Reducing HIV-associated post-hospital mortality through home-based care in South Africa: a randomized controlled trial.

BACKGROUND: Twenty-three percent of people with HIV (PWH) die within 6-months of hospital discharge. We tested the hypothesis whether a series of structured home visits could reduce mortality. METHODS: We designed a disease neutral home visit package with up to 6 home visits starting 1-week post-hospitalization and every 2 weeks thereafter. The home visit team used a structured assessment algorithm to evaluate and triage social and medical needs of the participant and provide nutritional support. We compared all-cause mortality 6-months following discharge for the intervention compared to usual care in a pilot randomized trial conducted in South Africa. To inform potential scale-up we also included and separately analyzed a group of people without HIV (PWOH). RESULTS: We enrolled 125 people with HIV and randomized them 1:1 to the home visit intervention or usual care. Fourteen were late exclusions because of death prior to discharge or delayed discharge leaving 111 for analysis. The median age was 39 years, 31% were men; and 70% had advanced HIV disease. At six months among PWH 4 (7.3%) in the home visit arm and 10 (17.9%) in the usual care arm (p = 0.09) had died. Among the 70 PWOH enrolled overall 6-month mortality was 10.1%. Of those in the home visit arm, 91% received at least one home visit. CONCLUSIONS: We demonstrated feasibility of delivering post-hospital home visits and demonstrated preliminary efficacy among PWH with a substantial, but not statistically significant, effect size (59% reduction in mortality). COVID-19 related challenges resulted in under-enrollment.

Fatal Case of Heartland Virus Disease Acquired in the Mid-Atlantic Region, United States.

Heartland virus (HRTV) disease is an emerging tickborne illness in the midwestern and southern United States. We describe a reported fatal case of HRTV infection in the Maryland and Virginia region, states not widely recognized to have human HRTV disease cases. The range of HRTV could be expanding in the United States.

Opioid use and HIV treatment services experiences among male criminal justice-involved persons in South Africa: a qualitative study.

BACKGROUND: Opioid use disorder (OUD) is overrepresented among people with criminal justice involvement; HIV is a common comorbidity in this population. This study aimed to examine how formerly incarcerated men living with HIV and OUD in South Africa experienced HIV and OUD services in correctional facilities and the community. METHODS: Three focus group discussions were conducted with 16 formerly incarcerated men living with HIV and OUD in Gauteng, South Africa. Discussions explored available healthcare services in correctional facilities and the community and procedural and practice differences in health care between the two types of settings. Data were analyzed thematically, using a comparative lens to explore the relationships between themes. RESULTS: Participants described an absence of medical services for OUD in correctional facilities and the harms caused by opioid withdrawal without medical support during incarceration. They reported that there were limited OUD services in the community and that what was available was not connected with public HIV clinics. Participants perceived correctional and community HIV care systems as readily accessible but suggested that a formal system did not exist to ensure care continuity post-release. CONCLUSIONS: OUD was perceived to be medically unaddressed in correctional facilities and marginally attended to in the community. In contrast, HIV treatment was widely available within the two settings. The current model of OUD care in South Africa leaves many of the needs of re-entrants unmet. Integrating harm reduction into all primary care medical services may address some of these needs. Successful HIV care models provide examples of approaches that can be applied to developing and expanding OUD services in South Africa.

Social support needs of HIV-positive individuals reentering community settings from correctional facilities in Johannesburg, South Africa.

Social networks and social support are important factors in medication adherence among people living with HIV (PLWH). Social networks can provide emotional, logistic, and material support leading to increased overall engagement in care. Certain populations of PLWH may have more limited access to social support, including those reentering community settings from correctional facilities. During periods of incarceration, social connections with family and friends may be frayed, reduced, or lost. This study, conducted in South Africa, explored the role of social support during community reentry among PLWH being released from correctional facilities. We conducted in-depth interviews with 41 community reentrants living with HIV. Qualitative analysis identified the challenges with establishing social support during reentry and the greater need for social support to remain engaged in HIV care in the community compared to in the correctional facility. These findings highlight challenges during community reentry and the importance of social support for these individuals.

"That makes me feel human": a qualitative evaluation of the acceptability of an HIV differentiated care intervention for formerly incarcerated people re-entering community settings in South Africa.

