Comorbidities among HIV-infected injection drug users in Chennai, India.

BACKGROUND & OBJECTIVE: HIV-infected injection drugs users (IDUs) are known to have high rates of co-infections. A few reports exist on comorbidities among HIV-infected IDUs in India. We carried out a retrospective study to analyse data on comorbidities in India and treatment challenges faced when treating HIV-infected IDUs in India. METHODS: A retrospective chart review of 118 HIV-infected IDUs who accessed care at the YRG Centre for Substance Abuse-Related Research, Chennai, between August 2005 and February 2006 was done. Demographic, laboratory and clinical information was extracted from medical records. Descriptive demographic and clinical characteristics and distributions of comorbidities across CD4 cell count strata were analysed. RESULTS: All IDUs were male with a median age of 35.5 yr. The majority were married with average monthly income less than INR 3000 per month. The prevalence of hepatitis B and C infections were 11.9 and 94.1 per cent, respectively. Other common co-morbidities included oral candidiasis (43.2%), tuberculosis (33.9%), anaemia (22.9%), lower respiratory tract infections (16.1%), cellulitis (6.8%), herpes zoster (9.3%) and herpes simplex (9.3%). Among participants with CD4+ < 200 cells/microl, the prevalence of TB was 60 per cent. INTERPRETATION & CONCLUSION: IDUs in Chennai were commonly co-infected with HBV, HCV and tuberculosis, complicating use of antiretroviral and anti-tuberculous therapy. The current regimens available for the management of HIV and TB in India may need to be re-assessed for IDUs given the potential for increased rates of hepatotoxicity.

Risk factors for Kaposi's sarcoma in patients with advanced human immunodeficiency virus disease treated with zidovudine. Zidovudine Epidemiology Study Group.

BACKGROUND: Although the cause of Kaposi's sarcoma (KS) is unknown, its unique epidemiology suggests that an infectious, sexually transmitted agent or agents may contribute to its pathogenesis. METHODS: To assess the natural history of KS associated with the acquired immunodeficiency syndrome and to identify factors associated with its development, data were analyzed from a multicenter, observational cohort study of 1044 persons with the acquired immunodeficiency syndrome or the acquired immunodeficiency syndrome-related complex and a total CD4 cell count of less than 0.25 x 10(9)/L who were treated with zidovudine between April 1987 and April 1988. Records were reviewed bi-monthly. Follow-up continued for 2 years or until death. RESULTS: One hundred thirty-one patients (13%) had KS a study enrollment, and 143 developed KS (14%) during follow-up, with a 2-year actuarial risk of 21%. The probability of KS at 2 years for patients with initial CD4 cell counts of less than 0.1 x 10(9)/L was 25%, compared with 15% for those with counts of 0.1 x 10(9)/L or more. By logistic regression, a baseline CD4 cell count of less than 0.1 x 10(9)/L (relative odds, 1.43; 95% confidence interval, 1.04 to 1.95), homosexuality (relative odds, 3.71; 95% confidence interval, 1.82 to 7.56), cytomegalovirus disease (relative odds, 1.56; 95% confidence interval, 1.01 to 2.41), and white race (relative odds, 1.64; 95% confidence interval, 1.11 to 2.43) were independently associated with KS. Median survival after KS was 408 days, and KS was an independent predictor of death (relative hazard, 1.78; 95% confidence interval, 1.26 to 2.52). CONCLUSIONS: Kaposi's sarcoma contributes to human immunodeficiency virus-related morbidity and mortality, especially among male homosexuals. This large cohort study provides further evidence for an association between risk for cytomegalovirus infection and KS.

Efficacy of salvage therapy containing ritonavir and saquinavir after failure of single protease inhibitor-containing regimens.

