Linkage to HIV care and survival following inpatient HIV counseling and testing.

Linkage to HIV care and survival in sub-Saharan Africa is not well documented. In 2004 we conducted a randomized trial among medical inpatients in Mulago Hospital to assess the impact of HIV counseling and testing (HCT) on linkage to care and survival. Participants were randomized to inpatient HCT (intervention) or outpatient HCT 1 week post-discharge (control); inpatient HCT was not available at Mulago during the study. Among 590 eligible patients, 85% (500) agreed to participate; 98.8% (248) in the intervention arm received HCT compared to 68.7% (171) in the control arm. Within 6 months, 62.2% (92) of surviving HIV-infected participants received HIV care; 15.0% (20) received antiretroviral medications (ARVs). Overall mortality among HIV-infected participants was 34.6% (72). HCT had significant impact on linkage to care among surviving participants. Referral for HCT was a missed opportunity for diagnosis. There is need for earlier diagnosis and linkage to HIV care among inpatients.

Prevalence, incidence and mortality associated with tuberculosis in HIV-infected patients initiating antiretroviral therapy in rural Uganda.

BACKGROUND: Tuberculosis (TB) is the leading cause of death among people with HIV in sub-Saharan Africa. Expanding access to antiretroviral therapy (ART) may reduce the burden of TB, but to what extent is unknown. METHODS: In a study of 1044 adults who initiated home-based ART in Tororo, Uganda between 1 May 2003 and 30 June 2005, participants were screened for active TB at baseline and then monitored at weekly home visits. Participants with TB at baseline or follow-up were compared with those without TB to determine factors associated with mortality in those with TB. RESULTS: At baseline, 75 (7.2%) subjects had TB and a total of 53 (5.5%) were diagnosed with TB over a median of 1.4 years of follow-up (3.90 cases/100 person years). Cumulative mortality was 17.9/100 person-years for those with TB and 3.8/100 person-years for those without TB (P < 0.001). Mortality was associated with low baseline CD4 cell counts [relative hazard (RH), 0.99 per 1 cell/microl increase; P = 0.03] and marginally associated with a body mass index

Adherence to antiretroviral therapy in a home-based AIDS care programme in rural Uganda.

BACKGROUND: Poverty and limited health services in rural Africa present barriers to adherence to antiretroviral therapy that necessitate innovative options other than facility-based methods for delivery and monitoring of such therapy. We assessed adherence to antiretroviral therapy in a cohort of HIV-infected people in a home-based AIDS care programme that provides the therapy and other AIDS care, prevention, and support services in rural Uganda. METHODS: HIV-infected individuals with advanced HIV disease or a CD4-cell count of less than 250 cells per muL were eligible for antiretroviral therapy. Adherence interventions included group education, personal adherence plans developed with trained counsellors, a medicine companion, and weekly home delivery of antiretroviral therapy by trained lay field officers. We analysed factors associated with pill count adherence (PCA) of less than 95%, medication possession ratio (MPR) of less than 95%, and HIV viral load of 1000 copies per mL or more at 6 months (second quarter) and 12 months (fourth quarter) of follow-up. FINDINGS: 987 adults who had received no previous antiretroviral therapy (median CD4-cell count 124 cells per muL, median viral load 217,000 copies per mL) were enrolled between July, 2003, and May, 2004. PCA of less than 95% was calculated for 0.7-2.6% of participants in any quarter and MPR of less than 95% for 3.3-11.1%. Viral load was below 1000 copies per mL for 894 (98%) of 913 participants in the second quarter and for 860 (96%) of 894 of participants in the fourth quarter. In separate multivariate models, viral load of at least 1000 copies per mL was associated with both PCA below 95% (second quarter odds ratio 10.6 [95% CI 2.45-45.7]; fourth quarter 14.5 [2.51-83.6]) and MPR less than 95% (second quarter 9.44 [3.40-26.2]; fourth quarter 10.5 [4.22-25.9]). INTERPRETATION: Good adherence and response to antiretroviral therapy can be achieved in a home-based AIDS care programme in a resource-limited rural African setting. Health-care systems must continue to implement, evaluate, and modify interventions to overcome barriers to comprehensive AIDS care programmes, especially the barriers to adherence with antiretroviral therapy.

