Trends in TB and HIV care and treatment cascade, Kenya, 2008-2018.

BACKGROUND: HIV infection is associated with high mortality among people with TB. Antiretroviral therapy (ART) reduces TB incidence and mortality among people living with HIV (PLHIV). Since 2005, Kenya has scaled up TB and HIV prevention, diagnosis and treatment. We evaluated the impact of these services on trends and TB treatment outcomes.METHODS: Using Microsoft Excel (2016) and Epi-Info 7, we analysed Kenya Ministry of Health TB surveillance data from 2008 to 2018 to determine trends in TB notifications, TB classification, HIV and ART status, and TB treatment outcomes.RESULTS: Among the 1,047,406 people reported with TB, 93% knew their HIV status, and 37% of these were HIV-positive. Among persons with TB and HIV, 69% received ART. Between 2008 and 2018, annual TB notifications declined from 110,252 to 96,562, and HIV-coinfection declined from 45% to 27%. HIV testing and ART uptake increased from 83% to 98% and from 30% to 97%, respectively. TB case fatality rose from 3.5% to 3.9% (P <0.018) among HIV-negative people and from 5.1% to 11.2% (P <0.001) among PLHIV on ART.CONCLUSION: TB notifications decreased in settings with suboptimal case detection. Although HIV-TB services were scaled-up, HIV-TB case fatality rose significantly. Concerted efforts are needed to address case detection and gaps in quality of TB care.

Can isoniazid preventive therapy be scaled up rapidly? Lessons learned in Kenya, 2014-2018.

BACKGROUND: TB is the leading cause of mortality among people living with HIV (PLHIV), for whom isoniazid preventive therapy (IPT) has a proven mortality benefit. Despite WHO recommendations, countries have been slow in scaling up IPT. This study describes processes, challenges, solutions, outcomes and lessons learned during IPT scale-up in Kenya.METHODS: We conducted a desk review and analyzed aggregated Ministry of Health (MOH) IPT enrollment data from 2014 to 2018 to determine trends and impact of program activities. We further analyzed IPT completion reports for patients initiated from 2015 to 2017 in 745 MOH sites in Nairobi, Central, Eastern and Western Kenya.RESULTS: IPT was scaled up 75-fold from 2014 to 2018: the number of PLHIV covered increased from 9,981 to 749,890. The highest percentage increases in the cumulative number of PLHIV on IPT were seen in the quarters following IPT pilot projects in 2014 (49%), national launch in 2015 (54%), and HIV treatment acceleration in 2016 (158%). Among 250,069 patients initiating IPT from 2015 to 2017, 97.5% completed treatment, 0.2% died, 0.8% were lost to follow-up, 1.0% were not evaluated, and 0.6% discontinued treatment.CONCLUSIONS: IPT can be scaled up rapidly and effectively among PLHIV. Deliberate MOH efforts, strong leadership, service delivery integration, continuous mentorship, stakeholder involvement, and accountability are critical to program success.

AIDS as a zoonosis: scientific and public health implications.

Evidence of simian immunodeficiency virus (SIV) infection has been reported for 26 different species of African nonhuman primates. Two of these viruses, SIVcpz from chimpanzees and SIVsm from sooty mangabeys, are the cause of acquired immunodeficiency syndrome (AIDS) in humans. Together, they have been transmitted to humans on at least seven occasions. The implications of human infection by a diverse set of SIVs and of exposure to a plethora of additional human immunodeficiency virus-related viruses are discussed.

AIDS--the leading cause of adult death in the West African City of Abidjan, Ivory Coast.

In 1988 to 1989, 698 adult cadavers in Abidjan's two largest morgues were studied, representing 38 to 43% of all adult deaths in the city over the study period, and 6 to 7% of annual deaths. Forty-one percent of male and 32% of female cadavers were infected with human immunodeficiency virus (HIV). Fifteen percent of adult male and 13% of adult female annual deaths are due to acquired immunodeficiency syndrome (AIDS). In Abidjan, AIDS is the leading cause of death and years of potential life lost in adult men, followed by unintentional injuries and tuberculosis. In women, AIDS is the second leading cause of death and premature mortality, after deaths related to pregnancy and abortion. AIDS-specific and AIDS-proportional mortality rates may be higher in other African cities where AIDS has been found for a longer time than in Abidjan.

