Severe Monkeypox in Hospitalized Patients - United States, August 10-October 10, 2022.

As of October 21, 2022, a total of 27,884 monkeypox cases (confirmed and probable) have been reported in the United States.§ Gay, bisexual, and other men who have sex with men have constituted a majority of cases, and persons with HIV infection and those from racial and ethnic minority groups have been disproportionately affected (1,2). During previous monkeypox outbreaks, severe manifestations of disease and poor outcomes have been reported among persons with HIV infection, particularly those with AIDS (3-5). This report summarizes findings from CDC clinical consultations provided for 57 patients aged ≥18 years who were hospitalized with severe manifestations of monkeypox¶ during August 10-October 10, 2022, and highlights three clinically representative cases. Overall, 47 (82%) patients had HIV infection, four (9%) of whom were receiving antiretroviral therapy (ART) before monkeypox diagnosis. Most patients were male (95%) and 68% were non-Hispanic Black (Black). Overall, 17 (30%) patients received intensive care unit (ICU)-level care, and 12 (21%) have died. As of this report, monkeypox was a cause of death or contributing factor in five of these deaths; six deaths remain under investigation to determine whether monkeypox was a causal or contributing factor; and in one death, monkeypox was not a cause or contributing factor.** Health care providers and public health professionals should be aware that severe morbidity and mortality associated with monkeypox have been observed during the current outbreak in the United States (6,7), particularly among highly immunocompromised persons. Providers should test all sexually active patients with suspected monkeypox for HIV at the time of monkeypox testing unless a patient is already known to have HIV infection. Providers should consider early commencement and extended duration of monkeypox-directed therapy†† in highly immunocompromised patients with suspected or laboratory-diagnosed monkeypox.§§ Engaging all persons with HIV in sustained care remains a critical public health priority.

Emerging priorities for HIV service delivery.

Nathan Ford and co-authors discuss global priorities in the provision of HIV prevention and treatment services.

Increase in Antiretroviral Therapy Enrollment Among Persons with HIV Infection During the Lusaka HIV Treatment Surge - Lusaka Province, Zambia, January 2018-June 2019.

Within Zambia, a landlocked country in southern-central Africa, the highest prevalence of human immunodeficiency virus (HIV) infection is in Lusaka Province (population 3.2 million), where approximately 340,000 persons are estimated to be infected (1). The 2016 Zambia Population-based HIV Impact Assessment (ZAMPHIA) estimated the adult HIV prevalence in Lusaka Province to be 15.7%, with a 62.7% viral load suppression rate (HIV-1 RNA <1,000 copies/mL) (2). ZAMPHIA results highlighted remaining treatment gaps in Zambia overall and by subpopulation. In January 2018, Zambia launched the Lusaka Province HIV Treatment Surge (Surge project) to increase enrollment of persons with HIV infection onto antiretroviral therapy (ART). The Zambia Ministry of Health (MoH), CDC, and partners analyzed the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) Monitoring and Evaluation Reporting data set to assess the effectiveness of the first 18 months of the Surge project (January 2018-June 2019). During this period, approximately 100,000 persons with positive test results for HIV began ART. These new ART clients were more likely to be persons aged 15-24 years. In addition, the number of persons with documented viral load suppression doubled from 66,109 to 134,046. Lessons learned from the Surge project, including collaborative leadership, efforts to improve facility-level performance, and innovative strategies to disseminate successful practices, could increase HIV treatment rates in other high-prevalence settings.

Trends in Prevalence of Advanced HIV Disease at Antiretroviral Therapy Enrollment - 10 Countries, 2004-2015.

Monitoring prevalence of advanced human immunodeficiency virus (HIV) disease (i.e., CD4+ T-cell count <200 cells/µL) among persons starting antiretroviral therapy (ART) is important to understand ART program outcomes, inform HIV prevention strategy, and forecast need for adjunctive therapies.*,†,§ To assess trends in prevalence of advanced disease at ART initiation in 10 high-burden countries during 2004-2015, records of 694,138 ART enrollees aged ≥15 years from 797 ART facilities were analyzed. Availability of national electronic medical record systems allowed up-to-date evaluation of trends in Haiti (2004-2015), Mozambique (2004-2014), and Namibia (2004-2012), where prevalence of advanced disease at ART initiation declined from 75% to 34% (p<0.001), 73% to 37% (p<0.001), and 80% to 41% (p<0.001), respectively. Significant declines in prevalence of advanced disease during 2004-2011 were observed in Nigeria, Swaziland, Uganda, Vietnam, and Zimbabwe. The encouraging declines in prevalence of advanced disease at ART enrollment are likely due to scale-up of testing and treatment services and ART-eligibility guidelines encouraging earlier ART initiation. However, in 2015, approximately a third of new ART patients still initiated ART with advanced HIV disease. To reduce prevalence of advanced disease at ART initiation, adoption of World Health Organization (WHO)-recommended "treat-all" guidelines and strategies to facilitate earlier HIV testing and treatment are needed to reduce HIV-related mortality and HIV incidence.