OBJECTIVE: To assess the efficacy of salvage therapy containing ritonavir and saquinavir after failure of indinavir- or nelfinavir-containing regimens, and to determine correlates of success or failure. DESIGN: Retrospective chart review. SETTING. The Moore Clinic - the HIV clinic of Johns Hopkins Hospital. PATIENTS: Forty-one HIV-infected patients were identified through physician contacts, referrals from other providers, and review of a comprehensive clinical database. MAIN OUTCOME MEASURES: To determine response to salvage therapy, HIV-1 viral RNA (absolute and log10-transformed) was measured using the Roche Amplicor quantitative HIV-1 RNA assay after initiation of the salvage regimen. Potential correlates of response included: viral RNA at the time of switch; viral RNA at the time of switch as a percentage of baseline viral RNA; magnitude of decline in viral RNA; and the interval between virologic failure of single protease inhibitor therapy and switch to the salvage regimen. RESULTS: Thirteen (56.5%) of 23 patients failing indinavir responded to salvage therapy (HIV RNA < 400 copies/ml) with persistence throughout the follow-up period (median of 37 weeks; range 18-67 weeks). Mean absolute viral RNA at the time of switch was 20 238 copies/ml (median, 9281) compared with 42 953 copies/ml (median, 24 650) for the 10 non-responders. Mean log10 viral RNA at switch was 3.804 for responders versus 4.405 for non-responders (P = 0.040). Among four responders who had failed nelfinavir, mean viral RNA was 9634 copies/ml and mean log10 viral RNA was 3.749 at the time of switch. Two non-responders had a mean viral RNA of 21 551 and a mean log10 viral RNA of 4.037 at switch. CONCLUSIONS: In contrast with previous reports, salvage regimens containing ritonavir and/or saquinavir can be effective and durable following the failure of combination regimens containing either indinavir or nelfinavir. Salvage therapy may be more likely to succeed when it is initiated early in failure at low viral loads.

Diagnostic accuracy of three clinical case definitions for advanced HIV disease.

OBJECTIVE: To assess the accuracy of three clinical case definitions for advanced HIV disease: the World Health Organization (WHO) case definition, and the original and revised Caracas case definitions. DESIGN: Retrospective chart review. SETTING: A clinic for patients with all stages of HIV infection at the Johns Hopkins Hospital, Baltimore, [correction of Bethesda] Maryland, USA, a tertiary care university hospital. PATIENTS, PARTICIPANTS: Two hundred and twenty-four HIV-positive adults who underwent initial evaluation between 1 January 1990 and 31 December 1990. MAIN OUTCOME MEASURES: A score for each definition was assigned based on initial evaluation. The sensitivity, specificity, and predictive values were calculated using the Centers for Disease Control (CDC) staging criteria, and results were correlated with total CD4 cell counts. RESULTS: The sensitivities of the WHO, and the original and revised Caracas definitions were 40, 67, and 60%, respectively, using CDC disease stage IV as a positive standard. Specificities were between 99 and 100%, using CDC stage II-III disease as a negative standard. Mean CD4 cell counts for patients with positive scores were 184, 160, and 158 x 10(6)/l, respectively, compared to 191 x 10(6)/l for CDC stage IV patients. Sensitivity was lower when the positive standard was expanded to include all patients with CD4 cell counts less than 200 x 10(6)/l. CONCLUSIONS: In our study population, case definitions were specific, but only moderately sensitive for advanced HIV disease. Prospective studies should be conducted in diverse geographic regions, using lymphocyte or CD4 cell counts when possible.

PIP: The 1st case definition for AIDS was developed by the Centers for Disease Control (CDC) in 1982. WHO adopted CDC definitions for use in some countries and also developed a clinical case definition where HIV serology tests were not feasible. A multivariate analysis of data of Brazilian AIDS patients with positive HIV serology provided the basis for the Caracas definition in 1989 and it subsequent revision. The accuracy of these 3 clinical definitions was evaluated to see their predictive value in an advanced stage of AIDS. The records of 224 HIV-positive adults were reviewed in 1990. Scores were assigned to various symptoms. 80% of men and 20% of women with a median age of 33 years; 1/4 were white and 2/3 were black. 1/3 were homosexuals and 1.2 were iv drug users. 139 were asymptomatic (CDC stage I-II) and 85 were symptomatic (CDC stage IV). 58 patients had total CD4 cell counts of over 500 x 1 million/1; 91 had 200-500 x 1 million/l; and 70 had 200 x 1 million/1. 48 were taking zidovudine and Pneumocytis carinii drugs. The sensitivities of the WHO, original Caracas definition, and revised Caracas definition were 40%, 67%. and 60%, respectively, with 99-100% specificities and positive predictive values of 97-100%. The mean CD4 cell counts for the WHO, original and revised Caracas definitions were 184, 160, and 158 x 1 million/1, respectively, compared with 199 x 1 million/1 of patients with CDC stage IV disease. The predictive values of the 3 definitions for CD4 cell counts 200 x 1 million/1 reached 62%, 73%, and 71% vs. only 59% for CDC stage IV patients. The combination of stage IV symptoms or a CD4 cell count 200 x 1 million/1 produced sensitivities of 31%, 53%, and 47%, respectively, with 100% specificity and positive predictive values. The definitions were highly specific, but only moderately sensitive for advanced AIDS; the Caracas definitions were more sensitive than the WHO definition.

