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Dominique Costagliola

Publications and source records attributed to Dominique Costagliola.

At least 19 recordsLinked to original sources
PubMed2006

Yearly number of patients diagnosed with primary HIV-1 infection in France estimated by a capture-recapture approach.

We used a two-source capture-recapture method to estimate the number of patients diagnosed at the time of primary HIV infection in France between 1999 and 2002. The sources were the French PRIMO cohort and the French Hospital Database on HIV. The estimated number of patients was 325 per year, which represents only 5% (approximately 6000 cases) of all new cases diagnosed each year and only 8% of all new infections (approximately 4000 cases).

Adult↗
PubMed2006

Comparative biological and clinical outcomes after a switch from a virologically unsuccessful first protease inhibitor-containing antiretroviral combination to a 3-drug regimen containing efavirenz, nevirapine, or abacavir.

BACKGROUND: Incomplete adherence is the main cause of antiretroviral therapy failure during initial combination antiretroviral therapy (cART). A switch to a protease inhibitor-sparing cART may be useful when a patient does not tolerate a first protease inhibitor-containing cART regimen. METHODS: To compare the biological and clinical outcomes of patients in whom a first protease inhibitor-containing cART regimen failed to control viral replication and whose treatment was switched to cART containing efavirenz, nevirapine, or abacavir, we studied 1440 patients from the French Hospital Database on HIV whose treatment was changed from a first protease inhibitor-containing cART to a 3-drug regimen with either efavirenz, nevirapine, or abacavir while their plasma viral load was detectable. RESULTS: Kaplan-Meier 12-month probabilities of virological suppression were 73.6%, 53.9%, and 66.1% among patients whose treatment was switched to efavirenz-cART, nevirapine-cART, and abacavir-cART, respectively. Factors associated with a lower likelihood of virological suppression were antiretroviral exposure before the first cART, higher plasma viral load values at the treatment switch, a stavudine-lamivudine backbone after the switch (instead of a zidovudine-lamivudine backbone), and a switch to nevirapine (adjusted hazard ratio, 0.63 [95% CI, 0.54-0.74], compared with efavirenz) or abacavir (adjusted hazard ratio, 0.84 [95% CI, 0.68-1.04] compared with efavirenz). There was no difference among the 3 groups with regard to immunological gain (>50 CD4+ T cells/mm3) or clinical outcome. CONCLUSION: When virological rebound occurs from receipt of protease inhibitor-containing cART, virological suppression can be obtained after a switch to a protease inhibitor-free cART--efavirenz-cART yielding the highest rate of virological suppression.

Adult↗
PubMed2006

Switch from a first virologically effective protease inhibitor-containing regimen to a regimen containing efavirenz, nevirapine or abacavir.

BACKGROUND: Treatment simplification in antiretroviral-experienced patients receiving protease inhibitor (PI)-containing antiretroviral regimens seems safe, but randomized trials have limited power to detect differences in virological rebound (VR) between different switch strategies. METHODS: From the French Hospital Database on HIV, we selected 2462 patients with undetectable viral load (VL) who switched from a first PI-containing antiretroviral combination (cART) to a combination containing efavirenz (EFV), nevirapine (NVP) or abacavir (ABC). Factors associated with VR and with immunological efficacy (gain of > or = 50 CD4(+) cells/microl) were identified by using Cox models. RESULTS: The 12-month Kaplan-Meier probabilities of VR were 6.8, 13.7 and 12.3% in patients switching to EFV-cART, NVP-cART and ABC-cART, respectively. Factors associated with VR were female sex, younger age, antiretroviral exposure before the first cART, time on first cART, higher VL at first cART initiation, a stavudine/didanosine backbone (rather than zidovudine/lamivudine) after the switch, and a switch to NVP or ABC [respective adjusted hazard ratio versus EFV: 1.53; 95% confidence interval (CI), 1.21-1.94; and 1.53; 95% CI, 1.12-2.08]. When the analyses were restricted to patients who were antiretroviral-naive before their first cART, NVP (but not ABC) was associated with VR. Immunological outcomes did not differ among the three switch regimens. CONCLUSION: When VL is undetectable on a first PI-cART regimen, switching to an EFV-containing regimen is more likely to avoid VR than switching to an ABC or NVP-containing regimen. ABC may be an alternative to EFV for patients who were not exposed to antiretroviral before their first cART regimen, after checking for ABC resistance mutations.