Provider-initiated HIV testing and counselling for TB patients and suspects in Nairobi, Kenya.

SETTING: Integrated tuberculosis (TB) and human immunodeficiency virus (HIV) services in a resource-constrained setting. OBJECTIVE: Pilot provider-initiated HIV testing and counselling (PITC) for TB patients and suspects. DESIGN: Through partnerships, resources were mobilised to establish and support services. After community sensitisation and staff training, PITC was introduced to TB patients and then to TB suspects from December 2003 to December 2005. RESULTS: Of 5457 TB suspects who received PITC, 89% underwent HIV testing. Although not statistically significant, TB suspects with TB disease had an HIV prevalence of 61% compared to 63% for those without. Of the 614 suspects who declined HIV testing, 402 (65%) had TB disease. Of 2283 patients referred for cotrimoxazole prophylaxis, 1951 (86%) were enrolled, and of 1727 patients assessed for antiretroviral treatment (ART), 1618 (94%) were eligible and 1441 (83%) started treatment. CONCLUSIONS: PITC represents a paradigm shift and is feasible and acceptable to TB patients and TB suspects. Clear directives are nevertheless required to change practice. When offered to TB suspects, PITC identifies large numbers of persons requiring HIV care. Community sensitisation, staff training, multitasking and access to HIV care contributed to a high acceptance of HIV testing. Kenya is using this experience to inform national response and advocate wide PITC implementation in settings faced with the TB-HIV epidemic.

Contribution of reinfection to recurrent tuberculosis in South African gold miners.

SETTING: A gold mine in South Africa. OBJECTIVE: To investigate incidence and risk factors for tuberculosis (TB) recurrence and the relative contribution of reinfection and relapse to recurrence. DESIGN: Prospective cohort study. METHODS: Employees cured of a first episode of culture-positive TB were followed up for recurrence, which was classified as reinfection or relapse by restriction fragment length polymorphism using an insertion sequence (IS) 6110 probe. RESULTS: Among 609 patients, 57 experienced recurrence during a median follow-up period of 1.02 years, corresponding to a recurrence rate of 7.89 per 100 person-years (py). The culture positive recurrence rate was 5.79/100 py, and was higher in human immunodeficiency virus (HIV) infected patients (8.86/100 py in HIV-infected vs. 3.35/100 py in non-HIV-infected). Among HIV-infected patients, the risk of culture-positive recurrence was higher with decreasing CD4 count (compared with CD4 < 200, hazard ratios for recurrence among individuals with CD4 200-500 and CD4 > 500 were 0.40 [95%CI 0.14-1.09] and 0.14 [95%CI 0.02-1.10], respectively, Ptrend = 0.01). IS6110 genotyping was available on both the initial and subsequent isolate for 16/42 (38%, 14 HIV-infected) patients with culture-positive recurrence, and showed reinfection in 11 (69%). CONCLUSION: HIV-infected gold miners, particularly those who are more immunosuppressed, are at higher risk of TB recurrence. TB control strategies need to take into account reinfection as an important cause of recurrent TB.

Tuberculosis risk among staff of a large public hospital in Kenya.

