PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-3 (3)
 

Clipboard (0)
None

Select a Filter Below

Journals
Authors
more »
Year of Publication
Document Types
1.  Switching HIV Treatment in Adults Based on CD4 Count Versus Viral Load Monitoring: A Randomized, Non-Inferiority Trial in Thailand 
PLoS Medicine  2013;10(8):e1001494.
Using a randomized controlled trial, Marc Lallemant and colleagues ask if a CD4-based monitoring and treatment switching strategy provides a similar clinical outcome compared to the standard viral load-based strategy for adults with HIV in Thailand.
Please see later in the article for the Editors' Summary
Background
Viral load (VL) is recommended for monitoring the response to highly active antiretroviral therapy (HAART) but is not routinely available in most low- and middle-income countries. The purpose of the study was to determine whether a CD4-based monitoring and switching strategy would provide a similar clinical outcome compared to the standard VL-based strategy in Thailand.
Methods and Findings
The Programs for HIV Prevention and Treatment (PHPT-3) non-inferiority randomized clinical trial compared a treatment switching strategy based on CD4-only (CD4) monitoring versus viral-load (VL). Consenting participants were antiretroviral-naïve HIV-infected adults (CD4 count 50–250/mm3) initiating non-nucleotide reverse transcriptase inhibitor (NNRTI)-based therapy. Randomization, stratified by site (21 public hospitals), was performed centrally after enrollment. Clinicians were unaware of the VL values of patients randomized to the CD4 arm. Participants switched to second-line combination with confirmed CD4 decline >30% from peak (within 200 cells from baseline) in the CD4 arm, or confirmed VL >400 copies/ml in the VL arm. Primary endpoint was clinical failure at 3 years, defined as death, new AIDS-defining event, or CD4 <50 cells/mm3. The 3-year Kaplan-Meier cumulative risks of clinical failure were compared for non-inferiority with a margin of 7.4%. In the intent to treat analysis, data were censored at the date of death or at last visit. The secondary endpoints were difference in future-drug-option (FDO) score, a measure of resistance profiles, virologic and immunologic responses, and the safety and tolerance of HAART. 716 participants were randomized, 356 to VL monitoring and 360 to CD4 monitoring. At 3 years, 319 participants (90%) in VL and 326 (91%) in CD4 were alive and on follow-up. The cumulative risk of clinical failure was 8.0% (95% CI 5.6–11.4) in VL versus 7.4% (5.1–10.7) in CD4, and the upper-limit of the one-sided 95% CI of the difference was 3.4%, meeting the pre-determined non-inferiority criterion. Probability of switch for study criteria was 5.2% (3.2–8.4) in VL versus 7.5% (5.0–11.1) in CD4 (p = 0.097). Median time from treatment initiation to switch was 11.7 months (7.7–19.4) in VL and 24.7 months (15.9–35.0) in CD4 (p = 0.001). The median duration of viremia >400 copies/ml at switch was 7.2 months (5.8–8.0) in VL versus 15.8 months (8.5–20.4) in CD4 (p = 0.002). FDO scores were not significantly different at time of switch. No adverse events related to the monitoring strategy were reported.
Conclusions
The 3-year rates of clinical failure and loss of treatment options did not differ between strategies although the longer-term consequences of CD4 monitoring would need to be investigated. These results provide reassurance to treatment programs currently based on CD4 monitoring as VL measurement becomes more affordable and feasible in resource-limited settings.
Trial registration
ClinicalTrials.gov NCT00162682
Please see later in the article for the Editors' Summary
Editors' Summary
Background
About 34 million people (most of them living in low-and middle-income countries) are currently infected with HIV, the virus that causes AIDS. HIV infection leads to the destruction of immune system cells (including CD4 cells, a type of white blood cell), leaving infected individuals susceptible to other infections. Early in the AIDS epidemic, most HIV-infected individuals died within 10 years of infection. Then, in 1996, highly active antiretroviral therapy (HAART)—combined drugs regimens that suppress viral replication and allow restoration of the immune system—became available. For people living in affluent countries, HIV/AIDS became a chronic condition but, because HAART was expensive, HIV/AIDS remained a fatal illness for people living in resource-limited countries. In 2003, the international community declared HIV/AIDS a global health emergency and, in 2006, it set the target of achieving universal global access to HAART by 2010. By the end of 2011, 8 million of the estimated 14.8 million people in need of HAART in low- and middle-income countries were receiving treatment.