BACKGROUND: Correctional settings in South Africa have disproportionately high rates of HIV infection; a large number of inmates living with HIV return to the community each year. The transition community adherence club (TCAC) intervention was a differentiated care delivery approach with structural and peer components designed to increase antiretroviral therapy (ART) adherence and HIV care engagement following release from incarceration. The objective of this study was to assess the acceptability of the TCAC intervention among HIV-infected community re-entrants to inform program revisions and future intervention designs. METHODS: This was a qualitative study set within a randomized controlled trial (RCT) of the TCAC intervention in South Africa. We conducted semi-structured, in-depth interviews with 16 re-entrants living with HIV and assigned to the intervention arm. All interviews were audio-recorded, transcribed, translated, and de-identified. Transcripts were coded and analyzed using content analysis, and acceptability was assessed using the Theoretical Framework of Acceptability (TFA). RESULTS: Overall, study participants reported that the TCAC intervention was acceptable. Development of supportive relationships between participants, non-judgmental attitudes from peer-facilitators, and perceived effectiveness of the intervention to support ART adherence and HIV care were noted as the most valued components. An altruistic desire to help other participants facing similar post-incarceration and HIV-related challenges was a key motivator for TCAC attendance. A lack of access to reliable transportation to intervention sites and clinic-based medication collection were described as burdens to program participation. Illicit drug use by other group members and negative social influences were also identified as potential barriers to optimal program engagement. CONCLUSION: The TCAC was a well-accepted model of differentiated care delivery among re-entrants living with HIV in South Africa. To further enhance intervention acceptability for future scale-ups, program revisions should address logistical barriers related to reaching TCAC sites and implementing ART distribution at TCAC group sessions.

Is HIV Post-test Counselling Aligned with Universal Test and Treat Goals? A Qualitative Analysis of Counselling Session Content and Delivery in South Africa.

Early identification of people living with HIV (PLHIV) and subsequent engagement into HIV treatment is a key to reducing HIV-related illness, HIV-related deaths, and HIV transmission through universal test and treat approaches. With the scale-up of antiretroviral therapy (ART) programmes, counselling that is provided immediately after the diagnosis of HIV (post-test counselling) is well placed to facilitate linkage to care and ART initiation. We sought to assess whether the current delivery of post-test counselling in a routine HIV programme was aligned with the goals of universal test and treat as articulated in local and international HIV testing service guidelines. We analysed transcripts of 40 post-test counselling sessions for HIV-positive clients, performed by 34 counsellors in ten public sector health facilities in the Ekurhuleni District of South Africa. We used thematic analysis to identify key aspects of counselling techniques and content provided to the client. We identified five key themes of counselling messages: (1) specific behaviour changes that are required to maintain or improve health when living with HIV, (2) the benefits of ART, (3) behaviour changes required for ART to be effective, (4) the need for clients to disclose their HIV status, and (5) a need for caution with ART due to a wide range of severe side effects. The counselling sessions were highly didactic, which limited the opportunities for clients to express concerns or counsellors to address client's needs during the counselling session. Based on our observations, a substantial re-adjustment is needed to deliver best-practice counselling. This may include a combination of digital media-based counselling, counselling scripts, and truly client-centred counselling for a sub-set of individuals who are at risk of not linking to care, or not initiated ART within a specified period.

Youth Preferences for HIV Testing in South Africa: Findings from the Youth Action for Health (YA4H) Study Using a Discrete Choice Experiment.

We conducted a discrete choice experiment (DCE) and quantified preferences for HIV testing among South African youth (Nov 2018 to Mar 2019). Six attributes and levels were identified through qualitative methods: source of HIV information; incentive amount and type; social support; testing method; and location. Each participant chose one of two options that comprised six attributes across 18 questions. Conditional logistic regression estimated the degree of preference [ß]. Of 130 participants, median age was 21 years (interquartile range 19-23 years), majority female (58%), and 85% previously tested for HIV. Testing alone over accompanied by a friend (ß = 0.22 vs. - 0.35; p < 0.01); SMS text over paper brochures (ß = 0.13 vs. - 0.10; p < 0.01); higher incentive values (R50) over no incentive (ß = 0.09 vs. - 0.07; p = 0.01); and food vouchers over cash (ß = 0.06 vs. ß = - 0.08; p = 0.01) were preferred. Testing at a clinic or home and family encouragement were important. Tailoring HTS to youth preferences may increase HIV testing.

Isoniazid Preventive Therapy and Pregnancy Outcomes in Women Living With Human Immunodeficiency Virus in the Tshepiso Cohort.