SETTING: In sub-Saharan Africa, high rates of tuberculosis (TB) and human immunodeficiency virus (HIV) infection pose a serious threat for occupationally acquired TB among health care workers. OBJECTIVE: To identify factors associated with TB disease among staff of an 1800-bed hospital in Kenya. DESIGN: We calculated TB incidence among staff and conducted a case-control study where cases (n = 65) were staff diagnosed with TB and controls (n = 316) were randomly selected staff without recent TB. RESULTS: The annual incidence of TB from 2001 to 2005 ranged from 645 to 1115 per 100000 population. Factors associated with TB disease were additional daily hours spent in rooms with patients (adjusted odds ratio [aOR] 1.3, 95%CI 1.2-1.5), working in areas where TB patients received care (aOR 2.1, 95%CI 1.1-4.2), HIV infection (aOR 29.1, 95%CI 5.1-167) and living in a slum (aOR 4.7, 95%CI 1.8-12.5) or hospital-provided low-income housing (aOR 2.6, 95%CI 1.2-5.6). CONCLUSION: Hospital exposures were associated with TB disease among staff at this hospital regardless of their job designation, even after controlling for living conditions, suggesting transmission from patients. Health care facilities should improve infection control practices, provide quality occupational health services and encourage staff testing for HIV infection to address the TB burden in hospital staff.

Natural history and spectrum of disease in adults with HIV/AIDS in Africa.

Progression from seroconversion to the development of AIDS in Africa may be shorter than in industrialized countries, but there are insufficient data to be certain. Although the data are not always directly comparable, survival after an AIDS diagnosis appears to be substantially shorter in African countries and this may be partly because of later diagnosis of AIDS in Africa, but may also be because of environmental factors such as increased exposure to pathogens of high virulence and lack of access to care. Tuberculosis and bacterial infections are the most important causes of morbidity and mortality among hospitalized patients. Bacteraemia is frequent, particularly due to non-typhoid salmonellae and S. pneumoniae. Cryptosporidia and I. belli are the most frequently isolated pathogens in patients with diarrhoea; non-typhoid salmonellae and Shigella species are also commonly isolated when stool cultures are performed. Cerebral toxoplasmosis, and meningitis due to Cryptococcus, tuberculosis and bacterial pathogens are the most frequent neurological infections and cognitive changes are frequently identified when specifically looked for. Infections with atypical mycobacteria and Pneumocystis carinii are rare, as is CMV retinitis. In women, HIV infection is associated with cervical human papillomavirus and with SIL, although there is currently no evidence for an association with invasive cervical cancer. Individuals infected with HIV-2 progress to AIDS and to death more slowly than those infected with HIV-1, but seem to experience the same spectrum of opportunistic disease when they reach the stage of advanced disease. The limited data available suggest that HIV-infected individuals in Africa develop opportunistic disease at broadly the same level of immunosuppression as do individuals in industrialized countries, but death occurs at a higher range of CD4 counts, although still in the range consistent with advanced disease. Data are still lacking concerning the aetiology of common clinical presentations of HIV disease and the relative frequencies of specific opportunistic diseases in different regions, particularly from southern Africa. Tuberculosis is the single most important HIV-related opportunistic infection in African countries, but diagnosis, particularly of extrapulmonary disease, remains difficult. The lack of laboratory facilities makes the diagnosis of bacterial infections difficult in many parts of the continent and, since this situation is unlikely to change in the near future, clinical algorithms for syndromic management need to be evaluated. More information is needed about gynaecological disease in HIV-infected women. The most important research questions concern the development and evaluation of cost-effective regimes for prophylaxis and treatment of opportunistic disease in order to prolong healthy life in HIV-infected individuals.

HIV-1 and HIV-2 infections and AIDS in West Africa.

PIP: The authors review advances in HIV-2 research since their last review of the subject, and summarize the current epidemiology of HIV-1 and HIV-2 infections and AIDS in West Africa. West Africa is considered to be comprised of those countries below the Sahara which belong to subregion 1 of the Africa Region as defined by the World Health Organization. Widely varying patterns of disease distribution exist across these countries. The epidemic spread of HIV-1 and HIV-2 in the region is recent, but these infections now occur throughout West Africa. The distribution of the two viral infections is both heterogenous and unstable. It is not clear whether social or biological reasons, or both, account for the apparently less successful epidemic spread of HIV-2. Important epidemiologic questions concerning HIV-2 which await resolution are its incubation period for disease and its efficiency of transmission compared with HIV-1. The authors note that for public health purposes, the two infections should be approached in the same fashion.^ieng

Rapid and simple screening and supplemental testing for HIV-1 and HIV-2 infections in west Africa.