The role of the law in reducing tuberculosis transmission in Botswana, South Africa and Zambia.

OBJECTIVE: To determine whether laws and regulations in Botswana, South Africa and Zambia - three countries with a high tuberculosis and HIV infection burden - address elements of the World Health Organization (WHO) policy on tuberculosis infection control. METHODS: An online desk review of laws and regulations that address six selected elements of the WHO policy on tuberculosis infection control in the three countries was conducted in November 2015 using publicly available domestic legal databases. The six elements covered: (i) national policy and legal framework; (ii) health facility design, construction and use; (iii) tuberculosis disease surveillance among health workers; (iv) patients' and health workers' rights; (v) monitoring of infection control measures; and (vi) relevant research. FINDINGS: The six elements were found to be adequately addressed in the three countries' laws and regulations. In all three, tuberculosis case-reporting is required, as is tuberculosis surveillance among health workers. Each country's legal and regulatory framework also addresses the need to respect individuals' rights and privacy while safeguarding public health. These laws and regulations create a strong foundation for tuberculosis infection control. Although the legal and regulatory frameworks thoroughly address tuberculosis infection control, their dissemination, implementation and enforcement were not assessed, nor was their impact on public health. CONCLUSION: Laws and regulations in Botswana, South Africa and Zambia address all six selected elements of the WHO policy on tuberculosis infection control. However, the lack of data on their implementation is a limitation. Future research should assess the implementation and public health impact of laws and regulations.

Trends in upper gastrointestinal diagnosis over four decades in Lusaka, Zambia: a retrospective analysis of endoscopic findings.

BACKGROUND AND AIMS: There a shortage of robust information about profiles of gastrointestinal disease in sub-Saharan Africa. The endoscopy unit of the University Teaching Hospital in Lusaka has been running without interruption since 1977 and this 38-year record is largely intact. We report an analysis of endoscopic findings over this period. METHODS: Written endoscopy records from 29th September 1977 to 16th December 2014 were recovered, computerised, coded by two experienced endoscopists and analysed. Temporal trends were analysed using tables, graphs, and unconditional logistic regression, with age, sex of patient, decade, and endoscopist as independent variables to adjust for inter-observer variation. RESULTS: Sixteen thousand nine hundred fifty-three records were identified and analysed. Diagnosis of gastric ulcer rose by 22 %, and that of duodenal ulcer fell by 14 % per decade. Endoscopically diagnosed oesophageal cancer increased by 32 % per decade, but gastric cancer rose only in patients under 60 years of age (21 % per decade). Oesophageal varices were the commonest finding in patients presenting with haematemesis, increasing by 14 % per decade in that patient group. Two HIV-related diagnoses, oesophageal candidiasis and Kaposi's sarcoma, rose from almost zero to very high levels in the 1990s but fell substantially after 2005 when anti-retroviral therapy became widely available. CONCLUSIONS: This useful dataset suggests that there are important trends in some endoscopic findings over four decades. These trends are not explained by inter-observer variation. Reasons for the divergent trends in incidence of peptic ulceration and apparent trends in diagnosis of upper gastrointestinal cancers merit further exploration.

Simultaneous detection of major drug resistance mutations in the protease and reverse transcriptase genes for HIV-1 subtype C by use of a multiplex allele-specific assay.