Why Was This Study Done?
At the time this trial was conceived, national and international recommendations were that HIV-positive individuals should start HAART when their CD4 count fell below 200 cells/mm3 and should have their CD4 count regularly monitored to optimize HAART. In 2013, the World Health Organization (WHO) recommendations were updated to promote expanded eligibility for HAART with a CD4 of 500 cells/mm3 or less for adults, adolescents, and older children although priority is given to individuals with CD4 count of 350 cells/mm3 or less. Because HIV often becomes resistant to first-line antiretroviral drugs, WHO also recommends that viral load—the amount of virus in the blood—should be monitored so that suspected treatment failures can be confirmed and patients switched to second-line drugs in a timely manner. This monitoring and switching strategy is widely used in resource-rich settings, but is still very difficult to implement for low- and middle-income countries where resources for monitoring are limited and access to costly second-line drugs is restricted. In this randomized non-inferiority trial, the researchers compare the performance of a CD4-based treatment monitoring and switching strategy with the standard viral load-based strategy among HIV-positive adults in Thailand. In a randomized trial, individuals are assigned different interventions by the play of chance and followed up to compare the effects of these interventions; a non-inferiority trial investigates whether one treatment is not worse than another.
What Did the Researchers Do and Find?
The researchers assigned about 700 HIV-positive adults who were beginning HAART for the first time to have their CD4 count (CD4 arm) or their CD4 count and viral load (VL arm) determined every 3 months. Participants were switched to a second-line therapy if their CD4 count declined by more than 30% from their peak CD4 count (CD4 arm) or if a viral load of more than 400 copies/ml was recorded (VL arm). The 3-year cumulative risk of clinical failure (defined as death, a new AIDS-defining event, or a CD4 count of less than 50 cells/mm3) was 8% in the VL arm and 7.4% in the CD4 arm. This difference in clinical failure risk met the researchers' predefined criterion for non-inferiority. The probability of a treatment switch was similar in the two arms, but the average time from treatment initiation to treatment switch and the average duration of a high viral load after treatment switch were both longer in the CD4 arm than in the VL arm. Finally, the future-drug-option score, a measure of viral drug resistance profiles, was similar in the two arms at the time of treatment switch.
What Do These Findings Mean?
These findings suggest that, in Thailand, a CD4 switching strategy is non-inferior in terms of clinical outcomes among HIV-positive adults 3 years after beginning HAART when compared to the recommended viral load-based switching strategy and that there is no difference between the strategies in terms of viral suppression and immune restoration after 3-years follow-up. Importantly, however, even though patients in the CD4 arm spent longer with a high viral load than patients in the VL arm, the emergence of HIV mutants resistant to antiretroviral drugs was similar in the two arms. Although these findings provide no information about the long-term outcomes of the two monitoring strategies and may not be generalizable to routine care settings, they nevertheless provide reassurance that using CD4 counts alone to monitor HAART in HIV treatment programs in resource-limited settings is an appropriate strategy to use as viral load measurement becomes more affordable and feasible in these settings.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001494.
The World Health Organization provides information on all aspects of HIV/AIDS (in several languages); its 2010 recommendations for antiretroviral therapy for HIV infection in adults and adolescents are available as well as the June 2013 Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach
The 2012 UNAIDS World AIDS Day Report provides up-to-date information about the AIDS epidemic and efforts to halt it
Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS
NAM/aidsmap provides basic information about HIV/AIDS and summaries of recent research findings on HIV care and treatment
Information is available from Avert, an international AIDS charity on many aspects of HIV/AIDS, including information on the global HIV/AIDS epidemic, on HIV and AIDS in Thailand, on universal access to AIDS treatment, and on starting, monitoring and switching HIV treatment (in English and Spanish)
The UK National Health Service Choices website provides information (including personal stories) about HIV and AIDS
More information about this trial (the PHPT-3 trial) is available
Patient stories about living with HIV/AIDS are available through Avert; the nonprofit website Healthtalkonline also provides personal stories about living with HIV, including stories about HIV treatment
doi:10.1371/journal.pmed.1001494
PMCID: PMC3735458  PMID: 23940461
2.  Effects of long-term use of HAART on oral health status of HIV-infected subjects 
BACKGROUND
The aim of this study was to determine the effects of long-term use of highly active antiretroviral therapy (HAART) on oral health status of HIV-infected subjects.