BACKGROUND: Both pregnancy and human immunodeficiency virus (HIV) increase the risk of tuberculosis disease, which results in poor maternal, pregnancy, and infant outcomes. Isoniazid preventive therapy (IPT) reduces mortality among individuals living with HIV in high-burden settings but has recently been associated with adverse pregnancy outcomes when initiated during pregnancy. METHODS: In this secondary analysis, we used multivariable logistic regression to evaluate the association between IPT exposure and adverse pregnancy outcomes (fetal demise, prematurity, low birth weight, congenital anomaly) in pregnant women living with HIV enrolled as controls in the Tshepiso study, a prospective observational cohort of pregnant women living with HIV with and without tuberculosis disease in Soweto, South Africa, from 2011-2014. RESULTS: There were 151 women enrolled with known pregnancy outcomes; 69 (46%) reported IPT initiation during pregnancy. Of the 69 IPT-exposed women, 11 (16%) had an adverse pregnancy outcome compared with 23 (28%) IPT-unexposed women. The adjusted odds of having an adverse pregnancy outcome was 2.5 (95% confidence interval, 1.0-6.5; P = .048) times higher in IPT-unexposed women compared with IPT-exposed women after controlling for maternal age, CD4 count, viral load, antiretroviral regimen, body mass index, and anemia. CONCLUSIONS: IPT exposure during pregnancy was not negatively associated with pregnancy outcomes after controlling for demographic, clinical, and HIV-related factors. These results provide some reassurance that IPT can be safely used in the second or third trimester of pregnancy. Additional research is needed to evaluate the safety of IPT and new short-course tuberculosis preventive therapies during pregnancy.

Addressing Common Mental Health Disorders Among Incarcerated People Living with HIV: Insights from Implementation Science for Service Integration and Delivery.

PURPOSE: Despite evidence of disproportionate burden of HIV and mental health disorders among incarcerated people, scarce services exist to address common mental health disorders, including major depressive and anxiety disorders, post-traumatic stress disorder, and substance use disorders, among incarcerated people living with HIV (PLHIV) in sub-Saharan Africa (SSA). This paper aims to summarize current knowledge on mental health interventions of relevance to incarcerated PLHIV and apply implementation science theory to highlight strategies and approaches to deliver mental health services for PLHIV in correctional settings in SSA. RECENT FINDINGS: Scarce evidence-based mental health interventions have been rigorously evaluated among incarcerated PLHIV in SSA. Emerging evidence from low- and middle-income countries and correctional settings outside SSA point to a role for cognitive behavioral therapy-based talking and group interventions implemented using task-shifting strategies involving lay health workers and peer educators. Several mental health interventions and implementation strategies hold promise for addressing common mental health disorders among incarcerated PLHIV in SSA. However, to deliver these approaches, there must first be pragmatic efforts to build corrections health system capacity, address human rights abuses that exacerbate HIV and mental health, and re-conceptualize mental health services as integral to quality HIV service delivery and universal access to primary healthcare for all incarcerated people.

Observational study of continuity of HIV care following release from correctional facilities in South Africa.

BACKGROUND: We sought to describe linkage to care, ART continuity, and factors associated with linkage to care among people with HIV following release from incarceration in South Africa. METHODS: We conducted a study of South African correctional service community reentrants who were receiving ART at the time of release. The study was implemented in three of 46 correctional service management areas. Participants were enrolled prior to corrections release and followed up to 90 days post-release to obtain self-reported linkage to care status and number of days of ART provided at corrections release. Clinic electronic and paper charts were sought and abstracted to verify self-reported linkage to care. Log-binomial regression, adjusted for facility, was used to identify associations with post-release linkage to care (self-reported and verified). We sought to specifically assess for associations with HIV diagnosis during index incarceration, ART initiation during index incarceration, and duration of incarceration. RESULTS: From May 2014 to December 2016, 554 inmates met eligibility and 516 (93%) consented to participate; 391 were released on ART, 40 of whom were excluded from analysis post-release. Of the remaining 351, 301 (86%) were men and the median age was 35 years (interquartile range 30, 40). Linkage to care was self-reported by 227 (64%) and linkage to care could be verified for 121 (34%). At most, 47% of participants had no lapse in ART supply. Initiating ART during the index incarceration showed a trend toward increased self-reported post-release linkage to care. Age > 35 years was associated with increased verified linkage to care while HIV diagnosis outside of a correctional setting and ART initiation during the index incarceration showed trends toward association with increased verified linkage to care. DISCUSSION: The results of our study are the first description of retention in care following correctional facility release from an African setting and indicate high levels of attrition during the transition from correctional facility to community care. Initiating ART within a correctional facility did not impair post-release linkage to care.