Adult↗
PubMed2006

On the comparison of artificial network and interpretation systems based on genotype resistance mutations in HIV-1-infected patients.

Comparing different genotypic interpretation systems is of interest to improve knowledge of the relationship between resistance mutations and virological response under a specific drug. The motivation for choosing a specific system should be based on comparison using appropriate statistical methods. There is some confusion as to the correct use of the linear regression model with its R(2) measure in this setting, especially when models using a single discrete variable are compared with a model using many variables.

Algorithms↗
PubMed2006

Antibodies to conserved epitopes of the HIV-1 envelope in sera from long-term non-progressors: prevalence and association with neutralizing activity.

OBJECTIVE: Previous studies have shown that broadly neutralizing antibodies (NAb) are more frequent in long-term non-progressors (LTNP) than in other HIV-1 infected patients, but nothing is known about the envelope regions targeted by these broadly NAb. We investigated whether the breadth of neutralizing activity of sera was associated with the presence of specific antibodies (2F5- and/or 4E10-like, b12-like or 2G12-like antibodies) directed against conserved epitopes known to be involved in broad neutralization. METHODS: We assessed the ability of sera from 67 LTNP of the French ANRS cohort (ANRS CO15) to neutralize four heterologous primary isolates of four various clades. Competitive and non-competitive ELISA were developed for the specific comparison of levels of antibodies against these specific epitopes in neutralizing and non-neutralizing sera from LTNP. RESULTS: We found that higher 2G12-like antibody levels were significantly associated with the broadest neutralizing activity in sera from LTNP. Levels of 2G12-like antibodies were higher in the sera that neutralized the four isolates than in the others, with a median of 5.7 microg/ml [interquartile range (IQR), 2.7-9.3 microg/ml] versus 2.3 microg/ml (IQR, 1.1-3.9 microg/ml) (Mann-Whitney test, P = 0.03). Levels of antibodies against the other targeted envelope epitopes did not differ significantly between broadly and non-broadly neutralizing sera. CONCLUSION: These results suggest that the antigenicity of the "silent face" of gp120 that exposes the 2G12 epitope should be analysed in more detail, to find ways to induce broadly neutralizing antibodies.

Antibody Specificity↗
PubMed2006

Specific adaptive humoral response against a gp41 motif inhibits CD4 T-cell sensitivity to NK lysis during HIV-1 infection.

OBJECTIVE: We have recently found that during HIV-1 infection, CD4 T cells overexpress a ligand of the NK activating receptor NKp44 (NKp44L) and are sensitized to NK lysis. Expression of NKp44L is triggered by a motif (3S) from the gp41, highly conserved in all HIV-1 clades. The objectives were to determine whether anti-3S antibodies were produced, could counteract 3S-CD4 interactions and were correlated to CD4 cell count and NKp44L expression in HIV-infected patients. DESIGN: Anti-3S antibodie production was studied in HIV-infected patients at various stages of the disease, including a longitudinal study in Asymptomatiques à Long Terme (ALT) patients. METHODS: Specimens from 193 HIV-1 infected patients were examined. Anti-3S antibodies were detected by ELISA, and NKp44L expression was analysed by flow cytometry. NK cytotoxicity against CD4NKp44L cells was determined in the presence of anti-3S antibodies. RESULTS: Anti-3S antibodies were detected in 28.5% of HIV-infected patients. They were positively correlated to CD4 cell counts (P = 0.01) and inversely correlated to NKp44L expression (P = 0.007). Particularly, in ALT patients, a longitudinal study revealed that the CD4 cell count slope differed according to the presence or absence of anti-3S antibodies (-0.98 cells/month versus -7.48 cells/month, P > 0.001). In addition, a clear inhibition of CD4NKp44L NK lysis was observed in relationship to anti-3S antibodies titres. CONCLUSIONS: These results strongly suggested that anti-3S antibodies might affect disease course in inhibiting NKp44L expression and CD4 sensitivity to NK lysis. In linking specific adaptive immunity to the innate immunity induced by the 3S motif, this study may have important implications for therapeutic vaccines against AIDS.

CD4 Antigens↗
PubMed2006

Phase II trial of CHOP plus rituximab in patients with HIV-associated non-Hodgkin's lymphoma.

