Condom failure (slippage or breakage) has been shown to be associated with HIV seroconversion among men who have sex with men (MSM), but predictors of failure have been poorly elucidated. Of 2592 HIV-seronegative MSM participants in the HIV Network for Prevention Trials (HIVNET) multisite Vaccine Preparedness Study who reported condom use for anal sex in the 6 months before enrollment, condom failure was reported by 16.6%, with failure rates of 2.1/100 episodes of condom usage (2.5 failures/100 episodes for receptive anal sex and 1.9/100 episodes for insertive anal sex). In separate multivariate models evaluating predictors of condom failure reported by the insertive and receptive partners, more frequent condom use was associated with a decreased per-condom failure rate and amphetamine and heavy alcohol use with increased rates in both models. Being employed, having private medical insurance, and using lubricants for >80% of anal sex acts were significantly associated with decreased failure rates in the insertive model. Safer sex counseling should particularly target men of lower socioeconomic status, promote proper and consistent use of condoms with appropriate lubricants, and address the impact of drug use, especially amphetamines and alcohol, on condom failure.

Persons attending sexually transmitted disease clinics at three sites in Thailand were recruited to participate in a 1-year study of HIV-1 incidence. Between September 1995 and February 1996, 31% (371 of 1205) of eligible men and 24% (161 of 659) of eligible women agreed to participate. At enrollment, HIV-1 seropositivity was 3.8% among men and 2.5% among women. Follow-up of the 514 participants who were seronegative at baseline was 78% at the 12-month visit. During the study period, 53% of men reported 2 or more sexual partners, 31% reported sex with a commercial sex worker (CSW), and 33% with a casual partner. Of those visiting CSWs, 72% reported consistent condom use. Among women, 11% reported 2 or more sexual partners. Decreased HIV risk behaviors among men were observed during the study. Four incident infections occurred in men (1.4/100 person-years, 95% confidence interval [CI] = 0.4-3.6) and none among women. Based on the observed HIV-1 incidence, HIV vaccine efficacy trials in such populations would have to be larger than previously planned or more selective of high risk subgroups for recruitment.

To investigate the genetic and biologic features of HIV-1 strains circulating in Cambodia, viruses from 95 HIV-1-seropositive individuals were subtyped by heteroduplex mobility assay (HMA) and 23 were further analyzed for their biologic characteristics. Eighty-nine individuals were clearly infected by HIV-1 subtype E. The other six samples were sequenced, together with 17 HMA subtype E samples. All but one of the 23 Cambodian env sequences clustered with previously described Thai and Vietnamese subtype E sequences, bearing a GPGQ motif at the tip of the V3 loop; the last had a GPGR motif and was phylogenetically equidistant from Asian and African subtype E viruses. Nonsyncytium-inducing, CCR5-dependent viruses predominated in patients of clinical stage B even in some with a high viral load and were detected in about 50% of the patients of stage C. All syncytium-inducing strains, mostly from AIDS patients, used both CCR5 and CXCR4. The presence of syncytium-inducing viruses did not correlate with the plasma viral load. These data show that CCR5-dependent HIV-1 subtype E is currently predominant in Cambodia. The analysis of clinical and virologic markers strongly supports the idea that dynamics of the viral population during subtype E infection in Southeast Asia is similar to that of subtype B infection in Europe and the United States.

HIV-1-infected children have higher plasma viral loads and progress to disease more quickly than infected adults. To gain insight into the accelerated pathogenesis of HIV-1 in children, viral dynamics were measured following the initiation of highly active antiretroviral therapy (HAART) and compared with those reported for adults. A biphasic decline in plasma HIV-1 RNA was observed, with a rapid decrease during the first 1 to 2 weeks of therapy (phase I) followed by a slower decline (phase II). The phase I and II decay rates were not significantly different among children of different ages, pretherapy plasma HIV-1 RNA levels, or CD4 cell counts. Estimated phase I decay rates were similar to those previously reported in adults with a mean of 0.43 days(-1) and a half-life of 1.6 days. The phase II decay rates were slower in children compared with adults with a mean of 0.016 days(-1) versus 0.066 days(-1), and a half-life of 43.3 versus 14.1 days, respectively (p < .05). The mean time required to reach viral levels below detection thresholds was also longer in these children compared with that in adults. These data suggest that HIV-1 dynamics may be different in children, and that these differences may necessitate different treatment strategies.