Correction to: Re-thinking Linkage to Care in the Era of Universal Test and Treat: Insights from Implementation and Behavioral Science for Achieving the Second 90.

The article "Re-thinking Linkage to Care in the Era of Universal Test and Treat: Insights from Implementation and Behavioral Science for Achieving the Second 90", written by Michael E. Herce• Benjamin H. Chi • Rodrigo C. Liao • Christopher J. Hoffmann, was originally published electronically on the publisher's internet portal (currently SpringerLink) on 3rd June 2019 without open access.

Re-thinking Linkage to Care in the Era of Universal Test and Treat: Insights from Implementation and Behavioral Science for Achieving the Second 90.

To successfully link to care, persons living with HIV must negotiate a complex series of processes from HIV diagnosis through initial engagement with HIV care systems and providers. Despite the complexity involved, linkage to care is often oversimplified and portrayed as a single referral step. In this article, we offer a new conceptual framework for linkage to care, tailored to the current universal test and treat era that presents linkage to care as its own nuanced pathway within the larger HIV care cascade. Conceptualizing linkage to care in this way may help better identify and specify processes posing a barrier to linkage, and allow for the development of targeted implementation and behavioral science-based approaches to address them. Such approaches are likely to be most relevant to programmatic and clinical settings with limited resources and high HIV burden.

"You Take Medications, You Live Normally": The Role of Antiretroviral Therapy in Mitigating Men's Perceived Threats of HIV in Côte d'Ivoire.

Men diagnosed with HIV face gender-related barriers to initiating and adhering to antiretroviral therapy (ART). This qualitative study (73 in-depth interviews; 28 focus group discussions), conducted with men in three urban sites in Côte d'Ivoire in 2016, examined perceptions of ART, including benefits and challenges, to explore how ART mitigates HIV's threats to men's sexuality, economic success, family roles, social status, and health. Participants perceived that adhering to ART would reduce risk of transmitting HIV to others, minimize job loss and lost productivity, and help maintain men's roles as decision makers and providers. ART adherence was thought to help reduce the threat of HIV-related stigma, despite concerns about unintentional disclosure. While ART was perceived to improve health directly, it restricted men's schedules. Side effects were also a major challenge. Social and behavior change approaches building on these insights may improve male engagement across the HIV care continuum.

Enhancing value and lowering costs of care: a qualitative exploration of a randomized linkage to care intervention in South Africa.

While interventions to improve HIV linkage and retention in care exist, none have demonstrated results sufficient to reach UNAIDS 90-90-90 goals. We explored values and costs of seeking clinical care through testing three strategies to improve linkage to care: Point of care CD4 testing alone (POC-CD4), POC-CD4 combined with transportation support and combined with care facilitation. We conducted in-depth interviews with participants and transcribed audio-recordings of care facilitation sessions. Participants described values and costs enhanced or addressed by the three interventions. Psychosocial support provided through the care facilitation intervention appeared salient. Participants named other values and costs of seeking care unrelated to the intervention, such as encouragement from healthcare workers and aversion to lifelong treatment. Combined with the quantitative results of this trial, these findings may point to why the care facilitation arm was successful but not the POC-CD4 only or transportation arms. It also provides guidance for future interventions.

Perceptions of Value and Cost of HIV Care Engagement Following Diagnosis in South Africa.

Understanding the role of contextual factors beyond individual behavioural determinants is critical to identify strategies to achieve engagement in HIV clinical care. We sought to examine how subjective and objective evaluations of clinic-level costs and value placed on allopathic care influenced HIV care engagement. We used repeat in-depth interviews over 6 months among newly HIV diagnosed adults in South Africa. Data were analysed using thematic analyses and framework matrices to explore individual trajectories over time. Three main patterns of care engagement emerged: failure to enrol in care within 3 months, disengagement after enrolment, and early enrolment with sustained engagement. Findings show that burdensome health systems coupled with low perceptions of the future value of HIV care, compromise HIV care engagement. Without addressing these costs and enhancing perceptions of value on clinical care, the number of people engaging in HIV care is likely to fall short of goals.