Impact of opportunistic disease on survival in patients with HIV infection.

OBJECTIVE: To assess the impact of opportunistic diseases on survival in patients with HIV disease. METHODS: A cohort of 2081 patients followed for a mean of 30 months was studied. Time-dependent Cox proportional hazards analyses were performed using incident opportunistic diseases and CD4 cell counts as independent variables. RESULTS: During follow-up, 730 (35%) patients died. The occurrence of Pneumocystis carinii pneumonia (PCP), cytomegalovirus (CMV) disease, Mycobacterium avium complex (MAC) disease, Candida esophagitis, Kaposi's sarcoma, lymphoma, progressive multifocal leukoencephalopathy (PML), dementia, wasting, toxoplasmosis, and cryptosporidiosis were all significantly associated with death, independently of CD4 cell count (all P<0.001 for opportunistic diseases controlling for CD4 cell count). The magnitude of increased risk was greatest for lymphoma [relative hazard (RH), 7.2], PML (RH, 3.9), MAC (RH, 3.0) and CMV (RH, 2.2). Cryptococcosis (RH, 0.94) and herpes zoster (RH, 0.85) were not associated with death. In a multivariate Cox proportional hazards analysis, MAC [RH, 2.56; 95% confidence interval (CI), 2.1-3.1], CMV (RH, 1.63; 95% CI, 1.3-2.1), toxoplasmosis (RH, 1.85; 95% CI, 1.3-2.6), PCP (RH, 1.29; 95% CI, 1.1-1.5), and CD4 cell count were significantly associated with death. Patients who had opportunistic diseases had significantly greatly monthly declines in CD4 counts (-11 x 10(6)/l per month) than those who did not (-6 x 10(6)/l per month; P <0.001). CONCLUSION: Most opportunistic diseases increase the risk of death independently of CD4 cell count. These data support the hypothesis that opportunistic diseases enhance HIV pathogenesis and further underscore the importance of prophylaxis.

Stavudine in zidovudine (ZDV)-experienced compared with ZDV-naive patients.

OBJECTIVE: To assess the effect of prior zidovudine (ZDV) use on subsequent response to stavudine (D4T)-containing regimens. DESIGN: Analysis of data from prospective observational database. METHODS: Patients were ZDV-experienced if they had previously received more than 90 days of ZDV and ZDV-naive if they had never received ZDV. HIV-1 RNA and CD4 cell counts were compared at 3, 6, and 12 months after initiation of D4T. Univariate and multivariate analyses were performed, adjusting for baseline HIV-1 RNA and CD4 cell count, age, sex, race, HIV transmission category, time since enrollment, and protease inhibitor use. RESULTS: No difference was found between ZDV-experienced (n = 130) and naive (n = 98) patients in age, sex, race, transmission category, use of a concurrent protease inhibitor, or baseline CD4 cell count and HIV-1 RNA. There was no difference in the median decline in HIV-1 RNA (-1.29 log10 copies/ml for experienced patients versus -1.19 log10 copies/ml for naive patients; P = 0.39), in achieving HIV-1 RNA < 400 copies/ml at 3 months (51% versus 49%; P = 0.79) or 6 months (48% versus 56%; P = 0.33). There was no difference in CD4 cell response (+73 x 10(6)/l versus + 87 x 10(6)/l; P = 0.51). By multivariate adjustment in a repeated measures analysis, there was no significant difference in achieving undetectable HIV-1 RNA or in CD4 cell response between experienced and naive patients. CONCLUSION: No difference in response to a D4T-containing regimen between ZDV-experienced and naive patients was found over a 1-year period. In contrast to previous trials, most patients in this study also received a protease inhibitor. These findings may be more relevant in the current era of highly active antiretroviral therapy.