OBJECTIVE: To evaluate a combination of rapid tests as a strategy for screening and supplemental testing of serum for HIV-1 and/or HIV-2 antibodies. DESIGN: Cross-sectional evaluation. SETTING: Projet RETRO-CI, an AIDS research project in Abidjan, Côte d'Ivoire. METHODS: Serum specimens were collected from 1000 consecutive women giving birth in an Abidjan maternal and child health centre and from 185 hospitalized patients. All serum specimens were tested for HIV-1 and HIV-2 antibodies by whole-virus enzyme immunoassay; repeatedly reactive specimens were further tested by virus-specific Western blot and synthetic peptide-based tests. This was the reference strategy against which the algorithm under evaluation was compared. All specimens were subsequently tested by a mixed (HIV-1 and HIV-2) recombinant antigen-based test (Abbott Testpack), followed, if positive, by a rapid synthetic peptide-based test (Genetic Systems Genie) as a supplemental test. RESULTS: According to the reference strategy the prevalence of HIV-1 and/or HIV-2 infection was 13% among the pregnant women and 78% among the hospitalized patients. Compared with the reference strategy, the combination of rapid tests was associated with a sensitivity of 99.6%, a specificity of 99.9%, and positive and negative predictive values of 99.6 and 99.9%, respectively. Four per cent of HIV-2-positive and 1% of HIV-1-positive specimens were considered dually reactive by the rapid test combination. CONCLUSIONS: Synthetic peptide-based tests provide an alternative to Western blots for supplemental testing for HIV-1 and HIV-2. This combination of rapid tests offers performance characteristics comparable to an enzyme immunoassay and Western blot-based strategy, without requiring running water, electricity, or a well-developed laboratory. High-quality serodiagnosis of HIV-1 and HIV-2 infections is possible at the most peripheral levels of the health-care system in developing countries, the limiting factors being the costs of tests and training of staff.

PIP: Researchers from an AIDS research project took blood samples from 1000 consecutive women during childbirth at a maternal and child health center in Abidjan, Cote d'Ivoire, and from 185 hospitalized patients to compare the results of a combination of synthetic peptide-based rapid tests (product names, Testpack and Genie), which check for HIV-1 and HIV-2 antibodies, with those of the Western Blot-based test. They also wanted to see whether the rapid test-based strategy could replace the Western Blot-based test as a supplemental test. The Western Blot indicated the HIV-1 and/or HIV-2 prevalence to be 13% among the new mothers and 78% among the hospitalized patients for an overall prevalence of 23%. 3.3% of all people were positive for both HIV-1 and HIV-2. 17.4% tested positive for just HIV-1. 2.1% were positive for HIV-2. The rapid tests had a sensitivity of 99.6% and a specificity of 99.9%. The positive predictive value was 99.6% and the negative predictive value was 99.9%. The rapid tests identified 4% of the HIV-2 positive samples and 1% of the HIV-1 samples to be dually reactive. These findings demonstrated that rapid synthetic peptide-based assays reliably detect HIV-1 and HIV-2 antibodies and can be supplemental tests. High quality HIV serology can be performed in a setting without running water and electricity which was the case in this study. A further advantage of this strategy is that each test takes only 10 minutes. These tests would have significant effects on HIV testing and counseling, diagnosis, and screening of blood for transfusion in rural areas of developing countries.

Cross-reactivity on western blots in HIV-1 and HIV-2 infections.

