Prevention and treatment of opportunistic infections and other coinfections in HIV-infected patients: May 2015.

Despite the huge advance that antiretroviral therapy represents for the prognosis of infection by the human immunodeficiency virus (HIV), opportunistic infections (OIs) continue to be a cause of morbidity and mortality in HIV-infected patients. OIs often arise because of severe immunosuppression resulting from poor adherence to antiretroviral therapy, failure of antiretroviral therapy, or unawareness of HIV infection by patients whose first clinical manifestation of AIDS is an OI. The present article updates our previous guidelines on the prevention and treatment of various OIs in HIV-infected patients, namely, infections by parasites, fungi, viruses, mycobacteria, and bacteria, as well as imported infections. The article also addresses immune reconstitution inflammatory syndrome.

Executive summary: Prevention and treatment of opportunistic infections and other coinfections in HIV-infected patients: May 2015.

Opportunistic infections continue to be a cause of morbidity and mortality in HIV-infected patients. They often arise because of severe immunosuppression resulting from poor adherence to antiretroviral therapy, failure of antiretroviral therapy, or unawareness of HIV infection by patients whose first clinical manifestation of AIDS is an opportunistic infection. The present article is an executive summary of the document that updates the previous recommendations on the prevention and treatment of opportunistic infections in HIV-infected patients, namely, infections by parasites, fungi, viruses, mycobacteria, and bacteria, as well as imported infections. The article also addresses immune reconstitution inflammatory syndrome. This document is intended for all professionals who work in clinical practice in the field of HIV infection.

Immune response and reactogenicity after immunization with two-doses of an experimental COVID-19 vaccine (CVnCOV) followed by a third-fourth shot with a standard mRNA vaccine (BNT162b2): RescueVacs multicenter cohort study.

Background: There is no evidence to date on immunogenic response among individuals who participated in clinical trials of COVID-19 experimental vaccines redirected to standard national vaccination regimens. Methods: This multicentre, prospective controlled cohort study included subjects who received a COVID-19 experimental vaccine (CVnCoV)(test group, TG) - and unvaccinated subjects (control group, CG), selected among individuals to be vaccinated according to the Spanish vaccination program. All study subjects received BNT162b2 as a standard national vaccination schedule, except 8 (from CG) who received mRNA-1273 and were excluded from immunogenicity analyses. Anti-RBD antibodies level and neutralising titres (NT50) against G614, Beta, Mu, Delta and Omicron variants were analysed. Reactogenicity was also assessed. Findings: 130 participants (TG:92; CG:38) completed standard vaccination. In TG, median (IQR) of anti-RBD antibodies after first BNT162b2 dose were 10740·0 BAU/mL (4466·0-12500) compared to 29·8 BAU/mL (14·5-47·8) in CG (p <0·0001). Median NT50 (IQR) of G614 was 2674·0 (1865·0-3997·0) in TG and 63·0 (16·0-123·1) in CG (p <0·0001). After second BNT162b2 dose, anti-RBD levels increased to ≥12500 BAU/mL (11625·0-12500) in TG compared to 1859·0 BAU/mL (915·4-3820·0) in CG (p <0·0001). NT50 was 2626·5 (1756·0-5472·0) and 850·4 (525·1-1608·0), respectively (p <0·0001). Variant-specific (Beta, Mu, Omicron) response was also assessed. Most frequent adverse reactions were headache, myalgia, and local pain. No severe AEs were reported. Interpretation: Heterologous BNT162b2 as third and fourth doses in previously suboptimal immunized individuals elicit stronger immune response than that obtained with two doses of BNT162b2. This apparent benefit was also observed in variant-specific response. No safety concerns arose. Funding: Partly funded by the Institute of Health Carlos-III and COVID-19 Fund, co-financed by the European Regional Development Fund (FEDER) "A way to make Europe".

Restoration of T cell responses to toxoplasma gondii after successful combined antiretroviral therapy in patients with AIDS with previous toxoplasmic encephalitis.