Impact of the 1993 revision of the AIDS case definition on the prevalence of AIDS in a clinical setting.

OBJECTIVE: To determine the impact of the 1993 revision of the Centers for Disease Control and Prevention (CDC) AIDS surveillance case definition on the prevalence of AIDS. DESIGN: Review of prospectively collected baseline clinical and demographic data on HIV-infected patients presenting for care between December 1988 and May 1991. SETTING: The HIV Clinic of the Johns Hopkins Hospital, an urban, primary care institution. MAIN OUTCOME MEASURE: Diagnosis of AIDS by the 1987 (specific indicator diseases) or the 1993 (indicator diseases, pulmonary tuberculosis, recurrent bacterial pneumonia, cervical carcinoma, or CD4 lymphocyte count < 200 x 10(6)/l) CDC case definition. RESULTS: Of 955 patients evaluated, 122 (13%) had AIDS by the 1987 case definition at presentation. An additional 126 (13%) met the 1993 but not the 1987 case definition. Patients meeting only the 1993 case definition were more likely to be female [28 versus 14%; odds ratio (OR), 2.4; 95% confidence interval (CI), 1.2-3.0; P = 0.01] and intravenous drug users (40 versus 26%; OR, 2.0; 95% CI, 1.1-3.3; P = 0.02) than patients meeting the 1987 case definition. Fifty-five per cent of patients meeting only the 1993 case definition were asymptomatic, and 7% (nine patients) had new indicator diseases but CD4 counts > 200 x 10(6)/l. Median time to progression from a diagnosis of AIDS by the 1993 case definition to diagnosis by the 1987 case definition was 435 days. Patients with AIDS by the 1987 case definition had a median survival of 594 days from presentation (2-year survival, 42%), while median survival time for patients with AIDS by the 1993 case definition only was 947 days (2-year survival, 60%; P < 0.005). CONCLUSIONS: The proposed 1993 revision of the AIDS surveillance case definition would double the number of prevalent AIDS cases, with significant increases in the proportion of cases who are female, intravenous drug users, or asymptomatic. Survival of patients meeting the 1993 case definition is significantly longer than that of patients meeting the 1987 case definition. The new AIDS case definition will have a major impact both on AIDS surveillance and on medical and social service programs that use diagnosis of AIDS as a criterion for eligibility for services.

Time to initiating highly active antiretroviral therapy among HIV-infected injection drug users.

OBJECTIVE: Studies have shown that HIV-infected injection drug users (IDUs) are less likely to receive antiretroviral therapy than non-drug users. We assess factors associated with initiating highly active antiretroviral therapy (HAART) in HIV-infected IDUs. METHODS: A cohort study of IDUs carried out between 1 January 1996 and 30 June 1999 at a community-based study clinic affiliated to the Johns Hopkins University, Baltimore, Maryland. The participants were a total of 528 HIV-infected IDUs eligible for HAART based on CD4+ cell count. The main outcome measure was the time from treatment eligibility to first self-reported HAART use, as defined by the International AIDS Society-USA panel (IAS-USA) guidelines. RESULTS: By 30 June 1999, 58.5% of participants had initiated HAART, most of whom switched from mono- or dual-combination therapy to a HAART regimen. Nearly one-third of treatment-eligible IDUs never received antiretroviral therapy. Cox proportional hazards regression showed that initiating HAART was independently associated with not injecting drugs, methadone treatment among men, having health insurance and a regular source of care, lower CD4+ cell count and a history of antiretroviral therapy. CONCLUSIONS: Self-reported initiation of HAART is steadily increasing among IDUs who are eligible for treatment; however, a large proportion continues to use non-HAART regimens and many remain treatment-naive. Although both groups appear to have lower health care access and utilization, IDUs without a history of antiretroviral therapy use would have more treatment options available to them once they become engaged in HIV care.

Comparative studies of two-times-daily versus three-times-daily indinavir in combination with zidovudine and lamivudine.

