Cohort study of human immunodeficiency virus infection in patients with tuberculosis in Nairobi, Kenya. Analysis of early (6-month) mortality.

Retrospective studies suggest that the mortality rate from HIV-1-associated tuberculosis is greater than that from tuberculosis alone, but it is not clear if this is due to failure of antituberculosis treatment or to the complications of HIV-1 infection. We have carried out a prospective cohort study of patients with tuberculosis in Nairobi, Kenya, to compare mortality rates, risk factors, and causes of death in HIV-1 positive and HIV-1 negative patients. One hundred seven HIV-1 positive and 174 HIV-1 negative patients with tuberculosis attending two tuberculosis treatment centers in Nairobi were enrolled and followed monthly. Mortality was significantly higher in HIV-1 positive than in HIV-1 negative patients within 6 months of the start of antituberculosis treatment after adjustment for age, sex, and education (rate ratio = 3.8; 95% confidence interval, 1.7 to 8.1; p less than 0.001). Most of the excess mortality occurred after the first month of treatment and was due to nontuberculous infections. Predictors for mortality differed greatly between HIV-1 positive and HIV-1 negative patients. Mortality was greater in HIV-1 positive patients treated with a "standard" regimen for tuberculosis than in HIV-1 positive patients receiving a "short-course" regimen (p = 0.08 when adjusted for all independent risk factors). Tuberculosis control programs in developing countries need to implement "short-course" regimens and train health workers to recognize and treat nontuberculous infections to maintain their effectiveness in the face of the HIV epidemic.     

Primary resistance to antituberculosis drugs: a national survey conducted in C?te d'Ivoire in 1995-1996. Ivoirian Study Group on Tuberculosis Resistance.

SETTING: A national survey of resistance to the antituberculosis drugs used in C?te d'Ivoire was conducted in 1995-1996. OBJECTIVE: To determine the rate of primary resistance to antituberculosis drugs. METHODS: Consecutive new tuberculous patients with positive smear were recruited from tuberculosis centres and rural health centres. Drug susceptibility testing was performed according to the proportion method. Positive cultures were tested against streptomycin, isoniazid, rifampicin, and ethambutol. All resistant strains and 10% of all randomly sampled cultures were sent to an external laboratory for quality control. Human immunodeficiency virus (HIV) tests were performed for consenting patients at the tuberculosis centres. RESULTS: Among the 430 samples, 320 were available for analysis. Primary resistance to antituberculosis drugs was observed for 13.4% of the patients (43/320); multidrug resistance (to at least isoniazid and rifampicin) was observed for 5.3% of the patients; 14.2% of HIV-negative and 16.2% of HIV-positive patients were resistant to at least one antituberculosis drug (P = 0.70). CONCLUSION: This study is representative of antituberculosis drug resistance in C?te d'Ivoire. The rate of primary resistance is high and emphasises the need for a sentinel survey of tuberculous resistance. The National Tuberculosis Control Programme needs to make improvements in its management of tuberculosis cases.     

3种用药方案治疗HIV/TB患者抗结核药物性肝损伤126例临床疗效分析

目的探讨3种不同治疗方案用于治疗HIV/TB患者抗结核药物性肝损伤的有效性及安全性。方法将126例患者随机分成3组,A组(还原型谷胱甘肽口服)、B组(复方甘草酸苷口服),C组(还原型谷胱甘肽+复方甘草酸苷静滴),观察比较疗效。结果 3种药物治疗方案有效率分别为92.9%、90.5%、97.6%(P>0.05),治愈率分别为52.4%、45.2%、71.4%(P<0.05),发生不良反应率分别为31%23.8%47.7%(P>0.05);三种方案治疗HIV/TB患者抗结核药物性肝损伤在有效率和不良反应发生率方面无显著差异,但在治愈率上三组有显著差异。结论 C组临床疗效最好。     