BACKGROUND: It is unknown whether a Toxoplasma gondii-specific T cell response is restored after successful combined antiretroviral therapy (cART) in patients with AIDS and current or previous toxoplasmic encephalitis (TE). METHODS: We performed a multicenter cross-sectional study with 17 healthy T. gondii-positive human immunodeficiency virus (HIV)-1-uninfected individuals and 90 patients coinfected with HIV-1 and T. gondii distributed in 5 groups according to their CD4(+) T cell counts and T. gondii infection (with or without current or previous TE). We investigated the lymphocyte proliferative response (LPR) and interferon (IFN)-γ production in response to T. gondii soluble antigen extract (SATg) and as CD4(+) and CD8(+) T cell subsets. RESULTS: SATg-specific LPR and IFN-γ production were not observed in many of the most immunosuppressed patients (CD4(+) T cell count, <200 cells/µL, with or without current or previous TE). By contrast, these responses occurred in a considerable percentage (LPR, 43%; IFN-γ production, 80%) of patients receiving successful cART (CD4(+) T cell count, >200 cells/µL) who presented with TE and had already stopped secondary TE prophylaxis. Similar results were found in immunocompetent asymptomatic patients who did not receive TE prophylaxis. The predictors of SATg-specific T cell responses and IFN-γ production were a cART-mediated increase in CD4(+) T cell count and LPR to phytohemagglutinin and viral suppression and a decrease in the activated (CD38(+)) CD8(+) T cell count, respectively. CONCLUSIONS: cART restores T. gondii-specific CD4 T cell responses in most patients with AIDS who had previous TE. Our data support the safety of withdrawing TE prophylaxis when the CD4(+) T cell count returns to levels >200 cells/µL.

Open Access of COVID-19-related publications in the first quarter of 2020: a preliminary study based in PubMed.

Background: The COVID-19 outbreak has made funders, researchers and publishers agree to have research publications, as well as other research outputs, such as data, become openly available. In this extraordinary research context of the SARS CoV-2 pandemic, publishers are announcing that their coronavirus-related articles will be made immediately accessible in appropriate open repositories, like PubMed Central, agreeing upon funders' and researchers' instigation. Methods: This work uses Unpaywall, OpenRefine and PubMed to analyse the level of openness of articles about COVID-19, published during the first quarter of 2020. It also analyses Open Access (OA) articles published about previous coronavirus (SARS CoV-1 and MERS CoV) as a means of comparison. Results: A total of 5,611 COVID-19-related articles were analysed from PubMed. This is a much higher amount for a period of 4 months compared to those found for SARS CoV-1 and MERS during the first year of their first outbreaks (335 and 116 articles, respectively).  Regarding the levels of openness, 88.8% of the SARS CoV-2 papers are freely available; similar rates were found for the other coronaviruses. Deeper analysis showed that (i) 67.4% of articles belong to an undefined Bronze category; (ii) 76.4% of all OA papers don't carry any license, followed by 10.4% which display restricted licensing. These patterns were found to be repeated in the three most frequent publishers: Elsevier, Springer and Wiley. Conclusions: Our results suggest that, although scientific production is much higher than during previous epidemics and is open, there is a caveat to this opening, characterized by the absence of fundamental elements and values ​​on which Open Science is based, such as licensing.

A case-control study of non-AIDS-defining cancers in a prospective cohort of HIV-infected patients. / Estudio caso-control de tumores no definitorios de sida en una cohorte prospectiva de pacientes infectados por el VIH.

INTRODUCTION: We present a case-control study of non-AIDS-defining cancers (NADCs) in a cohort of HIV-infected patients where we value the incidence, survival and prognostic factors of mortality. METHODS: All NADCs diagnosis conducted from 2007 to 2011 in 7 hospitals were collected prospectively, with a subsequent follow up until December 2013. A control group of 221 HIV patients without a diagnosis of cancer was randomly selected. RESULTS: Two hundred and twenty-one NADCs were diagnosed in an initial cohort of 7,067 HIV-infected patients. The most common were: hepatocellular carcinoma 20.5%, lung 18.7%, head and neck 11.9% and anal 10.5%. The incidence rate of NADCs development was 7.84/1,000 people-year. In addition to aging and smoking, time on ART (OR 1.11; 95% CI 1.05-1.17) and PI use (OR 1.72; 95% CI 1.0-2.96) increased the risk of developing a NADC. During follow-up 53.42% died, with a median survival time of 199.5 days. In the analysis of the prognostic factors of mortality the low values of CD4 at tumour diagnosis (OR 0.99; 95% CI 0.99-1.0; P=.033), and the previous diagnosis of AIDS (OR 2.06; 95% CI 1.08-3.92) were associated with higher mortality. CONCLUSIONS: Predictors of NADCs in our cohort were age, smoking, CD4 lymphocytes and time on ART. Mortality is high, with NADC risk factors being low CD4 count and previous diagnosis of AIDS.

Effectiveness and safety of simplification therapy with once-daily tenofovir, lamivudine, and efavirenz in HIV-1-infected patients with undetectable plasma viral load on HAART.

