the surveillance sites during the 2-year period of study. Since changes in the population studied did not occur between surveillance studies, it is believed that the observed stable trend reflects stable HIV seroprevalence rates in the general adult population of the surveillance sites. Collateral HIV seroprevalence data were available from 8,725 blood donors at 20 sites (six urban, 14 rural) in the province, who had an overall HIV seroprevalence of 4.6%. The higher HIV seroprevalence rate among blood donors was probably due to selection bias, since HIV seroprevalence rates in two blood banks, which relied nearly exclusively on replacement donors, were 2.7 and 2.8%, our best estimate for HIV seroprevalence in the three cities where blood banks exist and where no surveillance studies were carried out. The stable and relatively low HIV seroprevalence rates in Shaba province are in sharp contrast with the rapidly increasing and much higher rates in neighboring Zambia and other East African cities. Reasons for this discrepancy are unclear, and their eludication may yield critical information for HIV prevention programs.


Subject(s)
HIV Seroprevalence , Pregnancy Complications, Infectious/epidemiology , Adult , Blood Donors , Democratic Republic of the Congo/epidemiology , Female , Humans , Pregnancy
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