PURPOSE: To evaluate the safety and efficacy of rituximab adjunction to the cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) regimen in patients with newly diagnosed AIDS-related non-Hodgkin's lymphoma. PATIENTS AND METHODS: HIV-seropositive patients with high-grade lymphoma of B-cell origin were eligible if they had no more than one of the following characteristics: CD4 cell count less than 100/microL, prior AIDS, or performance status less than 2. This multicenter phase II trial evaluated the response rate and disease-free survival after six courses of rituximab plus CHOP. Results Sixty-one patients were enrolled. All the patients were assessable for safety and 52 were assessable for the tumor response after treatment completion. Characteristics of patients were median age, 41 years; median CD4 cells, 172/microL; histology, diffuse large B-cell lymphoma (n = 42), immunoblastic (n = 2), Burkitt lymphoma (n = 16), and plasmablastic (n = 1); 42 patients with stage III to IV; International Prognostic Index 0 to 1 (n=31), and 2 to 3 (n = 27). Grade 3 or 4 toxicity consisted of febrile neutropenia in nine patients, anemia in 16 patients, and thrombocytopenia in five patients. Complete remission (CR) or unconfirmed CR was achieved in 40 of the 52 assessable patients, partial remission was achieved in five patients, and seven patients experienced progression. Forty-three patients were alive after a median follow-up of 33 months. The estimated 2-year overall survival rate was 75% (95% CI, 64% to 86%). Eighteen patients died: 16 as a result of lymphoma, one as a result of infection, and one as a result of encephalitis. CONCLUSION: Rituximab adjunction to CHOP produced a CR rate of 77% and a 2-year survival rate of 75% in patients with AIDS-related non-Hodgkin's lymphoma, without increasing the risk of life-threatening infections.

Adult↗
PubMed2006

HIV treatment response and prognosis in Europe and North America in the first decade of highly active antiretroviral therapy: a collaborative analysis.

BACKGROUND: Highly active antiretroviral therapy (HAART) for the treatment of HIV infection was introduced a decade ago. We aimed to examine trends in the characteristics of patients starting HAART in Europe and North America, and their treatment response and short-term prognosis. METHODS: We analysed data from 22,217 treatment-naive HIV-1-infected adults who had started HAART and were followed up in one of 12 cohort studies. The probability of reaching 500 or less HIV-1 RNA copies per mL by 6 months, and the change in CD4 cell counts, were analysed for patients starting HAART in 1995-96, 1997, 1998, 1999, 2000, 2001, and 2002-03. The primary endpoints were the hazard ratios for AIDS and for death from all causes in the first year of HAART, which were estimated using Cox regression. RESULTS: The proportion of heterosexually infected patients increased from 20% in 1995-96 to 47% in 2002-03, and the proportion of women from 16% to 32%. The median CD4 cell count when starting HAART increased from 170 cells per muL in 1995-96 to 269 cells per muL in 1998 but then decreased to around 200 cells per muL. In 1995-96, 58% achieved HIV-1 RNA of 500 copies per mL or less by 6 months compared with 83% in 2002-03. Compared with 1998, adjusted hazard ratios for AIDS were 1.07 (95% CI 0.84-1.36) in 1995-96 and 1.35 (1.06-1.71) in 2002-03. Corresponding figures for death were 0.87 (0.56-1.36) and 0.96 (0.61-1.51). INTERPRETATION: Virological response after starting HAART improved over calendar years, but such improvement has not translated into a decrease in mortality.

Adolescent↗
PubMed2006

Effects of type of smoking (pipe, cigars or cigarettes) on biological indices of tobacco exposure and toxicity.