To examine cross-reactivity of antibodies to heterologous antigens, on HIV-1 and HIV-2 Western blots, we tested sera from 1362 consecutive tuberculosis (TB) patients and 2127 consecutive blood donors. Specimens positive on enzyme-linked immunosorbent assay (ELISA) for HIV-1 or HIV-2 were further characterized by synthetic peptide-based tests, and tested by HIV-1- and HIV-2-specific Western blots. Dual serologic reactivity on synthetic peptide tests was proportionately more frequent in HIV-positive TB patients than in blood donors, and HIV-2 reactivity less frequent. Positive HIV-1 Western blots were seen in 73-83% of specimens specifically characterized as positive for HIV-2 on synthetic peptide tests. Cross-reactivity to HIV-2 Western blots by HIV-1-positive specimens was significantly more frequent in TB patients (35%) than in asymptomatic donors (9%; P less than 0.001). Using recently recommended criteria for HIV-2 Western blot interpretation (presence of two env bands) reduced the overall proportion of HIV-1-positive specimens having a positive HIV-2 Western blot from 27.5 to 16.4%, with [corrected] minimal effect on sensitivity in the diagnosis of HIV-2 reactivity on specimens positive on synthetic peptide tests.

Autopsy-proven causes of death in HIV-infected patients treated for tuberculosis in Abidjan, Côte d'Ivoire.

OBJECTIVE: To determine autopsy-proven causes of death in HIV-infected patients treated for tuberculosis in Abidjan, Côte d'Ivoire. METHODS: A computerized listing of 9523 patients diagnosed with tuberculosis and tested for HIV infection at Abidjan's two large tuberculosis treatment centers from July 1989 to December 1991 was matched against a listing of 496 patients who were autopsied in Abidjan's largest public hospital in 1991-1992. RESULTS: Fifteen matching patients were identified including 11 adults with smear-positive pulmonary tuberculosis, three adults with extrapulmonary tuberculosis, and one child with smear-negative pulmonary tuberculosis. The autopsy-proven causes of death among the adults were tuberculosis (n = 4), bacterial infections (n = 3), cerebral toxoplasmosis (n = 2), pulmonary nocardiosis (n = 2), Pneumocystis carinii pneumonia (n = 1), atypical mycobacteriosis (n = 1), and wasting syndrome (n = 1). Tuberculosis was the primary cause of death in two of five smear-positive patients who had not completed therapy, in none of the six patients with smear-positive disease who had completed therapy, and in two of the three patients with extrapulmonary tuberculosis. CONCLUSIONS: Chemoprophylaxis with trimethoprim-sulfamethoxazole (TMP-SMX) might have provided benefit to eight (57%) of the 14 adults in this series who died either of bacterial infections, toxoplasmosis, nocardiosis, or pneumocystosis. Prospective studies are required to elucidate further the causes of increased mortality, and to evaluate the benefits of TMP-SMX prophylaxis in HIV-infected African patients with tuberculosis.

HIV status of female sex partners of men reactive to HIV-1, HIV-2 or both viruses in Abidjan, Côte d'Ivoire.

OBJECTIVES: To compare rates of serologic concordance in the female sex partners of men with HIV-1 and HIV-2 infections, and to determine the serologic status of sex partners of men who reacted serologically to both viruses. DESIGN: Cross-sectional study. SETTING: Infectious diseases service in a University Hospital in Abidjan, Côte d'Ivoire (West Africa). PARTICIPANTS: Hospitalized men reactive on synthetic peptide-based tests to HIV-1, HIV-2 or both viruses (dually reactive), and their spouses visiting them in hospital. OUTCOME MEASURES: Serologic status of female spouses of seropositive men. RESULTS: The serologic status of 540 spouses of 490 HIV-1- and/or HIV-2-positive, hospitalized men was studied. Similar proportions of spouses of HIV-1-infected men (49%) and HIV-2-infected men (44%) were concordantly seropositive. The overall prevalence of infection in spouses of dually reactive men (72%) was significantly higher than in spouses of other men; 44% of these spouses were infected with HIV-1, 8% with HIV-2, and 20% were themselves dually reactive. Considering only the seropositive female spouses of men monotypically reactive to HIV-1 or HIV-2, and the male spouses of women monotypically infected, rates of serologic discordance were significantly greater in men (24%) than women (7%). CONCLUSIONS: Men were likely to have been infected earlier than women because of their HIV-associated illness; also, men more frequently had serologic profiles indicative of infection outside of the union. Rates of serologic concordance in spouses of men with advanced HIV-1 or HIV-2 infection were similar (44-49%). Dually reactive hospitalized men frequently (72%) had seropositive sex partners, most of whom were HIV-1-positive. Dual reactivity was also frequent in these spouses, suggesting transmission of both HIV-1 and HIV-2, or of a cross-reactive strain, and a minority of partners were infected with HIV-2 alone. Prospective studies of discordant couples using quantitative molecular diagnostic techniques are required for better understanding of dual reactivity and transmission of HIV-1 and HIV-2.