3种用药方案治疗HIV/TB患者抗结核药物性肝损伤成本-效果分析

目的探讨3种不同治疗方案用于治疗HIV/TB患者抗结核药物性肝损的经济效果。方法将168例患者随机分成3组,A组还原型谷胱甘肽序贯、B组复方甘草酸苷序贯,C组还原型谷胱甘肽静滴序贯复方甘草酸苷口服,观察疗效和不良反应。结果 3种药物治疗方案成本分别为1221元、1076.5元、960.7元;发生不良反应率分别为50%、41.1%、44.6%(P>0.05);成本-效果比分别为12.91、12.83、10.55;有效率分别为94.6%、83.8%、91.1%(P<0.05);三种方案治疗HIV/TB患者抗结核药物性肝损在有效率上无显著差异,在A、B两组肝功能上(总胆红素)有显著差异。结论还原型谷胱甘肽静滴序贯复方甘草酸苷口服方案为较佳方案。     

Impact of hepatitis B virus co-infection on response to highly active antiretroviral treatment and outcome in HIV-infected individuals: a nationwide cohort study

BACKGROUND: The impact of chronic hepatitis B virus (HBV) infection on viral suppression, immune recovery and mortality in HIV-1 infected patients on highly active antiretroviral treatment (HAART) is a matter of debate. The impact of HBeAg status is unknown. METHODS: This prospective cohort study included all adult Danish HIV-1 infected patients who started HAART between 1 January 1995 and 1 December 2006 (3180 patients). Patients were classified as chronic HBV-infected (6%), HBV-negative (87%) or HBV-unknown (7%). HBV-positive patients were divided into HBeAg-positive or -negative (3.0 vs. 2.6%). Study endpoints were viral load, CD4 cell count and mortality. RESULTS: HBV co-infection had no impact on response to HAART regarding viral suppression or immune recovery. HBV co-infection was associated with several outcomes: overall mortality [mortality rate ratio (MRR) 1.5; 95% confidence interval (CI) 1.1-2.1], liver-related mortality (MRR 4.0; 95% CI 1.6-9.9) and AIDS-related deaths (MRR 1.7; 95% CI 1.0-3.0). The presence of HBeAg did not influence patients' response to HAART. CONCLUSIONS: In HIV patients, chronic HBV infection has no impact on response to HAART concerning viral load and increase in CD4 cell count. However, co-infected patients have an increased mortality compared to HIV-monoinfected patients.     

Rheumatic manifestations in populations at risk for HIV infection: the added effect of HIV.

We assessed the frequency and variability of rheumatologic manifestations in 2 populations with similar risk factors for human immunodeficiency virus (HIV) infection, of which only one was affected. We studied 2 populations at risk for HIV infection (homosexual and intravenous drug users). Group A: 89 individuals carried the virus; and Group B: 80 individuals were HIV negative. In Group A (HIV+) 66.1% had rheumatic manifestations including arthralgias, Reiter's syndrome, arthritis, enthesitis, psoriatic arthritis, Sj?gren's syndrome, myopathy, septic arthritis, and lupus-like illness. In contrast, in Group B (HIV-) only 2 had arthralgias, 2 Reiter's syndrome, and 1 rheumatoid arthritis. In summary, rheumatic complaints are common in patients with HIV, and HIV positivity confers an increased susceptibility in populations with similar risk factors for HIV infection.     