Although all forms of smoking are harmful, smoking pipes or cigars is associated with lower exposure to the lethal products of tobacco products and lower levels of morbidity and mortality than smoking cigarettes. Cytochrome P-450-1A (CYP1A) is a major pathway activating carcinogens from tobacco smoke. Our primary aim was to compare CYP1A2 activity in individuals smoking pipes or cigars only, cigarettes only and in non-smokers. We studied 30 smokers of pipes or cigars only, 28 smokers of cigarettes only, and 30 non-smokers male subjects matched for age. CYP1A2 activity was assessed as the caffeine metabolic ratio in plasma. One-day urine collection was used for determining exposure to products of tobacco metabolism. Nitrosamine and benzo[a]pyrene DNA adducts were measured in lymphocytes. CYP1A2 activity was greater (p<0.0001) in cigarette smokers (median: 0.61; interquartile range: 0.52-0.76) than in pipe or cigar smokers (0.27; 0.21-0.37) and non-smokers (0.34; 0.25-0.42) who did not differ significantly. Urinary cotinine and 1-hydroxypyrene levels were higher in cigarette smokers than in pipe or cigar smokers and higher in the later than in non-smokers. DNA adducts levels were significantly lower in pipe or cigar smokers than in cigarette smokers. In multivariate analysis, cigarette smoking was the only independent predictor of CYP1A2 activity (p<0.0001) and of 1-hydroxypyrene excretion in urine (p=0.0012). In this study, pipe or cigar smoking was associated with lower exposure to products of tobacco metabolism than cigarette smoking and to an absence of CYP1A2 induction. Cigarette smoking was the only independent predictor of CYP1A2 activity in smokers. However, inhalation behaviour, rather than the type of tobacco smoked, may be the key factor linked to the extent of tobacco exposure and CYP1A2 induction. Our results provide a reasonable explanation for the results of epidemiological studies showing pipe or cigar smoking to present fewer health hazards than cigarette smoking.

Adult↗
PubMed2006

Risk factors for osteonecrosis in HIV-infected patients: impact of treatment with combination antiretroviral therapy.

BACKGROUND: Osteonecrosis was increasingly associated with HIV infection in the 1990s. It is unclear whether its risk increases with the duration of HIV infection, the duration of combination antiretroviral therapy (cART) or both. OBJECTIVE: To analyse factors associated with the rate of symptomatic osteonecrosis, particularly the relative impacts of the duration of HIV infection and the duration of cART, using the French Hospital Database on HIV, which comprises a large number of subjects with substantial follow-up. METHODS: Poisson regression model was used to identify factors associated with the rate of osteonecrosis among patients enrolled in 1996-2002. RESULTS: The study involved 56,393 subjects with a total follow-up of 229,031 person-years. Symptomatic osteonecrosis was diagnosed in 104 subjects with an incidence rate of 4.5/10,000 person-years. Multivariate analysis identified three factors associated with the rate of osteonecrosis: prior AIDS-defining illnesses [adjusted relative rate (RR), 3.1; 95% confidence interval (CI), 2.0-4.9], the CD4 cell nadir [RR, 1.6 (95% CI, 0.9-2.9) for CD4 cell count 50-199 cells/microl; RR, 1.8 (95% CI, 1.0-3.3) for CD4 cell count < 50 cells/microl; both relative to CD4 cell count > or = 200 cells/microl] and exposure to cART. Compared with unexposed patients, the RR of osteonecrosis ranged from 2.6 (95% CI, 1.2-5.9) in patients treated with cART for < 12 months to 5.1 (95% CI, 2.1-12.6) in patients treated for > or = 60 months. CONCLUSIONS: Osteonecrosis appears to be a complication of both HIV infection and cART.

Adult↗
PubMed2006

Association of Gag cleavage sites to protease mutations and to virological response in HIV-1 treated patients.

OBJECTIVES: The sequence variability in the protease and in the 5 Gag cleavage sites (CS) were explored to look for eventual associations between the mutations. Moreover, we have evaluated associations between the Gag region sequence and the virological response to Protease Inhibitors (PI). METHODS: The protease and the 5 Gag CS sequences from 98 PI-experienced patients were sequenced and compared to the HXB2 reference sequence. Sixty patients, treated by Saquinavir plus Ritonavir, were studied to evaluate the clinical impact of the Gag region variability. RESULTS: The relationship between 63 protease mutations and 21 Gag CS mutations were explored. Two patterns of mutations in the protease were identified: (M46I/L, I54V, V82A/T/F) was associated to the A431V and (K20I/R/M, L89M/I) to the S373Q and L449P. None of the Gag CS mutations resulting from PI treatment was associated to the virological response to SQV/r. On the other hand, the S373P mutation had a negative impact on the virological response that remained statistically significant in a multivariate analysis after adjustment on the number of PI resistance mutations. CONCLUSIONS: These results evoke the pertinence to introduce some mutations found in the Gag CS in the algorithms used for the interpretation of resistance testing.