Effect of co-trimoxazole prophylaxis, antiretroviral therapy, and insecticide-treated bednets on the frequency of malaria in HIV-1-infected adults in Uganda: a prospective cohort study.

BACKGROUND: HIV-1 and malaria are common infections in Africa, and cause substantial morbidity and mortality. HIV infection has been associated with an increased incidence of malaria, and more severe disease. Our aim was to assess the effect of antiretroviral treatment (ART) on the frequency of clinical malaria in people with HIV, and to measure the additive effects of co-trimoxazole (trimethoprim and sulfamethoxazole) prophylaxis, ART, and insecticide-treated bednets. METHODS: In 2001, we enrolled 466 HIV-infected individuals aged 18 years or older in Uganda in a prospective cohort study that provided co-trimoxazole prophylaxis to 399 participants after 5 months of no intervention. In 2003, we enrolled 138 survivors from the initial study, and 897 new participants from the same community, to take antiretroviral therapy (ART) in addition to co-trimoxazole prophylaxis. The ART was in most cases a combination of stavudine, lamivudine, and nevirapine or efavirenz. In 2004, we also gave participants insecticide-treated bednets. Households were visited weekly by study staff to record fever, illness, or death in the preceding 7 days. In cases of reported fever in the previous 2 days, we took blood to test for malaria parasites. We compared the frequency of clinical malaria, adjusting for CD4-cell count, age, sex, and season. FINDINGS: 1035 individuals were given co-trimoxazole and ART (median age 38 years, 74% female, and median CD4-cell count 124 cells/microL); 985 of these, plus four new participants, received co-trimoxazole, ART, and bednets. There were 166 cases of clinical malaria in the study. Compared with a baseline malaria incidence of 50.8 episodes per 100 person-years, co-trimoxazole prophylaxis was associated with 9.0 episodes per 100 person-years (adjusted incidence rate ratio [IRR] 0.24, 95% CI 0.15-0.38); ART and co-trimoxazole with 3.5 episodes per 100 person-years (0.08, 0.04-0.17); and co-trimoxazole, ART, and bednets with 2.1 episodes per 100 person-years (0.05, 0.03-0.08). Malaria incidence was significantly lower during ART and co-trimoxazole than during co-trimoxazole alone (IRR 0.36 [95% CI 0.18-0.74], p=0.0056). INTERPRETATION: A combination of co-trimoxazole, antiretroviral therapy, and insecticide-treated bednets substantially reduced the frequency of malaria in adults with HIV.

Changes in sexual behavior and risk of HIV transmission after antiretroviral therapy and prevention interventions in rural Uganda.

BACKGROUND: The impact of antiretroviral therapy (ART) on sexual risk behavior and HIV transmission among HIV-infected persons in Africa is unknown. OBJECTIVE: To assess changes in risky sexual behavior and estimated HIV transmission from HIV-infected adults after 6 months of ART. DESIGN AND METHODS: A prospective cohort study was performed in rural Uganda. Between May 2003 and December 2004 a total of 926 HIV-infected adults were enrolled and followed in a home-based ART program that included prevention counselling, voluntary counseling and testing (VCT) for cohabitating partners and condom provision. At baseline and follow-up, participants' HIV plasma viral load and partner-specific sexual behaviors were assessed. Risky sex was defined as inconsistent or no condom use with partners of HIV-negative or unknown serostatus in the previous 3 months. The rates of risky sex were compared using a Poisson regression model and transmission risk per partner was estimated, based on established viral load-specific transmission rates. RESULTS: Six months after initiating ART, risky sexual behavior reduced by 70% [adjusted risk ratio, 0.3; 95% confidence interval (CI), 0.2-0.7; P = 0.0017]. Over 85% of risky sexual acts occurred within married couples. At baseline, median viral load among those reporting risky sex was 122 500 copies/ml, and at follow-up, < 50 copies/ml. Estimated risk of HIV transmission from cohort members declined by 98%, from 45.7 to 0.9 per 1000 person years. CONCLUSIONS: Providing ART, prevention counseling, and partner VCT was associated with reduced sexual risk behavior and estimated risk of HIV transmission among HIV-infected Ugandan adults during the first 6 months of therapy. Integrated ART and prevention programs may reduce HIV transmission in Africa.