Twice-a-day versus once-a-day interferon-beta therapy in chronic hepatitis C

BACKGROUND/AIMS: The intravenous administration of interferon-beta may be effective for the treatment of chronic hepatitis C, as is intramuscular interferon-beta. We compared the efficacy and safety of twice-a-day versus once-a-day of natural interferon-beta for the initial treatment of patients with chronic hepatitis C. METHODOLOGY: Forty-nine patients with chronic hepatitis C, with less than 5 Meq/mL serum hepatitis C virus-RNA, were randomly assigned into one of the two treatment groups A and B and treated with natural interferon-beta following two different protocols. Twenty-two patients were treated with twice-a-day interferon-beta (3 MU) for 3 weeks followed by once-a-day interferon-beta (6 MU) for 5 weeks (group A), and 20 patients were treated with once-a-day interferon-beta (6 MU) for 8 weeks (group B). Seven patients did not complete the treatment protocol. Efficacy was assessed by measuring the serum levels of hepatitis C virus-RNA and aminotransferase. RESULTS: The rate of sustained virological response was significantly higher in group A (14 of 22 patients, 63.6%) than in group B (6 of 20 patients, 30.0%) (P < 0.05). Among patients with hepatitis C virus-RNA level less than 1 Meq/mL, the sustained virological response rate was significantly higher in group A (13 of 15 patients, 86.7%) than in group B (5 of 12 patients, 41.7%) (P < 0.05). However, the sustained virological response rate in patients with hepatitis C virus levels more than 1 Meq/mL was not significantly different between group A (1 of 7 patients, 14.3%) and group B (1 of 8 patients, 12.5%). CONCLUSIONS: Twice-a-day interferon-beta therapy is more effective than once-a-day interferon-beta for the treatment of chronic hepatitis C patients with hepatitis C virus-RNA levels less than 1 Meq/mL.     

Effect of chemokine receptor gene polymorphisms on the response to potent antiretroviral therapy

BACKGROUND: Both the natural history of HIV infection and the response to antiretroviral therapy are heterogeneous. Polymorphisms in chemokine receptor genes modulate the natural history of HIV-1 infection. In comparison with subjects with other genotypes, the prognosis for HIV-1-infected CCR5-delta32 heterozygotes is more favorable and that for CCR5 promoter allele 59029A homozygotes is less favorable. METHODS: HIV-1-infected adults with a CD4+ lymphocyte count > or = 200 cells x 10(6)/l and a plasma HIV RNA level > or = 1000 copies/ml were treated with indinavir, zidovudine and lamivudine for 6 months. HIV RNA levels were measured at 4-week intervals. Genotyping for chemokine receptor gene polymorphisms (CCR5-delta32, CCR5 59029A/G, CCR2-641) was performed. We examined whether the time to first HIV RNA < 200 copies/ml, frequency of viral suppression failure (HIV RNA > or = 200 copies/ml between weeks 16 and 28 of therapy), or reduction from the pre-treatment HIV RNA level differed by genotype. RESULTS: Time to first HIV RNA < 200 copies/ml was not predicted by genotype. Among 272 Caucasian patients, viral suppression failure was more common among patients with the CCR5 +/+ ? CCR2+/+ ? CCR5-59029 A/A genotype (28%) than among all other subjects combined (relative risk, 2.0; P = 0.06). After 24 weeks of therapy, genotype groups differed in the reduction of the HIV RNA level from baseline (P = 0.02); patients with the CCR5 +/+ ? CCR2+/+ ? CCR5-59029 A/A genotype had a mean reduction of 2.12 log10 copies/ml compared to 2.64 log10 copies/ml among all other groups combined. CONCLUSION: Polymorphisms in chemokine receptor genes may explain some of the heterogeneity in sustaining viral suppression observed among patients receiving potent antiretroviral therapy.     

The association of tuberculosis and HIV infection in Burundi

AIDS and tuberculosis (TB) are both endemic in Bujumbura, Burundi. An 11% failure rate to standard antituberculosis treatment (n = 173) was observed at the Tuberculosis Treatment Center of Bujumbura (CATB) in 1985-1986. All resistant cases (n = 19) were HIV seropositive. Among 328 consecutive cases with tuberculosis at the CATB during a 3 month period in 1986, 54.5% were HIV seropositive, which is five times higher than the prevalence in the general population in Bujumbura. More female patients than male cases were HIV antibody positive (62 versus 49%, respectively; p less than 0.02). Persistent weight loss, cough, and an anergic tuberculin test were more common in the HIV-seropositive group. Among 48 household members of HIV-seropositive patients with tuberculosis, 6 (12.5%) new cases of tuberculosis were identified, compared with none among 28 household members of HIV-seronegative patients with tuberculosis (odds ratio, 3.8; 95% confidence interval, 0.43-33.2). HIV infection is a new risk factor for tuberculosis in Africa, and HIV-infected cases of tuberculosis may be more infectious than HIV-negative patients. The AIDS epidemic may drastically complicate the diagnosis, management, and control of tuberculosis in populations in which both infections are endemic.     