Impact of Antiretroviral Therapy on Liver Fibrosis Among Human Immunodeficiency Virus-Infected Adults With and Without HBV Coinfection in Zambia.

BACKGROUND: We investigated changes in hepatic fibrosis, based on transient elastography (TE), among human immunodeficiency virus (HIV)-infected patients with and without hepatitis B virus (HBV) coinfection on antiretroviral therapy (ART) in Zambia. METHODS: Patients' liver stiffness measurements (LSM; kiloPascals [kPa]) at ART initiation were categorized as no or minimal fibrosis (equivalent to Metavir F0-F1), significant fibrosis (F2-F3), and cirrhosis (F4). TE was repeated following 1 year of ART. Stratified by HBV coinfection status (hepatitis B surface antigen positive at baseline), we described LSM change and the proportion with an increase/decrease in fibrosis category. Using multivariable logistic regression, we assessed correlates of significant fibrosis/cirrhosis at 1 year on ART. RESULTS: Among 463 patients analyzed (61 with HBV coinfection), median age was 35 years, 53.7% were women, and median baseline CD4+ count was 240 cells/mm3. Nearly all (97.6%) patients received tenofovir disoproxil fumarate-containing ART, in line with nationally recommended first-line treatment. The median LSM change was -0.70 kPa (95% confidence interval, -3.0 to +1.7) and was similar with and without HBV coinfection. Significant fibrosis/cirrhosis decreased in frequency from 14.0% to 6.7% (P < .001). Increased age, male sex, and HBV coinfection predicted significant fibrosis/cirrhosis at 1 year (all P < .05). CONCLUSION: The percentage of HIV-infected Zambian adults with elevated liver stiffness suggestive of significant fibrosis/cirrhosis decreased following ART initiation-regardless of HBV status. This suggests that HIV infection plays a role in liver inflammation. HBV-coinfected patients were more likely to have significant fibrosis/cirrhosis at 1 year on ART. CLINICAL TRIALS REGISTRATION: NCT02060162.

Plasma Indoleamine 2, 3-Dioxygenase, a Biomarker for Tuberculosis in Human Immunodeficiency Virus-Infected Patients.

BACKGROUND: There is no biomarker for diagnosing active tuberculosis in patients with human immunodeficiency virus (HIV) infection. Indoleamine 2, 3-dioxygenase (IDO) is an immunoregulatory enzyme that breaks down tryptophan (Trp) to metabolites known as kynurenines (Kyns). We investigated whether IDO activity, as measured by the ratio of Kyn to Trp, could be used to diagnose or predict active tuberculosis disease in HIV-infected adults. METHODS: Kyn and Trp concentrations were measured using ultraperformance liquid chromatography mass spectrometry in plasma samples from 32 HIV-infected patients in whom active tuberculosis developed and who were followed up prospectively. We compared to 70 HIV-infected control subjects from the same cohort in whom tuberculosis did not develop, matched by age, sex, and CD4 cell count, and 37 unmatched HIV-infected patients with a diagnosis of pneumonia. Clinical parameters, including body mass index, CD4 cell count, HIV load, and C-reactive protein levels were analyzed. RESULTS: At the time of tuberculosis diagnosis, IDO activity was significantly higher in patients with tuberculosis than in controls (P < .001). Six months before tuberculosis diagnosis, IDO activity was significantly higher in all patients who later developed tuberculosis (P < .001) than controls. After 6 months of tuberculosis treatment, IDO activity in patients with tuberculosis declined to levels similar to those in controls. IDO activity was 4-fold higher in patients with tuberculosis than in those with pneumonia, and could be used to distinguish them. With a receiver operating characteristic curve, IDO activity had a sensitivity of 97%, a specificity of 99%, and positive and negative predictive values of 89% and 100% for detecting active tuberculosis disease. CONCLUSION: Plasma IDO activity is suitable as a biomarker of active tuberculosis in HIV-positive patients.

HIV and tuberculosis in prisons in sub-Saharan Africa.