Doubts about DOT: antiretroviral therapy for resource-poor countries.

INTRODUCTION: Directly observed therapy programs developed for tuberculosis (TB) have been suggested as a model for the provision of HIV medications in resource-poor countries in order to ensure adherence and prevent drug resistance. METHODS: Opinions were formed based on a review of scientific literature regarding the effectiveness of witnessed dosing in directly observed TB therapy programs, adherence to HIV antiretroviral therapy in resource-rich and resource-poor settings, relationship between adherence and HIV antiretroviral drug resistance, HIV viral load and risk of HIV transmission, and stigmatization concerns related to HIV and TB in resource-poor settings. RESULTS/CONCLUSIONS: We suggest that the enthusiasm for HIV directly observed therapy programs is premature based on: equivocal evidence that witnessed dosing is superior to self administered therapy; mistaken assumptions that resource-poor countries are a 'special case' with respect to adherence; possible paradoxical impact of good adherence on HIV drug resistance; unproven efficacy of antiretroviral therapy in preventing HIV transmission; and potential stigmatization of daily antiretroviral dosing.

Are untimed antiretroviral drug levels useful predictors of adherence behavior?

We examined cross-sectionally the relationship between untimed drug levels and adherence in 83 individuals. Abnormally low untimed antiretroviral drug levels were sensitive in identifying individuals adherent to 60% or less of medication doses over 3 - 5-week period. An abnormally low drug level was associated with a higher viral load. A single abnormally low untimed antiretroviral drug level can identify an individual with very low adherence at high risk of HIV disease progression and death.

Asymptomatic serum cryptococcal antigenemia and early mortality during antiretroviral therapy in rural Uganda.

OBJECTIVE: To evaluate the association between a positive serum cryptococcal antigen (CRAG) test at baseline and mortality during the first 12 weeks on antiretroviral therapy (ART). Cryptococcal meningitis is a leading cause of HIV-related mortality in Africa, but current guidelines do not advocate CRAG testing as a screening tool. METHODS: Between May 2003 and December 2004, we enrolled HIV-1 infected individuals into a study of ART monitoring in rural Uganda. CRAG testing was conducted retrospectively on stored pre-ART serum samples of participants whose baseline CD4 cell count was <100 cells/mul and who were without symptoms suggestive of disseminated cryptococcal disease at enrolment. RESULTS: Of 377 participants, 5.8% had serum CRAG titre >/=1:2. Of these, 23% died during follow-up. Controlling for CD4 cell count, HIV-1 viral load, anaemia, active tuberculosis and body mass index, relative risk of death during follow-up among those with asymptomatic cryptococcal antigenemia at baseline was 6.6 [95% confidence interval (CI) 1.86-23.61, P = 0.0036]. The population attributable risk for mortality associated with a positive CRAG at baseline was 18% (CI 2-33%), similar to that associated with active tuberculosis (19%, CI 1-36%). CONCLUSION: Asymptomatic cryptococcal antigenemia independently predicts death during the first 12 weeks of ART among individuals with advanced HIV disease in rural Uganda. Routine screening and provision of azole antifungal therapy prior to or simultaneous with the start of ART should be evaluated for the potential to prevent mortality in this population.

Clinical toxicity of highly active antiretroviral therapy in a home-based AIDS care program in rural Uganda.