Amino Acid Sequence↗
PubMed2006

Differential impact of combination antiretroviral therapy in preventing Kaposi's sarcoma with and without visceral involvement.

PURPOSE: To study the impact of different potent combined antiretroviral treatment (cART) on the incidence of HIV-associated Kaposi's sarcoma (KS) with and without visceral involvement. PATIENTS AND METHODS: Patients were selected from the French Hospital Database on HIV, a large hospital cohort. The risk of KS was estimated by using Cox proportional hazards models adjusting for age, the CD4 cell nadir, the HIV exposure category, prior AIDS, cART, and the type of cART regimen. cART regimens were distinguished according to whether they contained protease inhibitor (PI), non-nucleoside analog (NNRTI), both, or only nucleoside analog (NRTI). Separate analyzes were conducted according to the initial visceral involvement of KS. RESULTS: Among the 54,999 patients included in this study (182,756 person-years of follow-up), 1,634 patients were diagnosed with KS during follow-up, of whom 421 had visceral involvement at diagnosis. The KS incidence rate fell from 32 per 1,000 person-years in 1993 to 1994 to 3 per 1,000 person-years after 1999. PI-containing and NNRTI-containing cART regimens were associated with similar reductions in the risk of KS (hazard ratio, 0.68; 95%CI, 0.61 to 0.75; HR, 0.62; 95% CI, 0.54 to 0.71, respectively). The risk of visceral KS fell more strongly than the risk of cutaneous KS (> 50% and < 30%, respectively). CONCLUSION: The incidence of KS, and especially visceral KS, has fallen sharply since the advent of cART. This effect is likely due to immune restoration rather than to a specific effect on the tumoral process, as PI-containing and NNRTI-containing regimens had similar preventive efficacy.

Adult↗
PubMed2006

Predictors identified for losses to follow-up among HIV-seropositive patients.

BACKGROUND AND OBJECTIVE: This study aims to describe predictors of loss to follow-up (LFU) in the French Hospital Database on HIV infection (FHDH). METHODS: We studied the prevalence and predictors of LFU among 34,835 patients enrolled in FHDH in 1999. Impacts of demographic and clinical factors were studied by using multivariate logistic regression analysis. RESULTS: Among included patients, 1,478 (4.2%) died and 2,950 (8.5%) were lost to follow-up. LFU was more frequent among recently diagnosed patients (<1 year, 16.8%; > 1 year, 7.1). Among recently diagnosed patients, LFU was less frequent among men who have sex with men (MSM) [odds radio (OR) = 0.6, 95% confidence interval (CI) = (0.5;0.7)], and among patients with AIDS [OR = 0.5, 95%CI = (0.4;0.6)], and more frequent among immigrants [OR = 1.3, 95%CI = (1.0;1.5)]. Among less recently diagnosed patients, LFU was more frequent in French Departments of America than in the Paris area. The proportion of LFU fell with age, and LFU was more frequent among intravenous drug users (IVDU) than among MSM [OR = 1.2, 95%CI = (1.1;1.4)]. Patients with viral load >5,000 copies/mL or CD4 cell counts <200/mm(3) were more likely to be lost to follow-up. CONCLUSIONS: Recently diagnosed patients, IVDU, and immigrants are more often lost to follow-up, and should therefore receive special attention.

Adult↗
PubMed2006

Including pre-AIDS mortality in back-calculation model to estimate HIV prevalence in France, 2000.

Since the advent of highly active antiretroviral therapy (HAART) the lengthening of AIDS incubation time has led to a decrease of AIDS incidence and mortality, and to the increase of the proportion of pre-AIDS mortality. The objective was to develop an extension of the back-calculation model by including pre-AIDS mortality and to estimate HIV prevalence in France. Our previous back-calculation model was modified to take into account the probability of survival for HIV-infected individual using the relative risk to die at different period for an HIV-infected person versus the general population (psi). AIDS cases reported to InVS (Institut de Veille Sanitaire) until March 2003 were back-calculated to estimate HIV incidence until December 2000. AIDS deaths occurring until December 2000 were used to obtain HIV prevalence in 2000. Plausible intervals were calculated taking into account uncertainties on AIDS incubation time. Taking into account pre-AIDS mortality increased the goodness-of-fit of the model to the data. The relative risk, psi, was estimated as 3 for homo-bisexual men, haemophiliacs and transfused cases, 10 for intravenous drug users, and 4 for heterosexual cases, with no difference over period. HIV prevalence in 2000 was estimated as 88,200 (with a plausible interval of 52,300-168,000), versus 78,200 when mortality was not considered. Pre-AIDS mortality estimates show the amount of this mortality during the era of HAART but also evidenced its existence before HAART. Taking into account pre-AIDS mortality of HIV-infected person in the back-calculation model increased the estimated HIV prevalence.