High-throughput, sensitive, and cost-effective HIV drug resistance (HIVDR) detection assays are needed for large-scale monitoring of the emergence and transmission of HIVDR in resource-limited settings. Using suspension array technology, we have developed a multiplex allele-specific (MAS) assay that can simultaneously detect major HIVDR mutations at 20 loci. Forty-five allele-specific primers tagged with unique 24-base oligonucleotides at the 5' end were designed to detect wild-type and mutant alleles at the 20 loci of HIV-1 subtype C. The MAS assay was first established and optimized with three plasmid templates (C-wt, C-mut1, and C-mut2) and then evaluated using 148 plasma specimens from HIV-1 subtype C-infected individuals. All the wild-type and mutant alleles were unequivocally distinguished with plasmid templates, and the limits of detection were 1.56% for K219Q and K219E, 3.13% for L76V, 6.25% for K65R, K70R, L74V, L100I, K103N, K103R, Q151M, Y181C, and I47V, and 12.5% for M41L, K101P, K101E, V106A, V106M, Y115F, M184V, Y188L, G190A, V32I, I47A, I84V, and L90M. Analyses of 148 plasma specimens revealed that the MAS assay gave 100% concordance with conventional sequencing at eight loci and >95% (range, 95.21% to 99.32%) concordance at the remaining 12 loci. The differences observed were caused mainly by 24 additional low-abundance alleles detected by the MAS assay. Ultradeep sequencing analysis confirmed 15 of the 16 low-abundance alleles. This multiplex, sensitive, and straightforward result-reporting assay represents a new efficient genotyping tool for HIVDR surveillance and monitoring.

Self-reported dietary intake and appetite predict early treatment outcome among low-BMI adults initiating HIV treatment in sub-Saharan Africa.

OBJECTIVE: Low BMI is a major risk factor for early mortality among HIV-infected persons starting antiretrovial therapy (ART) in sub-Saharan Africa and the common patient belief that antiretroviral medications produce distressing levels of hunger is a barrier to treatment adherence. We assessed relationships between appetite, dietary intake and treatment outcome 12 weeks after ART initiation among HIV-infected adults with advanced malnutrition and immunosuppression. DESIGN: A prospective, observational cohort study. Dietary intake was assessed using a 24 h recall survey. The relationships of appetite, intake and treatment outcome were analysed using time-varying Cox models. SETTING: A public-sector HIV clinic in Lusaka, Zambia. SUBJECTS: One hundred and forty-two HIV-infected adults starting ART with BMI <16 kg/m2 and/or CD4+ lymphocyte count <50 cells/µl. RESULTS: Median age, BMI and CD4+ lymphocyte count were 32 years, 16 kg/m2 and 34 cells/µl, respectively. Twenty-five participants (18%) died before 12 weeks and another thirty-three (23%) were lost to care. A 500 kJ/d higher energy intake at any time after ART initiation was associated with an approximate 16% reduction in the hazard of death (adjusted hazard ratio = 0.84; P = 0.01), but the relative contribution of carbohydrate, protein or fat to total energy was not a significant predictor of outcome. Appetite normalized gradually among survivors and hunger was rarely reported. CONCLUSIONS: Poor early ART outcomes were strikingly high in a cohort of HIV-infected adults with advanced malnutrition and mortality was predicted by lower dietary intake. Intervention trials to promote post-ART intake in this population may benefit survival and are warranted.

A Systematic Review of COVID-19 Vaccine Antibody Responses in People With HIV.

HIV infection is a significant independent risk factor for severe coronavirus disease 2019 (COVID-19) disease and death. We summarize COVID-19 vaccine responses in people with HIV (PWH). A systematic literature review of studies from January 1, 2020, to March 31, 2022, of COVID-19 vaccine immunogenicity in PWH from multiple databases was performed. Twenty-eight studies from 12 countries were reviewed. While 22 (73%) studies reported high COVID-19 vaccine seroconversion rates in PWH, PWH with lower baseline CD4 counts, CD4/CD8 ratios, or higher baseline viral loads had lower seroconversion rates and immunologic titers. Data on vaccine-induced seroconversion in PWH are reassuring, but more research is needed to evaluate the durability of COVID-19 vaccine responses in PWH.

Effectiveness of non-nucleoside reverse-transcriptase inhibitor-based antiretroviral therapy in women previously exposed to a single intrapartum dose of nevirapine: a multi-country, prospective cohort study.