Given the dual epidemics of HIV and tuberculosis in sub-Saharan Africa and evidence suggesting a disproportionate burden of these diseases among detainees in the region, we aimed to investigate the epidemiology of HIV and tuberculosis in prison populations, describe services available and challenges to service delivery, and identify priority areas for programmatically relevant research in sub-Saharan African prisons. To this end, we reviewed literature on HIV and tuberculosis in sub-Saharan African prisons published between 2011 and 2015, and identified data from only 24 of the 49 countries in the region. Where data were available, they were frequently of poor quality and rarely nationally representative. Prevalence of HIV infection ranged from 2·3% to 34·9%, and of tuberculosis from 0·4 to 16·3%; detainees nearly always had a higher prevalence of both diseases than did the non-incarcerated population in the same country. We identified barriers to prevention, treatment, and care services in published work and through five case studies of prison health policies and services in Zambia, South Africa, Malawi, Nigeria, and Benin. These barriers included severe financial and human-resource limitations and fragmented referral systems that prevent continuity of care when detainees cycle into and out of prison, or move between prisons. These challenges are set against the backdrop of weak health and criminal-justice systems, high rates of pre-trial detention, and overcrowding. A few examples of promising practices exist, including routine voluntary testing for HIV and screening for tuberculosis upon entry to South African and the largest Zambian prisons, reforms to pre-trial detention in South Africa, integration of mental health services into a health package in selected Malawian prisons, and task sharing to include detainees in care provision through peer-educator programmes in Rwanda, Zimbabwe, Zambia, and South Africa. However, substantial additional investments are required throughout sub-Saharan Africa to develop country-level policy guidance, build human-resource capacity, and strengthen prison health systems to ensure universal access to HIV and tuberculsosis prevention, treatment, and care of a standard that meets international goals and human rights obligations.

Hepatitis B prevalence and treatment needs among Tibetan refugees residing in India.

Untreated chronic hepatitis B can lead to liver failure and/or liver cancer. These complications can be avoided through prevention with vaccination or treatment of disease. To inform health policy for the Tibetan community in India, we conducted study of hepatitis B prevalence and treatment needs. We conducted a cross-sectional study over 3 months of 2013. Households were randomly selected for participation via a satellite map; one boarding school and one residential monastery were also included. Participants were asked questions and a whole blood sample was collected for HBsAg assay. Participants with a positive HBsAg result were tested for hepatitis B e antigen, ALT, and AST. Participants with a negative HBsAg result were tested for anti-hepatitis B core antibodies. We recruited 2,769 participants; of which 247 (8.9%) were positive for HBsAg. Participants more likely to have a positive HBsAg result were those born in Tibet (12.4%) and aged 30-59 years old. Of those with a positive HBsAg result, 60.7% were positive for hepatitis B e antigen 7% of whom fit into a likely treatment-needed category; the others fit into management categories requiring repeat ALT testing with or without liver fibrosis assessment. Among participants negative for HBsAg, 52.9% from household sampling had anti-HBc antibodies. We identified a high endemicity of chronic hepatitis B in a Tibetan community in India. Resource appropriate approaches are needed for managing chronic hepatitis B in settings such as this one. J. Med. Virol. 88:1357-1363, 2016. © 2016 Wiley Periodicals, Inc.

CD4 count-based failure criteria combined with viral load monitoring may trigger worse switch decisions than viral load monitoring alone.

OBJECTIVE: CD4 count decline often triggers antiretroviral regimen switches in resource-limited settings, even when viral load testing is available. We therefore compared CD4 failure and CD4 trends in patients with viraemia with or without antiretroviral resistance. METHODS: Retrospective cohort study investigating the association of HIV drug resistance with CD4 failure or CD4 trends in patients on first-line antiretroviral regimens during viraemia. Patients with viraemia (HIV RNA >1000 copies/ml) from two HIV treatment programmes in South Africa (n = 350) were included. We investigated the association of M184V and NNRTI resistance with WHO immunological failure criteria and CD4 count trends, using chi-square tests and linear mixed models. RESULTS: Fewer patients with the M184V mutation reached immunologic failure criteria than those without: 51 of 151(34%) vs. 90 of 199 (45%) (P = 0.03). Similarly, 79 of 220 (36%) patients, who had major NNRTI resistance, had immunological failure, whereas 62 of 130 (48%) without (chi-square P = 0.03) did. The CD4 count decline among patients with the M184V mutation was 2.5 cells/mm(3) /year, whereas in those without M184V it was 14 cells/mm(3) /year (P = 0.1), but the difference in CD4 count decline with and without NNRTI resistance was marginal. CONCLUSION: Our data suggest that CD4 count monitoring may lead to inappropriate delayed therapy switches for patients with HIV drug resistance. Conversely, patients with viraemia but no drug resistance are more likely to have a CD4 count decline and thus may be more likely to be switched to a second-line regimen.