Efficacies of US Food and Drug Administration-licensed HIV-1-screening enzyme immunoassays for detecting antibodies to HIV-2.

To determine the efficacy of enzyme immunoassays (EIAs) for antibodies against HIV-1 in detecting HIV-2-infected blood, we tested 55 HIV-2-positive sera with seven Food and Drug Administration-licensed EIA kits. The percentage detection of HIV-2 sera giving positive reactions with these kits varied between the various manufacturers from 60 to 91%. Observations based on a small number of sera (n = 13), suggest that HIV-2-positive blood collected from apparently healthy people (blood donors, prenatal clinics) are detected with a greater frequency (means = 89%) than blood from AIDS patients or patients (n = 32) hospitalized with other infectious diseases (means = 72%). Based on these results and the low incidence of HIV-2 infection observed in the USA, it was concluded that screening with HIV-2-specific tests would not significantly increase the number of HIV-2-positive people detected by current screening programs. However, due to the poor sensitivity of certain HIV-1 assays for HIV-2 antibodies, HIV-2 sera without cross-reacting antibodies will escape detection. Surveillance for HIV-2 might then be improved by the availability of HIV-1 and HIV-2 combination assays.

Oligomeric nature of transmembrane glycoproteins of HIV-2: procedures for their efficient dissociation and preparation of Western blots for diagnosis.

Western blot (WB) analysis of various strains of HIV-2 indicated that transmembrane glycoprotein (TMP) of HIV-2 exists as trimers. These trimers have molecular weights and electrophoretic mobilities in the region of the major external glycoprotein, gp120, resulting in WB misidentification during diagnosis. A simple and rapid procedure was developed using trichloroacetic acid (TCA) to efficiently dissociate oligomeric forms of the TMP to monomers prior to the preparation of WB. This procedure permitted the unambiguous identification of antibodies to gp120 and to the TMP. Use of HIV-2 WB strips without any oligomeric forms of the TMP demonstrated (1) that cross reactivity of HIV-1-positive specimens on HIV-2 WB was mainly directed to Gag and Pol proteins, with some reactivity to gp36/gp41 TMP, but none to gp120; (2) that these strips can substantially reduce the number of specimens falsely identified as dually (HIV-1 and HIV-2) reactive; and (3) that HIV-2-positive specimens reacted to viral gp120 in a strain-specific manner, demonstrating high antigenic variation in this glycoprotein. It is recommended that this general procedure of viral protein dissociation be used for HIV-2 WB preparation.

HIV-1 and HIV-2 infections in men attending sexually transmitted disease clinics in Abidjan, Côte d'Ivoire.