OBJECTIVE: To evaluate the effectiveness and tolerability of a simplification regimen with tenofovir DF (TDF), lamivudine (3TC), and efavirenz (EFV) in HAART-experienced HIV-1-infected subjects with sustained viral suppression. METHOD: Patients with HIV-1 RNA <200 copies/mL during the previous 6 months and who switched their current twice-daily or three-times-daily HAART to a simplified once-daily regimen of TDF (300 mg), 3TC (300 mg), and EFV (600 mg) were included. RESULTS: 154 patients (70% males, mean age 42 years) were included. Previous HAART included a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen in 55% of the patients and a thymidine analog in 87%. The percentage of patients with viral load <200 copies/mL in the intent-to-treat (ITT) data set was 83% at 6 months and 75% at 12 months (98% and 96%, respectively, in the on-treatment [OT] analysis). Five patients (3%) were identified as virologic failures according to the study protocol. The mean CD4 T-cell count increased significantly 12 months after simplification (from 570 to 632 cells/mm3; p < .01). At 12 months, mean triglyceride levels decreased from 233 to 170 mg/dL (p < .01) and mean cholesterol levels decreased from 205 to 189 mg/dL (p < .01). Thirty-three patients (21%) discontinued the study treatment prior to completing the 12-month follow-up. CONCLUSION: Simplification to a once-daily regimen containing TDF, 3TC, and EFV is virologically and immunologically effective, well-tolerated, and safe with benefits in the lipid profile in the majority of patients.

Clinical course and prognostic factors of progressive multifocal leukoencephalopathy in patients treated with highly active antiretroviral therapy.

We analyzed survival rates, neurologic function, and prognostic factors for 118 consecutive patients with acquired immunodeficiency syndrome-associated progressive multifocal leukoencephalopathy (PML) treated with highly active antiretroviral therapy (HAART) in 11 hospitals throughout Spain. Seventy-five patients (63.6%) remained alive for a median of 114 weeks (2.2 years) after diagnosis of PML. Neurologic function of the survivors was categorized as cure or improvement in 33, stabilization or worsening in 40, and unknown in 2. The baseline CD4+ cell count was the only variable found with prognostic significance. The odds ratio of death was 2.71 (95% confidence interval, 1.19-6.15) for patients with CD4+ cell counts of <100 cells/microL, compared with patients who had CD4+ cell counts of > or =100 cells/microL. One-third of patients with PML died despite receipt of HAART; neurologic function improved in approximately one-half of the survivors. A CD4+ cell count of <100 cells/microL was associated with higher mortality.

Prognosis and clinical evaluation of infection caused by Rhodococcus equi in HIV-infected patients: a multicenter study of 67 cases.

OBJECTIVE: To assess the clinical characteristics and the factors that influenced the prognosis of patients with HIV and infection caused by Rhodococcus equi. DESIGN: Observational, multicenter study in 29 Spanish general hospitals. SETTING: These hospitals comprised a total of 20,250 beds for acute patients and served a population of 9,716,880 inhabitants. PATIENTS: All patients with HIV and diagnosed R equi infection until September 1998. RESULTS: During the study period, 19,374 cases of AIDS were diagnosed. Sixty-seven patients were included (55 male patients; mean +/- SD age, 31.7 +/- 5.8 years). At the time of diagnosis of R equi infection, the mean CD4+ lymphocyte count was 35/ micro L (range, 1 to 183/ micro L) and the stage of HIV infection was A3 in 10.4% of patients, B3 in 31.3%, C3 in 56.7%, and unknown in 1.5%. R equi was most commonly isolated in sputum (52.2%), blood cultures (50.7%), and samples from bronchoscopy (31.3%). Chest radiographic findings were abnormal in 65 patients (97%). Infiltrates were observed in all of them, with cavitations in 45 patients. The most active antibiotics against the strains isolated were vancomycin, amikacin, rifampicin, imipenem, ciprofloxacin, and erythromycin. After a mean follow-up of 10.7 +/- 12.8 months, 23 patients (34.3%) died due to causes related to R equi infection and 6 other patients showed evidence of progression of the infection. The absence of highly active antiretroviral therapy (HAART) was independently associated with mortality related to R equi infection (relative risk, 53.4; 95% confidence interval, 1.7 to 1,699). Survival of patients treated with HAART was much higher than that of patients who did not receive this therapy. CONCLUSIONS: Infection by R equi is an infrequent, opportunistic complication of HIV infection and occurs during advanced stages of immunodepression. In these patients, it leads to a severe illness that usually causes a bacteremic, cavitary pneumonia, although HAART can improve the prognosis.