Effect of interventions to control sexually transmitted disease on the incidence of HIV infection in female sex workers

OBJECTIVE: To compare the seroincidence of HIV infection among female sex workers in Abidjan, C?te d'Ivoire before and during an intervention study to control sexually transmitted diseases (STD) and to study the effect of two STD diagnosis and treatment strategies on the prevalence of STD and on the seroincidence of HIV infection. METHOD: A screening facility for STD and HIV had been available since October 1992 for female sex workers. From June 1994, women who were HIV seronegative or HIV-2 positive during the screening could enroll in the intervention study in which participants reported once a month to a confidential clinic where they received health education, condoms and STD treatment if indicated. Women in the study were randomized either to a basic STD diagnosis and treatment strategy, which included a gynecologic examination when symptomatic, or to an intensive strategy that included a gynecologic examination regardless of symptoms. An outcome assessment every 6 months included a gynecologic examination, HIV serology and laboratory tests for STD. RESULTS: Of 542 women enrolled in the study, 225 (42%) had at least one outcome assessment. The HIV-1 seroincidence rate during the intervention study was significantly lower than before the study (6.5 versus 16.3 per 100 person-years; P = 0.02). During the study, the HIV-1 seroincidence rate was slightly lower in the intensive than in the basic strategy (5.3 versus 7.6 per 100 person-years; P = 0.5). CONCLUSION: National AIDS control programs should consider adopting as policy the type of integrated approach used in this intervention study for HIV prevention in female sex workers.     

Three-year follow-up of patients with pulmonary tuberculosis in Guinea-Bissau, West Africa.

SETTING: Raoul Follereau Hospital, Bissau, Guinea-Bissau. OBJECTIVE: To study the long-term outcome of patients with bacteriologically verified tuberculosis (TB), with or without human immunodeficiency virus (HIV) co-infection. DESIGN: Sputum samples were collected from all patients referred to the hospital with clinical symptoms of pulmonary tuberculosis. Direct microscopy and culture was performed at the Health Laboratory. Patients with a culture positive for Mycobacterium tuberculosis were followed for 3 years, and underlying factors were analysed regarding the outcome of treatment. A group of sex and age-matched HIV-negative individuals was used as controls. RESULTS: Of 206 bacteriologically verified pulmonary TB patients, 168 were followed up. Antibodies to HIV-2 were found in 33 patients (19.6%); eight patients (4.8%) had antibodies to HIV-1 or showed dual reactivity. Of 149 patients discharged to follow ambulatory treatment, the survival rate of HIV-2-positive patients was 42.3% (11/26) and for HIV-negative patients it was 81.9% (95/116). The difference in survival between HIV-2-positive and HIV-negative patients was highly significant (P < 0.00001). HIV-negative TB patients had a significantly higher mortality than their controls (mortality ratio 3.75, 95% confidence interval 1.58-8.90). Most patients who survived, regardless of HIV status, also became free from symptoms compatible wtih pulmonary TB. CONCLUSION: Although the mortality rate among HIV-positive TB patients was very much higher than among HIV-negative patients, there are weighty arguments for active contact tracing and effective treatment of all TB patients.     

HIV disease progression and V3 serotypes in Brazil: is B different from B-Br?