Acquired Immunodeficiency Syndrome↗
PubMed2006

How was the French BSE epidemic underestimated?

In a previous study, we showed that estimates of the BSE epidemic in France were censored by cattle mortality and by a lack of diagnosis. Indeed, we estimated that 51 300 cattle were infected by the BSE agent between 1987 and 1997, whereas only 103 clinical BSE cases were detected by the passive surveillance system up to June 2000. The question thus arises as to the part played by each form of censorship in this underestimation. Here, using an updated cattle survival distribution, we estimated that 44 800 cattle were infected by the BSE agent between 1987 and 1997, and that 7100 of them showed clinical signs of BSE up to June 2000, showing the low efficiency of the surveillance system. Moreover, between 2087 and 5980 'infectious' cattle, with clinical or preclinical BSE, entered the human food chain before July 1996, the date of the ban on specified bovine offal.

Age Factors↗
PubMed2006

Repeated HIV-1 resistance genotyping external quality assessments improve virology laboratory performance.

The performance of French virology laboratories belonging to the ANRS network has been assessed annually for 3 years. The performance of these laboratories was compared between the years 2002 and 2003. Ten and 7 coded samples were sent to 38 virology laboratories in 2002 and 45 virology laboratories in 2003, respectively. Each panel of coded samples included at least one HIV-negative control, a pair of duplicate specimens, samples with a wide range of viral loads, and samples with a large number of resistance mutations. The laboratories used their standard sequencing procedures and were asked to report the amino acids at codons associated with resistance mutations, based on the IAS-USA expert panel list. The reference amino acid sequences were defined as those most frequently reported by the participants. The specificity of detection of RT mutations was significantly better in 2003 (99.9%) than in 2002 (99.7%) (P = 0.05). There was no difference between 2002 and 2003 in the specificity of detection of protease mutations (99.6% and 99.8%) or the sensitivity of detection of RT mutations (98.8% and 98.2%). The sensitivity of detection of protease mutations improved significantly between 2002 and 2003 (97.6% and 99.0%, respectively; P = 0.037). The proportion of laboratories reporting fully accurate results, in terms of amplification, specificity, sensitivity, and reproducibility, tended to increase between 2002 and 2003 (P = 0.077). No errors were made by 19% of laboratories in 2002, compared to 42% in 2003. These results show the value of repeated external quality assessments.

Clinical Laboratory Techniques↗
PubMed2006

The calculated genetic barrier for antiretroviral drug resistance substitutions is largely similar for different HIV-1 subtypes.

BACKGROUND: The genetic barrier, defined as the number of mutations required to overcome drug-selective pressure, is an important factor for the development of HIV drug resistance. Because of high variability between subtypes, particular HIV-1 subtypes could have different genetic barriers for drug resistance substitutions. This study compared the genetic barrier between subtypes using some 2000 HIV-1 sequences (>600 of non-B subtype) isolated from anti-retroviral-naive patients in Europe. METHODS: The genetic barrier was calculated as the sum of transitions (scored as 1) and/or transversions (2.5) required for evolution to any major drug resistance substitution. In addition, the number of minor protease substitutions was determined for every subtype. RESULTS: Few dissimilarities were found. An increased genetic barrier was calculated for I82A (subtypes C and G), V108I (subtype G), V118I (subtype G), Q151M (subtypes D and F), L210W (subtypes C, F, G, and CRF02_AG), and P225H (subtype A) (P < 0.001 compared with subtype B). A decreased genetic barrier was found for I82T (subtypes C and G) and V106M (subtype C) (P < 0.001 vs subtype B). Conversely, minor protease substitutions differed extensively between subtypes. CONCLUSIONS: Based on the calculated genetic barrier, the rate of drug resistance development may be similar for different HIV-1 subtypes. Because of differences in minor protease substitutions, protease inhibitor resistance could be enhanced in particular subtypes once the relevant major substitutions are selected.

Adult↗