[Epidemiological characteristics of new HIV infections compared with AIDS cases. The HIV/AIDS epidemic in the Basque Country]. / Características epidemiológicas de las nuevas infecciones causadas por el VIH comparadas con los casos de sida. La epidemia de VIH/sida en el País Vasco.

OBJECTIVE: To describe the epidemiological characteristics of new cases of HIV infection diagnosed from 1997-2001 and compare them with AIDS cases (1991-2001). METHODS: Data were retrospectively collected on new cases of HIV infection detected in the Basque Country (1997-2001) and were compared with AIDS cases (1991-2001). RESULTS: A total of 912 new cases of HIV infection were diagnosed. In 299 of the new cases (32.8%), HIV and AIDS were diagnosed simultaneously. The most common mechanism of transmission was heterosexual transmission, followed by intravenous and homo/bisexual transmission. Significant epidemiological differences (p < 0.001) were found with regard to AIDS cases. CONCLUSIONS: Sexual transmission has replaced intravenous drug use as the most common mechanism of HIV transmission. A large percentage of patients were simultaneously diagnosed with HIV and AIDS, indicating the need for new prevention strategies.

Immune reconstitution in severely immunosuppressed antiretroviral-naive HIV type 1-infected patients using a nonnucleoside reverse transcriptase inhibitor-based or a boosted protease inhibitor-based antiretroviral regimen: three-year results (The Advanz Trial): a randomized, controlled trial.

Late diagnosis of HIV-1 infection is quite frequent in Western countries. Very few randomized clinical trials to determine the best antiretroviral treatment in patients with advanced HIV-1 infection have been performed. To compare immune reconstitution in two groups of very immunosuppressed (less than 100 CD4(+) cells/microl), antiretroviral-naive HIV-1-infected adults, 65 patients were randomly assigned in a 1:1 ratio to receive zidovudine + lamivudine + efavirenz (group A, 34 patients) or zidovudine + lamivudine + ritonavir-boosted indinavir (group B, 31 patients). The median (interquartile range) CD4(+) cell increase after 12 and 36 months was +199 (101, 258) and +299 (170, 464) cells/microl in the efavirenz arm and +136 (57, 235) and +228 (119, 465) cells/microl in the ritonavir-boosted indinavir arm (p > 0.05 for all time points). The proportion (95% confidence interval) of patients achieving HIV-1 RNA levels under 50 copies/ml was significantly greater in the efavirenz arm at 3 years by the intention-to-treat analysis [59% (41%, 75%) vs. 23% (10%, 41%)], whereas no differences were found in the on-treatment analysis. Immune activation (CD8(+)CD38(+) and CD8(+)CD38DR(+) T cells) was significantly lower for the efavirenz arm from month 6 to month 24. Adverse events were more frequent in the ritonavir-boosted indinavir arm. Almost all cases of disease progression and death were observed in the first year of treatment, with no significant differences between the two arms (p = 0.79 by the log-rank test). At 1 and 3 years, the immune reconstitution induced by an efavirenz-based regimen in very immunosuppressed patients was at least as potent as that induced by a ritonavir-boosted protease inhibitor-based antiretroviral regimen.

[Tuberculosis in the Bajo Deba area (Guipúzcoa, Spain) from 1995 to 2006]. / Tuberculosis en la comarca del Bajo Deba (Guipúzcoa) en el período 1995-2006.