OBJECTIVES: To compare the efficacy and safety of two-times-daily versus three-times-daily indinavir in combination with zidovudine and lamivudine. DESIGN: Two multicenter, open-label, randomized 24-week studies. METHODS: Adults HIV-1 infection, HIV-1 RNA greater than 10000 copies/ml, and no prior lamivudine or protease inhibitor therapy were eligible. In a pilot study (Study A), patients received indinavir at 800 mg every 8 h, 1000 mg every 12 h, or 1200 mg every 12 h. In a subsequent study (Study B), patients received indinavir at 800 mg every 8 h or 1200 mg every 12 h. All subjects received zidovudine (300 mg) and lamivudine (150 mg) every 12 h. An intent-to-treat analysis was used. RESULTS: In Study A, which enrolled 88 patients, neither HIV-1 RNA nor CD4 cell responses differed significantly between treatment groups at 24 weeks when corrected for multiple comparisons. Study B enrolled 433 patients, but was prematurely discontinued when interim analysis suggested greater efficacy of three-times-daily indinavir. Of the first 87 patients reaching week 24, HIV-1 RNA was less than 400 copies/ml in 91% receiving three-times-daily versus 64% receiving two-times-daily indinavir (P < 0.01). CONCLUSION: Three-times-daily indinavir appears more efficacious than two-times-daily dosing when administered with zidovudine and lamivudine. Two-times-daily indinavir dosing should only be considered in situations characterized by favorable pharmacokinetic drug-drug interactions.

Acyclovir in combination with zidovudine does not prolong survival in advanced HIV disease.

The aim of this study was to evaluate the association between acyclovir use and survival in HIV-infected patients. To achieve this, we used survival analysis in an observational cohort of HIV-infected patients enrolled in primary care at an urban HIV clinic. We measured survival in a cohort of HIV-infected patients who had CD4 cell counts < or = 500/mm3 and who enrolled for care at a single urban HIV clinic between December 1988 and April 1995. We compared survival in users of acyclovir alone, zidovudine alone, and acyclovir and zidovudine in combination with the survival of those using neither drug. Factors associated with improved survival were identified using Cox proportional hazards analysis. Among the 1408 patients enrolled, there were no significant differences in overall survival between acyclovir users and non-users. After adjustment for CD4 cell count, the use of other antiretroviral agents, race, transmission risk and a history of herpesvirus infection, acyclovir use alone was independently associated with a relative hazard (RH) of death of 1.008 (P = 0.969); zidovudine use alone with a RH of 0.559 (P < 0.001); and combination use of acyclovir and zidovudine associated with a RH of 1.062 (P = 0.788). Therefore we conclude that the use of acyclovir is not associated with prolonged survival in this cohort of HIV-infected patients.

Pneumocystis carinii thyroiditis.

A 38-year-old black man with a history of acquired immunodeficiency syndrome associated with intravenous drug abuse presented with two weeks of left-sided neck swelling. Results of thyroid function tests were within normal limits. Thyroid scan demonstrated nonvisualization of the left lobe. Fine-needle aspiration of the thyroid revealed the presence of Pneumocystis carinii organisms in the thyroid tissue. Although chest radiography and computerized tomography of the chest detected several nodules and cavitary lesions, the results of bronchoalveolar lavage and transbronchial biopsy were negative for P. carinii. The patient showed a response to treatment with trimethoprim/sulfamethoxazole. Thyroidal involvement with P. carinii has previously been documented only in the setting of overwhelming, fatal pulmonary infection. The current case expands the clinical spectrum of extrapulmonary pneumocystosis and documents its successful treatment.

Oropharyngeal candidiasis in patients with HIV: suggested guidelines for therapy.

The high frequency of oropharyngeal candidiasis in immunocompromised patients has led many institutions to develop protocols to guide the use of antifungal agents in the treatment of this opportunistic infection. However, few specific recommendations have been made for directing the management of oropharyngeal candidiasis in patients infected with HIV. To meet this need, a panel of experts representing a variety of disciplines met to formulate a consensus and devise a treatment strategy for clinical application. Among other recommendations, the algorithm calls for use of a topical agent for the treatment of initial and recurring oropharyngeal candidiasis in HIV-infected patients, provided there is no esophageal involvement, patients' CD4+ lymphocyte cell count is >50 cells/mm3, and they are currently receiving or expected to receive effective antiretroviral treatment. For episodes of oropharyngeal candidiasis with concurrent esophageal involvement or where patients have a CD4+ cell count of <50 cells/mm3, are not receiving or anticipating highly active antiretroviral therapy (HAART), and have a high viral load, the algorithm suggests a systemic oral azole as the more appropriate treatment choice. Acute treatment of all oropharyngeal candidiasis episodes is preferred. Chronic suppressive antifungal treatment is to be avoided in recognition of the potential for the development of drug-resistant infection.