OBJECTIVE: (1) To determine the prevalence of HIV-1 and HIV-2 infections and associated risk factors in men attending Abidjan's three sexually transmitted disease (STD) clinics; (2) to examine the use of such sites for epidemiological surveillance. DESIGN: Cross-sectional study. SETTING: Abidjan's two main STD clinics (Clinics A and T), and the University Hospital Dermatology outpatients clinic. PATIENTS: Consecutive patients with genitourinary symptoms. MAIN OUTCOME MEASURES: Prevalence of reactivity to HIV-1, HIV-2, and both viruses; descriptive characteristics of clinic attenders; clinical diagnoses of STD; risk factors associated with HIV-1 and HIV-2 positivity. RESULTS: The overall prevalence of HIV (HIV-1 and/or HIV-2) infection was 21% (250 out of 1169; 16% HIV-1, 2% HIV-2, 3% dual reactivity). Overall prevalence varied by clinic: University Hospital Dermatology outpatients clinic, 39%; Clinic T, 19%; Clinic A, 10%. Men with STD had an overall prevalence of 31% (155 out of 506), compared with 14% in men without physical signs of STD (odds ratio 2.6, 95% confidence interval 2.0-3.6). The highest prevalence, 46%, was in men with genital ulcer disease. Risk factors associated with HIV-1 as well as with HIV-2 infection after multivariate analysis were a history of sex with prostitutes, lack of circumcision, being unskilled, and a history of prior genital ulcer. Current genital ulcer, current STD and positive Treponema pallidum haemagluttination assay were associated with HIV-1 and dual reactivity. CONCLUSIONS: Risk factors for HIV-2 infection in men attending Abidjan STD clinics were broadly similar to those for HIV-1 infection. HIV-1 infection was more strongly associated with current STD. Important differences between the three clinics were observed in STD prevalence and type, and HIV seroprevalence. Such differences should be taken into account in the planning of HIV serosurveillance in STD clinics.

HIV infection and primary resistance to antituberculosis drugs in Abidjan, Côte d'Ivoire.

OBJECTIVE: To determine the prevalence of Mycobacterium tuberculosis resistance to antituberculosis drugs, and to relate this resistance to HIV serologic status. DESIGN: Cross-sectional prevalence study. SETTING: The two major outpatient tuberculosis clinics in Abidjan, Côte d'Ivoire, West Africa. PATIENTS: Sixty individuals with newly diagnosed pulmonary tuberculosis and sputum smears positive for acid-fast bacilli. MAIN OUTCOME MEASURES: HIV serologic status and in vitro testing for susceptibility of M. tuberculosis isolates to antituberculosis drugs. RESULTS: M. tuberculosis was isolated from 82% (49 out of 60) of sputum specimens. Thirty-five per cent (17 out of 49) were obtained from HIV-seropositive and 65% (32 out of 49) from HIV-seronegative patients. There was no statistically significant difference in the proportion of resistant isolates from HIV-seropositive versus HIV-seronegative patients, although the relatively small sample size limited power. Of the total number of isolates, 17% were resistant to isoniazid; resistance was less to streptomycin (7%), rifampin (2%), pyrazinamide (0%), and ethambutol (0%). Eighteen and 21% of mycobacterial isolates from HIV-seropositive and HIV-seronegative individuals, respectively, were resistant to one or more of these drugs. CONCLUSIONS: Surveys of this type are useful in planning and evaluating tuberculosis preventive therapy in individuals with dual infection.

Immunological comparison of HIV-1-, HIV-2- and dually-reactive women delivering in Abidjan, Côte d'Ivoire.