BACKGROUND: Intrapartum and neonatal single-dose nevirapine (NVP) reduces the risk of mother-to-child HIV transmission but also induces viral resistance to non-nucleoside reverse transcriptase inhibitor (NNRTI) drugs. This drug resistance largely fades over time. We hypothesized that women with a prior single-dose NVP exposure would have no more than a 10% higher cumulative prevalence of failure of their NNRTI-containing antiretroviral therapy (ART) over the first 48 wk of therapy than would women without a prior exposure. METHODS AND FINDINGS: We enrolled 355 NVP-exposed and 523 NVP-unexposed women at two sites in Zambia, one site in Kenya, and two sites in Thailand into a prospective, non-inferiority cohort study and followed them for 48 wk on ART. Those who died, discontinued NNRTI-containing ART, or had a plasma viral load >or=400 copies/ml at either the 24 wk or 48 wk study visits and confirmed on repeat testing were characterized as having failed therapy. Overall, 114 of 355 NVP-exposed women (32.1%) and 132 of 523 NVP-unexposed women (25.2%) met criteria for treatment failure. The difference in failure rates between the exposure groups was 6.9% (95% confidence interval [CI] 0.8%-13.0%). The failure rates of women stratified by our predefined exposure interval categories were as follows: 47 of 116 women in whom less than 6 mo elapsed between exposure and starting ART failed therapy (40%; p<0.001 compared to unexposed women); 25 of 67 women in whom 7-12 mo elapsed between exposure and starting ART failed therapy (37%; p = 0.04 compared to unexposed women); and 42 of 172 women in whom more than 12 mo elapsed between exposure and starting ART failed therapy (24%; p = 0.82 compared to unexposed women). Locally weighted regression analysis also indicated a clear inverse relationship between virologic failure and the exposure interval. CONCLUSIONS: Prior exposure to single-dose NVP was associated with an increased risk of treatment failure; however, this risk seems largely confined to women with a more recent exposure. Women requiring ART within 12 mo of NVP exposure should not be prescribed an NNRTI-containing regimen as first-line therapy.

How late is too late? Timeliness to scheduled visits as an antiretroviral therapy adherence measure in Nairobi, Kenya and Lusaka, Zambia.

Collecting self-reported data on adherence to highly active antiretroviral therapy (HAART) can be complicated by patients' reluctance to report poor adherence. The timeliness with which patients attend visits might be a useful alternative to estimate medication adherence. Among Kenyan and Zambian women receiving twice daily HAART, we examined the relationship between self-reported pill taking and timeliness attending scheduled visits. We analyzed data from 566 Kenyan and Zambian women enrolled in a prospective 48-week HAART-response study. At each scheduled clinic visit, women reported doses missed over the preceding week. Self-reported adherence was calculated by summing the total number of doses reported taken and dividing by the total number of doses asked about at the visit attended. A participant's adherence to scheduled study visits was defined as "on time" if she arrived early or within three days, "moderately late" if she was four-seven days late, and "extremely late/missed" if she was more than eight days late or missed the visit altogether. Self-reported adherence was <95% for 29 (10%) of 288 women who were late for at least one study visit vs. 3 (1%) of 278 who were never late for a study visit (odds ratios [OR] 10.3; 95% confidence intervals [95% CI] 2.9, 42.8). Fifty-one (18%) of 285 women who were ever late for a study visit experienced virologic failure vs. 32 (12%) of 278 women who were never late for a study visit (OR 1.7; 95% CI 1.01, 2.8). A multivariate logistic regression model controlling for self-reported adherence found that being extremely late for a visit was associated with virologic failure (OR 2.0; 95% CI 1.2, 3.4). Timeliness to scheduled visits was associated with self-reported adherence to HAART and with risk for virologic failure. Timeliness to scheduled clinic visits can be used as an objective proxy for self-reported adherence and ultimately for risk of virologic failure.

Clinical and ultrasonographic features of abdominal tuberculosis in HIV positive adults in Zambia.