BACKGROUND: Within the Multicenter Project on Tuberculosis Research performed in Spain in 1996-1997, the Bajo Deba Area reported the highest incidence of tuberculosis in the Basque Country. We analyzed the clinical and epidemiological characteristics of the tuberculosis population diagnosed in our area during the period of 1995 to 2006. METHODS: Ambispective, observational study. RESULTS: A total of 584 patients were diagnosed with tuberculosis. The disease affected the respiratory tract in 509 cases and other sites in 75 cases. The mean annual incidence rate of tuberculosis was 64.5 cases per 100 000 inhabitants (91.6 in 1995-1998; 34.9 in 2003-2006). The mean annual incidence rate of smear-positive patients was 20.7 cases per 100 000 inhabitants (33.8 in 1995-1998; 12.9 in 2003-2006). The 15 to 24-year-old group was the most highly affected during the period of 1995 to 1998 (mean annual incidence rate 199.4 cases per 100 000); in contrast, the > 75-year-old group was the most highly affected during the period of 2003 to 2006 (121.1 cases per 100 000 inhabitants). Fifty-three patients were co-infected by HIV (9%) (yearly mean of 11.6% in 1995-1998 and 7% in 2003-2006). Löwenstein culture was positive in 431 cases (73.8%). Resistance to isoniazid was detected in 1.4% out of a total of 287 strains tested, and multidrug resistance was not observed. Nine patients were immigrants (1.5%). Treatment completion was greater in our area (505 patients, 86.4%), as compared to that recorded in the Guipuzcoa province during the same period (1956 of 2525 patients, 77.5%) (P < .01). CONCLUSIONS: The Bajo Deba Area presented a high incidence of tuberculosis in the 1995 to 2006 period. Epidemiological trends showed a progressive decrease in the number of tuberculosis patients, with a shift from younger to older persons as the most highly affected age group. The impact of drug resistance and immigration was negligible on tuberculosis rates. The percentage of microbiologically confirmed cases was high. Treatment completion was satisfactory.

[The infectious disease specialty in Europe and America]. / La infectología en Europa y América.

Infectious Diseases is a recognised clinical specialty in almost all European countries, in the United States of America, Canada and most countries in Central and South America. Even though the training programs are heterogeneous in the different European countries, the Infectious Diseases section of the UEMS (European Union of Medical Specialties) is working to harmonise them. In 1998, the European Board of Infectious Diseases recommended a 6-year training period, similar to that of other medical specialties, including 2 years of general internal medicine training and 2 years of specific training. The clinical activity and services provided by Infectious Diseases units in Spanish hospitals is similar to that in other countries. In this article, training programs, clinical activity and scientific activities in Infectious Diseases in the different countries is reviewed.

[Paludism due to Plasmodium falciparum in visitors to the Dominican Republic]. / Paludismo por Plasmodium falciparum en viajeros a República Dominicana.

We present two cases of P. falciparum malaria in visitors to tourist resorts on the East Coast of the Dominican Republic, traditionally believed to be an area without risk of malaria. In both patients the malaria was severe (with 20% parasitization in one) and there was a long interval between the onset of symptoms and diagnosis. These cases are possibly related (along with a further 17 reports by the Centers for Disease Control and Prevention) to an increase in the population of Anopheles sp as a consequence of increased rainfall and floods provoked by a hurricane in September 2004, as well as to the presence of a semi-immune population (Haitian immigrants working in the construction and tourist sectors). Both physicians and patients should be aware of this outbreak so that adequate precautions can be taken and early diagnoses can be made.

Prevention of opportunistic infections in adult and adolescent patients with HIV infection. GESIDA/National AIDS Plan guidelines, 2004 [correction].

OBJECTIVE: To provide an update of guidelines from the Spanish AIDS Study Group (GESIDA) and the National AIDS Plan (PNS) committee on the prevention of opportunistic infections in adult and adolescent HIV-infected patients. METHODS: These consensus recommendations have been produced by a group of experts from GESIDA and/or the PNS after reviewing the earlier document and the scientific advances in this field in the last years. The system used by the Infectious Diseases Society of America and the United States Public Health Service has been used to classify the strength and quality of the data. RESULTS: This document provides a detailed review of the measures for the prevention of infections caused by viruses, bacteria, fungi and parasites in the context of HIV infection. Recommendations are given for preventing exposure and for primary and secondary prophylaxis for each group of pathogens. In addition, criteria are established for the withdrawal of prophylaxis in patients who respond well to highly active antiretroviral therapy (HAART). CONCLUSIONS: HAART is the best strategy for the prevention of opportunistic infections in HIV-positive patients. Nevertheless, prophylaxis is still necessary in countries with limited economic resources, in highly immunodepressed patients until HAART achieves beneficial effects, in patients who refuse to take or who cannot take HAART, in those in whom HAART is not effective, and in the small group of infected patients with inadequate recovery of CD4+ T lymphocyte counts despite good inhibition of HIV replication.

[Recommendations of the Spanish AIDS Study Group (GESIDA) and the National Aids Plan (PNS) for antiretroviral treatment in adult patients with human immunodeficiency virus infection in 2002]. / Recomendaciones de GESIDA/Plan Nacional sobre el Sida respecto al tratamiento antirretroviral en pacientes adultos infectados por el virus de la inmunodeficiencia humana en el año 2002.