HIV-1 serotype B-Br (GWGR) is rare in the United States but predominates in Brazil. Differences in prognosis for patients infected with serotype B-Br or serotype B (GPGR) have not been addressed previously. In this prospective cohort study, we compared the rate of disease progression between patients infected with the HIV-1 V3 serotype B or B-Br in Brazil. Progression to AIDS or death was studied by the Kaplan-Meier and Cox proportional hazard methods. Among 445 HIV-infected patients who were tested with a specific enzyme immune assay, 204 (46%) had serotype B-Br infection and 127 (28%) had serotype B infection. Both groups were similar with regard to baseline CD4+ cell count, serum HIV RNA viral load, initial clinical stage, and the proportions who were treated with antiretroviral drugs. Patients with serotype B infection were significantly younger (p = 0.005) and tended to report homosexual behavior more frequently (p = 0.08). Mean follow-up was 30 +/- 13.5 months. During the study period, 41 (32%) patients infected with serotype B and 44 (22%) infected with serotype B-Br developed AIDS (p = 0.03). In a regression model adjusted for age and risk factor for HIV infection, progression to AIDS was faster in patients infected with serotype B (hazard ratio [HR] 1.59; 95% CI, 1.03-2.43; p = 0.03). A similar trend was observed in a model that considered AIDS or death as the outcome (HR, 1.43; 95% CI, 0.95-2.0; p = 0.09). These results suggest that patients infected with closely related HIV-1 serotypes may differ in the rate of progression to AIDS and indicate that serotype should be taken into account in HIV vaccine studies in Brazil.     

Causes of death among Danish HIV patients compared with population controls in the period 1995–2008

Purpose

To compare the mortality and causes of death in human immunodeficiency syndrome (HIV) patients with the background population.

Methods

All adult HIV patients treated in Danish HIV centers from 1995 to 2008 and 14 controls for each HIV patient were included. Age-adjusted mortality rates (MR) and mortality rate ratios (MRR) were estimated using direct standardization and Poisson regression analyses. Up to four contributory causes of death for each person were included in analyses of cause-specific MR.

Results

A total of 5,137 HIV patients and 71,918 controls were followed for 37,838 and 671,339 person-years (PY), respectively. Among non-injection drug use (IDU) HIV patients, the acquired immune deficiency syndrome (AIDS)-related MR/1,000 PY declined dramatically from 122.9 [95?% confidence interval (CI) 106.8?C141.4] in 1995 to 5.0 (95?% CI 3.1?C8.1) in 2008. The non-AIDS-related MR did not change substantially from 6.9 (95?% CI 3.8?C12.5) to 5.6 (95?% CI 3.6?C8.8). The MR of unnatural causes declined from 6.9 (95?% CI 3.8?C12.5) to 2.7 (95?% CI 1.4?C5.1). The MRR of infections declined from 46.6 (95?% CI 19.6?C110.9) to 3.3 (95?% CI 1.6?C6.6). The MRR of other natural causes of death remained constant.

Conclusions

After the introduction of highly active antiretroviral therapy (HAART), the AIDS-related mortality has decreased substantially, but the long-term exposure to HIV and HAART has not translated into increasing mortality from malignancy, cardiovascular, and hepatic diseases.     

Performance of the integrated management of childhood illness algorithm for diagnosis of HIV-1 infection among African infants

OBJECTIVES:: Early infant HIV-1 diagnosis and treatment substantially improve survival. Where virologic HIV-1 testing is unavailable, integrated management of childhood illness (IMCI) clinical algorithms may be used for infant HIV-1 screening. We evaluated the performance of the 2008 WHO IMCI HIV algorithm in a cohort of HIV-exposed Kenyan infants. METHODS:: From 1999 to 2003, 444 infants had monthly clinical assessments and quarterly virologic HIV-1 testing. Using archived clinical data, IMCI sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated using virologic testing as a gold standard. Linear regression and survival analyses were used to determine the effect of age on IMCI performance and timing of diagnosis. RESULTS:: Overall IMCI sensitivity, specificity, PPV, and NPV value were 58, 87, 52, and 90%, respectively. Sensitivity (1.4%) and PPV (14%) were lowest at 1 month of age, when 81% of HIV infections already had occurred. Sensitivity increased with age (P?相似文献   