The effect of adjunctive corticosteroids for the treatment of Pneumocystis carinii pneumonia on mortality and subsequent complications.

OBJECTIVE: To assess the long-term safety of adjunctive corticosteroids in the treatment of Pneumocystis carinii pneumonia (PCP). DESIGN: Analysis of data from a large prospective observational database. SETTING: HIV clinic at a large urban teaching hospital. PATIENTS: One hundred seventy-four patients who developed PCP after being enrolled in the database. RESULTS: Fifty-three patients (30%) received adjunctive corticosteroids and 121 (70%) did not. Survival did not differ between groups after adjusting for CD4 count (relative risk for adjunctive corticosteroids = 0.74, p = 0.13). There were no differences in the incidence of cytomegalovirus disease (adjunctive corticosteroids: 18.5 cases per 100 person-years vs no adjunctive corticosteroids: 15.7, p = 0.22), Mycobacterium avium complex (23.4 vs 27.0, p = 0.73), cryptococcal meningitis (1.8 vs 4.1, p = 0.58), toxoplasmosis (3.6 vs 11.0, p = 0.28), Kaposi's sarcoma (1.8 vs 2.2, p = 0.92), herpes simplex (27.1 vs 42.7, p = 0.66), herpes zoster (3.8 vs 6.9, p = 0.71), oropharyngeal candidiasis (18.9 vs 10.9, p = 0.09), or non-Hodgkin's lymphoma (3.5 vs 4.2, p = 0.92). Esophageal candidiasis was more common among adjunctive corticosteroid recipients (45.1 vs 26.6, p = 0.01). Results were similar for time to development of opportunistic conditions. CONCLUSIONS: Adjunctive corticosteroids do not increase mortality or the risk of most common HIV-associated complications.

The impact of prophylaxis on outcome and resource utilization in Pneumocystis carinii pneumonia.

STUDY OBJECTIVE: Pneumocystis carinii pneumonia (PCP) is a major late complication of HIV infection associated with morbidity and mortality. Because chemoprophylaxis is highly effective, cases of PCP can be viewed as failures in the management of HIV disease. METHODS: We reviewed demographic, clinical, and cost data for all cases of confirmed HIV-related PCP at The Johns Hopkins Hospital in 1991 to determine consequences of missed prophylaxis. We also analyzed hospital discharge data for Maryland in 1991 to assess hospital charges, length of stay, and outcome for all patients with a principal diagnosis of HIV-related PCP. RESULTS: Pneumocystis carinii pneumonia was diagnosed in 79 patients. Of the 79 patients, 61 (77%) did not receive prophylaxis, including 26 who were not previously known to have HIV infection, 17 who did not have prophylaxis prescribed, and 18 who had prophylaxis prescribed, but were not compliant with the regimen. Patients not taking prophylaxis accounted for all 12 deaths ascribed to PCP. This group also accounted for 85% of the hospital days, 100% of the ICU days, and 89% of the inpatient charges. The total hospital charges were $849,540. Extrapolation of these figures for the state of Maryland suggest that the failure to receive prophylaxis in 1991 resulted in 62 patient deaths and a cost of approximately $4.7 million. CONCLUSION: Patients who developed PCP despite prophylaxis had a better outcome and used fewer resources than patients not receiving preventive therapy. This study emphasizes the impact of PCP prophylaxis on the morbidity, mortality, and economics of HIV health care.

Efficacy of nelfinavir in patients switched from ritonavir/saquinavir combination antiretroviral therapy.