OBJECTIVE: To provide an update of recommendation on antiretroviral treatment (ART) in HIV-infected adults.Methods. These recommendations have been agreed by consensus by a committee of the spanish AIDS Study Group (GESIDA) and the National AIDS Plan. To do so, advances in the physiopathology of AIDS and the results on efficacy and safety in clinical trials, cohort and pharmacokinetics studies published in biomedical journals or presented at congresses in the last few years have been reviewed. Three levels of evidence have been defined according to the data source: randomized studies (level A), case-control or cohort studies (level B) and expert opinion (level C). Whether to recommend, consider, or not to recommend ART has been established for each situation. RESULTS: Currently, ART with combinations of at least three drugs constitutes the treatment of choice in chronic HIV infection. In patients with symptomatic HIV infection, initiation of ART is recommended. In asymptomatic patients initiation of ART should be based on the CD41/mL lymphocyte count and on the plasma viral load (PVL): a) in patients with CD41 lymphocytes < 200 cells/mL, initiation of ART is recommended; b) in patients with CD41 lymphocytes between 200 and 300 cells/mL, initiation of ART should, in most cases, be recommended; however, it could be delayed when the CD41 lymphocyte count remains close to 350 cells/mL and the PVL is low, and c) in patients with CD41 lymphocytes > 350 cells/mL, initiation of ART can be delayed. The aim of ART is to achieve an undetectable PVL. Adherence to ART plays a role in the durability of the antiviral response. Because of the development of cross-resistance, the therapeutic options in treatment failure are limited. In these cases, genotypic analysis is useful. Toxicity limits ART. The criteria for ART in acute infection, pregnancy and postexposure prophylaxis and in the management of coinfection with HIV and hepatitis C and B virus are controversial. CONCLUSIONS: The current approach to initiating ART is more conservative than in previous recommendations. In asymptomatic patients, the CD41 lymphocyte count is the most important reference factor for initiating ART. Because of the considerable number of drugs available, more sensitive monitoring methods (PVL) and the possibility of determining resistance, therapeutic strategies have become much more individualized.

[Spanish GESIDA/Nacional AIDS Plan Recommendations for antiretroviral therapy in HIV-infected Adults (October 2004)]. / Recomendaciones de GESIDA/Plan Nacional sobre el Sida respecto al tratamiento antirretroviral en pacientes adultos infectados por el VIH (octubre 2004).

OBJECTIVE: This consensus document is an update of antiretroviral therapy (ART) recommendations for adult patients infected with the human immunodeficiency virus (HIV). METHODS: To formulate these recommendations, a panel composed of members of the Grupo de Estudio de Sida (GESIDA; AIDS Study Group) and the Plan Nacional sobre el Sida (PNS; Spanish AIDS Plan) reviewed the advances in current understanding of the pathophysiology of HIV, the safety and efficacy findings from clinical trials, and the results from cohort and pharmacokinetic studies published in biomedical journals or presented at scientific meetings over the last years. Three levels of evidence were defined according to the source of the data: randomized studies (level A), cohort or case-control studies (level B), and expert opinion (level C). The decision to recommend, consider or not recommend ART was established in each of these situations. RESULTS: ART consisting of at least three drugs is currently the initial treatment of choice for chronic HIV infection. These regimens should include 2 NRTI + 1 NNRTI or 2 NRTI + 1 PI. Initiation of ART is recommended in patients with symptomatic HIV infection. In asymptomatic patients, initiation of ART is recommended on the basis of CD4+ lymphocyte counts per L and plasma viral load, as follows: 1) Therapy should be started in patients with CD4+ counts of < 200 cells/microL; 2) Therapy should be started in most patients with CD4+ counts of 200-350 cells/microL, although it can be delayed when CD4+ count persists at around 350 cells/microL and viral load is low; and 3) Initiation of therapy can be delayed in patients with CD4+ counts of > 350 cells/microL. The initial objective of ART is to achieve an undetectable viral load. Adherence to therapy plays an essential role in maintaining the antiviral response. Because of the development of cross resistance, therapeutic options are limited when ART fails. Genotype studies are useful in these cases. Toxicity is a limiting factor in the use of ART, although the benefits outweigh the risks. In addition, the criteria for the use of ART are discussed in situations of acute infection, pregnancy, and post-exposure prophylaxis, and in the management of co-infection of HIV with HCV or HBV. CONCLUSIONS: CD4+ lymphocyte count is the most important reference factor for initiating ART in asymptomatic patients. The large number of available drugs, the increased sensitivity of tests to monitor viral load, and the possibility to determine viral resistance is leading to a more individualized approach to therapy.