BACKGROUND: We evaluated clinical toxicity in HIV-infected persons receiving antiretroviral therapy (ART) in Uganda. METHODS: From May 2003 through December 2004, adults with a CD4 cell count < or =250 cells/microL or World Health Organization stage 3/4 HIV disease were prescribed ART. We calculated probabilities for time to toxicity and single-drug substitution as well as multivariate-adjusted hazard ratios for development of toxicity. RESULTS: ART (stavudine plus lamivudine with nevirapine [96%] or efavirenz [4%]) was prescribed for 1029 adults, contributing 11,268 person-months of observation. Toxicities developed in 543 instances in 411 (40%) patients (incidence rate = 4.47/100 person-months): 36% peripheral neuropathy (9% severe); 6% rash (2% severe); 2% hypersensitivity reaction; < or =0.5% acute hepatitis, anemia, acute pancreatitis, or lactic acidosis; and 13% other. Probabilities of remaining free from any toxicity at 6, 12, and 18 months were 0.76, 0.59, and 0.47 and from any severe toxicity at 6, 12, and 18 months were 0.92, 0.86, and 0.85, respectively. For 217 patients (21%), 222 single-drug substitutions were made, mostly because of peripheral neuropathy or rash. CONCLUSIONS: Clinical toxicities were common, but no patients discontinued ART because of toxicity. The most common toxicities, peripheral neuropathy and rash, were managed with single-drug substitutions. In resource-limited settings, toxicity from ART regimens containing stavudine or nevirapine is manageable but more tolerable regimens are needed.

HIV counseling and testing practices at an urban hospital in Kampala, Uganda.

While the majority of medical inpatients in Uganda are assumed to be HIV-positive, HIV testing is limited in inpatient settings. This study describes HIV testing practices and risk behavior among medical inpatients at an urban hospital in Uganda. We interviewed 395 adults on the day of discharge. Overall, 46% tested for HIV before or during admission. Of the 20% tested during hospitalization, 64% were HIV-positive. Among 47% who had sex in the previous year, only 14% used condoms consistently and only 20% knew the HIV status of their sexual partner, indicating that participants would benefit from risk-reduction counseling. Yet, only 26% of participants tested during hospitalization received post-test counseling. Half of the participants with HIV-related illnesses left the hospital without being offered the test, a missed opportunity for HIV prevention counseling and care. The findings indicate that hospitals are important venues for HIV counseling and testing.

The Evolving Role of HIV Counseling and Testing in Resource-limited Settings: HIV Prevention and Linkage to Expanding HIV Care Access.

The role of voluntary counseling and testing (VCT) of HIV in resource-limited settings has recently broadened from primarily that of a prevention intervention to its identification as the key entry point into expanding access to life-saving antiretroviral therapy, additional HIV--specific medical care, and other support services. To fulfill this expanded mandate, calls for routine counseling and testing in diverse health care settings, in addition to other innovative approaches to traditional VCT, are emerging. The efficacy and cost effectiveness of traditional facility-based VCT with respect to risk-behavior reduction of HIV have been demonstrated rigorously in resource-limited settings. Additional research is needed urgently to evaluate the feasibility, acceptability, and effectiveness of streamlined counseling and testing interventions that seek to reach as many individuals as possible to meet dual prevention and treatment goals.

The evolving role of HIV counseling and testing in resource-limited settings: HIV prevention and linkage to expanding HIV care access.

The role of voluntary counseling and testing (VCT)of HIV in resource-limited settings has recently broadened from primarily that of a prevention intervention to its identification as the key entry point into expanding access to life-saving antiretroviral therapy, additional HIV-specific medical care, and other support services. To fulfill this expanded mandate, calls for routine counseling and testing in diverse health care settings, in addition to other innovative approaches to traditional VCT, are emerging. The efficacy and cost-effectiveness of traditional facility-based VCT with respect to risk-behavior reduction of HIV have been demonstrated rigorously in resource-limited settings. Additional research is needed urgently to evaluate the feasibility, acceptability, and effectiveness of streamlined counseling and testing interventions that seek to reach as many individuals as possible to meet dual prevention and treatment goals.