BACKGROUND: The diagnosis of abdominal tuberculosis (TB) is difficult, especially so in health care facilities in developing countries where laparoscopy and colonoscopy are rarely available. There is little information on abdominal TB in HIV infection. We estimated the prevalence and clinical features of abdominal (excluding genitourinary) TB in HIV infected adults attending the University Teaching Hospital, Zambia. METHODS: We screened 5,609 medical inpatients, and those with fever, weight loss, and clinical features suggestive of abdominal pathology were evaluated further. A clinical algorithm was used to specify definitive investigations including laparoscopy or colonoscopy, with culture of biopsies and other samples. RESULTS: Of 140 HIV seropositive patients with these features, 31 patients underwent full evaluation and 22 (71%) had definite or probable abdominal TB. The commonest presenting abdominal features were ascites and persistent tenderness. The commonest ultrasound findings were ascites, para-aortic lymphadenopathy (over 1 cm in size), and hepatomegaly. Abdominal TB was associated with CD4 cell counts over a wide range though 76% had CD4 counts <100 cells/microL. CONCLUSION: The clinical manifestations of abdominal TB in our HIV-infected patients resembled the well-established pattern in HIV-uninfected adults. Patients with fever, weight loss, abdominal tenderness, abdominal lymphadenopathy, ascites and/or hepatomegaly in Zambia have a high probability of abdominal TB, irrespective of CD4 cell count.

Gastrointestinal pathology in the University Teaching Hospital, Lusaka, Zambia: review of endoscopic and pathology records.

There is a shortage of information on the epidemiology of digestive disease in developing countries. In the belief that such information will inform public health priorities and epidemiological comparisons between different geographical regions, we analysed 2132 diagnostic upper gastrointestinal endoscopy records from 1999 to 2005 in the University Teaching Hospital, Lusaka, Zambia. In order to clarify unexpected impressions about the age distribution of cancers, a retrospective analysis of pathology records was also undertaken. No abnormality was found in 31% of procedures, and in 42% of procedures in children. In patients with gastrointestinal haemorrhage, the common findings were oesophageal varices (26%), duodenal ulcer (17%) and gastric ulcer (12%). Gastrointestinal malignancy was found in 8.8% of all diagnostic procedures, in descending order of frequency: gastric adenocarcinoma, oesophageal squamous carcinoma, Kaposi's sarcoma, oesophageal adenocarcinoma. Data from endoscopy records and pathology records strongly suggest that the incidence in adults under the age of 45 years is higher than in the USA or UK, and pathology records suggest that this effect is particularly marked for colorectal carcinoma.

Cytokine activation is predictive of mortality in Zambian patients with AIDS-related diarrhoea.

BACKGROUND: Mortality in Zambian AIDS patients is high, especially in patients with diarrhoea, and there is still unacceptably high mortality in Zambian patients just starting anti-retroviral therapy. We set out to determine if high concentrations of serum cytokines correlate with mortality. METHODS: Serum samples from 30 healthy controls (HIV seropositive and seronegative) and 50 patients with diarrhoea (20 of whom died within 6 weeks) were analysed. Concentrations of tumour necrosis factor receptor p55 (TNFR p55), macrophage migration inhibitory factor (MIF), interleukin (IL)-6, IL-12, interferon (IFN)-gamma and C-reactive protein (CRP) were measured by ELISA, and correlated with mortality after 6 weeks follow-up. RESULTS: Apart from IL-12, concentrations of all cytokines, TNFR p55 and CRP increased with worsening severity of disease, showing highly statistically significant trends. In a multivariable analysis high TNFR p55, IFN-gamma, CRP and low CD4 count (CD4 count <100) were predictive of mortality. Although nutritional status (assessed by body mass index, BMI) was predictive in univariate analysis, it was not an independent predictor in multivariate analysis. CONCLUSION: High serum concentrations of TNFR p55, IFN-gamma, CRP and low CD4 count correlated with disease severity and short-term mortality in HIV-infected Zambian adults with diarrhoea. These factors were better predictors of survival than BMI. Understanding the cause of TNFR p55, IFN-gamma and CRP elevation may be useful in development of interventions to reduce mortality in AIDS patients with chronic diarrhoea in Africa.

A pragmatic approach to monitor and evaluate implementation and impact of differentiated ART delivery for global and national stakeholders.