Antituberculosis drug‐induced hepatotoxicity is uncommon in Tanzanian hospitalized pulmonary TB patients

Data on antituberculosis drug‐induced hepatotoxicity in sub Saharan Africa are limited, probably because liver function tests are not carried out routinely during tuberculosis treatment in most African countries. We monitored the liver function of 112 Tanzanian hospitalized pulmonary tuberculosis patients during the first 2 months (i.e. the intensive phase) of tuberculosis treatment. The rate of hepatotoxicity in our study was 0.9% (95% CI 0.04–4.3%). It is encouraging to find a lower rate of antituberculosis drug‐induced hepatotoxicity than one would expect based on the high prevalence of risk factors such as HIV and hepatitis B.     

Clinical and immunological follow-up of previously hospitalized HIV-2 seropositive patients in Bissau, Guinea-Bissau.

A follow-up study was done in Bissau on 113 HIV-2 seropositive patients and 97 HIV-2 seronegative patients 3-15 months after hospitalization. Follow-up totalled 63.5 person years for seropositive patients and 62 for seronegative patients. The mortality during the follow-up period was 43.3% among the seropositive patients (rate 72/100 person years; p.y.) and 25.8% among the seronegative patients (40/100 p. y.). Among 25 HIV-2 associated AIDS cases the mortality was 80% (rate 117/100 p. y.). The median survival time for the AIDS patients was 8 months. Among 48 HIV-2 seropositive patients who lacked signs or symptoms included in the WHO case definition for AIDS at the time of hospitalization 6 patients (12.5%) developed AIDS related symptoms (ARS) during altogether 31.5 person years of follow-up (rate 19/100 p. y.). Tuberculin anergy was demonstrated in 83.3% (15/18) of HIV-2 seropositive patients with AIDS or ARS, in 14.3% (6/42) of seropositive patients without HIV-related symptoms and in 6.9% (5/72) of seronegative patients. A low CD4 T-lymphocyte count in combination with a low CD4/CD8 T-cell ratio was found significantly more often in HIV-2 seropositive patients with AIDS or ARS (62.5%, 10/16) than in HIV-2 seropositive patients without HIV associated symptoms (6.9%, 2/29) or in seronegative patients (2.7%, 1/37). Thus the mortality among recently hospitalized HIV-2 seropositive patients was high and a high proportion of seropositive patients with HIV-related symptoms had evidence of immunodeficiency.     

Liver transplantation for hepatocellular carcinoma: the impact of human immunodeficiency virus infection

Liver transplantation (LT) has become an accepted therapy for end-stage liver disease in human immunodeficiency virus-positive (HIV+) patients, but the specific results of LT for hepatocellular carcinoma (HCC) are unknown. Between 2003 and 2008, 21 HIV+ patients and 65 HIV- patients with HCC were listed for LT at a single institution. Patient characteristics and pathological features were analyzed. Univariate analysis for overall survival (OS) and recurrence-free survival (RFS) after LT was applied to identify the impact of HIV infection. HIV+ patients were younger than HIV- patients [median age: 48 (range = 41-63 years) versus 57 years (range = 37-72 years), P < 0.001] and had a higher alpha-fetoprotein (AFP) level [median AFP level: 16 (range = 3-7154 μg/L] versus 13 μg/L (range = 1-552 μg/L), P = 0.04]. There was a trend toward a higher dropout rate among HIV+ patients (5/21, 23%) versus HIV- patients (7/65, 10%, P = 0.08). Sixteen HIV+ patients and 58 HIV- patients underwent transplantation after median waiting times of 3.5 (range = 0.5-26 months) and 2.0 months (range = 0.5-24 months, P = 0.18), respectively. No significant difference was observed in the pathological features of HCC. With median follow-up times of 27 (range = 5-74 months) and 36 months (range = 3-82 months, P = 0.40), OS after LT at 1 and 3 years reached 81% and 74% in HIV+ patients and 93% and 85% in HIV- patients, respectively (P = 0.08). RFS rates at 1 and 3 years were 69% and 69% in HIV+ patients and 89% and 84% in HIV- patients, respectively (P = 0.09). In univariate analysis, HIV status did not emerge as a prognostic factor for OS or RFS. CONCLUSION: Because of a higher dropout rate among HIV+ patients, HIV infection impaired the results of LT for HCC on an intent-to-treat basis but had no significant impact on OS and RFS after LT.     