OBJECTIVES: To compare the basic immunological changes induced by HIV-1 and HIV-2 infection and to assess the immune status of subjects serologically reactive to both HIV-1 and HIV-2 (dually-reactive). DESIGN: Immune parameters were studied cross-sectionally in women delivering in Abidjan, Côte d'Ivoire, West Africa, where HIV-1 and HIV-2 are endemic. In this area, a significant number of sera from infected individuals are reactive to both HIV-1 and HIV-2. SUBJECTS AND METHODS: Two hundred and twenty-eight women delivering in a major maternity clinic were screened for HIV-1 and HIV-2 using an enzyme-linked immunosorbent assay. Seropositivity was confirmed by Western blot. The immune parameters studied were CD4+ and CD8+ lymphocyte subsets, immunoglobulin (Ig) serum levels, neopterin and beta 2-microglobulin (beta 2M) serum levels. RESULTS: Similar but less pronounced immune changes were present in HIV-2-reactive subjects compared with HIV-1- and dually-reactive subjects. The observed differences between the HIV-seropositive groups could not be explained by differences in age or disease stage but paralleled differences in the frequency of persistent generalized lymphadenopathy (PGL). The intermediate immune profile of HIV-2-reactives (between seronegatives and HIV-1- and dually-reactives) was most clearly reflected by the number of CD8+ lymphocytes, the CD4:CD8 ratio and the IgG serum level. Median neopterin and beta 2M levels, though significantly increased in all HIV-seropositive groups, did not differ significantly between HIV-2-, HIV-1- and dually-reactives. CONCLUSIONS: HIV-2 infection is associated with typical HIV-related immunological changes. Immunologically, dually-reactives resemble HIV-1-reactives more closely than HIV-2-reactive subjects.

HIV infection and silicosis: the impact of two potent risk factors on the incidence of mycobacterial disease in South African miners.

OBJECTIVE: To investigate the combined effects of HIV infection and silicosis on mycobacterial disease. DESIGN AND SETTING: A retrospective cohort of 1374 HIV-positive and 2648 HIV-negative miners who attended a South African gold mining hospital and primary health clinics. PARTICIPANTS: Miners who had been tested for HIV, with consent, at primary health clinics during 1991-1996, predominantly because of a symptomatic sexually transmitted disease. RESULTS: Tuberculosis (TB) incidence was 4.9 and 1.1 per 100 person-years in HIV-positive and HIV-negative miners respectively. The incidence of Mycobacterium kansasii disease was also high (0.32 and 0.10 per 100 person-years, respectively). Silicosis was highly prevalent, implying inadequate dust control, and was a significant TB risk factor among both HIV-positive and HIV-negative men (adjusted incidence rate ratios 1.4-2.5 according to radiological severity). The data were consistent with the risks of silicosis and HIV combining multiplicatively, but did not fit an additive model. The incidence of HIV-associated TB increased significantly during the study, with no corresponding change in HIV-negative rates, to reach 16.1 per 100 person-years among HIV-positive silicotics. CONCLUSIONS: The risks of silicosis and HIV infection combine multiplicatively, so that TB remains as much a silica-related occupational disease in HIV-positive as in HIV-negative miners, and HIV-positive silicotics have considerably higher TB incidence rates than those reported from other HIV-positive Africans. The increasing impact of HIV over time may indicate epidemic TB transmission with rapid disease development in HIV-infected miners. Similar but currently unrecognized interactions may be contributing to TB control problems in other industrializing countries affected by the HIV epidemic.

Summary of track B: clinical science.

AIM: To review Track B on clinical science. Major topics covered were quantitative HIV-1 plasma RNA measurement, combination antiretroviral therapy, protease inhibitors, treatment of primary HIV-1 infection, HIV-1 drug resistance, future use of antiretroviral drugs, paediatric HIV-1 infection, opportunistic infections and HIV/AIDS in developing countries. QUANTITATIVE HIV-1 PLASMA RNA MEASUREMENT: Quantification of HIV-1 RNA is a predictor of progression of immune deficiency and death in HIV-infected adults and children, and is useful in monitoring response to antiretroviral therapy. THERAPY: Combination antiretroviral therapy is now the standard of care, although questions about optimal starting time and the best initial regimen remain unresolved. Protease inhibitors are a powerful new class of antiretroviral agents which in combination with other drugs can produce profound reductions in plasma HIV-1 RNA levels. Trials are in progress of combination antiretroviral therapy, including protease inhibitors, in persons recently infected with HIV-1 to assess the feasibility of permanent suppression or eradication of HIV-1. Adherence to therapy and drug resistance will become increasingly important subjects. CONCLUSIONS: The genuine improvements in patient management are out of reach to the majority of the world's HIV-infected persons, a conclusion with implications which dampened the optimism generated by the conference.