INTRODUCTION: The World Health Organization's (WHO) recommendation of "Treat All" has accelerated the call for differentiated antiretroviral therapy (ART) delivery, a method of care that efficiently uses limited resources to increase access to HIV treatment. WHO has further recommended that stable individuals on ART receive refills every 3 to 6 months and attend clinical visits every 3 to 6 months. However, there is not yet consensus on how to ensure that the quality of services is maintained as countries strive to meet these standards. This commentary responds to this gap by defining a pragmatic approach to the monitoring and evaluation (M&E) of the scale up of differentiated ART delivery for global and national stakeholders. DISCUSSION: Programme managers need to demonstrate that the scale up of differentiated ART delivery is achieving the desired effectiveness and efficiency outcomes to justify continued support by national and global stakeholders. To achieve this goal, the two existing global WHO HIV treatment indicators of ART retention and viral suppression should be augmented with two broad aggregate measures. The addition of indicators measuring the frequency of (1) clinical and (2) refill visits by PLHIV per year will allow evaluation of the pace of scale up while monitoring its overall effect on the quality and efficiency of services. The combination of these four routinely collected aggregate indicators will also facilitate the comparison of outcomes among facilities, regions or countries implementing different models of ART delivery. Enhanced monitoring or additional assessments will be required to answer other critical questions on the process of implementation, acceptability, effectiveness and efficiency. CONCLUSIONS: These proposed outcomes are useful markers for the effectiveness and efficiency of the health system's attempts to deliver quality treatment to those who need it-and still reserve as much of the available resource pool as possible for other key elements of the HIV response.

Early clinical and immune response to NNRTI-based antiretroviral therapy among women with prior exposure to single-dose nevirapine.

OBJECTIVE: To determine whether prior exposure to single-dose nevirapine (NVP) for prevention of mother-to-child HIV transmission (PMTCT) is associated with attenuated CD4 cell response, death, or clinical treatment failure in women starting antiretroviral therapy (ART) containing non-nucleoside reverse transcriptase inhibitors (NNRTI). METHODS: Open cohort evaluation of outcomes for women in program sites across Zambia. HIV treatment was provided according to Zambian/World Health Organization guidelines. RESULTS: Peripartum NVP exposure status was known for 6740 women initiating NNRTI-containing ART, of whom 751 (11%) reported prior use of NVP for PMTCT. There was no significant difference in mean CD4 cell change between those exposed or unexposed to NVP at 6 (+202 versus +182 cells/microl; P = 0.20) or 12 (+201 versus +211 cells/microl; P = 0.60) months. Multivariable analyses showed no significant differences in mortality [adjusted hazard ratio (HR), 1.2; 95% confidence interval (CI), 0.8-1.8] or clinical treatment failure (adjusted HR, 1.1; 95% CI, 0.8-1.5). Comparison of recent NVP exposure with remote exposure suggested a less favorable CD4 cell response at 6 (+150 versus +219 cells/microl; P = 0.06) and 12 (+149 versus +215 cells/microl; P = 0.39) months. Women with recent NVP exposure also had a trend towards elevated risk for clinical treatment failure (adjusted HR, 1.6; 95% CI, 0.9-2.7). CONCLUSION: Exposure to maternal single-dose NVP was not associated with substantially different short-term treatment outcomes. However, evidence was suggestive that exposure within 6 months of ART initiation may be a risk factor for poor treatment outcomes, highlighting the importance of ART screening and initiation early in pregnancy.

Promotion of couples' voluntary counselling and testing for HIV through influential networks in two African capital cities.

BACKGROUND: Most new HIV infections in Africa are acquired from cohabiting heterosexual partners. Couples' Voluntary Counselling and Testing (CVCT) is an effective prevention strategy for this group. We present our experience with a community-based program for the promotion of CVCT in Kigali, Rwanda and Lusaka, Zambia. METHODS: Influence Network Agents (INAs) from the health, religious, non-governmental, and private sectors were trained to invite couples for CVCT. Predictors of successful promotion were identified using a multi-level hierarchical analysis. RESULTS: In 4 months, 9,900 invitations were distributed by 61 INAs, with 1,411 (14.3%) couples requesting CVCT. INAs in Rwanda distributed fewer invitations (2,680 vs. 7,220) and had higher response rates (26.9% vs. 9.6%), than INAs in Zambia. Context of the invitation event, including a discreet location such as the INA's home (OR 3.3-3.4), delivery of the invitation to both partners in the couple (OR 1.6-1.7) or to someone known to the INA (OR 1.7-1.8), and use of public endorsement (OR 1.7-1.8) were stronger predictors of success than INA or couple-level characteristics. CONCLUSION: Predictors of successful CVCT promotion included strategies that can be easily implemented in Africa. As new resources become available for Africans with HIV, CVCT should be broadly implemented as a point of entry for prevention, care and support.

HIVCorps: using volunteers to rapidly expand HIV health services across Zambia.