Occult hepatitis B virus infection among Mexican human immunodeficiency virus-1-infected patients

AIM: To determine the frequency of occult hepatitis B infection (OHBI) in a group of human immunodeficiency virus (HIV)-1+/ hepatitis B surface antigen negative (HBsAg)- patients from Mexico.METHODS: We investigated the presence of OHBI in 49 HIV-1+/HBsAg- patients. Hepatitis B virus (HBV) DNA was analyzed using nested PCR to amplify the Core (C) region and by real-time PCR to amplify a region of the S and X genes. The possible associations between the variables and OHBI were investigated using Pearson’s χ² and/or Fisher’s exact test.RESULTS: We found that the frequency of OHBI was 49% among the group of 49 HIV-1+/HBsAg- patients studied. The presence of OHBI was significantly associated with the HIV-1 RNA viral load [odds ratio (OR) = 8.75; P = 0.001; 95%CI: 2.26-33.79] and with HIV-antiretroviral treatment with drugs that interfere with HBV replication (lamivudine, tenofovir or emtricitabine) (OR = 0.25; P = 0.05; 95%CI: 0.08-1.05).CONCLUSION: The OHBI frequency is high among 49 Mexican HIV-1+/HBsAg- patients and it was more frequent in patients with detectable HIV RNA, and less frequent in patients who are undergoing HIV-ARV treatment with drugs active against HBV.     

High prevalence of HIV-1 subtype G and natural polymorphisms at the protease gene among HIV-infected immigrants in Madrid

OBJECTIVES: Genetic characterization of HIV-1 subtypes among immigrants and natives infected overseas. METHODS: Phylogenetic analysis of HIV-1 protease sequences obtained from 109 foreigners (mainly Africans) and 32 native individuals infected overseas attending a reference HIV/AIDS centre located in Madrid, Spain. RESULTS: The overall rate of infection with HIV-1 non-B subtypes was 50.3% (71/141). Whereas 94.3% (67/71) belonged to immigrants (mostly Africans, 60/67), only 5.6% (4/71) were from native individuals (P < 0.05). The distribution of non-B subtypes was: 49 G, eight C, six A, four D, two F and two H. The high prevalence of subtype G was mainly related to individuals from west-central Africa. Interestingly, substitutions at three or more positions associated with protease inhibitor (PI) resistance were recognized in 52.6% of naive subjects carrying non-B subtypes, but only in 8% of those infected with B viruses (P < 0.05). The genotypes most frequently recognized among non-B and B subtypes occurred, respectively, at positions 36 (100 versus 12%), 20 (77.2 versus 0%), 63 (40.3 versus 64%), 82 (17.5 versus 0%), 10 (14 versus 12%), 77 (3.5 versus 34%), and 71 (0 versus 2%). Accordingly, changes I-36 and I-20 may be considered specific genetic markers for non-B, group M variants and subtype G infections, respectively. CONCLUSION: Nearly two-thirds of foreigners with HIV-1 infection in Madrid carry non-B subtypes, subtype G (protease) being the most common among west-central African immigrants. The high rate of natural polymorphisms at the protease gene in non-B viruses may compromise the response to PI. Therefore, HIV subtyping should be considered in treatment guidelines.