Zidovudine (ZDV) therapy during pregnancy and to the neonate reduced perinatal HIV transmission by nearly 70% in Pediatric AIDS Clinical Trials Group (PACTG) protocol 076. ZDV has been reported as positive in several in vitro carcinogenicity screening tests. We evaluated the short-term risk for tumors in 727 children with known ZDV exposure enrolled into the PACTG 076/219 and the Women and Infants Transmission Study (WITS). ZDV exposure in utero (antepartum) occurred in 97% and 99% of infants in PACTG 076/219 or WITS, respectively. Mean follow-up was 38.3 months with 366.9 person years follow-up for PACTG 076/219 and 14.5 months with 743.7 person years follow-up for WITS. No tumors of any nature were observed; relative risk was 0 (95% confidence interval [CI], 0-17.6). These data are reassuring regarding the short-term lack of tumors for ZDV-exposed infants observed to date. Longitudinal, standardized follow-up for infants with in utero antiretroviral exposure is necessary to assess long-term carcinogenicity.

The enzyme-linked immunospot (ELISPOT) assay was adapted to detect and enumerate HIV-1-producing cells at the single cell level. With CEM cells or peripheral blood mononuclear cells (PBMC) infected in vitro with HIV-1, the ELISPOT assay detected cells that produced HIV-1 antigens and showed that between 5.4% and 9.5% of the p24 antigen-positive CEM cells and 11.1% to 23.6% of the p24 antigen-positive PBMC were productively infected. In HIV-1-infected patients in early stage of the disease and without antiretroviral therapy, up to 4.54 HIV-1-producing cells per 10(6) CD4+ T lymphocytes were detected in peripheral blood and up to 277.75 HIV-1-producing cells per 10(6) CD4+ T lymphocytes were detected in splenic lymphoid tissue. Our results indicate that the ELISPOT assay could represent a new tool to study HIV-1 replication in vivo.

HIV-1 V3 serotyping is a classification of immunodeficiency viruses based on antibody binding to V3 peptides that allows obtaining information on circulating subtypes that could be important for population-based epidemiologic studies. Recently, several laboratories have developed V3 enzyme-immunoassays (EIAs) using V3 peptides of subtypes A to E. In the present study, the utility of including additional peptides of subtypes F to H to the EIA was evaluated on a panel of 203 well-characterized serum samples from patients with diverse geographic origins (22 countries) and known HIV-1 genotype (79 A, 61 B, 21 C, 7 D, 7 E, 21 F, 6 G, 1 H). The results indicate a high predictive value (ppv) for serotypes B (> or =0.86), D (1) and E (0.88), and confirm the difficulty of predicting genotype A or C based on serotype A or C. Results also indicate that inclusion of the F peptide in the V3 EIAs may be useful (ppv = 0.61), but introduction of peptides G and H failed to demonstrate significant sensitivity or specificity for these subtypes. Correlation between serotyping and amino-acid sequences of the V3 region from 103 samples allowed the identification of key amino-acids that appear essential for subtype-specific seroreactivity.

Immune cell death or dysfunction is induced by HIV infection and results in an immunocompromised state. Newer treatments are able to control viral replication to prevent massive cytoreduction. Attention must now focus on therapies that will rapidly reconstitute the immune system to provide defense against future HIV attacks as well as opportunistic infections. In addition to increasing the rate of differentiation of myeloid and lymphoid precursors from marrow stem cells, ideal therapies should improve thymic function as well. Growth hormone (GH), a member of the hematopoietic cytokine superfamily and its receptors, is expressed in multiple sites within the immune system. GH has been shown to have a stimulatory effect on the function of thymic cells, as well as other immune cell types. In this paper, we consider the use of GH to reconstitute the immune system following cytoreduction due to HIV infection.