In 2004, we created HIVCorps, an international volunteer program to involve pre-medical, medical, and public health students in the scale-up of HIV care and prevention services in Zambia. In our first year, we used 27 American and Zambian volunteers to assist with the administrative and logistical aspects of program implementation. Ten volunteers were based in the capital Lusaka; the remaining 17 were stationed across five rural districts. Supervision was provided by local health care providers, district officials, and hospital administrators. In our setting, the use of volunteers has proven feasible and effective for program support. Depending on a program's immediate needs, use of many basic field personnel may be more beneficial than employment of one to two trained clinicians. Formal volunteer programs like HIVCorps should be developed alongside initiatives focused on deploying more specialized, experienced healthcare workers aboard.

Rapid scale-up of antiretroviral therapy at primary care sites in Zambia: feasibility and early outcomes.

CONTEXT: The Zambian Ministry of Health has scaled-up human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) care and treatment services at primary care clinics in Lusaka, using predominately nonphysician clinicians. OBJECTIVE: To report on the feasibility and early outcomes of the program. DESIGN, SETTING, AND PATIENTS: Open cohort evaluation of antiretroviral-naive adults treated at 18 primary care facilities between April 26, 2004, and November 5, 2005. Data were entered in real time into an electronic patient tracking system. INTERVENTION: Those meeting criteria for antiretroviral therapy (ART) received drugs according to Zambian national guidelines. MAIN OUTCOME MEASURES: Survival, regimen failure rates, and CD4 cell response. RESULTS: We enrolled 21,755 adults into HIV care, and 16,198 (75%) started ART. Among those starting ART, 9864 (61%) were women. Of 15,866 patients with documented World Health Organization (WHO) staging, 11,573 (73%) were stage III or IV, and the mean (SD) entry CD4 cell count among the 15,336 patients with a baseline result was 143/microL (123/microL). Of 1142 patients receiving ART who died, 1120 had a reliable date of death. Of these patients, 792 (71%) died within 90 days of starting therapy (early mortality rate: 26 per 100 patient-years), and 328 (29%) died after 90 days (post-90-day mortality rate: 5.0 per 100 patient-years). In multivariable analysis, mortality was strongly associated with CD4 cell count between 50/microL and 199/microL (adjusted hazard ratio [AHR], 1.4; 95% confidence interval [CI], 1.0-2.0), CD4 cell count less than 50/microL (AHR, 2.2; 95% CI, 1.5-3.1), WHO stage III disease (AHR, 1.8; 95% CI, 1.3-2.4), WHO stage IV disease (AHR, 2.9; 95% CI, 2.0-4.3), low body mass index (<16; AHR,2.4; 95% CI, 1.8-3.2), severe anemia (<8.0 g/dL; AHR, 3.1; 95% CI, 2.3-4.0), and poor adherence to therapy (AHR, 2.9; 95% CI, 2.2-3.9). Of 11,714 patients at risk, 861 failed therapy by clinical criteria (rate, 13 per 100 patient-years). The mean (SD) CD4 cell count increase was 175/microL (174/microL) in 1361 of 1519 patients (90%) receiving treatment long enough to have a 12-month repeat. CONCLUSION: Massive scale-up of HIV and AIDS treatment services with good clinical outcomes is feasible in primary care settings in sub-Saharan Africa. Most mortality occurs early, suggesting that earlier diagnosis and treatment may improve outcomes.

Transmission of HIV-1 and HLA-B allele-sharing within serodiscordant heterosexual Zambian couples.

Factors that might increase risk of HIV-1 transmission include age, sex, and amount of HIV-1 RNA in plasma, but findings for HLA allele-sharing are not in agreement. We tested the hypothesis that allele sharing at HLA loci is associated with increased risk of transmission of HIV-1 infection in cohabiting heterosexual Zambian couples. We studied 125 initially serodiscordant partners with sequence-confirmed interpartner HIV-1 transmission and 104 couples who were persistently serodiscordant, and we analysed relations with molecularly typed HLA-A, B, and C alleles by survival techniques. After adjustment for other genetic and non-genetic risk factors seen with heterosexual transmission of HIV-1 in this cohort, sharing of HLA-B alleles was independently associated with accelerated intracouple transmission (relative hazard 2.23, 95% CI 1.52-3.26, p<0.0001). Selective pressure by HLA-B alleles on transmitted viruses accords with current understanding of the effect of B locus polymorphism in HIV-1 and perhaps other infections.