UNLABELLED: Based on available data and expert opinion, the IAS-USA treatment guidelines recommend "selective substitution" of the medication thought most likely to be causing a side effect for one that should have a different side effect profile. PURPOSE: This study evaluates the short-term virological efficacy of selective substitution with nelfinavir-nucleoside combination therapy in individuals with plasma viral RNA below 400 copies/mL. METHOD: This study involved a retrospective chart review at five large urban HIV Clinical practice settings and included 19 patients taking combination therapy including ritonavir with saquinavir. We performed selective substitution with a nelfinavir combination. Our main outcome measure was plasma HIV-1 RNA (Amplicor) obtained during the period between weeks 12 to 18. RESULTS: We identified 19 HIV-1-infected individuals with evidence of viral suppression as defined by a viral load below 400 copies/mL while taking dual nucleoside reverse transcriptase inhibitors with ritonavir/saquinavir. Reasons for switching included adverse effects (37%) or preference for nelfinavir due to the possibility of a better defined salvage regimen (63%). We defined a composite viral endpoint indicative of continued viral suppression using the first 12 to 18 weeks following the medication change. We found that 73% maintained undetectable viral loads (plasma HIV RNA below 400 copies/mL) during this period. CONCLUSION: These data suggest that any medication adjustment should be made cautiously, as there may be some potential risk in a substitution. Selective substitution of a medication that has undesirable side effects or other characteristics should be considered when the possible risks of the loss of viral suppression are outweighed by the potential benefits of that substitution.

Infectious complications of HIV disease.

HIV disease is associated with a wide variety of infections caused by bacteria, viruses, parasites, and fungi. Although some infections occur only in patients with very low CD4 cell counts, others require only mild to moderate immunosuppression. This article discusses the opportunistic infections associated with HIV disease and reviews their clinical presentation, diagnosis, treatment, and prevention, with an emphasis on emergency department diagnosis and management.

Antiretroviral therapy in the treatment-experienced patient.

Despite the growing number of new antiretroviral agents, planning therapy for treatment-experienced patients remains extremely challenging. Cross-resistance within the three currently available classes of drugs limits the number of sequential drug regimens that can be expected to suppress viral replication effectively. An understanding of resistance and cross-resistance, together with judicious use of resistance testing, can help clinicians design better treatment regimens for patients experiencing virologic failure while taking antiretroviral therapy.

A review of dual protease inhibitor therapy.

AIDS: The 1998 Retrovirus Conference in Chicago presented what is known about specific dual-protease inhibitor (PI) therapies. The effectiveness of the following therapies are highlighted: ritonavir/saquinavir, nelfinavir/saquinavir, ritonavir/indinavir, indinavir/saquinavir, amprenavir in dual-protease inhibitor combinations, and ABT-378/ritonavir. Growing evidence supports the use of dual PIs in treating HIV disease. Effectiveness is enhanced when they are combined with reverse transcriptase inhibitors. Ritonavir/saquinavir is the therapy of choice so far, particularly for salvage therapy. Less support is found for nelfinavir/saquinavir, following the failure of other PIs. Failure on dual PI therapy is likely to cause extensive cross-resistance within the PI class. Therefore, caution is warranted in using dual PI therapy in patients who have problems with adherence.^ieng

Antiretroviral news.

AIDS: The 12th World AIDS Conference in Geneva explored issues associated with the use of antiretrovirals and resistance. Areas examined included resistance to new antiretroviral agents, the use of Hydroxyurea as a standard therapy, novel dosing strategies, new antiretroviral agents, and dual protease inhibitor therapy. Major conference themes involving antiretroviral resistance examined resistance profiles of new antiretroviral agents, cross-resistance within and across drug classes, the use of genotype and phenotype analysis, and the transmission of multi-drug resistant virus. While information on salvage therapy remains disappointing, it is noted that several ongoing trials are continuing to address the issue.^ieng

Antiretroviral therapy: rehashes, leftovers, and a pinch of new data.

AIDS: The 38th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) presented a number of updates and important highlights. The target cell availability hypothesis was one of the most provocative subjects discussed, with some trial results implying that early therapy, initiated when the target cells are plentiful, could increase the probability of drug failure. Other studies supported deferral of therapy for chronically infected individuals, citing the issues of adherence and drug resistance as reasons for delaying the start of aggressive treatment. Presentations also addressed current drug studies, protease inhibitor dosing, and salvage therapies.^ieng