METHODS
Oral examination and measurement of saliva flow rate of both unstimulated and wax-stimulated whole saliva were performed in HIV-infected subjects with and without HAART, and in non-HIV individuals. The following data were recorded; duration and risk of HIV infection, type and duration of HAART, CD4 cell count, viral load, presence of orofacial pain, oral dryness, oral burning sensation, oral lesions, cervical caries, and periodontal pocket. Multiple logistic regression analysis was performed to determine the effects of long-term use of HAART on oral health status of HIV-infected subjects. RESULTS: One hundred and fifty-seven HIV-infected subjects – 99 on HAART (age range 23–57 years, mean 39 years) and 58 not on HAART (age range 20–59 years, mean 34 years) – and 50 non-HIV controls (age range 19–59 years, mean 36 years) were enrolled. The most common HAART regimen was 2 NRTI + 2 NNRTI. HIV-infected subjects without HAART showed greater risks of having orofacial pain, oral dryness, oral lesions, and periodontal pockets than those with short-term HAART (P < 0.01). The subjects with long-term HAART were found to have a greater risk of having oral lesions than those with short-term HAART (P < 0.05). The unstimulated and stimulated salivary flow rates of the subjects with HAART were significantly lower than in those without HAART (P < 0.05).
CONCLUSION
We conclude that long-term HAART has adverse effects on oral health status of HIV-infected subjects.
doi:10.1111/j.1600-0714.2009.00875.x
PMCID: PMC3217232  PMID: 20202089
HAART; HIV; oral health; oral lesion; risk factor; salivary flow rate
3.  Detection of HIV-1 DNA resistance mutations by a sensitive assay at initiation of antiretroviral therapy is associated with virologic failure 
Background
Antiretroviral therapy (ART) has become more available throughout the developing world during the past five years. The World Health Organization recommends nonnucleoside reverse transcriptase inhibitor-based regimens as initial ART. However, their efficacy may be compromised by resistance mutations selected by single-dose nevirapine (sdNVP) used to prevent mother-to-child-transmission of HIV-1 (PMTCT). There is no simple and efficient method to detect such mutations at initiation of ART.
Methods
181 women participating in a PMTCT clinical trial who started NVP-ART after they had received sdNVP or placebo were tested for nevirapine-resistance point-mutations (K103N, Y181C, and G190A) using 100 copies of HIV-1 DNA with a sensitive oligonucleotide ligation assay (OLA) able to detect mutants at low concentrations (≥5% of the viral population). Virologic failure was defined as plasma HIV-1 RNA confirmed >50 copies/mL between 6–18 months of NVP-ART.
Results
At initiation of NVP-ART, resistance mutations were identified in 26% of 148 participants given sdNVP (K103N-13%, Y181C-5%, G190A-19%; ≥2 mutations-10%) at a median 9.3 months after sdNVP. The risk of virologic failure was .62 (95% confidence interval (CI), 0.46–0.77) in women with ≥1 resistance mutation, compared to 0.25 (95% CI, 0.17–0.35) in those without detectable resistance mutations (P<.0001). Failure was independently associated with resistance, an interval of <6 months between sdNVP and NVP-ART initiation, and a viral load above the median at NVP-ART initiation.
Conclusions
Access to simple and inexpensive assays to detect low-concentrations of NVP-resistant HIV-1 DNA prior to the initiation of ART could help improve the outcome of first-line antiretroviral therapy.
doi:10.1086/652148
PMCID: PMC2856716  PMID: 20377404
HIV-1; resistance mutations; nevirapine; HAART; oligonucleotide ligation assay; developing countries

Results 1-3 (3)